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Phase II Study of Nivolumab in Combination With Ipilimumab for Uveal Melanoma

This study is currently recruiting participants.
Verified October 2017 by M.D. Anderson Cancer Center
Sponsor:
ClinicalTrials.gov Identifier:
NCT01585194
First Posted: April 25, 2012
Last Update Posted: October 6, 2017
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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborators:
Bristol-Myers Squibb
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
April 23, 2012
April 25, 2012
October 6, 2017
November 2012
November 2019   (Final data collection date for primary outcome measure)
Overall Response Rate [ Time Frame: 12 weeks ]
Response defined as those patients who achieve RECIST complete response plus partial response (CR + PR). Overall response applied for interpreting the criteria of the Simon two-stage design.
Maximum Tolerated Dose (MTD) [ Time Frame: 12 weeks ]
Tumor assessments occur at baseline, week 24, and every 6 months thereafter for the adjuvant arm. Tumor assessments occur at baseline, week 12, week 16, week 20, week 24, and every 12 weeks thereafter for the metastatic arm. Tumor assessments in the form of CT chest, abdomen, and pelvis with oral and intravenous contrast or alternative body imaging at the discretion of investigator.
Complete list of historical versions of study NCT01585194 on ClinicalTrials.gov Archive Site
Progression-Free Survival [ Time Frame: 1 year ]
Kaplan-Meier method used to assess the distribution of time-to-event variables, including overall survival, progression-free survival, and landmark analysis where possible.
Overall Survival [ Time Frame: 1 year ]
Kaplan-Meier method to assess distribution of time-to-event variables, including overall survival, progression-free survival, and distant metastasis-free survival, separately by arm and cohort.
Not Provided
Not Provided
 
Phase II Study of Nivolumab in Combination With Ipilimumab for Uveal Melanoma
Phase II Study of Nivolumab in Combination With Ipilimumab for Uveal Melanoma

The goal of this clinical research study is to learn if ipilimumab and nivolumab can help to control uveal melanoma.

Ipilimumab is designed to increase the immune system's ability to fight cancer.

Nivolumab is an antibody (a protein that attacks foreign cells) that is designed to allow the body's immune system to work against tumor cells.

This is an investigational study.

Ipilimumab is FDA approved and commercially available to treat metastatic melanoma, including uveal melanoma. Nivolumab is FDA approved and commercially available to treat metastatic melanoma, including uveal melanoma, that has gotten worse while taking ipilimumab. Combining these 2 drugs to treat of uveal melanoma is investigational.

Up to 52 patients will take part in this study. All will be enrolled at MD Anderson.

Study Drug Administration:

If you are found to be eligible to take part in this study, you will receive ipilimumab by vein over 90 minutes (+/- 15 minutes) each time. You will receive nivolumab by vein over 60 minutes (+/- 15 minutes) each time.

You will receive ipilimumab and nivolumab every 3 weeks (+/- 7 days) for a total of 4 doses (Weeks 1, 4, 7, and 10). You will continue to receive nivolumab every 2 weeks after that.

Study Visits:

At Weeks 1, 4, 7, and 10:

  • You will have a physical exam, including measurement of your vital signs and weight. If your screening visit occurred within 14 days of your first on-study visit, it will not need to be repeated on Day 1 of Cycle 1.
  • You will be asked about any symptoms or side effects you may have had and any drugs you may be taking.
  • Your performance status will be recorded.
  • Blood (about 1 tablespoon) will be drawn for routine tests and to check your liver and thyroid function.
  • If you are able to become pregnant, you will have a blood (about 1 teaspoon) or urine pregnancy test.

At Week 13 and every 4 weeks after that, if you are able to become pregnant, you will have a blood (about 1 teaspoon) or urine pregnancy test.

At Week 13 and every 6 weeks after that:

  • You will have a physical exam, including measurement of your vital signs and weight.
  • You will be asked about any symptoms or side effects you may have had and any drugs you may be taking.
  • Your performance status will be recorded.

At Week 13 and every 2 weeks after that, blood (about 2 tablespoons) will be drawn for routine and liver function tests.

Sometime during Cycles 2-4, you will have a core or excisional biopsy of the tumor for biomarker testing, including genetic biomarkers. Biomarkers are found in the blood/tissue and may be related to your reaction to the study drug. To perform a core biopsy, a sample of tissue is removed using a hollow core needle that has a cutting edge. To perform an excisional biopsy, the area of abnormal skin, including a portion of normal skin area is removed by cutting it out. You may receive stitches after an excisional biopsy.

At Week 13 and every 12 weeks after that (+/- 7 days):

  • Blood (about 1 tablespoon ) will be drawn to check your thyroid function.
  • You will have a scan such as a CT scan to check the status of the disease. This may include imaging of the brain if the doctor thinks it is needed.

Length of Treatment:

You may receive up to 4 doses of ipilimumab and may continue taking nivolumab for as long as the doctor thinks it is in your best interest.

You may no longer be able to take the study drugs if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.

Your participation on the study will be over once you have completed the end-of-treatment visit, and follow-up.

End-of-Treatment Visit:

After you are finished taking the study drugs:

  • You will have a physical exam, including measurement of your vital signs.
  • You will be asked about any symptoms or side effects you may have had and any side drugs you may be taking.
  • Blood (about 1 tablespoon) will be drawn for routine tests and to check your liver and thyroid function.

Follow-Up:

For at least 60 days after you are finished taking the study drugs, you will have follow-up by phone or at the clinic. You will be asked how you are doing.

Interventional
Phase 2
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • Melanoma
  • Uveal Melanoma
  • Drug: Nivolumab

    Induction Phase:

    1 mg/kg by vein for a total of four doses (week 1, 4, 7, 10). The induction phase continues through week 12.

    Other Names:
    • BMS-936558
    • Opdivo
  • Drug: Ipilimumab

    Induction Phase:

    3 mg/kg by vein for a total of four doses (week 1, 4, 7, 10). The induction phase continues through week 12.

    Maintenance Phase:

    For patients who have not experienced disease progression or unmanageable toxicity by week 12:

    Nivolumab 3 mg/kg by vein every 2 weeks until disease progression or unmanageable toxicity as deemed by the clinical investigator.

    Other Names:
    • Yervoy
    • BMS-734016
    • MDX010
Experimental: Nivolumab + Ipilimumab

Induction Phase:

Nivolumab 1 mg/kg plus Ipilimumab 3 mg/kg (+/- 7 days) for total of four doses (week 1, 4, 7, 10), continues through week 12.

Maintenance Phase:

For participants with no disease progression or unmanageable toxicity by week 12, Nivolumab monotherapy 3 mg/kg every 2 weeks until disease progression or unmanageable toxicity.

Interventions:
  • Drug: Nivolumab
  • Drug: Ipilimumab
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
52
November 2019
November 2019   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Willing and able to give written informed consent.
  2. History of uveal melanoma and documented metastatic disease with at least one measurable lesion is required. which is >/= 1 cm x 1 cm (on spiral CT or equivalent).
  3. Any number of prior therapies is allowed.
  4. Required values for initial laboratory tests: WBC >/= 2000/uL, ANC >/= 1500/uL, Platelets >/= 100 x 10^3/uL, Hemoglobin >/= 9 g/dL, Creatinine </= 1.5 x ULN or creatinine clearance (CrCl) > 40 mL/min (using the Cockcroft-Gault formula): Female CrCl = (140 - age in years) x weight in kg x 0.85, 72 x serum creatinine in mg/dL, Male CrCl = (140 - age in years) x weight in kg x 1.00 72 x serum creatinine in mg/dL, AST/ALT</= 3 x ULN for patients without liver metastasis,</= 5 x ULN for liver metastases, Bilirubin </= 1.5 x ULN, (except patients with Gilbert's Syndrome, who must have a total bilirubin less than 3.0 mg/dL)
  5. In suspected patients no active or chronic infection with HIV, Hepatitis B, or Hepatitis C.
  6. Performance status ECOG 0-1.
  7. Men and women, >/= 18 years of age. Because no dosing or adverse event data are currently available on the use of ipilimumab in patients </= 18 years of age, minors are excluded from this study.
  8. Baseline imaging in the form of CT chest, abdomen, pelvis with oral and intravenous contrast within 28 days of study entry. For patients with a contrast allergy, choice of alternative body imaging will be at the discretion of the investigator or his designee. MRI of the brain is only needed if clinically indicated.
  9. Prior to start of treatment must be more than 21 days elapsed from surgery, radiation therapy, or prior chemotherapy. More than 42 days elapsed from prior immune therapy including vaccines.
  10. Women of childbearing potential (WOCBP) and fertile men with partners of childbearing potential must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 26 weeks after the last dose of investigational product, in such a manner that the risk of pregnancy is minimized.

Exclusion Criteria:

  1. Untreated primary uveal melanoma except in cases where metastatic disease is diagnosed at the time of primary disease.
  2. Metastatic uveal melanoma patients with bone-only disease.
  3. Any other malignancy from which the patient has been disease-free for less than 2 years, with the exception of adequately treated and cured basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix, breast, or prostate.
  4. Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment,
  5. Any underlying medical or psychiatric condition, which in the opinion of the investigator will make the administration of ipilimumab hazardous or obscure the interpretation of AEs, such as a condition associated with frequent diarrhea.
  6. Any non-oncology vaccine therapy used for prevention of infectious diseases (for up to 1 month before or after any dose of ipilimumab).
  7. Concomitant therapy with any of the following: tamoxifen, toremifene, IL 2, interferon, or other non-study immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive agents; other investigation therapies; or chronic use of systemic corticosteroids greater than physiologic replacement doses. Ocular steroid use is acceptable.
  8. Women of childbearing potential (WOCBP)who: (a.) are unwilling or unable to use an acceptable method of contraception to avoid pregnancy for their entire study period and for up to 26 weeks after cessation of study drug, or (b.) have a positive pregnancy test at baseline, or (c.) are pregnant or breastfeeding.
  9. Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) illness.
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
No
Contact: Sapna P. Patel, MD 713-792-2921
United States
 
 
NCT01585194
2011-0919
NCI-2012-00665 ( Registry Identifier: NCI CTRP )
1R21CA208609-01 ( U.S. NIH Grant/Contract )
No
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Not Provided
M.D. Anderson Cancer Center
M.D. Anderson Cancer Center
  • Bristol-Myers Squibb
  • National Cancer Institute (NCI)
Principal Investigator: Sapna P. Patel, MD M.D. Anderson Cancer Center
M.D. Anderson Cancer Center
October 2017

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