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Ipilimumab vs Ipilimumab Plus Nivolumab in Patients With Stage III-IV Melanoma Who Have Progressed or Relapsed on PD-1 Inhibitor Therapy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02731729
Recruitment Status : Completed
First Posted : April 7, 2016
Results First Posted : February 21, 2021
Last Update Posted : December 23, 2022
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Parker Institute for Cancer Immunotherapy

Tracking Information
First Submitted Date  ICMJE April 4, 2016
First Posted Date  ICMJE April 7, 2016
Results First Submitted Date  ICMJE January 12, 2021
Results First Posted Date  ICMJE February 21, 2021
Last Update Posted Date December 23, 2022
Actual Study Start Date  ICMJE June 21, 2016
Actual Primary Completion Date August 27, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 2, 2021)
Overall Response Rate (ORR) as Defined by RECIST v1.1 at Week 18 [ Time Frame: Week 18 ]
Overall Response Rate was defined as any participant who had a Complete Response (CR) or Partial Response (PR) as defined by RECIST v1.1 by week 18 of treatment.
Original Primary Outcome Measures  ICMJE
 (submitted: April 6, 2016)
objective response as defined by RECIST v1.1 criteria [ Time Frame: week 18 ]
as defined by RECIST v1.1 criteria by week 18.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 2, 2021)
  • Disease Control Rate (DCR) Status at Week 18 [ Time Frame: Week 18 ]
    Disease Control Rate was defined as any participant who achieved a complete response (CR), partial response (PR), or who remained stable (SD) as defined in Recist v1.1 at week 18.
  • Time to Treatment Failure (TTF) [ Time Frame: The time from treatment initiation until a subsequent therapy is started or death. ]
    Time to Treatment Failure is defined as the time from treatment initiation until the participant starts a subsequent therapy or death, whichever comes first.
  • Overall Survival (OS) [ Time Frame: Death ]
    Overall Survival is defined as the time of treatment initiation to death by any cause
  • Number of Participants With Grade 3 or 4 Adverse Events [ Time Frame: AE were monitored during each treatment cycle and could be reported until 30 days after the last dose of study treatment had been administered. ]
    The occurrence of Grade 3 and Grade 4 adverse events (AE) assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
  • Disease Control Rate (DCR) Status at Week 12 [ Time Frame: Week 12 ]
    Disease Control Rate was defined as any participant who achieved a complete response (CR), partial response (PR), or who remained stable (SD) as defined in Recist v1.1 at week 12.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Ipilimumab vs Ipilimumab Plus Nivolumab in Patients With Stage III-IV Melanoma Who Have Progressed or Relapsed on PD-1 Inhibitor Therapy
Official Title  ICMJE A Randomized, Phase 2 Study of Ipilimumab vs Ipilimumab Plus Nivolumab in Patients With Stage III-IV Melanoma Who Have Progressed or Relapsed on PD-1 Inhibitor Therapy
Brief Summary The purpose of this research study is to learn whether patients whose disease grows after being treated with nivolumab or pembrolizumab respond to ipilimumab (Yervoy®) alone or in combination with nivolumab (Opdivo®).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Melanoma
Intervention  ICMJE
  • Drug: ipilimumab
    Other Name: Yervoy
  • Drug: nivolumab
    Other Name: Opdivo
Study Arms  ICMJE
  • Experimental: ipilimumab and nivolumab
    For patients in the combination arm, nivolumab will first be administered intravenously at a dose of 1 mg/kg of body weight over a period of 60 minutes, once every 3 weeks for four doses. Thirty minutes after the completion of each nivolumab infusion, patients will receive 3 mg/kg of ipilimumab over a period of 30 minutes.
    Interventions:
    • Drug: ipilimumab
    • Drug: nivolumab
  • Experimental: ipilimumab
    In the ipilimumab monotherapy group, patients will receive 3 mg/kg of ipilimumab over a period of 30 minutes once every 3 weeks for four doses.
    Intervention: Drug: ipilimumab
Publications * Friedman CF, Spencer C, Cabanski CR, Panageas KS, Wells DK, Ribas A, Tawbi H, Tsai K, Postow M, Shoushtari A, Chapman P, Karakunnel J, Bucktrout S, Gherardini P, Hollmann TJ, Chen RO, Callahan M, LaVallee T, Ibrahim R, Wolchok J. Ipilimumab alone or in combination with nivolumab in patients with advanced melanoma who have progressed or relapsed on PD-1 blockade: clinical outcomes and translational biomarker analyses. J Immunother Cancer. 2022 Jan;10(1):e003853. doi: 10.1136/jitc-2021-003853.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 2, 2021)
20
Original Estimated Enrollment  ICMJE
 (submitted: April 6, 2016)
70
Actual Study Completion Date  ICMJE February 13, 2019
Actual Primary Completion Date August 27, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Main Inclusion Criteria:

  1. American Joint Committee on Cancer (AJCC) (2009) Stage IV cutaneous melanoma or Stage III cutaneous, acral or mucosal melanoma that is judged inoperable. Patients with a history of uveal melanoma are not eligible.
  2. Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >20 mm with conventional techniques or as >10 mm with computerized tomography (CT) scan. Patients must have at least one measurable lesion by Response Evaluation Criteria in Solid Tumors (RECIST) and a separate lesion amenable to biopsy.
  3. Histologic proof of melanoma reviewed and confirmed by the enrolling site.
  4. Previous treatment with a programmed cell death protein 1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor with documented progression of disease on most recent CT scan. Progression of disease is defined as 1) the appearance of a new measureable lesion (>10 mm) on cross-sectional imaging or physical examination OR 2) enlargement of previously detected lesions on two consecutive imaging studies OR 3) enlargement of a previously detected lesion with correlative symptomatology on one cross-sectional imaging study. Patients remain eligible if they had a previous response to a PD-1 inhibitor, including patients who had a complete response, partial response or stable disease (SD). Primary progressing patients are defined as those who received anti-PD-1 therapy within 2 months of study enrollment. Patients with relapsed disease are defined as those who received their last dose of PD-1 blocking antibody ≥2 months prior to enrollment.
  5. Patients who received adjuvant PD-1 therapy who then develop measurable disease are eligible. However, they must have received their last dose of PD-1/PD-L1 blockade within two months of enrollment in this study. They will be stratified with patients who have primary progressive disease.
  6. Life expectancy of greater than 3 months.
  7. Age ≥ 18 years old.
  8. Eastern Cooperative Oncology Group performance status = 0 or 1 or Karnofsky Performance Status equivalent.
  9. Patients must have adequate organ and marrow function as defined below:

    1. White blood cells >2, 000/microliter (mcL)
    2. Absolute neutrophil count >1,500/mcL
    3. Platelets >100,000/mcL
    4. Hemoglobin > 9.0 g/dL
    5. Total bilirubin ≤ 1.5 X institution's upper limit of normal
    6. Aspartate aminotransferase (serum glutamic oxaloacetic transaminase)/alanine aminotransferase (serum glutamic pyruvic transaminase) ≤ 2.5 X institution's upper limit of normal for patients with no concurrent liver metastases, OR ≤ 5 X institution's upper limit of normal for patients with concurrent liver metastases
    7. Serum creatinine < 1.5x OR creatinine clearance of at least 40
  10. Women of childbearing potential must have a negative serum pregnancy test within 24 hours prior to the start of study drug. A woman of childbearing potential is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or is not postmenopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman over age 50 in the absence of other biologic or physiologic causes.
  11. Women with child bearing potential and men with reproductive potential must be willing to practice acceptable methods of contraception.
  12. Ability to understand and the willingness to sign a written informed consent document.
  13. Willingness to undergo biopsy of metastatic site or site of unresectable disease prior to randomization.

Main Exclusion Criteria:

  1. History of another malignancy except for those who have been disease-free for 3 years, or patients with a history of completely resected non-melanoma skin cancer and/or patients with indolent secondary malignancies not requiring active therapy, are eligible. Consult the study Medical Monitor if unsure whether second malignancies meet the requirements specified above.
  2. Any major surgical procedures or external beam radiotherapy within 14 days prior to study drug administration.
  3. Use of other investigational drugs within 28 days prior to study drug administration.
  4. Symptomatic or untreated leptomeningeal or brain metastases or spinal cord compression. Treated brain metastases must have been stable for at least 1 month and require treatment with less than 10mg/day prednisone equivalent for at least 2 weeks prior to study drug administration.
  5. Prior exposure to either ipilimumab or combined checkpoint blockade.
  6. Any diagnosis of autoimmune disease. Patients with Type I diabetes mellitus, hypothyroidism only requiring hormone replacement, adrenal insufficiency on replacement dose steroids, skin disorders (such as vitiligo, psoriasis or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
  7. Pregnant women and lactating women.
  8. History of uveal melanoma.
  9. Known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) infection (with the exception of chronic or cleared HBV or HCV infection, which will be allowed). Once-documented negative result for HIV, HBV, and HCV is sufficient.
  10. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection and psychiatric illness/social situations that would limit compliance with study requirements.
  11. Patients with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement steroid doses > 10 mg daily prednisone equivalent are permitted.
  12. Patients with history of any grade 4 toxicity during previous anti PD-1 treatment or history of Grade 3 or higher pneumonitis.
  13. Patients with a history of Grade ≥2 neuropathy.
  14. Prisoners or patients who are involuntarily incarcerated.
  15. Children under the age of 18.
  16. Patients who require hemodialysis.
  17. Patients with a history of allergy to study drug components or history of a severe hypersensitivity reaction to any monoclonal antibody.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02731729
Other Study ID Numbers  ICMJE PICI0001
16-043 ( Other Identifier: Memorial Sloan Kettering Cancer Center )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Parker Institute for Cancer Immunotherapy
Original Responsible Party Memorial Sloan Kettering Cancer Center
Current Study Sponsor  ICMJE Parker Institute for Cancer Immunotherapy
Original Study Sponsor  ICMJE Memorial Sloan Kettering Cancer Center
Collaborators  ICMJE Bristol-Myers Squibb
Investigators  ICMJE
Study Director: Ramy Ibrahim, MD Parker Institute for Cancer Immunotherapy
PRS Account Parker Institute for Cancer Immunotherapy
Verification Date December 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP