Ipilimumab for Uveal Melanoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by M.D. Anderson Cancer Center
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01585194
First received: April 23, 2012
Last updated: October 7, 2014
Last verified: October 2014
  Purpose

The goal of this clinical research study is to learn the highest tolerable dose of ipilimumab that can be given to patients with uveal melanoma. Researchers also want to learn if ipilimumab can help to control the disease.

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


Condition Intervention Phase
Melanoma
Drug: Ipilimumab
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Study of Ipilimumab for Uveal Melanoma

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) of Ipilimumab [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Overall Survival [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 141
Study Start Date: November 2012
Estimated Primary Completion Date: November 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Adjuvant Arm

Adjuvant arm will enroll patients into two cohorts: Cohort 1 defined as high-risk uveal melanoma patients with Class 2 gene expression signature and Cohort 2 defined as high-risk uveal melanoma patients with monosomy 3 or apical thickness greater than 8.0-mm on echography.

Study conducted in two parts: a dose-finding phase followed by a dose expansion of the maximum tolerated dose (MTD). Once the MTD has been determined, the study will proceed in two phases: an induction phase followed by a maintenance phase

Administration of ipilimumab will be either 3 mg/kg or 10 mg/kg intravenously over a 90 minute period +/- 15 minutes. Administration of Ipilimumab will occur every cycle and is defined as every 21 days (+/- 7 days).

Drug: Ipilimumab

Phase I

Dose-Finding Phase Starting Dose for Adjuvant Arm and Metastatic Arm: 3 mg/kg by vein every 21 days.

Dose Expansion Phase for Adjuvant Arm and Metastatic Arm: Maximum tolerated dose from Dose-Finding Phase.

Phase II

Dose Expansion Induction Phase Adjuvant and Metastatic Arms Starting Dose: Maximum tolerated dose (MTD) from Phase I Dose Expansion Phase given by vein every 3 weeks for four doses (week 1, 4, 7, 10). The induction phase continues through week 24.

Maintenance Phase Adjuvant Arm: MTD of ipilimumab every 12 weeks beginning at week 24 for up to one year (week 24, 36, 48).

Maintenance Phase Metastatic Arm: MTD of ipilimumab every 12 weeks beginning at week 24 until disease progression or unmanageable toxicity occurs.

Other Names:
  • Yervoy
  • BMS-734016
  • MDX010
Experimental: Metastatic Arm

Metastatic Arm: Uveal melanoma patients with at least one measureable lesion.

Study conducted in two parts: a dose-finding phase followed by a dose expansion of the maximum tolerated dose (MTD).

Administration of ipilimumab will be either 3 mg/kg or 10 mg/kg intravenously over a 90 minute period +/- 15 minutes. Administration of Ipilimumab will occur every cycle and is defined as every 21 days (+/- 7 days).

Drug: Ipilimumab

Phase I

Dose-Finding Phase Starting Dose for Adjuvant Arm and Metastatic Arm: 3 mg/kg by vein every 21 days.

Dose Expansion Phase for Adjuvant Arm and Metastatic Arm: Maximum tolerated dose from Dose-Finding Phase.

Phase II

Dose Expansion Induction Phase Adjuvant and Metastatic Arms Starting Dose: Maximum tolerated dose (MTD) from Phase I Dose Expansion Phase given by vein every 3 weeks for four doses (week 1, 4, 7, 10). The induction phase continues through week 24.

Maintenance Phase Adjuvant Arm: MTD of ipilimumab every 12 weeks beginning at week 24 for up to one year (week 24, 36, 48).

Maintenance Phase Metastatic Arm: MTD of ipilimumab every 12 weeks beginning at week 24 until disease progression or unmanageable toxicity occurs.

Other Names:
  • Yervoy
  • BMS-734016
  • MDX010

  Hide Detailed Description

Detailed Description:

Study Drug Administration:

If you are found to be eligible to take part in this study, you will be assigned to a study group based on when you join this study. Up to 4 groups of 3 participants will be enrolled in the Phase I portion of the study. Up to 129 participants will be enrolled in Phase II. This includes up to 83 participants with a history of uveal melanoma that is at high risk to spread and up to 46 patients with metastatic cancer.

If you are enrolled in the Phase I portion, the dose of ipilimumab you receive will depend on when you joined this study. Two (2) dose levels will be tested in each status type of uveal melanoma: participants with a history of uveal melanoma that is at high risk to spread (the "adjuvant" group) and participants with metastatic cancer.

The first group of participants in each cancer status type will receive the lowest dose level of ipilimumab. The next group of participants will receive a higher dose of ipilimumab than the group before it, if intolerable side effects are seen in no more than 1/3 of participants at the lower dose. This process is designed to find the highest tolerable dose of ipilimumab.

If you are enrolled in the Phase II portion, you will receive ipilimumab at the highest dose that was tolerated in the Phase I portion.

You will receive ipilimumab by vein over 90 minutes (+/- 15 minutes) each time.

You will receive ipilimumab every 3 weeks (+/- 7 days) for a total of 4 doses (Weeks 1, 4, 7, and 10). Starting at Week 24, if you are in the adjuvant group, you will receive ipilimumab every 12 weeks (+/- 7 days) for up to 1 year (Weeks 24, 36, and 48). Starting at Week 24, if you are in the metastatic group, you will receive ipilimumab every 12 weeks (+/- 7 days) for as long as the study doctor thinks it is in your best interest.

Study Visits:

At Weeks 1, 4, 7, 10, 12, 18, 24, and every 12 weeks after that:

  • 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.
  • If you are able to become pregnant, you will have a blood (about 1 teaspoon) or urine pregnancy test.

If you are in the metastatic group, at Weeks 12, 18, 24, and every 12 weeks after that, you will have scans such as a CT scan to check the status of the disease.

If you are in the adjuvant group, you will have scans such as a CT scan to check the status of the disease at Week 24 and Week 48.

Length of Treatment:

If you are in the adjuvant group, you may continue taking the study drug for up to 1 year. All other study participants may continue taking the study drug for as long as the doctor thinks it is in your best interest.

You may no longer be able to take the study drug 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 drug:

  • 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.
  • If your doctor thinks it is needed, you will have scans such as a CT scan to check the status of the disease.

Follow-Up:

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

This is an investigational study. Ipilimumab is FDA approved and commercially available to treat metastatic melanoma, including uveal melanoma. It is investigational to study ipilimumab in a group of patients that has uveal melanoma, specifically, and to give it in the dosing schedules in this study.

Up to 141 patients will take part in this study. All will be enrolled at MD Anderson.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Willing and able to give written informed consent.
  2. History of uveal melanoma. For the adjuvant arm, eligible patients must have completed local therapy for the eye no more than 12 months prior to enrollment. For the metastatic arm, documented metastatic disease with at least one measurable lesion is required which is >/=1 cm x 1 cm (on spiral CT or equivalent)
  3. For the adjuvant arm, patients must be identified as high-risk based on any of the following: Class 2 gene expression signature using DecisionDx-UM and/or complete testing, or monosomy 3 and/or apical thickness greater than 8.0-mm. If a patient is eligible for both Cohort 1 and Cohort 2 based on multiple factors, the patient will be enrolled on Cohort 1.
  4. Any number of prior therapies is allowed.
  5. Required values for initial laboratory tests: WBC >/= 2000/uL, ANC >/= 1000/uL, Platelets >/= 75 x 103/uL, Hemoglobin >/= 9 g/dL, Creatinine </= 2.0 x ULN, AST/ALT</= 2.5 x ULN for patients without liver metastasis,</= 5 x ULN for liver metastases, Bilirubin </= 2.0 x ULN, (except patients with Gilbert's Syndrome, who must have a total bilirubin less than 3.0 mg/dL)
  6. No active or chronic infection with HIV, Hepatitis B, or Hepatitis C.
  7. Performance status ECOG 0-1.
  8. 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.
  9. 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.
  10. 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.
  11. 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. Autoimmune disease: Patients with a history of inflammatory bowel disease, including ulcerative colitis and Crohn's Disease, are excluded from this study, as are patients with a history of symptomatic disease (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [e.g., Wegener's Granulomatosis]); motor neuropathy considered of autoimmune origin (e.g. Guillain-Barre Syndrome and Myasthenia Gravis).
  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. A history of prior treatment with ipilimumab or prior CD137 agonist or CTLA 4 inhibitor or agonist.
  8. 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. Ocular steroid use is acceptable.
  9. 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.
  10. Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) illness.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01585194

Contacts
Contact: Sapna P. Patel, MD 713-792-2921

Locations
United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Bristol-Myers Squibb
Investigators
Principal Investigator: Sapna P. Patel, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01585194     History of Changes
Other Study ID Numbers: 2011-0919, NCI-2012-00665
Study First Received: April 23, 2012
Last Updated: October 7, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
Melanoma
History of Uveal Melanoma
Metastatic
Ipilimumab
Yervoy
BMS-734016
MDX010

Additional relevant MeSH terms:
Melanoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Neuroectodermal Tumors
Neuroendocrine Tumors
Nevi and Melanomas

ClinicalTrials.gov processed this record on October 23, 2014