Trials / Active Not Recruiting
Active Not RecruitingNCT02834013
Nivolumab and Ipilimumab in Treating Patients With Rare Tumors
DART: Dual Anti-CTLA-4 and Anti-PD-1 Blockade in Rare Tumors
- Status
- Active Not Recruiting
- Phase
- Phase 2
- Study type
- Interventional
- Enrollment
- 818 (estimated)
- Sponsor
- National Cancer Institute (NCI) · NIH
- Sex
- All
- Age
- 18 Years
- Healthy volunteers
- Not accepted
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 (closed to accrual) 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) 15. Transitional cell carcinoma other than that of the renal, pelvis, ureter, or bladder (closed to accrual) 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) 17. Epithelial tumors of penis - squamous adenocarcinoma cell carcinoma with variants of penis (closed to accrual) 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.) (closed to accrual) 23. Neuroendocrine carcinoma including carcinoid of the lung (closed to accrual 12/19/2017) 24. Pheochromocytoma, malignant (closed to accrual) 25. Paraganglioma (closed to accrual 11/29/2018) 26. Carcinomas of pituitary gland, thyroid gland parathyroid gland and adrenal cortex (closed to accrual) 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 (closed to accrual) 36. MetaPLASTIC carcinoma (of the breast) (closed to accrual) 37. Gastrointestinal stromal tumor (GIST) (closed to accrual 09/26/2018) 38. Perivascular epithelioid cell tumor (PEComa) 39. Apocrine tumors/extramammary Paget's disease (closed to accrual) 40. Peritoneal mesothelioma 41. Basal cell carcinoma (temporarily closed to accrual 04/29/2020) 42. Clear cell cervical cancer 43. Esthenioneuroblastoma (closed to accrual) 44. Endometrial carcinosarcoma (malignant mixed Mullerian tumors) (closed to accrual) 45. Clear cell endometrial cancer 46. Clear cell ovarian cancer (closed to accrual) 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 (closed to accrual) 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. 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. Treatment repeats every 42 days for up to 17 cycles (2 years) in the absence of disease progression or unacceptable toxicity. Patients who complete 17 cycles (2 years) of therapy, may continue receiving the same treatment with nivolumab and ipilimumab, or receive nivolumab once every 14 or 28 days (2 weeks or 4 weeks) per physician discretion in the absence of disease progression or unacceptable toxicity. Patients who stop treatment prior to the completion of 17 cycles of therapy may receive nivolumab once every 14 or 28 days (2 weeks or 4 weeks) in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography (ECHO) during screening and on study. Patients also undergo magnetic resonance imaging (MRI) or computed tomography (CT) throughout the trial. Additionally, patients undergo blood sample collection throughout the trial. ARM II (PD-L1 AMPLIFIED COHORT): Patients receive nivolumab IV over 30 minutes on days 1, 15 and 29. Treatment repeats every 42 days for up to 17 cycles (2 years) in the absence of disease progression or unacceptable toxicity. After 17 cycles (2 years) of therapy, patients may receive nivolumab once every 14 or 28 days (2 weeks or 4 weeks) in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO during screening and on study. Patients also undergo MRI or CT throughout the trial. Additionally, patients undergo blood sample collection throughout the trial. After completion of study treatment, patients are followed up for 10 years from registration.
Conditions
- Acinar Cell Carcinoma
- Adenoid Cystic Carcinoma
- Adrenal Cortical 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
- Breast Metaplastic Carcinoma
- Cervical Adenocarcinoma
- Cholangiocarcinoma
- Chordoma
- Colorectal Squamous Cell Carcinoma
- Desmoid 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
- Human Papillomavirus-Independent Cervical Adenocarcinoma, Clear Cell-Type
- Intestinal Neuroendocrine Carcinoma
- Intrahepatic Cholangiocarcinoma
- Lung Neuroendocrine Tumor
- Lung Sarcomatoid Carcinoma
- Major Salivary Gland Carcinoma
- Malignant Neoplasm of Unknown Primary
- Malignant Odontogenic Neoplasm
- Malignant Peripheral Nerve Sheath Tumor
- Malignant Solid Neoplasm
- Malignant Testicular Sex Cord-Stromal Tumor
- Metastatic Pituitary Neuroendocrine Tumor
- Minimally Invasive Lung Adenocarcinoma
- Mixed Mesodermal (Mullerian) Tumor
- Mucinous Adenocarcinoma
- Mucinous Cystadenocarcinoma
- Nasal Cavity Adenocarcinoma
- Nasal Cavity Carcinoma
- Nasopharyngeal Carcinoma
- Nasopharyngeal Low Grade Papillary Adenocarcinoma
- Nasopharyngeal Undifferentiated Carcinoma
- Oral Cavity Carcinoma
- Oropharyngeal Undifferentiated Carcinoma
- Ovarian 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
- Penile Squamous Cell Carcinoma
- Peritoneal Mesothelial Neoplasm
- 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
- Spindle Cell Neoplasm
- 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
Interventions
| Type | Name | Description |
|---|---|---|
| PROCEDURE | Biospecimen Collection | Undergo blood sample collection |
| PROCEDURE | Computed Tomography | Undergo CT |
| PROCEDURE | Echocardiography Test | Undergo ECHO |
| BIOLOGICAL | Ipilimumab | Given IV |
| PROCEDURE | Magnetic Resonance Imaging | Undergo MRI |
| BIOLOGICAL | Nivolumab | Given IV |
Timeline
- Start date
- 2017-01-30
- Primary completion
- 2026-05-01
- Completion
- 2026-05-01
- First posted
- 2016-07-15
- Last updated
- 2026-04-13
Locations
1,009 sites across 2 countries: United States, Guam
Regulatory
- FDA-regulated drug study
Source: ClinicalTrials.gov record NCT02834013. Inclusion in this directory is not an endorsement.