Evaluation of Tumor Response to Ipilimumab in the Treatment of Melanoma With Brain Metastases

NCT ID: NCT00623766

Last Updated: 2014-06-09

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

99 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-07-31

Study Completion Date

2012-10-31

Brief Summary

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To assess the response of melanoma with brain metastases to ipilimumab treatment while maintaining acceptable tolerability.

Detailed Description

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Conditions

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Melanoma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Ipilimumab, 10 mg/kg, IV in corticosteroid-free patients

Participants who had not received corticosteroid therapy for at least 10 days before starting study drug received ipilimumab,10 mg/kg, as a 90-minute intravenous (IV) infusion every 3 weeks (Weeks 1, 4, 7, and 10) during the Induction Phase. Those eligible (patients who did not discontinue due to toxicity, did not show progression at 24 weeks, and who remained clinically stable) for the Maintenance Phase continued to receive ipilimumab, 10 mg/kg IV, every 12 weeks, beginning at Week 24.

Group Type EXPERIMENTAL

Ipilimumab

Intervention Type DRUG

10 mg/kg, administered as an intravenous infusion every 3 weeks during induction and every 12 weeks during maintenance

Ipilimumab, 10 mg/kg, IV in corticosteroid-dependent patients

Participants who were dependent on corticosteroid therapy received ipilimumab, 10 mg/kg, as a 90-minute intravenous (IV) infusion every 3 weeks (Weeks 1, 4, 7, and 10) during the Induction Phase. Those eligible (patients who did not discontinue due to toxicity, did not show progression at 24 weeks, and who remained clinically stable) for the Maintenance Phase continued to receive ipilimumab, 10 mg/kg IV, every 12 weeks, beginning at Week 24.

Group Type EXPERIMENTAL

Ipilimumab

Intervention Type DRUG

10 mg/kg, administered as an intravenous infusion every 3 weeks during induction and every 12 weeks during maintenance

Corticosteroid: Betamethasone

Intervention Type DRUG

Participants in the corticosteroid-dependent arm for whom adequate control of metastatic brain lesion-related neurologic signs and symptoms required concurrent corticosteroid therapy with betamethasone

Corticosteroid: Dexamethasone

Intervention Type DRUG

Participants in the corticosteroid-dependent arm for whom adequate control of metastatic brain lesion-related neurologic signs and symptoms required concurrent corticosteroid therapy with dexamethasone

Corticosteroid: Fludrocortisone

Intervention Type DRUG

Participants in the corticosteroid-dependent arm for whom adequate control of metastatic brain lesion-related neurologic signs and symptoms required concurrent corticosteroid therapy with fludrocortisone

Corticosteroid: Hydrocortisone

Intervention Type DRUG

Participants in the corticosteroid-dependent arm for whom adequate control of metastatic brain lesion-related neurologic signs and symptoms required concurrent corticosteroid therapy with hydrocortisone

Corticosteroid: Meprednisone

Intervention Type DRUG

Participants in the corticosteroid-dependent arm for whom adequate control of metastatic brain lesion-related neurologic signs and symptoms required concurrent corticosteroid therapy with meprednisone

Corticosteroid: Methylprednisolone

Intervention Type DRUG

Participants in the corticosteroid-dependent arm for whom adequate control of metastatic brain lesion-related neurologic signs and symptoms required concurrent corticosteroid therapy with methylprednisolone

Corticosteroid: Prednisolone

Intervention Type DRUG

Participants in the corticosteroid-dependent arm for whom adequate control of metastatic brain lesion-related neurologic signs and symptoms required concurrent corticosteroid therapy with prednisolone

Corticosteroid: Prednisone

Intervention Type DRUG

Participants in the corticosteroid-dependent arm for whom adequate control of metastatic brain lesion-related neurologic signs and symptoms required concurrent corticosteroid therapy with prednisone

Corticosteroid: Triamcinolone

Intervention Type DRUG

Participants in the corticosteroid-dependent arm for whom adequate control of metastatic brain lesion-related neurologic signs and symptoms required concurrent corticosteroid therapy with triamcinolone

Interventions

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Ipilimumab

10 mg/kg, administered as an intravenous infusion every 3 weeks during induction and every 12 weeks during maintenance

Intervention Type DRUG

Corticosteroid: Betamethasone

Participants in the corticosteroid-dependent arm for whom adequate control of metastatic brain lesion-related neurologic signs and symptoms required concurrent corticosteroid therapy with betamethasone

Intervention Type DRUG

Corticosteroid: Dexamethasone

Participants in the corticosteroid-dependent arm for whom adequate control of metastatic brain lesion-related neurologic signs and symptoms required concurrent corticosteroid therapy with dexamethasone

Intervention Type DRUG

Corticosteroid: Fludrocortisone

Participants in the corticosteroid-dependent arm for whom adequate control of metastatic brain lesion-related neurologic signs and symptoms required concurrent corticosteroid therapy with fludrocortisone

Intervention Type DRUG

Corticosteroid: Hydrocortisone

Participants in the corticosteroid-dependent arm for whom adequate control of metastatic brain lesion-related neurologic signs and symptoms required concurrent corticosteroid therapy with hydrocortisone

Intervention Type DRUG

Corticosteroid: Meprednisone

Participants in the corticosteroid-dependent arm for whom adequate control of metastatic brain lesion-related neurologic signs and symptoms required concurrent corticosteroid therapy with meprednisone

Intervention Type DRUG

Corticosteroid: Methylprednisolone

Participants in the corticosteroid-dependent arm for whom adequate control of metastatic brain lesion-related neurologic signs and symptoms required concurrent corticosteroid therapy with methylprednisolone

Intervention Type DRUG

Corticosteroid: Prednisolone

Participants in the corticosteroid-dependent arm for whom adequate control of metastatic brain lesion-related neurologic signs and symptoms required concurrent corticosteroid therapy with prednisolone

Intervention Type DRUG

Corticosteroid: Prednisone

Participants in the corticosteroid-dependent arm for whom adequate control of metastatic brain lesion-related neurologic signs and symptoms required concurrent corticosteroid therapy with prednisone

Intervention Type DRUG

Corticosteroid: Triamcinolone

Participants in the corticosteroid-dependent arm for whom adequate control of metastatic brain lesion-related neurologic signs and symptoms required concurrent corticosteroid therapy with triamcinolone

Intervention Type DRUG

Other Intervention Names

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BMS-734016 MDX-010

Eligibility Criteria

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Inclusion Criteria

* Histologically confirmed malignant melanoma
* At least 1 measurable index brain metastasis \>0.5 cm and no larger than 3 cm in diameter that had not been previously irradiated, and/or 2 measurable lesions \>0.3 cm visible on contrast magnetic resonance
* Index brain lesion must have resolved consequences of prior therapy that could have confounded attribution of tumor response including edema and hemorrhage
* Participants in ipilimumab monotherapy arm (including the first 21 who were enrolled in Stage 1) were to be free of neurologic symptoms related to metastatic brain lesions and must not have required or received systemic corticosteroid therapy in the 10 days prior to beginning ipilimumab therapy
* Eastern Cooperative Oncology Group performance status of 0 or 1
* Required values for initial laboratory tests:

* White blood cell count ≥2000/μL
* Absolute neutrophil count ≥1000/μL
* Platelets ≥100\*10\^3/μL
* Hemoglobin level ≥9 g/dL (may have been transfused)
* Aspartate aminotransferase/alanine aminotransferase (AST/ALT) level ≤2.5\*ULN for participants without liver metastasis
* AST/ALT level ≤5\*ULN for those with liver metastasis
* Bilirubin level ≤2\*ULN (except participants with Gilbert's Syndrome, who must have had a total bilirubin level less than 3.0 mg/dL)
* Age 16 years and older
* Males and females
* Women of childbearing potential (WOBP) 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. WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not postmenopausal.

Exclusion Criteria

* History of carcinomatous meningitis, with prior stereotactic or highly conformal radiotherapy and/or whole brain irradiation within 14 days before the first dose of ipilimumab, and documented history of autoimmune disease
* Prior stereotactic or highly conformal radiotherapy and/or whole brain irradiation within 14 days prior to start of ipilimumab dosing for this study. Note the stereotactic radiotherapy field must not have included the brain index lesion or the lesion must have been detected and confirmed to be active and progressing after receiving whole brain irradiation.
Minimum Eligible Age

16 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Medarex

INDUSTRY

Sponsor Role collaborator

Bristol-Myers Squibb

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Bristol-Myers Squibb

Role: STUDY_DIRECTOR

Bristol-Myers Squibb

Locations

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Mayo Clinic Arizona

Scottsdale, Arizona, United States

Site Status

City Of Hope

Duarte, California, United States

Site Status

The Angeles Clinic & Research Institute

Los Angeles, California, United States

Site Status

Yale University School Of Medicine

New Haven, Connecticut, United States

Site Status

Loyola University Medical Center

Maywood, Illinois, United States

Site Status

Oncology Specialists, S.C.

Park Ridge, Illinois, United States

Site Status

Indiana University Cancer Center

Indianapolis, Indiana, United States

Site Status

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

Local Institution

The Bronx, New York, United States

Site Status

Providence Portland Med Ctr

Portland, Oregon, United States

Site Status

Vanderbilt-Ingram Cancer Ctr

Nashville, Tennessee, United States

Site Status

Seattle Cancer Care Alliance

Seattle, Washington, United States

Site Status

Countries

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United States

References

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Schadendorf D, Hodi FS, Robert C, Weber JS, Margolin K, Hamid O, Patt D, Chen TT, Berman DM, Wolchok JD. Pooled Analysis of Long-Term Survival Data From Phase II and Phase III Trials of Ipilimumab in Unresectable or Metastatic Melanoma. J Clin Oncol. 2015 Jun 10;33(17):1889-94. doi: 10.1200/JCO.2014.56.2736. Epub 2015 Feb 9.

Reference Type DERIVED
PMID: 25667295 (View on PubMed)

Johnson DB, Friedman DL, Berry E, Decker I, Ye F, Zhao S, Morgans AK, Puzanov I, Sosman JA, Lovly CM. Survivorship in Immune Therapy: Assessing Chronic Immune Toxicities, Health Outcomes, and Functional Status among Long-term Ipilimumab Survivors at a Single Referral Center. Cancer Immunol Res. 2015 May;3(5):464-9. doi: 10.1158/2326-6066.CIR-14-0217. Epub 2015 Feb 3.

Reference Type DERIVED
PMID: 25649350 (View on PubMed)

Iwama S, De Remigis A, Callahan MK, Slovin SF, Wolchok JD, Caturegli P. Pituitary expression of CTLA-4 mediates hypophysitis secondary to administration of CTLA-4 blocking antibody. Sci Transl Med. 2014 Apr 2;6(230):230ra45. doi: 10.1126/scitranslmed.3008002.

Reference Type DERIVED
PMID: 24695685 (View on PubMed)

Margolin K, Ernstoff MS, Hamid O, Lawrence D, McDermott D, Puzanov I, Wolchok JD, Clark JI, Sznol M, Logan TF, Richards J, Michener T, Balogh A, Heller KN, Hodi FS. Ipilimumab in patients with melanoma and brain metastases: an open-label, phase 2 trial. Lancet Oncol. 2012 May;13(5):459-65. doi: 10.1016/S1470-2045(12)70090-6. Epub 2012 Mar 27.

Reference Type DERIVED
PMID: 22456429 (View on PubMed)

Related Links

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Other Identifiers

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CA184-042

Identifier Type: -

Identifier Source: org_study_id

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