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Nivolumab Plus Ipilimumab in Patients With Renal Medullary Carcinoma

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ClinicalTrials.gov Identifier: NCT03274258
Recruitment Status : Recruiting
First Posted : September 6, 2017
Last Update Posted : September 14, 2018
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:

Any time the words "you," "your," "I," or "me" appear, it is meant to apply to the potential participant.

The goal of this clinical research study is to learn if a combination of nivolumab and ipilimumab can help to control locally advanced or metastatic (has spread) renal medullary carcinoma (RMC).

This is an investigational study. Nivolumab is FDA approved and commercially available to treat many types of cancer, including renal cell cancer after patients have received therapy to control blood vessel growth. Ipilimumab is FDA approved and commercially available to treat metastatic melanoma. It is considered investigational to use nivolumab and ipilimumab to treat RMC.

The study doctor can explain how the study drugs are designed to work.

Up to 30 participants will be enrolled in this study. All will take part at MD Anderson.


Condition or disease Intervention/treatment Phase
Renal Medullary Carcinoma Other Disorders of Kidney and Ureter Drug: Nivolumab Drug: Ipilimumab Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 35 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Trial of Nivolumab Plus Ipilimumab in Patients With Renal Medullary Carcinoma
Actual Study Start Date : December 13, 2017
Estimated Primary Completion Date : July 2020
Estimated Study Completion Date : July 2020


Arm Intervention/treatment
Experimental: Nivolumab + Ipilimumab

During Part A of this study, each study cycle is 21 days (3 weeks). During Part B of this study, each study cycle is 14 days (2 weeks).

During Part A, Nivolumab and Ipilimumab given by vein over about 30 minutes each on Day 1 of Cycles 1-4.

During Part B, Nivolumab given alone by vein over about 60 minutes on Day 1 of each cycle.

Study drugs given in combination for up to 4 cycles. After that, Nivolumab given alone for up to 2 years or until the disease gets worse, whichever comes first.

Drug: Nivolumab

During Part A, Nivolumab 3 mg/kg given by vein over about 30 minutes each on Day 1 of Cycles 1-4.

During Part B, Nivolumab 480 mg by vein every 4 weeks for up to 2 years, or until disease progression or unacceptable treatment-related toxicity.

Other Names:
  • BMS-936558
  • Opdivo

Drug: Ipilimumab
During Part A, Ipilimumab 1 mg/kg given by vein over about 30 minutes each on Day 1 of Cycles 1-4.
Other Names:
  • Yervoy
  • BMS-734016
  • MDX010




Primary Outcome Measures :
  1. Overall Response Rate (ORR) of Nivolumab Plus Ipilimumab in Patients With Renal Medullary Carcinoma [ Time Frame: Day 1 of treatment up to 2 years ]
    ORR defined as the proportion of patients with a best response of complete response (CR) or partial response (PR) by RECIST criteria recorded between Day 1 of the study and the date of objectively documented progression per RECIST or the date of subsequent anti-cancer therapy, whichever occurs first.


Secondary Outcome Measures :
  1. Progression-Free Survival (PFS) of Nivolumab Plus Ipilimumab in Patients With Renal Medullary Carcinoma [ Time Frame: Day 1 of treatment up to 2 years ]
    PFS determined by RECIST criteria.

  2. Safety of Nivolumab Plus Ipilimumab in Patients With Renal Medullary Carcinoma by CTCAE v4.03 [ Time Frame: Day 1 up to 100 days after treatment ]
    Safety determined by Common Terminology Criteria for Adverse Events (CTCAE) v4.03.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients must give written informed consent prior to initiation of therapy, in keeping with the policies of the institution. Patients with a history of major psychiatric illness must be judged able to fully understand the investigational nature of the study and the risks associated with the therapy.
  2. Patients with locally advanced or metastatic RMC histologically confirmed by expert pathology review and loss of SMARCB1 staining by immunohistochemistry. Patients with advanced or metastatic unclassified renal cell carcinoma with medullary phenotype (a rare SMARCB1 negative RMC variant occurring in individuals without sickle hemoglobinopathies) are also eligible. The Principal Investigator (PI) is the final arbiter in questions related to eligibility.
  3. Patients will be eligible regardless of whether they have had prior nephrectomy or still have their primary tumor in-situ.
  4. Patients must have at least one measurable site of disease, defined as a lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) and measures >/= 15 mm with conventional techniques or >/= 10 mm with more sensitive techniques such as magnetic resonance imaging (MRI) or spiral computerized tomography (CT) scan. If the patient has had previous radiation to the marker lesion(s), there must be evidence of progression since the radiation.
  5. Patients should be willing to provide a newly obtained fresh core biopsy of a tumor lesion. Not required if there is a recently obtained fresh specimen on an IRB approved correlated trial up to 6 weeks (42 days) prior to initiation of treatment on Day 1.
  6. Patients can be either naïve for any previous systemic treatment or have had any number of prior systemic therapies. However, patients must not have received prior anticancer therapy with anti-PD1, anti-PD-L1, or anti-CTLA-4 immune checkpoint inhibitors.
  7. There must be evidence of progression on or after last treatment regimen received. NOTE: If subject is unable to walk due to paralysis, but is mobile in a wheelchair, subject is considered to be ambulatory for the purpose of assessing their performance status.
  8. Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  9. Consent to MD Anderson companion laboratory protocol 2014-0938.
  10. Age (at the time of consent): >/= 18 years
  11. Within 14 days of the first dose of the study drugs, patients must have adequate organ and marrow function prior to study entry as defined below: 1) Hemoglobin >/=9 g/dl (treatment allowed); 2) Absolute neutrophil count >/= 1000/mcL; 3) Platelets >/=75,000/μL; 4) Total Bilirubin </=1.5 mg/dl; 5) AST(SGOT) or ALT (SGPT) </=2.5 X institutional ULN, except in known hepatic metastasis, wherein may be </=5 x ULN; 6) Serum Creatinine </=1.5 x ULN by gender (as long as patient does not require dialysis); May receive transfusion; Without growth factor support (filgrastim or pegfilgrastim) for at least 14 days; If creatinine is not <1.5×ULN, then calculate by Cockcroft-Gault methods or local institutional standard and CrCl must be >30 mL/kg/1.73 m²
  12. INR and PTT </=1.5 x ULN prior to study entry. Therapeutic anticoagulation with warfarin is allowed if target INR </= 3 on a stable dose of warfarin or on a stable dose of low molecular weight (LMW) heparin for > 2 weeks (14 days) at the time of enrollment.
  13. Patients with controlled brain metastases are allowed on protocol if they had solitary brain metastases that was surgically resected or treated with radiosurgery or Gamma knife, without recurrence or edema for 1 month (4 weeks).
  14. Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of the study drug.
  15. Women must not be breastfeeding.
  16. WOCBP must agree to follow instructions for method(s) of contraception from the time of enrollment for the duration of treatment with study drug (s) plus 5 half-lives of study drug (s) plus 30 days (duration of ovulatory cycle) for a total of 5 months post treatment completion.
  17. Men who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug (s) plus 5 half-lives of study drug (s) plus 90 days duration of sperm turnover) for a total of 5 months post-treatment completion.
  18. Azoospermic males and WOCBP who are continuously not heterosexually active are exempt from contraceptive requirements. However WOCBP must still undergo pregnancy testing as described in these sections.

Exclusion Criteria:

  1. Patients must not have any other malignancies within the past 2 years except for in situ carcinoma of any site, or adequately treated (without recurrence post-resection or post-radiotherapy) carcinoma of the cervix or basal or squamous cell carcinomas of the skin.
  2. Patients currently receiving anticancer therapies or who have received anticancer therapies (including chemotherapy and targeted therapy) within 2 weeks (14 days) prior to study Day are excluded. Patients who have completed palliative radiation therapy more than 14 days prior to the first dose of the combination ipilimumab plus nivolumab are eligible.
  3. Patients, who have had a major surgery or significant traumatic injury (injury requiring > 4 weeks (28 days) to heal) within 4 weeks (28 days) of start of study drug, patients who have not recovered from the side effects of any major surgery (defined as requiring general anesthesia) or patients that are expected to require major surgery, other than cytoreductive nephrectomy +/- retroperitoneal lymph node dissection, during the course of the study.
  4. Patients who have organ allografts.
  5. Known or suspected autoimmune disease. Patients with a history of inflammatory bowel disease (including Crohn's disease and ulcerative colitis) and autoimmune disorders such as rheumatoid arthritis, systemic progressive sclerosis [scleroderma], Systemic Lupus Erythematosus or autoimmune vasculitis [e.g., Wegener's Granulomatosis] are excluded from this study. Patients with a history of Hashimoto's thyroiditis only requiring hormone replacement, Type I diabetes, or psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are allowed to participate.
  6. Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
  7. Positive test for hepatitis B virus (HBV) using HBV surface antigen (HBVsAg) test or positive test for hepatitis C virus (HCV) using HCV ribonucleic acid (RNA) or HCV antibody test indicating acute or chronic infection. If hepatitis C antibody test is positive then active infection has to be confirmed by hepatitis C RNA testing for the patient to be excluded.
  8. Any underlying medical condition, which in the opinion of the Investigator, will make the administration of study drug hazardous or obscure the interpretation of adverse events, such as a condition associated with frequent diarrhea, uncontrolled nausea or vomiting
  9. Patients must not have received prior anticancer therapy with anti-PD1, anti-PD-L1, or anti- CTLA-4 immune checkpoint inhibitors.
  10. Patients receiving any concomitant systemic therapy for renal cell cancer are excluded.
  11. Patients must not be scheduled to receive another experimental drug while on this study.
  12. Patients who are on high dose steroid (e.g., > 10mg prednisone daily or equivalent) or other more potent immune suppression medications (e.g., infliximab). Topical, inhaled, intraarticular, ocular, or intranasal corticosteroids (with minimal systemic absorption) are allowed. A brief course (<48 hours) of systemic corticosteroids for prophylaxis (eg, from contrast dye allergy) is permitted. Physiological corticosteroid replacement therapy for adrenal insufficiency is also permitted.
  13. Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as: a) Symptomatic congestive heart failure of New York heart Association Class III or IV; b) Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease; c) Severely impaired lung function as defined as 02 saturation that is 92% or less at rest on room air; d) Uncontrolled diabetes as defined by fasting serum glucose >1.5 x ULN; e) Systemic fungal, bacterial, viral, or other infection that is not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement) despite appropriate antibiotics or other treatment; f) Known active or symptomatic viral hepatitis or chronic liver disease. Uncontrolled adrenal insufficiency
  14. Patients must not have history of other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of ipilimumab or nivolumab or that might affect the interpretation of the results of the study or render the subject at high risk from treatment complications.
  15. Patients should not receive immunization with attenuated live vaccines within one week (7 days) of study entry or during study period; Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.
  16. Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases.
  17. Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods as defined above. If barrier contraceptives are being used, these must be continued throughout the trial by both sexes. Hormonal contraceptives are not acceptable as a sole method of contraception.
  18. Any patients who cannot be compliant with the appointments required in this protocol must not be enrolled in this study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03274258


Contacts
Contact: Pavlos Msaouel, MD 713-792-2830 pmsaouel@mdanderson.org

Locations
United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact       pmsaouel@mdanderson.org   
Sponsors and Collaborators
M.D. Anderson Cancer Center
Bristol-Myers Squibb
Investigators
Principal Investigator: Pavlos Msaouel, MD M.D. Anderson Cancer Center

Additional Information:
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT03274258     History of Changes
Other Study ID Numbers: 2017-0201
NCI-2018-01066 ( Registry Identifier: NCI CTRP )
First Posted: September 6, 2017    Key Record Dates
Last Update Posted: September 14, 2018
Last Verified: September 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by M.D. Anderson Cancer Center:
Renal Medullary Carcinoma
RMC
Locally advanced or metastatic
Nivolumab
BMS-936558
Opdivo
Ipilimumab
Yervoy
BMS-734016
MDX010

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Medullary
Thyroid Neoplasms
Carcinoma, Neuroendocrine
Kidney Diseases
Ureteral Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Adenocarcinoma
Neoplasms, Ductal, Lobular, and Medullary
Neoplasms, Nerve Tissue
Endocrine Gland Neoplasms
Neoplasms by Site
Head and Neck Neoplasms
Endocrine System Diseases
Thyroid Diseases
Urologic Diseases
Nivolumab
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs