818 Participants Needed

Nivolumab + Ipilimumab for Rare Cancers

Recruiting at 1132 trial locations
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial
Breakthrough TherapyThis drug has been fast-tracked for approval by the FDA given its high promise

Trial Summary

What is the purpose of this trial?

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)

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, you must not be on any other investigational agents or systemic anti-cancer therapy at the time of registration. It's best to discuss your specific medications with the trial team to ensure they don't interfere with the study.

What data supports the effectiveness of the drug combination of Nivolumab and Ipilimumab for rare cancers?

Research shows that the combination of Nivolumab (Opdivo) and Ipilimumab (Yervoy) has been effective in treating advanced non-small cell lung cancer and advanced melanoma, leading to longer survival and better outcomes compared to other treatments. This suggests potential benefits for other types of cancers as well.12345

Is the combination of Nivolumab and Ipilimumab safe for humans?

The combination of Nivolumab and Ipilimumab has been used in treating various cancers and is known to cause immune-related side effects, which can be more frequent and severe when used together. These side effects are often manageable with medications like glucocorticoids (a type of steroid), but close monitoring by experienced healthcare providers is necessary to ensure safety.46789

How is the drug combination of nivolumab and ipilimumab unique for treating rare cancers?

The combination of nivolumab and ipilimumab is unique because it uses two immunotherapy drugs that work together to boost the body's immune system to fight cancer, which is different from traditional chemotherapy that directly targets cancer cells. This combination has shown durable and long-term efficacy in other cancers like advanced non-small cell lung cancer and renal cell carcinoma, suggesting potential benefits for rare cancers as well.1251011

Research Team

SP

Sandip P Patel

Principal Investigator

SWOG Cancer Research Network

Eligibility Criteria

This trial is for patients with rare cancers, including various carcinomas and tumors. Eligible participants must have progressed after standard therapy or have no survival-prolonging treatment available. They should not have uncontrolled illnesses or active infections like HBV/HCV, and must agree to use birth control if of reproductive potential. A negative pregnancy test is required for women of childbearing age.

Inclusion Criteria

I have been cancer-free from another type for at least one year.
I have a rare cancer type and can provide samples, except if I have GTD.
My cancer has PD-L1 amplification, confirmed by a study chair.
See 18 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks
1 visit (in-person)

Treatment

Participants receive nivolumab and ipilimumab intravenously, with treatment repeating every 42 days for up to 17 cycles (2 years) in the absence of disease progression or unacceptable toxicity

2 years
Visits on days 1, 15, and 29 every 42 days

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

10 years
Regular follow-up visits

Treatment Details

Interventions

  • Ipilimumab
  • Nivolumab
Trial OverviewThe study tests nivolumab and ipilimumab, two immunotherapy drugs that may help the immune system fight cancer by stopping tumor cells from growing. It's a phase II trial where patients are grouped based on their specific type of rare tumor to see how well these treatments work.
Participant Groups
2Treatment groups
Experimental Treatment
Group I: Arm II (nivolumab)Experimental Treatment5 Interventions
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.
Group II: Arm I (nivolumab, ipilimumab)Experimental Treatment6 Interventions
Patients receive nivolumab 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 ECHO during screening and on study. Patients also undergo MRI or CT throughout the trial. Additionally, patients undergo blood sample collection throughout the trial.

Ipilimumab is already approved in United States, European Union for the following indications:

🇺🇸
Approved in United States as Yervoy for:
  • Advanced melanoma
  • Stage III unresectable melanoma
  • Stage IV metastatic melanoma
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Approved in European Union as Yervoy for:
  • Advanced melanoma
  • Stage III unresectable melanoma
  • Stage IV metastatic melanoma

Find a Clinic Near You

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials
14,080
Recruited
41,180,000+

Findings from Research

Nivolumab plus ipilimumab showed durable and long-term efficacy in treating advanced non-small cell lung cancer (NSCLC) compared to chemotherapy, regardless of tumor PD-L1 expression levels.
These findings are based on updated results from part 1 of the phase 3 CheckMate 227 trial, indicating that this combination therapy could be a more effective frontline treatment option for NSCLC patients.
Nivolumab/Ipilimumab Combo Yields Durable Efficacy in Advanced NSCLC.Kahl, KL.[2021]
In a pooled analysis of 1332 patients with advanced non-small-cell lung cancer (NSCLC), the combination of nivolumab and ipilimumab showed a median overall survival (OS) of 18.6 months and a 3-year OS rate of 35%, indicating significant long-term survival benefits compared to traditional chemotherapy.
The study found that patients who responded to treatment at 6 months had markedly better survival rates, with a 3-year OS of 66% for responders, highlighting the importance of early response in predicting long-term outcomes.
Long-term survival with first-line nivolumab plus ipilimumab in patients with advanced non-small-cell lung cancer: a pooled analysis.Borghaei, H., Ciuleanu, TE., Lee, JS., et al.[2023]
In a phase 2 trial involving 142 patients with untreated advanced melanoma, the combination of nivolumab and ipilimumab resulted in a 2-year overall survival rate of 63.8%, compared to 53.6% for those receiving ipilimumab alone, suggesting improved survival outcomes with the combination therapy.
However, the combination treatment was associated with a higher incidence of severe side effects, with 54% of patients experiencing grade 3-4 adverse events compared to 20% in the ipilimumab-only group, indicating a trade-off between efficacy and safety.
Combined nivolumab and ipilimumab versus ipilimumab alone in patients with advanced melanoma: 2-year overall survival outcomes in a multicentre, randomised, controlled, phase 2 trial.Hodi, FS., Chesney, J., Pavlick, AC., et al.[2022]

References

Nivolumab/Ipilimumab Combo Yields Durable Efficacy in Advanced NSCLC. [2021]
Long-term survival with first-line nivolumab plus ipilimumab in patients with advanced non-small-cell lung cancer: a pooled analysis. [2023]
Combined nivolumab and ipilimumab versus ipilimumab alone in patients with advanced melanoma: 2-year overall survival outcomes in a multicentre, randomised, controlled, phase 2 trial. [2022]
First-line nivolumab + ipilimumab in advanced NSCLC: CheckMate 227 subpopulation analyses in Asian patients. [2022]
European Medicines Agency extension of indication to include the combination immunotherapy cancer drug treatment with nivolumab (Opdivo) and ipilimumab (Yervoy) for adults with intermediate/poor-risk advanced renal cell carcinoma. [2021]
Safety of First-Line Nivolumab Plus Ipilimumab in Patients With Metastatic NSCLC: A Pooled Analysis of CheckMate 227, CheckMate 568, and CheckMate 817. [2023]
Combined immune checkpoint blockade (anti-PD-1/anti-CTLA-4): Evaluation and management of adverse drug reactions. [2022]
Retrospective Side Effect Profiling of the Metastatic Melanoma Combination Therapy Ipilimumab-Nivolumab Using Adverse Event Data. [2022]
Prognostic Impact of Immune-Related Adverse Events as First-Line Therapy for Metastatic Renal Cell Carcinoma Treated With Nivolumab Plus Ipilimumab: A Multicenter Retrospective Study. [2023]
Cost-Effectiveness of Nivolumab Plus Ipilimumab With and Without Chemotherapy for Advanced Non-Small Cell Lung Cancer. [2022]
Nivolumab plus ipilimumab as first-line treatment for advanced non-small-cell lung cancer (CheckMate 012): results of an open-label, phase 1, multicohort study. [2022]