Clinical Trials /

Serial Measurements of Molecular and Architectural Responses to Therapy (SMMART) PRIME Trial

NCT03878524

Description:

This phase Ib trial determines if samples from a patient's cancer can be tested to find combinations of drugs that provide clinical benefit for the kind of cancer the patient has. This study is also being done to understand why cancer drugs can stop working and how different cancers in different people respond to different types of therapy.

Related Conditions:
  • Acute Lymphoblastic Leukemia
  • Acute Myeloid Leukemia
  • Chronic Lymphocytic Leukemia
  • Chronic Myeloid Leukemia
  • Hodgkin Lymphoma
  • Malignant Solid Tumor
  • Multiple Myeloma
  • Myelodysplastic Syndromes
  • Myelodysplastic/Myeloproliferative Neoplasm
  • Non-Hodgkin Lymphoma
  • Pancreatic Adenocarcinoma
  • Primary Myelofibrosis
  • Small Lymphocytic Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Serial Measurements of Molecular and Architectural Responses to Therapy (SMMART) PRIME Trial
  • Official Title: Serial Measurements of Molecular and Architectural Responses to Therapy (SMMART) Trial: PRIME

Clinical Trial IDs

  • ORG STUDY ID: STUDY00015588
  • SECONDARY ID: NCI-2020-02743
  • SECONDARY ID: STUDY00015588
  • SECONDARY ID: P30CA069533
  • NCT ID: NCT03878524

Conditions

  • Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive
  • Anatomic Stage IV Breast Cancer AJCC v8
  • Anemia
  • Ann Arbor Stage III Hodgkin Lymphoma
  • Ann Arbor Stage III Non-Hodgkin Lymphoma
  • Ann Arbor Stage IIIA Hodgkin Lymphoma
  • Ann Arbor Stage IIIB Hodgkin Lymphoma
  • Ann Arbor Stage IV Hodgkin Lymphoma
  • Ann Arbor Stage IV Non-Hodgkin Lymphoma
  • Ann Arbor Stage IVA Hodgkin Lymphoma
  • Ann Arbor Stage IVB Hodgkin Lymphoma
  • Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative
  • Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive
  • Castration-Resistant Prostate Carcinoma
  • Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive
  • Hematopoietic and Lymphoid Cell Neoplasm
  • Locally Advanced Pancreatic Adenocarcinoma
  • Metastatic Breast Carcinoma
  • Metastatic Malignant Solid Neoplasm
  • Metastatic Pancreatic Adenocarcinoma
  • Myelodysplastic/Myeloproliferative Neoplasm With Ring Sideroblasts and Thrombocytosis
  • Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable
  • Primary Myelofibrosis
  • Prognostic Stage IV Breast Cancer AJCC v8
  • Recurrent Acute Lymphoblastic Leukemia
  • Recurrent Acute Myeloid Leukemia
  • Recurrent Chronic Lymphocytic Leukemia
  • Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive
  • Recurrent Hematologic Malignancy
  • Recurrent Hodgkin Lymphoma
  • Recurrent Myelodysplastic Syndrome
  • Recurrent Myelodysplastic/Myeloproliferative Neoplasm
  • Recurrent Myeloproliferative Neoplasm
  • Recurrent Non-Hodgkin Lymphoma
  • Recurrent Plasma Cell Myeloma
  • Recurrent Small Lymphocytic Lymphoma
  • Refractory Acute Lymphoblastic Leukemia
  • Refractory Acute Myeloid Leukemia
  • Refractory Chronic Lymphocytic Leukemia
  • Refractory Chronic Myelogenous Leukemia, BCR-ABL1 Positive
  • Refractory Chronic Myelomonocytic Leukemia
  • Refractory Hematologic Malignancy
  • Refractory Hodgkin Lymphoma
  • Refractory Malignant Solid Neoplasm
  • Refractory Myelodysplastic Syndrome
  • Refractory Myelodysplastic/Myeloproliferative Neoplasm
  • Refractory Non-Hodgkin Lymphoma
  • Refractory Plasma Cell Myeloma
  • Refractory Primary Myelofibrosis
  • Refractory Small Lymphocytic Lymphoma
  • Stage II Pancreatic Cancer AJCC v8
  • Stage IIA Pancreatic Cancer AJCC v8
  • Stage IIB Pancreatic Cancer AJCC v8
  • Stage III Pancreatic Cancer AJCC v8
  • Stage IV Pancreatic Cancer AJCC v8
  • Stage IV Prostate Cancer AJCC v8
  • Stage IVA Prostate Cancer AJCC v8
  • Stage IVB Prostate Cancer AJCC v8
  • Unresectable Pancreatic Adenocarcinoma

Interventions

DrugSynonymsArms
AbemaciclibLY-2835219, LY2835219, VerzenioTreatment (biospecimen collection, 2 drug combination)
AbirateroneCB 7598Treatment (biospecimen collection, 2 drug combination)
AfatinibBIBW 2992, BIBW2992Treatment (biospecimen collection, 2 drug combination)
BevacizumabAnti-VEGF, Anti-VEGF Humanized Monoclonal Antibody, Anti-VEGF rhuMAb, Avastin, Bevacizumab awwb, Bevacizumab Biosimilar BEVZ92, Bevacizumab Biosimilar BI 695502, Bevacizumab Biosimilar CBT 124, Bevacizumab Biosimilar CT-P16, Bevacizumab Biosimilar FKB238, Bevacizumab Biosimilar HD204, Bevacizumab Biosimilar HLX04, Bevacizumab Biosimilar IBI305, Bevacizumab Biosimilar LY01008, Bevacizumab Biosimilar MIL60, Bevacizumab Biosimilar QL 1101, Bevacizumab Biosimilar RPH-001, Bevacizumab Biosimilar SCT501, BP102, BP102 Biosimilar, HD204, Immunoglobulin G1 (Human-Mouse Monoclonal rhuMab-VEGF Gamma-Chain Anti-Human Vascular Endothelial Growth Factor), Disulfide With Human-Mouse Monoclonal rhuMab-VEGF Light Chain, Dimer, Recombinant Humanized Anti-VEGF Monoclonal Antibody, rhuMab-VEGF, SCT501Treatment (biospecimen collection, 2 drug combination)
BicalutamideCasodex, Cosudex, ICI 176,334, ICI 176334Treatment (biospecimen collection, 2 drug combination)
Bortezomib[(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid, LDP 341, MLN341, PS-341, PS341, VelcadeTreatment (biospecimen collection, 2 drug combination)
CabazitaxelJevtana, RPR-116258A, Taxoid XRP6258, XRP-6258Treatment (biospecimen collection, 2 drug combination)
CabozantinibTreatment (biospecimen collection, 2 drug combination)
CapecitabineRo 09-1978/000, XelodaTreatment (biospecimen collection, 2 drug combination)
CarboplatinBlastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carboplatinum, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, RibocarboTreatment (biospecimen collection, 2 drug combination)
CelecoxibBenzenesulfonamide, 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]-, Celebrex, SC-58635, YM 177Treatment (biospecimen collection, 2 drug combination)
CobimetinibCotellic, GDC-0973, MEK Inhibitor GDC-0973, XL518Treatment (biospecimen collection, 2 drug combination)
CopanlisibBAY 80-6946, PI3K Inhibitor BAY 80-6946Treatment (biospecimen collection, 2 drug combination)
DabrafenibBRAF Inhibitor GSK2118436, GSK-2118436, GSK-2118436A, GSK2118436Treatment (biospecimen collection, 2 drug combination)
DacomitinibEGFR Inhibitor PF-00299804, PF-00299804, PF-00299804-03, PF-299804, VizimproTreatment (biospecimen collection, 2 drug combination)
DarolutamideAntiandrogen ODM-201, BAY 1841788, BAY-1841788, BAY1841788, ODM 201, ODM-201Treatment (biospecimen collection, 2 drug combination)
DasatinibBMS-354825, Dasatinib Hydrate, Dasatinib Monohydrate, SprycelTreatment (biospecimen collection, 2 drug combination)
DoxorubicinAdriablastin, Hydroxydaunomycin, Hydroxyl Daunorubicin, HydroxyldaunorubicinTreatment (biospecimen collection, 2 drug combination)
DurvalumabImfinzi, Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer, MEDI-4736, MEDI4736Treatment (biospecimen collection, 2 drug combination)
EnzalutamideASP9785, MDV3100, XtandiTreatment (biospecimen collection, 2 drug combination)
ErlotinibTreatment (biospecimen collection, 2 drug combination)
Everolimus42-O-(2-Hydroxy)ethyl Rapamycin, Afinitor, Certican, RAD 001, RAD001, Votubia, ZortressTreatment (biospecimen collection, 2 drug combination)
Fluorouracil5 Fluorouracil, 5 Fluorouracilum, 5 FU, 5-Fluoro-2,4(1H, 3H)-pyrimidinedione, 5-Fluorouracil, 5-Fluracil, 5-Fu, 5FU, AccuSite, Carac, Fluoro Uracil, Fluouracil, Flurablastin, Fluracedyl, Fluracil, Fluril, Fluroblastin, Ribofluor, Ro 2-9757, Ro-2-9757Treatment (biospecimen collection, 2 drug combination)
IdelalisibCAL-101, GS 1101, GS-1101, Phosphoinositide-3 Kinase Delta Inhibitor CAL-101, ZydeligTreatment (biospecimen collection, 2 drug combination)
ImatinibTreatment (biospecimen collection, 2 drug combination)
IpilimumabAnti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, MDX-010, MDX-CTLA4, YervoyTreatment (biospecimen collection, 2 drug combination)
LenvatinibE7080, ER-203492-00, Multi-Kinase Inhibitor E7080Treatment (biospecimen collection, 2 drug combination)
LeucovorinFolinic acidTreatment (biospecimen collection, 2 drug combination)
Lorlatinib2H-4,8-Methenopyrazolo(4,3-H)(2,5,11)benzoxadiazacyclotetradecine-3-carbonitrile, 7-amino-12-fluoro-10,15,16,17-tetrahydro-2,10,16-trimethyl-15-oxo-, (10R)-, Lorbrena, PF-06463922Treatment (biospecimen collection, 2 drug combination)
LosartanTreatment (biospecimen collection, 2 drug combination)
Nab-paclitaxelABI 007, ABI-007, Abraxane, Albumin-bound Paclitaxel, Albumin-Stabilized Nanoparticle Paclitaxel, Nanoparticle Albumin-bound Paclitaxel, Nanoparticle Paclitaxel, Paclitaxel Albumin, paclitaxel albumin-stabilized nanoparticle formulation, Protein-bound PaclitaxelTreatment (biospecimen collection, 2 drug combination)
Neratinib(2E)-N-(4-((3-chloro-4-((pyridin-2-yl)methoxy)phenyl)amino)-3-cyano-7-ethoxyquinolin-6-yl)-4-(dimethylamino)but-2-enamide, HKI 272, HKI-272, PB 272, PB-272Treatment (biospecimen collection, 2 drug combination)
NivolumabBMS-936558, MDX-1106, NIVO, ONO-4538, OpdivoTreatment (biospecimen collection, 2 drug combination)
OlaparibAZD 2281, AZD-2281, AZD2281, KU-0059436, Lynparza, PARP Inhibitor AZD2281Treatment (biospecimen collection, 2 drug combination)
Oxaliplatin1-OHP, Ai Heng, Aiheng, Dacotin, Dacplat, Diaminocyclohexane Oxalatoplatinum, Eloxatin, Eloxatine, JM-83, Oxalatoplatin, Oxalatoplatinum, RP 54780, RP-54780, SR-96669Treatment (biospecimen collection, 2 drug combination)
Palbociclib6-Acetyl-8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-8h-pyrido(2,3-d)pyrimidin-7-one, Ibrance, PD 0332991, PD 332991, PD 991, PD-0332991Treatment (biospecimen collection, 2 drug combination)
PanobinostatFaridak, Farydak, LBH589Treatment (biospecimen collection, 2 drug combination)
PembrolizumabKeytruda, Lambrolizumab, MK-3475, SCH 900475Treatment (biospecimen collection, 2 drug combination)
Pertuzumab2C4, 2C4 Antibody, MoAb 2C4, Monoclonal Antibody 2C4, Omnitarg, Perjeta, rhuMAb2C4, RO4368451Treatment (biospecimen collection, 2 drug combination)
PonatinibAP-24534, AP24534Treatment (biospecimen collection, 2 drug combination)
RegorafenibBAY 73-4506, StivargaTreatment (biospecimen collection, 2 drug combination)
RuxolitinibINCB-18424, INCB18424, Jakafi, Oral JAK Inhibitor INCB18424Treatment (biospecimen collection, 2 drug combination)
SirolimusAY 22989, RAPA, Rapamune, Rapamycin, SILA 9268A, WY-090217Treatment (biospecimen collection, 2 drug combination)
SorafenibBA4 43 9006, BAY 43-9006, Bay-439006Treatment (biospecimen collection, 2 drug combination)
SunitinibTreatment (biospecimen collection, 2 drug combination)
TrametinibGSK1120212, JTP-74057, MEK Inhibitor GSK1120212, MekinistTreatment (biospecimen collection, 2 drug combination)
Trastuzumab EmtansineAdo Trastuzumab Emtansine, ADO-Trastuzumab Emtansine, Kadcyla, PRO132365, RO5304020, T-DM1, Trastuzumab-DM1, Trastuzumab-MCC-DM1, Trastuzumab-MCC-DM1 Antibody-Drug Conjugate, Trastuzumab-MCC-DM1 ImmunoconjugateTreatment (biospecimen collection, 2 drug combination)
Tretinoin2,4,6,8-Nonatetraenoic acid, 3, 7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-, (all-E)-, Aberel, Airol, Aknoten, all trans-Retinoic acid, All-trans Retinoic Acid, All-trans Vitamin A Acid, all-trans-Retinoic acid, all-trans-Vitamin A acid, ATRA, Avita, beta-Retinoic Acid, Cordes Vas, Dermairol, Epi-Aberel, Eudyna, Renova, Retin-A, Retin-A MICRO, Retin-A-Micro, Retinoic Acid, Retisol-A, Ro 5488, Stieva-A, Stieva-A Forte, Trans Retinoic Acid, Trans Vitamin A Acid, trans-Retinoic Acid, Tretinoinum, Vesanoid, Vitamin A Acid, Vitamin A acid, all-trans-, VitinoinTreatment (biospecimen collection, 2 drug combination)
VemurafenibBRAF (V600E) kinase inhibitor RO5185426, BRAF(V600E) Kinase Inhibitor RO5185426, PLX-4032, PLX4032, RG 7204, RG7204, RO 5185426, ZelborafTreatment (biospecimen collection, 2 drug combination)
VenetoclaxABT-0199, ABT-199, ABT199, GDC-0199, RG7601, Venclexta, VenclyxtoTreatment (biospecimen collection, 2 drug combination)
VismodegibErivedge, GDC-0449, Hedgehog Antagonist GDC-0449Treatment (biospecimen collection, 2 drug combination)
VorinostatL-001079038, MSK-390, SAHA, Suberanilohydroxamic Acid, Suberoylanilide Hydroxamic Acid, ZolinzaTreatment (biospecimen collection, 2 drug combination)

Purpose

This phase Ib trial determines if samples from a patient's cancer can be tested to find combinations of drugs that provide clinical benefit for the kind of cancer the patient has. This study is also being done to understand why cancer drugs can stop working and how different cancers in different people respond to different types of therapy.

Detailed Description

      PRIMARY OBJECTIVE:

      I. To determine the feasibility of implementing an individualized treatment strategy for
      advanced solid tumor and hematological malignancies based upon a comprehensive assessment of
      tumor and patient characteristics.

      SECONDARY OBJECTIVES:

      I. To describe the tolerability of implementing an individualized treatment strategy,
      particularly by measuring unanticipated toxicity associated with the administration of
      different combinations of two therapeutic agents given to an individual participant.

      II. To assess the duration of treatment for participants receiving Serial Measurements of
      Molecular and Architectural Responses to Therapy (SMMART)-PRIME Therapy #1.

      III. To determine overall survival of participants with advanced solid tumors and
      hematological malignancies.

      IV. To determine the time to decline in a participant's ability to perform activities of
      daily living.

      EXPLORATORY OBJECTIVES:

      I. To measure quality of life among enrolled participants. II. To evaluate immune-mediated
      tumor response among participants receiving an immunomodulatory study drug.

      III. To determine the rates of response and benefit to SMMART-PRIME Therapy #1, as an
      individualized treatment strategy for participants with advanced solid tumor and
      hematological malignancies.

      IV. To determine the progression-free and disease-free survival of participants with advanced
      solid tumors and hematological malignancies.

      OUTLINE:

      TUMOR BIOPSY: Patients undergo collection of tissue samples. Clinical analytics are performed
      on the samples and analyzed by a clinical tumor board to recommend a treatment option based
      on those analytics. The findings from these Clinical Study Analytics are intended to provide
      the basis for selection of two drugs that, when administered in combination, provide an
      optimal and individualized treatment approach. This may or may not include a SMMART-PRIME
      treatment. The decision to initiate any SMMART-PRIME Therapy ultimately resides with the
      treating physician in conjunction with the study participant.

      SMMART-PRIME TREATMENT: Patients receive a combination of 2 drugs (Drug A and Drug B,
      selected from interventions below). Doses will be escalated within individual patients over
      time. As described in detail below, escalation will occur on a monthly basis and is
      anticipated to occur as follows: first month -- 100% Food and Drug Administration (FDA)
      approved dose Drug A + 25% FDA approved dose Drug B; second month -- 100% dose Drug A + 50%
      dose Drug B; third month -- 100% dose Drug A + 100% dose Drug B. All dose-escalations will be
      reviewed and approved by an independent consultant outside of Oregon Health & Science
      University (OHSU).

      Treatment will continue for up to the end of 6 treatment cycles (cycle length is between
      21-28 days) in the absence of disease progression or unacceptable toxicity. Patients whose
      treatment is discontinued as a result of excess toxicity or lack of efficacy may switch to a
      different combination of drugs. Beyond six cycles, participants will be considered
      off-protocol directed treatment, and will move into long term follow-up.

      After completion of study treatment, patients are followed for up to 5 years.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (biospecimen collection, 2 drug combination)ExperimentalSee Detailed Description.
  • Abemaciclib
  • Abiraterone
  • Afatinib
  • Bevacizumab
  • Bicalutamide
  • Bortezomib
  • Cabazitaxel
  • Cabozantinib
  • Capecitabine
  • Carboplatin
  • Celecoxib
  • Cobimetinib
  • Copanlisib
  • Dabrafenib
  • Dacomitinib
  • Darolutamide
  • Dasatinib
  • Doxorubicin
  • Durvalumab
  • Enzalutamide
  • Erlotinib
  • Everolimus
  • Fluorouracil
  • Idelalisib
  • Imatinib
  • Ipilimumab
  • Lenvatinib
  • Leucovorin
  • Lorlatinib
  • Losartan
  • Nab-paclitaxel
  • Neratinib
  • Nivolumab
  • Olaparib
  • Oxaliplatin
  • Palbociclib
  • Panobinostat
  • Pembrolizumab
  • Pertuzumab
  • Ponatinib
  • Regorafenib
  • Ruxolitinib
  • Sirolimus
  • Sorafenib
  • Sunitinib
  • Trametinib
  • Trastuzumab Emtansine
  • Tretinoin
  • Vemurafenib
  • Venetoclax
  • Vismodegib
  • Vorinostat

Eligibility Criteria

        Key Inclusion Criteria:

          -  Ability to understand and the willingness to sign a written informed consent document

          -  Participants, both men and women, must agree to use an adequate method of
             contraception prior to study entry, for the duration of study participation, and for 4
             months after completion of study

          -  Women of childbearing potential must have a negative serum or urine pregnancy test
             within 14 days prior to start of study drug administration

          -  Patients must have a histologically or cytologically-confirmed metastatic solid tumor
             or hematological malignancy that has progressed as follows:

               -  Patients with a solid tumor must have metastatic disease and have progressed on
                  at least 1 line of established therapy that is known to provide clinical benefit,
                  or for whom no standard curative therapy exists. Participants with newly
                  diagnosed, unresectable, locally-advanced or metastatic pancreatic adenocarcinoma
                  and are beginning first-line treatment with a course of chemotherapy are eligible
                  OR

               -  Participants must have a hematological malignancy that is advanced, relapsed, or
                  refractory to at least 1 line of established therapy that is known to provide
                  clinical for the treatment of their disease. Hematological disease included in
                  this study are as follows:

                    -  Acute myelogenous leukemia (AML), or

                    -  Myelodysplastic syndrome (MDS), or

                    -  MDS/myeloproliferative neoplasms (MDS/MPN), or

                    -  Primary myelofibrosis (PMF)

                    -  Acute lymphoblastic leukemia (ALL)

                    -  Chronic myelogenous leukemia (CML)

                    -  Non-Hodgkin lymphoma (NHL) or Hodgkin's disease (HD)

                    -  Chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL)

                    -  Multiple myeloma (MM)

          -  Participants with a metastatic solid tumor or advanced hematological malignancy whom,
             due to medical issues cannot receive standard therapy shown to prolong survival, will
             be eligible, if other eligibility criteria are met

               -  Patients with a metastatic solid tumor or advanced hematological malignancy that
                  actively refuse chemotherapy that is considered standard treatment for their
                  cancer, despite being informed by the investigator about the treatment options,
                  are eligible for this study on a case-by-case basis (in consultation with the
                  principal investigator [PI]). Potential participants actively refusing
                  chemotherapy must have had progression or refractory disease prior to starting
                  study treatment, and their refusal must be documented

          -  Participants must have measurable disease:

               -  Patients with solid tumors must have measurable disease as defined by Response
                  Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. At least one lesion
                  that can be accurately measured in at least one dimension (longest diameter to be
                  recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm with
                  conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan,
                  per RECIST (v1.1). Note: Participants with lesions on a bone scan that are
                  considered distinctly metastatic will also be included

               -  Patients with lymphoma must have at least one non-irradiated tumor mass > 15 mm
                  (long axis of lymph node) or > 10 mm (short axis of lymph node or extranodal
                  lesions) on spiral CT-scan

               -  Patients with CLL must have presence of radiographically measurable
                  lymphadenopathy (defined as the presence of >= 1 nodal lesion that measures >=
                  2.0 cm in the longest diameter [LD] and >= 1.0 cm in the longest perpendicular
                  diameter [LPD] as assessed by CT or magnetic resonance imaging [MRI])

               -  Patients with MM must have at least one of the following: serum monoclonal
                  component > 1 g/dL (IgG), or > 0.5 g/dL (IgA), or Bence-Jones (BJ) proteinuria >
                  200 mg/24 hour, or measurable plasmacytoma (not previously irradiated)

          -  Participants with a hematological malignancy must have their bone marrow biopsy and
             aspirate reviewed at Oregon Health & Science University (OHSU)

          -  Participants with a solid tumor must have lesions meeting the above criteria also and
             must be amenable to biopsy procedures performed per institutional standards

          -  Participants must not currently be receiving any other investigational agents

          -  Participants must have Eastern Cooperative Oncology Group (ECOG) performance status =<
             2 and a physician assessed life expectancy of >= 6 months

          -  Absolute neutrophil count (ANC) >= 1,500/mcL (at time of registration and within 4
             weeks prior to initiating on-protocol treatment)

               -  Waived for those with hematological malignancy; and may be waived on a
                  case-by-case basis for patient populations recognized to have normal baseline
                  values below this level

          -  Platelets >= 100,000/mcL (at time of registration and within 4 weeks prior to
             initiating on-protocol treatment)

               -  Waived for those with hematological malignancy

          -  Hemoglobin >= 9 g/dL or >= 5.6 mmol/L (at time of registration and within 4 weeks
             prior to initiating on-protocol treatment)

               -  Waived for those with hematological malignancy

          -  Creatinine =< 1.5 x upper limit of normal (ULN) OR measured or calculated creatinine
             clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or
             creatinine clearance [CrCl]) >= 60 mL/min/1.73 m^2 for participants with creatinine
             levels > 1 x institutional ULN (at time of registration and within 4 weeks prior to
             initiating on-protocol treatment)

               -  Waived for those with hematological malignancy; and may be waived on a
                  case-by-case basis for patient populations recognized to have normal baseline
                  values below this level

          -  Total bilirubin =< 1.5 x ULN OR direct bilirubin =< ULN for participants with total
             bilirubin levels > 1.5 x ULN (at time of registration and within 4 weeks prior to
             initiating on-protocol treatment)

               -  Creatinine clearance should be calculated per institutional standard. For
                  participants with a baseline calculated creatinine clearance below normal
                  institutional laboratory values, a measured baseline creatinine clearance should
                  be determined. Individuals with higher values felt to be consistent with inborn
                  errors of metabolism will be considered on a case-by-case basis

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and
             alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x
             ULN (at time of registration and within 4 weeks prior to initiating on-protocol
             treatment)

          -  International normalized ratio (INR) or prothrombin time (PT) =< 1.5 x ULN unless
             participant is receiving anticoagulant therapy as long as PT or partial thromboplastin
             time (PTT) is within therapeutic range of intended use of anticoagulants (at time of
             registration and within 4 weeks prior to initiating on-protocol treatment)

          -  Activated partial thromboplastin time (aPTT) or PTT =< 1.5 x ULN unless participant is
             receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of
             intended use of anticoagulants (at time of registration and within 4 weeks prior to
             initiating on-protocol treatment)

          -  Body mass index (BMI) > 1.6 and < 3.5 kg/m^2 (at time of registration and within 4
             weeks prior to initiating on-protocol treatment)

               -  Participants with a BMI of >= 3.0 will use ideal body weight indices in
                  calculating the delivery of agents that are dosed based upon body surface area
                  (i.e., mg agent/meter squared) or weight (i.e., mg agent/kg body weight)

          -  Any prior therapy, radiotherapy (except palliative radiation therapy of 30 Gy or
             less), or major surgery must have been completed >= 4 weeks prior to start of study
             treatment. All adverse events due to prior therapy must have resolved to a grade 1 or
             better (except alopecia and lymphopenia for all disease cohorts, and hematologic
             toxicity for those with a hematological malignancy) by start of treatment. Palliative
             radiation therapy must have been completed at least 2 weeks prior to start of
             treatment. The radiotherapy must not be to a lesion that is included as measurable
             disease

          -  Additional cancer-specific inclusion criteria must also be met

        Key Exclusion Criteria:

          -  Participants with metastases to the central nervous system that are considered
             uncontrolled and/or were diagnosed within the past 4 weeks of screening for this study

          -  Participants cannot have an active malignancy of another cancer. Those with a history
             of prior malignancy will be considered on a case-by-case basis. Guiding examples for
             those who can be enrolled include: individuals who have been disease free for > 5
             years; individuals who are considered to have a high likelihood of being cured (e.g.,
             prior history of stage 1 rectal cancer and currently otherwise disease free);
             adequately treated localized non-melanomatous skin cancer

          -  Participants cannot be on other forms of anti-cancer therapy at the same time, except
             as described within this protocol. There must be at least a washout period that
             accounts for 5 half-lives (or >= 21 days, whichever is longer) of last therapy

               -  Participants with prostate cancer (PCa) will continue treatment with androgen
                  deprivation therapy, either by prior castration or treatment with luteinizing
                  hormone-releasing hormone (LHRH) antagonists or agonists, as is standard practice

               -  Participants with breast cancer (BCa) who are HER2 positive may continue to
                  receive anti-HER2 therapy per standard practice guidelines, while participants
                  who are hormone receptor positive may continue to receive hormone therapy per
                  standard practice guidelines

               -  Participants with a hematological malignancy may continue to receive hydroxyurea
                  or other hypomethylating agent for two cycles of SMMART-PRIME therapy, as
                  described in this protocol

          -  Uncontrolled intercurrent illness including, but not limited to, symptomatic
             congestive heart failure, unstable angina pectoris, serious cardiac arrhythmia,
             myocardial infarction within 6 months prior to enrollment, New York Heart Association
             (NYHA) class III or IV heart failure

          -  Chronic graft versus host disease (GVHD) or on immunosuppressive therapy for the
             control of GVHD

          -  Participants with uncontrolled infection will not be enrolled until infection is
             treated

          -  Participant is seropositive with human immunodeficiency virus (HIV) or has active
             infection with hepatitis B virus (HBV) or hepatitis C virus (HCV)

               -  HIV-infected patients on effective anti-retroviral therapy with undetectable
                  viral load within 6 months are eligible for this trial

               -  For patients with evidence of chronic HBV infection, the HBV viral load must be
                  undetectable on suppressive therapy, if indicated

               -  Individuals with a history of HCV infection must have been treated and cured. For
                  patients with HCV infection who are currently on treatment, they are eligible if
                  they have an undetectable HCV viral load

          -  Participants with medical conditions, inclusive of psychiatric, that in the opinion of
             the investigators would jeopardize the patient or the study will be excluded

          -  Participants that are pregnant or breast feeding

          -  ON-TREATMENT: Individuals that have medical and/or psychiatric conditions that in the
             opinion of investigators would jeopardize participant safety or study integrity if
             they were to receive on-study treatment will not proceed further treatment and will be
             removed from study

          -  ON-TREATMENT: If performance status is ECOG > 2

          -  ON-TREATMENT: History of allergic reaction to a recommended study agent or its
             excipients

          -  Additional cancer-specific exclusion criteria requirements
      
Maximum Eligible Age:N/A
Minimum Eligible Age:21 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Feasibility of implementing an individualized treatment strategy
Time Frame:From date of tumor board recommendation to first dose of SMMART-PRIME Therapy #1 (up to 3 months)
Safety Issue:
Description:Measured as the number of participants to receive the first dose of Serial Measurements of Molecular and Architectural Responses to Therapy (SMMART)-PRIME therapy (Therapy #1) within 3 months from the date of Clinical Tumor Board providing a recommended drug combination.

Secondary Outcome Measures

Measure:Incidence of grade 3+ toxicities attributable to assigned study drug(s)
Time Frame:30 days post completion of each SMMART-PRIME Therapy (up to 6 months)
Safety Issue:
Description:Measured with National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Criteria version 5.0.
Measure:Time to treatment discontinuation
Time Frame:Completion of SMMART-PRIME Therapy #1 (up to 6 months)
Safety Issue:
Description:Measured as time (days) from start of SMMART-PRIME Therapy #1 to discontinuation for any reason.
Measure:Overall survival (OS)
Time Frame:Death from any cause (up to 60 months after the last dose of SMMART-PRIME Therapy #1)
Safety Issue:
Description:Overall survival (OS) is defined as the time (days) from start of SMMART-PRIME Therapy #1 to death from any reason.
Measure:Time to decline (TTD)
Time Frame:Completion of SMMART-PRIME Therapy #1 (up to 6 months)
Safety Issue:
Description:Measured time (days) from start of SMMART-PRIME Therapy #1 to recorded Eastern Cooperative Oncology Group (ECOG) performance status >= 3 using cumulative incidence methods.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:OHSU Knight Cancer Institute

Last Updated

June 26, 2020