Clinical Trials /

My Pathway: A Study Evaluating Herceptin/Perjeta, Tarceva, Zelboraf/Cotellic, Erivedge, Alecensa, and Tecentriq Treatment Targeted Against Certain Molecular Alterations in Participants With Advanced Solid Tumors

NCT02091141

Description:

This multicenter, non-randomized, open-label study will evaluate the efficacy and safety of six treatment regimens in participants with advanced solid tumors for whom therapies that will convey clinical benefit are not available and/or are not suitable options per the treating physician's judgment.

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Breast Carcinoma
  • Colorectal Carcinoma
  • Gastric Carcinoma
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: My Pathway: A Study Evaluating Herceptin/Perjeta, Tarceva, Zelboraf/Cotellic, Erivedge, Alecensa, and Tecentriq Treatment Targeted Against Certain Molecular Alterations in Participants With Advanced Solid Tumors
  • Official Title: My Pathway: An Open-Label Phase IIa Study Evaluating Trastuzumab/Pertuzumab, Erlotinib, Vemurafenib/Cobimetinib, Vismodegib, Alectinib, and Atezolizumab in Patients Who Have Advanced Solid Tumors With Mutations or Gene Expression Abnormalities Predictive of Response to One of These Agents

Clinical Trial IDs

  • ORG STUDY ID: ML28897
  • SECONDARY ID: PRO 02
  • NCT ID: NCT02091141

Conditions

  • Neoplasms

Interventions

DrugSynonymsArms
TrastuzumabHerceptinTrastuzumab Plus Pertuzumab
PertuzumabPerjetaTrastuzumab Plus Pertuzumab
ErlotinibTarcevaErlotinib
VemurafenibZelborafVemurafenib Plus Cobimetinib
CobimetinibCotellicVemurafenib Plus Cobimetinib
VismodegibErivedgeVismodegib
AlectinibAlecensaAlectinib
AtezolizumabTecentriqAtezolizumab

Purpose

This multicenter, non-randomized, open-label study will evaluate the efficacy and safety of six treatment regimens in participants with advanced solid tumors for whom therapies that will convey clinical benefit are not available and/or are not suitable options per the treating physician's judgment.

Trial Arms

NameTypeDescriptionInterventions
Trastuzumab Plus PertuzumabExperimentalParticipants will receive trastuzumab 8 milligrams per kilogram (mg/kg) intravenous (IV) infusion as loading dose, followed by 6 mg/kg IV infusion every 3 weeks; and pertuzumab 840 mg IV infusion as loading dose, followed by 420 mg IV infusion every 3 weeks.
  • Trastuzumab
  • Pertuzumab
ErlotinibExperimentalParticipants will receive erlotinib 150 milligrams (mg) orally once daily in each 28-day cycle.
  • Erlotinib
Vemurafenib Plus CobimetinibExperimentalParticipants will receive vemurafenib 960 mg orally twice daily (BID) in each 28-day cycle; and cobimetinib 60 mg orally once daily for 21 days on and 7 days off in each 28-day cycle.
  • Vemurafenib
  • Cobimetinib
VismodegibExperimentalParticipants will receive vismodegib 150 mg orally once daily in each 28-day cycle.
  • Vismodegib
AlectinibExperimentalParticipants will receive alectinib 600 mg orally BID in each 28-day cycle.
  • Alectinib
AtezolizumabExperimentalParticipants will receive atezolizumab 1200 mg IV infusion every 3 weeks.
  • Atezolizumab

Eligibility Criteria

        General Inclusion Criteria:

          -  Life expectancy greater than or equal to (>/=) 12 weeks

          -  Histologically documented metastatic cancer (solid tumors, not including hematologic
             malignancies)

          -  Participants who have received standard first-line therapy for metastatic cancer
             (except for the tumors for which no first-line therapy exists) and in whom a trial of
             targeted therapy is considered the best available treatment option. Eligible
             participants should not have available therapies that will convey clinical benefit
             and/or are not suitable options per the treating physician's judgment

          -  No previous treatment with the specific assigned study drug or any other drug sharing
             the same target

          -  Measurable or evaluable disease by RECIST v1.1

          -  Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0, 1, or 2

          -  Adequate hematologic, renal, and liver function

          -  If applicable, use of contraception methods or abstinence as defined by the protocol

        Study-Drug Specific Inclusion Criteria:

        Trastuzumab plus Pertuzumab

          -  Molecular testing results from clinical laboratory improvement amendments
             (CLIA)-certified laboratories (using tissue and/or blood) demonstrating HER2
             overexpression, amplification, or HER2-activating mutation

             a) For participants screened using a blood assay: obtain tissue-based testing result
             confirming study eligibility (within first 4 weeks after enrollment)

          -  Participants with breast, gastric, or gastroesophageal junction cancer must have
             HER2-activating mutation

          -  Left ventricular ejection fraction (LVEF) greater than (>) 50 percent (%) or above the
             lower limit of the institutional normal range, whichever is lower

          -  Availability of an archival or new pretreatment tissue sample is required if molecular
             testing was not performed by Foundation Medicine. Any available tumor tissue sample
             can be submitted. The tissue sample may be submitted within 4 weeks after enrolment

        Erlotinib

          -  Molecular testing results from CLIA-certified laboratories (using tissue and/or blood)
             demonstrating EGFR-activating mutations

        Vemurafenib plus Cobimetinib

          -  Molecular testing results from CLIA-certified laboratories (using tissue and/or blood)
             demonstrating BRAF V600 mutations a) For participants screened using a blood assay:
             obtain tissue-based testing result confirming study eligibility (within first 4 weeks
             after enrolment)

        Vismodegib

          -  Molecular testing results from CLIA-certified laboratories (using tissue and/or blood)
             demonstrating hedgehog pathway relevant mutation (activating mutation of smoothened
             [SMO] or loss-of-function mutation of protein patched homolog-1 [PTCH-1])

             a) For participants screened using a blood assay: obtain tissue-based testing result
             confirming study eligibility (within first 4 weeks after enrollment)

          -  All non-hematological adverse events related to any prior chemotherapy, surgery, or
             radiotherapy must have resolved to National Cancer Institute Common Terminology
             Criteria for Adverse Events (NCI CTCAE) Grade less than or equal to (</=) 2 prior to
             starting therapy

        Alectinib

          -  Molecular testing results from CLIA-certified laboratories (using tissue and/or blood)
             demonstrating anaplastic lymphoma kinase (ALK) gene rearrangements, ALK mutations, ALK
             copy number gain or (for melanoma only) increased ALK expression or presence of
             ALK-alternative transcription initiation transcript (ALKATI) a) For participants
             screened using a blood assay: obtain tissue-based testing result confirming study
             eligibility (within first 4 weeks after enrolment)

        Atezolizumab

          -  Molecular testing results from CLIA-certified laboratories (using tissue)
             demonstrating programmed death-ligand 1 (PD-L1) copy number gain/amplification,
             deficiency in mismatch repair enzymes (dMMR), high levels of microsatellite
             instability (MSI-H), high tumor mutational burden (TMB-H), alterations of
             deoxyribonucleic acid (DNA) proofreading/repair genes (example., polymerase epsilon
             [POLE], polymerase delta 1 [POLD1])

          -  Availability of an archival or new pretreatment tissue sample is required if molecular
             testing was not performed by Foundation Medicine. Any available tumor tissue sample
             can be submitted. The tissue sample may be submitted within 4 weeks after enrollment

        General Exclusion Criteria:

          -  Participants with hematologic malignancies

          -  Concurrent administration of any other anti-cancer therapy (except male participants
             with prostate cancer receiving androgen blockade: Bisphosphonates and denosumab are
             allowed; Most recent anti-cancer therapy </=28 days and have not recovered from the
             side effects, excluding alopecia; Radiaiton therapy within </=14 days

          -  Active or untreated brain metastases

          -  History of carcinomatous meningitis

          -  Uncontrolled concurrent malignancy (early stage is allowed if not requiring active
             therapy or intervention)

          -  Pregnant or breastfeeding women, or intending to become pregnant during the study

          -  Any significant cardiovascular events within 6 months prior to study entry

          -  Pulmonary embolism within 30 days prior to study entry

          -  History or presence of clinically significant ventricular or atrial dysrhythmia >Grade
             2 per NCI CTCAE v4.0

          -  Any other severe acute or chronic medical or psychiatric condition or laboratory
             abnormality that may increase the risk associated with study participation or may
             interfere with the interpretation of study results

          -  Psychological, familial, sociological, or geographical conditions that do not permit
             compliance with the protocol

          -  Eligible for another actively accruing Roche/Genentech-sponsored interventional
             clinical trial

        Study-Drug Specific Exclusion Criteria:

        Trastuzumab plus Pertuzumab

          -  Breast, gastric, or gastroesophageal junction cancer identified by HER2 amplification
             or overexpression

          -  Previous treatment with any HER2-targeted therapy

        Erlotinib

          -  Non-small cell lung cancer (NSCLC) or pancreatic cancer identified by exon 19
             deletions or exon 21 L858R substitution mutations

          -  EGFR amplifications in the absence of EGFR-activating mutations

          -  Cancers with exon 20 mutations

          -  Previous treatment with erlotinib or any other EGFR inhibitor

          -  Inability to swallow pills

          -  Refractory nausea and vomiting, malabsorption, external biliary shunt, or significant
             bowel resection that would preclude absorption of erlotinib

        Vemurafenib plus Cobimetinib

          -  Malignant melanoma, papillary thyroid cancer, colorectal cancer, or hematologic
             malignancy including multiple myeloma

          -  LVEF below institutional lower level of normal (LLN) or below 50%, whichever is lower

          -  History of or evidence of retinal pathology on ophthalmologic examination that is
             considered a risk factor for neurosensory retinal detachment, retinal vein occlusion
             (RVO), or neovascular macular degeneration

          -  Presence of any of the following conditions, which are risk factors for RVO:
             Uncontrolled glaucoma with intraocular pressure >21 millimetres of mercury (mm Hg);
             Serum cholesterol >/=Grade 2; Hypertriglyceridemia >/=Grade 2; Hyperglycemia (fasting)
             >/=Grade 2; Grade >/=2 uncontrolled hypertension (participants with a history of
             hypertension controlled with anti-hypertensive medication to Grade </=1 are eligible)

          -  Prior or concurrent malignancy with known RAS mutation

          -  Previous treatment with vemurafenib or any other BRAF inhibitor (prior sorafenib is
             allowed)

          -  Previous treatment with cobimetinib or any other mitogen-activated
             protein/extracellular signal-regulated kinase (MEK) inhibitor

          -  Prior treatment with a RAF inhibitor

          -  Inability to swallow pills

          -  Refractory nausea and vomiting, malabsorption, external biliary shunt, or significant
             bowel resection that would preclude absorption of vemurafenib

          -  History of congenital long QT syndrome or mean (average of triplicate measurements)
             corrected QT (QTc) measured using Fridericia's method >/=450 millisecond (ms) at
             baseline or uncorrectable abnormalities in serum electrolytes (sodium, potassium,
             calcium, magnesium, phosphorus)

        Vismodegib

          -  Basal cell carcinoma of the skin, medulloblastoma, small-cell lung cancer, or
             hematologic malignancies

          -  Previous treatment with vismodegib or any other hedgehog pathway inhibitor

          -  Inability to swallow pills

          -  Refractory nausea and vomiting, malabsorption, external biliary shunt, or significant
             bowel resection that would preclude absorption of vismodegib

        Alectinib

          -  ALK-positive NSCLC, neuroblastoma, and childhood tumors

          -  Previous treatment with alectinib or any other ALK inhibitor

          -  Participants with symptomatic bradycardia

          -  Administration of strong/potent cytochrome P3A4 (CYP3A4) inhibitors or inducers within
             14 days prior to the first dose of study treatment and while on treatment with
             alectinib

          -  Inability to swallow pills

          -  Refractory nausea and vomiting, malabsorption, external biliary shunt, or significant
             bowel resection that would preclude absorption of alectinib

        Atezolizumab

          -  Metastatic NSCLC, metastatic urothelial carcinoma or microsatellite instability high
             metastatic colorectal cancer

          -  Previous treatment with atezolizumab or another programmed death-1 (PD-1)/PD-L1
             inhibitor

          -  History of severe allergic, anaphylactic, or other hypersensitivity reactions to
             chimeric or humanized antibodies or fusion proteins

          -  Known hypersensitivity to biopharmaceutical agents produced in Chinese hamster ovary
             cells

          -  Known allergy or hypersensitivity to any component of the atezolizumab formulation

          -  Active or history of autoimmune disease or immune deficiency

          -  Prior allogeneic stem cell or solid organ transplantation

          -  History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis
             obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of
             active pneumonitis on screening chest computed tomography (CT) scan

          -  Positive human immunodeficiency virus (HIV) test, active hepatitis B virus (HBV)
             infection, active hepatitis C virus (HCV) infection or active tuberculosis

          -  Severe infection within 4 weeks prior to initiation of study treatment

          -  Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation
             of study treatment

          -  Significant cardiovascular disease, such as New York Heart Association cardiac disease
             (Class II or greater), myocardial infarction, or cerebrovascular accident within 3
             months prior to initiation of study treatment, unstable arrhythmia, or unstable angina

          -  Major surgical procedure other than for diagnosis within 4 weeks prior to initiation
             of study treatment, or anticipation of need for a major surgical procedure during the
             course of the study

          -  Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study
             treatment, or anticipation of need for such a vaccine during the course of the study

          -  History of other malignancy within 5 years prior to screening, with the exception of
             those with a negligible risk of metastasis or death, such as adequately treated
             carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate
             cancer, ductal carcinoma in situ, or Stage I uterine cancer

          -  Any other disease, metabolic dysfunction, physical examination finding, or clinical
             laboratory finding that contraindicates the use of an investigational drug, may affect
             the interpretation of the results, or may render the participant at high risk from
             treatment complications

          -  Prior treatment with cluster of differentiation 137 (CD137) agonists or immune
             checkpoint blockade therapies

          -  Treatment with systemic immunostimulatory agents within 4 weeks or five half-lives of
             the drug (whichever is longer) prior to randomization

          -  Treatment with systemic immunosuppressive medication within 2 weeks prior to
             initiation of study treatment, or anticipation of need for systemic immunosuppressive
             medication during the course of the study
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of Participants With Overall Response
Time Frame:From the date of first study treatment until disease progression or death from any cause, whichever occurs first (up to approximately 5 years)
Safety Issue:
Description:Tumor response will be assessed using Response Evaluation Criteria in Solid Tumors (RECIST) for all arms except atezolizumab; immune-modified RECIST (imRECIST) will be used for atezolizumab arm.

Secondary Outcome Measures

Measure:Percentage of Participants With Disease Control
Time Frame:From the date of first study treatment until disease progression or death from any cause, whichever occurs first (up to approximately 5 years)
Safety Issue:
Description:Tumor response will be assessed using RECIST for all arms except atezolizumab; imRECIST will be used for atezolizumab arm.
Measure:Progression-Free Survival (PFS)
Time Frame:From the date of first study treatment until disease progression or death from any cause, whichever occurs first (up to approximately 5 years)
Safety Issue:
Description:Tumor response will be assessed using RECIST for all arms except atezolizumab; imRECIST will be used for atezolizumab arm.
Measure:Percentage of Participants who are Alive at Year 1
Time Frame:1 year
Safety Issue:
Description:
Measure:Duration of Response
Time Frame:From the date of first documented response (complete response [CR] or partial response [PR]) to the time of disease progression or death from any cause, whichever occurs first (up to approximately 5 years)
Safety Issue:
Description:Tumor response will be assessed using RECIST for all arms except atezolizumab; imRECIST will be used for atezolizumab arm.
Measure:Percentage of Participants With Overall Response as Determined by Independent Review Committee (IRC) in Colorectal Cancer Participants With Human Epidermal Growth Factor Receptor 2 (HER2) Amplification or Overexpression With a Tumor Response of CR or PR
Time Frame:From the date of first study treatment until disease progression or death from any cause, whichever occurs first (up to approximately 5 years)
Safety Issue:
Description:Tumor response will be assessed using RECIST for all arms except atezolizumab; imRECIST will be used for atezolizumab arm.
Measure:Percentage of Participants With Adverse Events
Time Frame:From first study treatment administration to 30 days (45 days for vismodegib, 90 days for atezolizumab) after the last dose (up to approximately 5 years)
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Genentech, Inc.

Last Updated

August 18, 2017