Last updated on November 2019

Nivolumab and Ipilimumab in Treating Patients With Rare Tumors


Brief description of study

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])
  2. Adenocarcinoma and variants of nasal cavity, sinuses, and nasopharynx (closed to accrual 07/27/2018)
  3. Epithelial tumors of major salivary glands (closed to accrual 03/20/2018)
  4. Salivary gland type tumors of head and neck, lip, esophagus, stomach, trachea and lung, breast and other location (closed to accrual)
  5. Undifferentiated carcinoma of gastrointestinal (GI) tract
  6. Adenocarcinoma with variants of small intestine (closed to accrual 05/10/2018)
  7. Squamous cell carcinoma with variants of GI tract (stomach small intestine, colon, rectum, pancreas) (closed to accrual 10/17/2018)
  8. Fibromixoma and low grade mucinous adenocarcinoma (pseudomixoma peritonei) of the appendix and ovary (closed to accrual 03/20/2018)
  9. Rare pancreatic tumors including acinar cell carcinoma, mucinous cystadenocarcinoma or serous cystadenocarcinoma. Pancreatic adenocarcinoma is not eligible
  10. Intrahepatic cholangiocarcinoma (closed to accrual 03/20/2018)
  11. Extrahepatic cholangiocarcinoma and bile duct tumors (closed to accrual 03/20/2018)
  12. Sarcomatoid carcinoma of lung
  13. Bronchoalveolar carcinoma lung. This condition is now also referred to as adenocarcinoma in situ, minimally invasive adenocarcinoma, lepidic predominant adenocarcinoma, or invasive mucinous adenocarcinoma
  14. Non-epithelial tumors of the ovary: A) Germ cell tumor of ovary B) Mullerian mixed tumor and adenosarcoma (closed to accrual 03/30/2018)
  15. Trophoblastic tumor: A) Choriocarcinoma (closed to accrual 04/15/2019)
  16. Transitional cell carcinoma other than that of the renal, pelvis, ureter, or bladder (closed to accrual 04/15/2019)
  17. 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)
  18. Epithelial tumors of penis - squamous adenocarcinoma cell carcinoma with variants of penis
  19. Squamous cell carcinoma variants of the genitourinary (GU) system
  20. Spindle cell carcinoma of kidney, pelvis, ureter
  21. Adenocarcinoma with variants of GU system (excluding prostate cancer) (closed to accrual 07/27/2018)
  22. Odontogenic malignant tumors
  23. Pancreatic neuroendocrine tumor (PNET) (formerly named: Endocrine carcinoma of pancreas and digestive tract.)
  24. Neuroendocrine carcinoma including carcinoid of the lung (closed to accrual 12/19/2017)
  25. Pheochromocytoma, malignant
  26. Paraganglioma (closed to accrual 11/29/2018)
  27. Carcinomas of pituitary gland, thyroid gland parathyroid gland and adrenal cortex
  28. Desmoid tumors
  29. Peripheral nerve sheath tumors and NF1-related tumors (closed to accrual 09/19/2018)
  30. Malignant giant cell tumors
  31. Chordoma (closed to accrual 11/29/2018)
  32. Adrenal cortical tumors (closed to accrual 06/27/2018)
  33. Tumor of unknown primary (Cancer of Unknown Primary; CuP) (closed to accrual 12/22/2017)
  34. 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)
  35. Adenoid cystic carcinoma (closed to accrual 02/06/2018)
  36. Vulvar cancer
  37. MetaPLASTIC carcinoma (of the breast)
  38. Gastrointestinal stromal tumor (GIST) (closed to accrual 09/26/2018)
  39. Perivascular epithelioid cell tumor (PEComa)
  40. Apocrine tumors/extramammary Paget's disease
  41. Peritoneal mesothelioma
  42. Basal cell carcinoma
  43. Clear cell cervical cancer
  44. Esthenioneuroblastoma
  45. Endometrial carcinosarcoma (malignant mixed Mullerian tumors) (closed to accrual)
  46. Clear cell cervical endometrial cancer
  47. Clear cell ovarian cancer
  48. Gestational trophoblastic disease (GTD)
  49. Gallbladder cancer
  50. Small cell carcinoma of the ovary, hypercalcemic type
  51. PD-L1 amplified tumors
  52. Angiosarcoma
  53. 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
  54. Treatment-emergent small-cell neuroendocrine prostate cancer (t-SCNC)

Detailed Study 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.

Clinical Study Identifier: NCT02834013

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