Nivolumab and Ipilimumab in Treating Patients With Rare Tumors

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 \[To obtain permission to enroll in the NOC cohort, contact: [email protected]\] (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)

Timeline

Start

2017-01-30

Primary completion

2026-05-01

Completion

2027-06-01

Publications

• Chae YK, Czeskleba J, Patel SP, Mentor A, Robinson W, Jones NL, Rampurwala M, Naing A, Beck JM, Moloney-Lineen C, Chung LI, McLeod CM, Chen HX, Sharon E, Threlkel S, Othus M, Ryan CW, Blanke CD, Kurzrock R. A phase II basket trial of Dual Anti-CTLA-4 and Anti-PD-1 Blockade in Rare Tumors (DART) SWOG S1609: vaginal cancer sub cohort results. J Gynecol Oncol. 2026 Mar 25. doi: 10.3802/jgo.2026.37.e92. Online ahead of print.
• Swiecicki PL, Othus M, Patel SP, Kwang-Chae Y, Kurzrock R. Baseline tumor burden and outcomes in patients with rare cancers treated with immunotherapy (Southwest Oncology Group trial S1609). Cancer. 2026 Apr 1;132(7):e70374. doi: 10.1002/cncr.70374.
• Chae YK, Othus M, Patel SP, Backes FJ, O'Malley DM, Cristea M, Naing A, Kurnit K, Eskander RN, T Goodrich S, Robinson WR, Scalici J, Chan J, Ali-Ahmad H, Hays J, McCormick C, Kim EJ, Sueblinvong T, Ahmed A, Siedel J, Thomes Pepin J, Bottsford-Miller JN, Fagbemi SO, Jaslowski AJ, Kim HS, Chung LI, Moloney-Lineen C, McLeod CM, Chen HX, Sharon E, Streicher H, Ryan CW, Blanke CD, Kurzrock R. DART/SWOG/NCI phase II anti-CTLA-4/PD-1 trial: clear cell carcinomas of ovary, endometrium, cervix. J Immunother Cancer. 2026 Feb 11;14(2):e012805. doi: 10.1136/jitc-2025-012805.
• Patel SP, Fisher J, Chae YK, Soto LS, Kasi A, Konda B, Walshauser M, Parra E, Zhang J, Duault C, Gonzalez-Kozlova E, Manyam G, Zhang J, Chen H, Duose DY, Laberiano Fernandez C, Luthra R, Al-Atrash G, Kim-Schulze S, Maecker HT, Wistuba II, Gnjatic S, Lee JJ, Zhang J, Magner CM, Chen HX, Sharon E, Othus M, Ryan CW, Blanke C, Haymaker CL, Kurzrock R. Phase II basket trial of Dual Anti-CTLA-4 and anti-PD-1 blockade in Rare Tumors (DART) SWOG S1609: pancreatic neuroendocrine neoplasm (PNEN) cohort. J Immunother Cancer. 2025 Jun 30;13(6):e011760. doi: 10.1136/jitc-2025-011760.
• Patel SP, Cano-Linson E, Chae YK, Schokrpur S, Lao CD, Powers BC, Victor AI, Onitilo AA, Shin S, Takebe N, Threlkel S, McLeod CM, Chen HX, Sharon E, Othus M, Ryan CW, Blanke CD, Kurzrock R. Dual anti-CTLA-4 and anti-PD-1 blockade in metastatic basal cell carcinoma. NPJ Precis Oncol. 2025 Jan 24;9(1):24. doi: 10.1038/s41698-024-00798-1.
• Chae YK, Othus M, Patel SP, Gerber DE, Tanvetyanon T, Kim HS, Chung LI, McLeod CM, Lopez G, Chen HX, Sharon E, Streicher H, Ryan CW, Blanke CD, Kurzrock R. Phase II trial of dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors SWOG/NCI experience: invasive mucinous or non-mucinous lepidic adenocarcinoma of the lung (formerly bronchioloalveolar carcinoma). Ther Adv Med Oncol. 2024 Nov 22;16:17588359241293401. doi: 10.1177/17588359241293401. eCollection 2024.
• Chae YK, Othus M, Patel S, Powers B, Hsueh CT, Govindarajan R, Bucur S, Kim HS, Chung LI, McLeod C, Chen HX, Sharon E, Streicher H, Ryan CW, Blanke C, Kurzrock R. Phase II basket trial of dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART) SWOG S1609: the desmoid tumors. J Immunother Cancer. 2024 Sep 28;12(9):e009128. doi: 10.1136/jitc-2024-009128.
• Patel SP, Othus M, Chae YK, Huynh T, Tan B, Kuzel T, McLeod C, Lopez G, Chen HX, Sharon E, Streicher H, Ryan CW, Blanke C, Kurzrock R. Phase II basket trial of Dual Anti-CTLA-4 and Anti-PD-1 blockade in Rare Tumors (DART) SWOG S1609: adrenocortical carcinoma cohort. J Immunother Cancer. 2024 Jul 27;12(7):e009074. doi: 10.1136/jitc-2024-009074.
• Patel SP, Guadarrama E, Chae YK, Dennis MJ, Powers BC, Liao CY, Ferri WA Jr, George TJ, Sharon E, Ryan CW, Othus M, Lopez G, Blanke CD, Kurzrock R. SWOG 1609 cohort 48: anti-CTLA-4 and anti-PD-1 for advanced gallbladder cancer. Cancer. 2024 Sep 1;130(17):2918-2927. doi: 10.1002/cncr.35243. Epub 2024 Feb 15.
• Othus M, Patel SP, Chae YK, Dietrich E, Streicher H, Sharon E, Kurzrock R. Correlation between tumor size change and outcome in a rare cancer immunotherapy basket trial. J Natl Cancer Inst. 2024 May 8;116(5):673-680. doi: 10.1093/jnci/djae009.
• Adams S, Othus M, Patel SP, Miller KD, Chugh R, Schuetze SM, Chamberlin MD, Haley BJ, Storniolo AMV, Reddy MP, Anderson SA, Zimmerman CT, O'Dea AP, Mirshahidi HR, Ahnert JR, Brescia FJ, Hahn O, Raymond JM, Biggs DD, Connolly RM, Sharon E, Korde LA, Gray RJ, Mayerson E, Plets M, Blanke CD, Chae YK, Kurzrock R. A Multicenter Phase II Trial of Ipilimumab and Nivolumab in Unresectable or Metastatic Metaplastic Breast Cancer: Cohort 36 of Dual Anti-CTLA-4 and Anti-PD-1 Blockade in Rare Tumors (DART, SWOG S1609). Clin Cancer Res. 2022 Jan 15;28(2):271-278. doi: 10.1158/1078-0432.CCR-21-2182. Epub 2021 Oct 29.
• Wagner MJ, Othus M, Patel SP, Ryan C, Sangal A, Powers B, Budd GT, Victor AI, Hsueh CT, Chugh R, Nair S, Leu KM, Agulnik M, Sharon E, Mayerson E, Plets M, Blanke C, Streicher H, Chae YK, Kurzrock R. Multicenter phase II trial (SWOG S1609, cohort 51) of ipilimumab and nivolumab in metastatic or unresectable angiosarcoma: a substudy of dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART). J Immunother Cancer. 2021 Aug;9(8):e002990. doi: 10.1136/jitc-2021-002990.
• Patel SP, Mayerson E, Chae YK, Strosberg J, Wang J, Konda B, Hayward J, McLeod CM, Chen HX, Sharon E, Othus M, Ryan CW, Plets M, Blanke CD, Kurzrock R. A phase II basket trial of Dual Anti-CTLA-4 and Anti-PD-1 Blockade in Rare Tumors (DART) SWOG S1609: High-grade neuroendocrine neoplasm cohort. Cancer. 2021 Sep 1;127(17):3194-3201. doi: 10.1002/cncr.33591. Epub 2021 Apr 21.
• Dai C, Liang S, Sun B, Kang J. The Progress of Immunotherapy in Refractory Pituitary Adenomas and Pituitary Carcinomas. Front Endocrinol (Lausanne). 2020 Dec 11;11:608422. doi: 10.3389/fendo.2020.608422. eCollection 2020.
• Patel SP, Othus M, Chae YK, Giles FJ, Hansel DE, Singh PP, Fontaine A, Shah MH, Kasi A, Baghdadi TA, Matrana M, Gatalica Z, Korn WM, Hayward J, McLeod C, Chen HX, Sharon E, Mayerson E, Ryan CW, Plets M, Blanke CD, Kurzrock R. A Phase II Basket Trial of Dual Anti-CTLA-4 and Anti-PD-1 Blockade in Rare Tumors (DART SWOG 1609) in Patients with Nonpancreatic Neuroendocrine Tumors. Clin Cancer Res. 2020 May 15;26(10):2290-2296. doi: 10.1158/1078-0432.CCR-19-3356. Epub 2020 Jan 22.

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Indications