Clinical Trials /

Nivolumab and Ipilimumab in Treating Patients With Rare Tumors

NCT02834013

Description:

This clinical trial studies nivolumab and ipilimumab in treating patients with rare tumors. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. This trial enrolls participants for the following cohorts based on condition: 1. Epithelial tumors of nasal cavity, sinuses, nasopharynx: A) Squamous cell carcinoma with variants of nasal cavity, sinuses, and nasopharynx and trachea (excluding laryngeal, nasopharyngeal cancer [NPC], and squamous cell carcinoma of the head and neck [SCCHN]) B) Adenocarcinoma and variants of nasal cavity, sinuses, and nasopharynx (closed to accrual 07/27/2018) 2. Epithelial tumors of major salivary glands (closed to accrual 03/20/2018) 3. Salivary gland type tumors of head and neck, lip, esophagus, stomach, trachea and lung, breast and other location (closed to accrual) 4. Undifferentiated carcinoma of gastrointestinal (GI) tract 5. Adenocarcinoma with variants of small intestine (closed to accrual 05/10/2018) 6. Squamous cell carcinoma with variants of GI tract (stomach small intestine, colon, rectum, pancreas) (closed to accrual 10/17/2018) 7. Fibromixoma and low grade mucinous adenocarcinoma (pseudomixoma peritonei) of the appendix and ovary (closed to accrual 03/20/2018) 8. Rare pancreatic tumors including acinar cell carcinoma, mucinous cystadenocarcinoma or serous cystadenocarcinoma. Pancreatic adenocarcinoma is not eligible 9. Intrahepatic cholangiocarcinoma (closed to accrual 03/20/2018) 10. Extrahepatic cholangiocarcinoma and bile duct tumors (closed to accrual 03/20/2018) 11. Sarcomatoid carcinoma of lung 12. Bronchoalveolar carcinoma lung. This condition is now also referred to as adenocarcinoma in situ, minimally invasive adenocarcinoma, lepidic predominant adenocarcinoma, or invasive mucinous adenocarcinoma 13. Non-epithelial tumors of the ovary: A) Germ cell tumor of ovary B) Mullerian mixed tumor and adenosarcoma (closed to accrual 03/30/2018) 14. Trophoblastic tumor: A) Choriocarcinoma (closed to accrual 04/15/2019) 15. Transitional cell carcinoma other than that of the renal, pelvis, ureter, or bladder (closed to accrual 04/15/2019) 16. Cell tumor of the testes and extragonadal germ tumors: A) Seminoma and testicular sex cord cancer B) Non seminomatous tumor C) Teratoma with malignant transformation (closed to accrual 3/15/2019) 17. Epithelial tumors of penis - squamous adenocarcinoma cell carcinoma with variants of penis 18. Squamous cell carcinoma variants of the genitourinary (GU) system 19. Spindle cell carcinoma of kidney, pelvis, ureter 20. Adenocarcinoma with variants of GU system (excluding prostate cancer) (closed to accrual 07/27/2018) 21. Odontogenic malignant tumors 22. Pancreatic neuroendocrine tumor (PNET) (formerly named: Endocrine carcinoma of pancreas and digestive tract.) 23. Neuroendocrine carcinoma including carcinoid of the lung (closed to accrual 12/19/2017) 24. Pheochromocytoma, malignant 25. Paraganglioma (closed to accrual 11/29/2018) 26. Carcinomas of pituitary gland, thyroid gland parathyroid gland and adrenal cortex 27. Desmoid tumors 28. Peripheral nerve sheath tumors and NF1-related tumors (closed to accrual 09/19/2018) 29. Malignant giant cell tumors 30. Chordoma (closed to accrual 11/29/2018) 31. Adrenal cortical tumors (closed to accrual 06/27/2018) 32. Tumor of unknown primary (Cancer of Unknown Primary; CuP) (closed to accrual 12/22/2017) 33. Not Otherwise Categorized (NOC) Rare Tumors [To obtain permission to enroll in the NOC cohort, contact: S1609SC@swog.org] (closed to accrual 03/15/2019) 34. Adenoid cystic carcinoma (closed to accrual 02/06/2018) 35. Vulvar cancer 36. MetaPLASTIC carcinoma (of the breast) 37. Gastrointestinal stromal tumor (GIST) (closed to accrual 09/26/2018) 38. Perivascular epithelioid cell tumor (PEComa) 39. Apocrine tumors/extramammary Paget's disease 40. Peritoneal mesothelioma 41. Basal cell carcinoma 42. Clear cell cervical cancer 43. Esthenioneuroblastoma 44. Endometrial carcinosarcoma (malignant mixed Mullerian tumors) (closed to accrual) 45. Clear cell cervical endometrial cancer 46. Clear cell ovarian cancer 47. Gestational trophoblastic disease (GTD) 48. Gallbladder cancer 49. Small cell carcinoma of the ovary, hypercalcemic type 50. PD-L1 amplified tumors 51. Angiosarcoma 52. High-grade neuroendocrine carcinoma (pancreatic neuroendocrine tumor [PNET] should be enrolled in Cohort 22; prostatic neuroendocrine carcinomas should be enrolled into Cohort 53). Small cell lung cancer is not eligible 53. Treatment-emergent small-cell neuroendocrine prostate cancer (t-SCNC)

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Nivolumab and Ipilimumab in Treating Patients With Rare Tumors
  • Official Title: DART: Dual Anti-CTLA-4 and Anti-PD-1 Blockade in Rare Tumors

Clinical Trial IDs

  • ORG STUDY ID: NCI-2016-01041
  • SECONDARY ID: NCI-2016-01041
  • SECONDARY ID: S1609
  • SECONDARY ID: S1609
  • SECONDARY ID: S1609
  • SECONDARY ID: U10CA180888
  • NCT ID: NCT02834013

Conditions

  • Acinar Cell Carcinoma
  • Adrenal Cortex Carcinoma
  • Adrenal Gland Pheochromocytoma
  • Anal Canal Neuroendocrine Carcinoma
  • Anal Canal Undifferentiated Carcinoma
  • Appendix Mucinous Adenocarcinoma
  • Bladder Adenocarcinoma
  • Bronchioloalveolar Carcinoma
  • Cervical Adenocarcinoma
  • Cervical Squamous Cell Carcinoma, Not Otherwise Specified
  • Cholangiocarcinoma
  • Chordoma
  • Colorectal Squamous Cell Carcinoma
  • Dermoid Cyst
  • Endometrioid Adenocarcinoma
  • Esophageal Neuroendocrine Carcinoma
  • Esophageal Undifferentiated Carcinoma
  • Extrahepatic Bile Duct Carcinoma
  • Fallopian Tube Adenocarcinoma
  • Fibromyxoid Tumor
  • Gastric Neuroendocrine Carcinoma
  • Gastric Squamous Cell Carcinoma
  • Giant Cell Carcinoma
  • Intestinal Neuroendocrine Carcinoma
  • Intrahepatic Cholangiocarcinoma
  • Lung Carcinoid Tumor
  • Lung Sarcomatoid Carcinoma
  • Major Salivary Gland Carcinoma
  • Malignant Odontogenic Neoplasm
  • Malignant Peripheral Nerve Sheath Tumor
  • Malignant Testicular Sex Cord-Stromal Tumor
  • Metastatic Malignant Neoplasm of Unknown Primary Origin
  • Mixed Mesodermal (Mullerian) Tumor
  • Mucinous Adenocarcinoma
  • Mucinous Cystadenocarcinoma
  • Nasal Cavity Adenocarcinoma
  • Nasal Cavity Carcinoma
  • Nasopharyngeal Carcinoma
  • Nasopharyngeal Papillary Adenocarcinoma
  • Nasopharyngeal Undifferentiated Carcinoma
  • Oral Cavity Carcinoma
  • Oropharyngeal Undifferentiated Carcinoma
  • Ovarian Adenocarcinoma
  • Ovarian Germ Cell Tumor
  • Ovarian Mucinous Adenocarcinoma
  • Ovarian Squamous Cell Carcinoma
  • Pancreatic Acinar Cell Carcinoma
  • Pancreatic Neuroendocrine Carcinoma
  • Paraganglioma
  • Paranasal Sinus Adenocarcinoma
  • Paranasal Sinus Carcinoma
  • Parathyroid Gland Carcinoma
  • Pituitary Gland Carcinoma
  • Placental Choriocarcinoma
  • Placental-Site Gestational Trophoblastic Tumor
  • Primary Peritoneal High Grade Serous Adenocarcinoma
  • Pseudomyxoma Peritonei
  • Scrotal Squamous Cell Carcinoma
  • Seminal Vesicle Adenocarcinoma
  • Seminoma
  • Serous Cystadenocarcinoma
  • Small Intestinal Adenocarcinoma
  • Small Intestinal Squamous Cell Carcinoma
  • Spindle Cell Neoplasm
  • Squamous Cell Carcinoma of the Penis
  • Teratoma With Malignant Transformation
  • Testicular Non-Seminomatous Germ Cell Tumor
  • Thyroid Gland Carcinoma
  • Tracheal Carcinoma
  • Transitional Cell Carcinoma
  • Undifferentiated Gastric Carcinoma
  • Ureter Adenocarcinoma
  • Ureter Squamous Cell Carcinoma
  • Urethral Adenocarcinoma
  • Urethral Squamous Cell Carcinoma
  • Vaginal Adenocarcinoma
  • Vaginal Squamous Cell Carcinoma, Not Otherwise Specified
  • Vulvar Adenocarcinoma
  • Vulvar Squamous Cell Carcinoma

Interventions

DrugSynonymsArms
IpilimumabAnti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, MDX-010, MDX-CTLA4, YervoyTreatment (nivolumab, ipilimumab)
NivolumabBMS-936558, MDX-1106, NIVO, ONO-4538, OpdivoTreatment (nivolumab, ipilimumab)

Purpose

This clinical trial studies nivolumab and ipilimumab in treating patients with rare tumors. Monoclonal antibodies, such as nivolumab and ipilimumab, may interfere with the ability of tumor cells to grow and spread.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To evaluate the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 overall
      response rate (ORR) in subsets of patients with advanced rare cancers treated with
      ipilimumab plus nivolumab combination immunotherapy.

      SECONDARY OBJECTIVES:

      I. To evaluate toxicities in each cohort. II. To estimate overall survival (OS),
      progression-free survival (PFS), clinical benefit rate; and to estimate immune-related ORR
      (irORR), and immune-related PFS (irPFS) by unidimensional immune-related response criteria.

      III. To collect specimens for banking for use in future correlative biomarker research
      studies.

      OUTLINE:

      Patients receive nivolumab intravenously (IV) over 30 minutes on days 1, 15, and 29 and
      ipilimumab IV over 60 minutes on day 1. Courses repeat every 42 days in the absence of
      disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up for 10 years from
      registration.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (nivolumab, ipilimumab)ExperimentalPatients receive nivolumab IV over 30 minutes on days 1, 15, and 29 and ipilimumab IV over 60 minutes on day 1. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity.

    Eligibility Criteria

            Inclusion Criteria:
    
              -  Patients must have histologically confirmed rare cancer and/or cancer of unknown
                 primary, that did not have a match to a molecularly-guided therapy on EAY131
                 "National Cancer Institute (NCI)-Molecular Analysis for Therapy Choice (MATCH)"
                 protocol or who progressed on molecularly-matched therapy and have no further
                 molecularly-matched treatment recommendations per EAY131, "NCI-MATCH"
    
                   -  All baseline assessments must have been completed within 28 days prior to
                      registration
    
              -  Patients that do not qualify for one of the histologic cohorts may be considered for
                 registration in the "Not Otherwise Categorized" Rare Tumors cohort with confirmation
                 of the study chairs via email
    
              -  Patients that are determined to have a rare cancer with unknown primary site are
                 eligible provided that there is histologic documentation of metastatic malignancy
                 with no discernible primary site identified from histopathologic review, physical
                 exam and associated cross-sectional imaging of the chest, abdomen, and pelvis
    
              -  Patients must have a diagnostic quality computed tomography (CT) scan or magnetic
                 resonance imaging (MRI), performed within 28 days prior to registration, which
                 demonstrates measurable disease, as defined in RECIST v. 1.1; all disease must be
                 assessed and documented on the S1609 Baseline Tumor Assessment Form
    
              -  No other prior malignancy is allowed except for the following:
    
                   -  Adequately managed stage I or II cancer from which the patient is currently in
                      complete remission
    
                   -  Any other cancer from which the patient has been disease free for five years
    
                   -  Adequately managed stage I or II follicular thyroid or prostate cancer is also
                      eligible, wherein patient is not required to be in complete remission
    
              -  Patients who have received prior anti-CTLA4 or other anti-PD-1/anti-PD-L1 therapy,
                 not both, provided that it is completed >= 4 weeks prior to registration for
                 monoclonal therapy, >= 8 weeks prior to registration if therapy involved
                 immunestimulatory monoclonal antibody (mAb)s, and >= 28 days for all other
                 immunotherapy
    
              -  Patients who had prior immune-related adverse event (grade 3 or higher immune-related
                 pneumonitis, hepatitis, colitis, endocrinopathy) with prior immunotherapy (e.g.
                 cancer vaccine, cytokine, etc.) are not eligible
    
              -  Patients with clinically controlled thyroiditis or pituitary disorders on stable
                 replacement therapy are eligible
    
              -  Patients are not eligible if they have had or are planned for solid organ transplant;
                 patients who have received allogeneic hematopoietic stem cell transplant are eligible
                 if the transplant occurred at least 90 days prior to registration, patient has no
                 prior acute graft versus host disease (GVHD), and within 48 hours of registration,
                 patient demonstrates at least 90% engraftment, defined as: absolute neutrophil count
                 (ANC) >= 500 mcl, measured over 3 consecutive days or 1 day with an ANC >= 1,000 mcl,
                 or platelets >= 50,000 mcl measured, wherein the patient did not receive any platelet
                 transfusions within 7 days prior to laboratory assessment, patients with autoimmune
                 disease who are otherwise eligible under criterion 5.3 k must not have received
                 steroid and immunosuppressive therapy within 28 days prior to registration
    
              -  Patients with brain metastases or primary brain tumors must have completed treatment,
                 surgery or radiation therapy >= 28 days prior to registration and have stable disease
                 at time of registration; metastatic brain parenchymal disease must have been treated
                 and patient must be off steroids for 7 days prior to registration
    
              -  Patients must not currently be receiving any other investigational agents or any
                 other systemic anti-cancer therapy (including radiation); in event patient recently
                 received any other systemic anti-cancer therapy, patient must be off therapy at least
                 7 days prior to registration and any therapy-induced toxicity must have recovered to
                 =< grade 1
    
              -  Patients must have a Zubrod performance status of 0-2
    
              -  ANC >= 1,000/mcL
    
              -  Platelets >= 75,000/mcL
    
              -  Hemoglobin >= 8 g/dL
    
              -  Total bilirubin =< 3.0 x institutional upper limit of normal (IULN) or for
                 documented/suspected Gilbert's disease
    
              -  Total bilirubin =< 3.0 x IULN
    
              -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) both =< 3 x IULN
    
              -  Serum creatinine =< 2.0 IULN
    
              -  Creatinine clearance (CrCl) >= 50 mL/min., as estimated by the Cockcroft and Gault
                 formula; estimated creatinine clearance is based on actual body weight
    
              -  Patients must have adequate thyroid function, as evidenced by thyroid-stimulating
                 hormone (TSH), free thyroxine (T4) serum tests demonstrating values within the normal
                 range, within 28 days prior to registration; Note: TSH, with reflex T4 is allowable
                 if per institutional standard; otherwise, both TSH and free-T4 must be obtained
    
              -  Patients must have adequate adrenal axis function, as evidenced by
                 Adrenocorticotropic Hormone (ACTH) values within the normal ranges, within 28 days
                 prior to registration
    
              -  Females of childbearing potential must have negative serum pregnancy test 14 days
                 prior to registration and agree to use birth control throughout study and for 23
                 weeks after completion of protocol therapy; patients must not be pregnant or nursing;
                 women/men of reproductive potential must have agreed to use an effective
                 contraceptive method; a woman is considered to be of "reproductive potential" if she
                 has had menses at any time in the preceding 12 consecutive months; in addition to
                 routine contraceptive methods, "effective contraception" also includes heterosexual
                 celibacy and surgery intended to prevent pregnancy (or with a side-effect of
                 pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral
                 tubal ligation; however, if at any point a previously celibate patient chooses to
                 become heterosexually active during the time period for use of contraceptive measures
                 outlined in the protocol, he/she is responsible for beginning contraceptive measures
    
              -  Men of reproductive potential must have agreed to use birth control throughout the
                 study and for 31 weeks after completion of protocol therapy; in addition to routine
                 contraceptive methods, "effective contraception" also includes heterosexual celibacy
                 and surgery intended to prevent pregnancy (vasectomy); however, if at any point a
                 previously celibate patient chooses to become heterosexually active during the time
                 period for use of contraceptive measures outlined in the protocol, he is responsible
                 for beginning contraceptive measures
    
              -  Patients must not have known active hepatitis B virus (HBV) or hepatitis virus (HCV)
                 infection at time of registration; patients with HBV or HCV that have an undetectable
                 viral load, or in the opinion of the treating investigator is well-controlled, are
                 eligible
    
              -  Patients who are known to be human immunodeficiency virus (HIV)-positive at
                 registration are eligible at the time of registration:
    
                   1. Cluster of differentiation (CD)4+ cell count greater or equal to 250 cells/mm^3
    
                   2. If patient is on antiretroviral therapy, there must be minimal interactions or
                      overlapping toxicity of the antiretroviral therapy with the experimental cancer
                      treatment; once daily combinations that use pharmacologic boosters may not be
                      used
    
                   3. No history of non-malignancy acquired immunodeficiency syndrome (AIDS)-defining
                      conditions other than historical low CD4+ cell counts
    
                   4. Probable long-term survival with HIV if cancer were not present
    
              -  Patients must not have active autoimmune disease that has required systemic treatment
                 in past 2 years (i.e., with use of disease modifying agents, immunosuppressive drugs,
                 or corticosteroids with doses higher than prednisone 10mg or equivalent). Replacement
                 therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy
                 for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic
                 treatment. Autoimmune diseases include but are not limited to autoimmune hepatitis,
                 inflammatory bowel disease, multiple sclerosis, vasculitis, or glomerulonephritis;
                 patients with well-controlled systemic lupus erythematous or rheumatoid arthritis may
                 be eligible after communication with the study chairs at S1609SC@swog.org; vitiligo,
                 alopecia, hypothyroidism on stable doses of thyroid replacement therapy, psoriasis
                 not requiring systemic therapy within the past 3 years is permitted; short-term
                 steroid premedication for contrast allergy is permitted
    
              -  Patients must not have any uncontrolled intercurrent illness including (not limited
                 to): symptomatic congestive heart failure (CHF) (New York Heart Association [NYHA]
                 III/IV), unstable angina pectoris or coronary angioplasty, or stenting within 24
                 weeks prior to registration, unstable cardiac arrhythmia (ongoing cardiac
                 dysrhythmias of NCI Common Terminology Criteria for Adverse Events [CTCAE] version
                 [v] 4 grade >= 2), known psychiatric illness that would limit study compliance,
                 intra-cardiac defibrillators, known cardiac metastases, or abnormal cardiac valve
                 morphology (>= grade 3)
    
                   -  Note: Echocardiography (ECHO) and electrocardiogram (EKG) are clinically
                      indicated at baseline for any patient with a history of CHF or a risk due to
                      underlying cardiovascular disease or prior exposure to cardiotoxic drugs; if
                      patient has any evidence of CHF, MI, cardiomyopathy, or myositis cardiac
                      evaluation (NYHA I/II) patient, cardiology consultation is also clinically
                      indicated at baseline (in addition to ECHO and EKG), with creatine phosphokinase
                      (CPK) and troponin testing
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:ORR defined as confirmed and unconfirmed complete and partial response, assessed by RECIST 1.1
    Time Frame:Up to 10 years
    Safety Issue:
    Description:

    Secondary Outcome Measures

    Measure:Best response calculated from the sequence of RECIST 1.1 and immune-related response criteria (irRC) objectives
    Time Frame:Up to 10 years
    Safety Issue:
    Description:Assuming 16 eligible patients per stratum, this will be sufficient to estimate each binary version of this endpoint within +/- 25% (95% confidence interval).
    Measure:Clinical benefit rate defined as complete response, partial response, or stable disease, estimated using both RECIST and irRC
    Time Frame:6 months
    Safety Issue:
    Description:Assuming 16 eligible patients per stratum, this will be sufficient to estimate each binary version of this endpoint within +/- 25% (95% confidence interval).
    Measure:Incidence of adverse events graded by NCI CTCAE version 4.0
    Time Frame:Up to 10 years
    Safety Issue:
    Description:Assuming 16 eligible patients per stratum, this will be sufficient to estimate each binary version of this endpoint within +/- 25% (95% confidence interval).
    Measure:OS, estimated using both RECIST and irRC
    Time Frame:From date of registration to date of death due to any cause, assessed up to 10 years
    Safety Issue:
    Description:Assuming 16 eligible patients per stratum, this will be sufficient to estimate each binary version of this endpoint within +/- 25% (95% confidence interval).
    Measure:PFS, estimated using both RECIST and irRC
    Time Frame:From date of registration to date of first documentation of progression or symptomatic deterioration or death, assessed up to 10 years
    Safety Issue:
    Description:Assuming 16 eligible patients per stratum, this will be sufficient to estimate each binary version of this endpoint within +/- 25% (95% confidence interval).

    Details

    Phase:Phase 2
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:National Cancer Institute (NCI)

    Last Updated

    April 20, 2017