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Nivolumab and Ipilimumab in Treating Patients With Rare Tumors

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ClinicalTrials.gov Identifier: NCT02834013
Recruitment Status : Recruiting
First Posted : July 15, 2016
Last Update Posted : December 12, 2019
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Tracking Information
First Submitted Date  ICMJE July 13, 2016
First Posted Date  ICMJE July 15, 2016
Last Update Posted Date December 12, 2019
Actual Study Start Date  ICMJE January 13, 2017
Estimated Primary Completion Date August 31, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 5, 2019)
Overall response rate (ORR) [ Time Frame: Up to 10 years ]
Defined as confirmed and unconfirmed complete and partial response. Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
Original Primary Outcome Measures  ICMJE
 (submitted: July 13, 2016)
ORR defined as confirmed and unconfirmed complete and partial response, assessed by RECIST 1.1 [ Time Frame: Up to 10 years ]
Change History Complete list of historical versions of study NCT02834013 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 5, 2019)
  • Incidence of adverse events [ Time Frame: Up to 10 years ]
    Graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Assuming 16 eligible patients per stratum, this will be sufficient to estimate each binary version of this endpoint within +/- 25% (95% confidence interval).
  • Best response [ Time Frame: Up to 10 years ]
    Calculated from the sequence of RECIST 1.1 and immune-related (i)RECIST objectives. Assuming 16 eligible patients per stratum, this will be sufficient to estimate each binary version of this endpoint within +/- 25% (95% confidence interval).
  • Clinical benefit rate [ Time Frame: 6 months ]
    Defined as complete response, partial response, or stable disease, estimated using both RECIST and iRECIST. Assuming 16 eligible patients per stratum, this will be sufficient to estimate each binary version of this endpoint within +/- 25% (95% confidence interval).
  • Overall survival (OS) [ Time Frame: From date of registration to date of death due to any cause, assessed up to 10 years ]
    Estimated using both RECIST and irRC. Assuming 16 eligible patients per stratum, this will be sufficient to estimate each binary version of this endpoint within +/- 25% (95% confidence interval).
  • Progression free survival (PFS) [ Time Frame: From date of registration to date of first documentation of progression or symptomatic deterioration or death, assessed up to 10 years ]
    Estimated using both RECIST and irRC. Assuming 16 eligible patients per stratum, this will be sufficient to estimate each binary version of this endpoint within +/- 25% (95% confidence interval).
Original Secondary Outcome Measures  ICMJE
 (submitted: July 13, 2016)
  • Best response calculated from the sequence of RECIST 1.1 and immune-related response criteria (irRC) objectives [ Time Frame: Up to 10 years ]
    Assuming 16 eligible patients per stratum, this will be sufficient to estimate each binary version of this endpoint within +/- 25% (95% confidence interval).
  • Clinical benefit rate defined as complete response, partial response, or stable disease, estimated using both RECIST and irRC [ Time Frame: 6 months ]
    Assuming 16 eligible patients per stratum, this will be sufficient to estimate each binary version of this endpoint within +/- 25% (95% confidence interval).
  • Incidence of adverse events graded by NCI CTCAE version 4.0 [ Time Frame: Up to 10 years ]
    Assuming 16 eligible patients per stratum, this will be sufficient to estimate each binary version of this endpoint within +/- 25% (95% confidence interval).
  • 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 ]
    Assuming 16 eligible patients per stratum, this will be sufficient to estimate each binary version of this endpoint within +/- 25% (95% confidence interval).
  • 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 ]
    Assuming 16 eligible patients per stratum, this will be sufficient to estimate each binary version of this endpoint within +/- 25% (95% confidence interval).
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Nivolumab and Ipilimumab in Treating Patients With Rare Tumors
Official Title  ICMJE DART: Dual Anti-CTLA-4 and Anti-PD-1 Blockade in Rare Tumors
Brief Summary

This phase II 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)
Detailed Description

PRIMARY OBJECTIVES:

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

II. To evaluate the overall response rate (ORR) in patients with gestational trophoblastic tumors treated with ipilimumab plus nivolumab combination immunotherapy.

III. To evaluate the RECIST v1.1 overall response rate (ORR) in patients PD-L1 amplified cancers treated with nivolumab 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 (i)RECIST ORR (iORR), and iRECIST PFS (iPFS) across cohorts and within each cohort.

TRANSLATIONAL MEDICINE OBJECTIVES:

I. Across strata, to evaluate the association of tumor mutational burden measured by tissue sequencing with durable response (complete response [CR] or partial response [PR] lasting 24 weeks or more).

II. Within strata, to describe the mutational load and targeted sequencing of well-known oncogenes and changes in these markers of patients at up to three time points (baseline, cycle 2, and progression), and across strata to describe associations with survival outcomes.

III. Within strata, to describe the presence of germline mutations, and across strata to evaluate association with outcome.

IV. Within strata, to describe patient risk category as defined by the biodesix protein signature and change over time at up to three time points (baseline, cycle 2, progression), and across strata to evaluate associations with outcomes.

V. Across strata, to evaluate the association of PD-L1 expression (positive versus negative) with response and survival outcomes, and within strata, to characterize baseline PD-L1 prevalence.

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

OUTLINE: Patients are assigned to 1 of 2 arms.

ARM I (ALL COHORTS EXCEPT THE PD-L1 AMPLIFIED COHORT): Patients receive nivolumab intravenously (IV) over 30 minutes on days 1, 15, and 29 and ipilimumab IV over 60 minutes on day 1. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity.

ARM II (PD-L1 AMPLIFIED COHORT): Patients receive nivolumab IV over 30 minutes on days 1, 15 and 29. Cycles 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Acinar Cell Carcinoma
  • Adenoid Cystic Carcinoma
  • Adrenal Cortex Carcinoma
  • Adrenal Gland Pheochromocytoma
  • Anal Canal Neuroendocrine Carcinoma
  • Anal Canal Undifferentiated Carcinoma
  • Angiosarcoma
  • Apocrine Neoplasm
  • Appendix Mucinous Adenocarcinoma
  • Bartholin Gland Transitional Cell Carcinoma
  • Basal Cell Carcinoma
  • Bladder Adenocarcinoma
  • Cervical Adenocarcinoma
  • Cervical Clear Cell Adenocarcinoma
  • Cholangiocarcinoma
  • Chordoma
  • Colorectal Squamous Cell Carcinoma
  • Desmoid-Type Fibromatosis
  • Endometrial Transitional Cell Carcinoma
  • Endometrioid Adenocarcinoma
  • Esophageal Neuroendocrine Carcinoma
  • Esophageal Undifferentiated Carcinoma
  • Extrahepatic Bile Duct Carcinoma
  • Extramammary Paget Disease
  • Fallopian Tube Adenocarcinoma
  • Fallopian Tube Transitional Cell Carcinoma
  • Fibromyxoid Tumor
  • Gallbladder Carcinoma
  • Gastric Neuroendocrine Carcinoma
  • Gastric Squamous Cell Carcinoma
  • Gastric Undifferentiated Carcinoma
  • Gastrointestinal Stromal Tumor
  • Gestational Trophoblastic Tumor
  • 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
  • Metaplastic Breast Carcinoma
  • Metastatic Malignant Neoplasm of Unknown Primary
  • Minimally Invasive Lung Adenocarcinoma
  • 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 Clear Cell Adenocarcinoma
  • Ovarian Germ Cell Tumor
  • Ovarian Mucinous Adenocarcinoma
  • Ovarian Squamous Cell Carcinoma
  • Ovarian Transitional Cell Carcinoma
  • Pancreatic Acinar Cell Carcinoma
  • Pancreatic Neuroendocrine Carcinoma
  • Paraganglioma
  • Paranasal Sinus Adenocarcinoma
  • Paranasal Sinus Carcinoma
  • Parathyroid Gland Carcinoma
  • PEComa
  • Peritoneal Mesothelioma
  • Pituitary Gland Carcinoma
  • Placental Choriocarcinoma
  • Primary Peritoneal High Grade Serous Adenocarcinoma
  • Pseudomyxoma Peritonei
  • Rare Disorder
  • Scrotal Squamous Cell Carcinoma
  • Seminal Vesicle Adenocarcinoma
  • Seminoma
  • Serous Cystadenocarcinoma
  • Small Intestinal Adenocarcinoma
  • Small Intestinal Squamous Cell Carcinoma
  • Solid Neoplasm
  • Spindle Cell Neoplasm
  • Squamous Cell Carcinoma of the Penis
  • Teratoma With Somatic-Type Malignancy
  • Testicular Non-Seminomatous Germ Cell Tumor
  • Thyroid Gland Carcinoma
  • Tracheal Carcinoma
  • Transitional Cell Carcinoma
  • Ureter Adenocarcinoma
  • Ureter Squamous Cell Carcinoma
  • Urethral Adenocarcinoma
  • Urethral Squamous Cell Carcinoma
  • Vaginal Adenocarcinoma
  • Vaginal Squamous Cell Carcinoma, Not Otherwise Specified
  • Vulvar Carcinoma
Intervention  ICMJE
  • Procedure: Biospecimen Collection
    Undergo optional collection of biopsy tissue and blood
  • Biological: Ipilimumab
    Given IV
    Other Names:
    • Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody
    • BMS-734016
    • MDX-010
    • MDX-CTLA4
    • Yervoy
  • Biological: Nivolumab
    Given IV
    Other Names:
    • BMS-936558
    • MDX-1106
    • NIVO
    • ONO-4538
    • Opdivo
Study Arms  ICMJE
  • Experimental: Arm I (nivolumab, ipilimumab)
    Patients receive nivolumab IV over 30 minutes on days 1, 15, and 29 and ipilimumab IV over 60 minutes on day 1. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Procedure: Biospecimen Collection
    • Biological: Ipilimumab
    • Biological: Nivolumab
  • Experimental: Arm II (nivolumab)
    Patients receive nivolumab IV over 30 minutes on days 1, 15 and 29. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Procedure: Biospecimen Collection
    • Biological: Nivolumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 11, 2019)
818
Original Estimated Enrollment  ICMJE
 (submitted: July 13, 2016)
334
Estimated Study Completion Date  ICMJE August 31, 2021
Estimated Primary Completion Date August 31, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients are eligible under ONE of the following criteria:

    • For all cohorts except the gestational trophoblastic disease (GTD) (Cohort #47), patients must have histologically and/or biochemically confirmed rare cancer and must be able to submit specimens. To be eligible for the GTD cohort: patients must have disease confirmed by quantitative serum beta-human chorionic gonadotropin (hCG) within 28 days prior to registration and must be able to submit blood specimens (tissue submission is not required for patients who will be registered to the GTD cohort [Cohort #47]); NOTE: Subsequent to site's Institutional Review Board (IRB) approval of revision 3, patients are NOT required to participate in EAY131 "National Cancer Institute (NCI)-Molecular Analysis for Therapy Choice (MATCH)" to register to S1609 OR
    • FOR PATIENTS WITH PD-L1 AMPLIFICATION ONLY: All solid tumors (excluding lymphoma) are allowed for the PD-L1 amplified cohort if they have PD-L1 amplification; PD-L1 amplification is defined as having deoxyribonucleic acid (DNA) copy number of equal to or greater than six by any of the following Clinical Laboratory Improvement Act (CLIA)-approved next generation sequencing (NGS) tests: Foundation Medicine, Caris, MSK Impact, MD Anderson, Tempus, or Neogenomics; (fluorescence in situ hybridization [FISH] is not allowed); the assay must be done at or after the diagnosis of advanced disease, but PRIOR TO REGISTRATION OR
    • FOR PATIENTS ENROLLED IN EAY131 "NCI-MATCH" PRIOR TO EAY131 ADDENDUM 10 ONLY: Patients must have histologically confirmed rare cancer that did not have a match to a molecularly-guided therapy on EAY131 "NCI-MATCH" protocol or who are off protocol treatment on EAY131, "NCI-MATCH" and have no further molecularly-matched treatment recommendations per EAY131, "NCI-MATCH" or who are otherwise unable to receive EAY131, "NCI-MATCH" therapy
  • Patients who do not qualify for one of the histologic cohorts and are not on the ineligible histology list may be considered for registration in the "Not Otherwise Categorized" Rare Tumors cohort with confirmation of at least one of the study chairs via email

    • NOTE: The "Not Otherwise Categorized" Rare Tumors cohort was permanently closed to accrual on 3/15/2019
  • Patients who are determined to have a rare cancer with unknown primary site are eligible under cohort #32 (tumor of unknown primary [cancer of unknown primary; CuP]), 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

    • NOTE: The "Tumor of unknown primary (Cancer of Unknown Primary; CuP" cohort was permanently closed to accrual on 12/22/2017
  • Patients must also meet one of the following:

    • Patients must have progressed following at least one line of standard systemic therapy and there must not be other approved/standard therapy available that has been shown to prolong overall survival (i.e. in a randomized trial against another standard treatment or by comparison to historical controls); patients who cannot receive other standard therapy that has been shown to prolonged survival due to medical issues will be eligible, if other eligibility criteria are met; OR
    • Patients for whose disease no standard treatment exists that has been shown to prolong overall survival
  • For all cohorts except the GTD cohort (Cohort #47): 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; scans must include imaging of the chest, abdomen and pelvis, with the exception of patients with head/neck cancer, who must have imaging of the chest, abdomen, pelvis and neck; if there is clinical suspicion for bone metastases at the time of enrollment (in the judgement of the treating investigator) bone scan should be performed; bone scans done within 42 days prior to registration may be used to establish baseline condition at registration
  • 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 one year
    • Adequately managed stage I or II follicular thyroid or prostate cancer is also eligible, wherein patient is not required to be in complete remission
    • Note: Second primary tumors are not allowed concurrent with any of the eligible rare cancers
  • For all cohorts except the PD-L1 amplified tumors cohort (Cohort # 50): Patients may have received either prior anti-CTLA4 or other prior anti-PD-1/anti-PD-L1 therapy, but not both, provided that it is completed >= 4 weeks prior to registration. To be eligible for the PD-L1 amplified tumors cohort (Cohort #50): Patients must not have received anti-PD-1/anti-PD-L1 therapy; prior anti-CTLA-4 is allowed provided that it is completed >= 4 weeks prior to registration
  • Patients who had prior grade 3 or higher immune-related adverse event (e.g. 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 with autoimmune disease who are otherwise eligible 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; these patients must also have a CT or MRI of the brain to evaluate for CNS disease within 42 days prior to registration to S1609; 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, excluding RANKL inhibitors and bisphosphonates); 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, except alopecia and =< grade 2 neuropathy which are allowed; any planned radiation therapy must be completed before registration to S1609
  • Patients must not have prior history of allergy or known hypersensitivity to nivolumab or ipilimumab
  • Hormonal or endocrine blockade is permitted as long as patient has demonstrated progression on prior therapy (e.g. gonadotrophin releasing hormone [GnRH], somatostatin); long-acting somatostatin analogs (including octreotide) and androgen deprivation treatment (including long-acting leuprolide) are permitted while on protocol therapy
  • Patients must have a Zubrod performance status of 0-2
  • Absolute neutrophil count (ANC) >= 1,000/mcL (within 28 days prior to registration)
  • Platelets >= 75,000/mcL (within 28 days prior to registration)
  • Hemoglobin >= 8 g/dL (within 28 days prior to registration)
  • Total bilirubin =< 2.0 x institutional upper limit of normal (IULN) or for documented/suspected Gilbert's disease, total bilirubin =< 3.0 x IULN (within 28 days prior to registration)
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) both =< 3 x IULN (within 28 days prior to registration)
  • Serum creatinine =< 2.0 x IULN (within 28 days prior to registration)
  • Creatinine clearance (CrCl) >= 50 mL/min., as estimated by the Cockcroft and Gault formula; estimated creatinine clearance is based on actual body weight (within 28 days prior to registration)
  • Patients must have adequate thyroid function, as evidenced by either thyroid-stimulating hormone (TSH) or, 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; patients who have undergone thyroidectomy or who are on thyroid suppression for their cancer are not required to have normal TSH and free T4
  • Patients must have adequate adrenal axis function, as evidenced by adrenocorticotropic hormone (ACTH) values within the institutional normal ranges OR cortisol levels within institutional normal ranges (ante meridiem [AM] cortisol preferred), within 28 days prior to registration; Note: ACTH and cortisol levels are not required for patients with primary adrenal tumors (e.g. adrenocortical carcinoma)
  • For women of childbearing potential, the local investigator must rule out pregnancy; Except for Cohorts 13 and 47, where tumor types may express beta-hCG, women of childbearing potential must have a serum or urine pregnancy test within 7 days prior to registration; for Cohorts 13 and 47, where tumor types may produce hCG (e.g. germ cell tumors or trophoblastic disease), other pregnancy exclusion methods should be used to rule out pregnancy, such as ultrasound examination, documented history of effective contraception, or documented infertility; all females of childbearing potential must have been demonstrated not to be pregnant within 7 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 due to risk of fetal or nursing infant harm; women of childbearing potential must have agreed to use an effective contraceptive method; a woman is considered to be of "childbearing 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, 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:

    • CD4+ cell count greater or equal to 250 cells/mm^3
    • No history of non-malignancy acquired immunodeficiency syndrome (AIDS)-defining conditions other than historical low CD4+ cell counts
  • 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 10 mg 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 (including ulcerative colitis and Chron's disease), as well as symptomatic disease (e.g. rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [e.g., Wegener's Granulomatosis]); CNS or motor neuropathy considered of autoimmune origin (e.g., Guillain-Barre syndrome and myasthenia gravis, multiple sclerosis or glomerulonephritis); vitiligo, alopecia, hypothyroidism on stable doses of thyroid replacement therapy, psoriasis not requiring systemic therapy within the past 2 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: Patients with history of CHF or patients who are deemed at risk because of underlying cardiovascular disease or exposure to cardiotoxic drugs should have an electrocardiogram (EKG) and echocardiogram (ECHO), as clinically indicated, at baseline and at the start of each cycle; patients who have evidence at baseline (or subsequently) of CHF, myocardial infarction (MI), cardiomyopathy, or myositis cardiac evaluation (NYHA I/II) should have additional consult by a cardiologist, including review of EKG, creatine phosphokinase (CPK), troponin, echocardiogram, as clinically indicated
  • Patients must have amylase or lipase within =< 1.5 x IULN without symptoms of pancreatitis at registration, within 28 days prior to registration
  • Patients must not have symptomatic interstitial lung disease or pneumonitis
  • Patients must have fully recovered from any adverse effects of major surgery (to =< grade 1) at least 14 days prior to registration
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02834013
Other Study ID Numbers  ICMJE NCI-2016-01041
NCI-2016-01041 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
S1609
S1609 ( Other Identifier: SWOG )
S1609 ( Other Identifier: CTEP )
U10CA180888 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Cancer Institute (NCI)
Study Sponsor  ICMJE National Cancer Institute (NCI)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Sandip P Patel Southwest Oncology Group
PRS Account National Cancer Institute (NCI)
Verification Date November 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP