Clinical trial NCT00623766: Evaluation of Tumor Response to Ipilimumab in the Treatment of Melanoma With Brain Metastases
Official title: A Multi-Center Phase II Study to Evaluate Tumor Response to Ipilimumab (BMS-734016) Monotherapy in Subjects With Melanoma Brain Metastases
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Melanoma
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
Collaborators: name: Medarex
First posted: 2008-02-26
Enrollment: 99
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


Eligibility criteria: Key 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.

Key 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.

Primary outcomes:
measure: Disease Control Rate by Modified World Health Organization (mWHO) Tumor Assessment Criteria
timeFrame: From Day 1, first dose to end of Week 12
Secondary outcomes:
measure: Disease Control Rate by Immune-related Response Criteria (irRC)
timeFrame: From Day 1, first dose to end of Week 12
measure: Best Overall Response Rate (BORR) by Modified World Health Organization (mWHO) Criteria and by Immune-relate Response Criteria (irRC)
timeFrame: From Day 1, first dose until the last tumor assessment, Week 12
measure: Duration of Response (DOR) by Modified World Health Organization (mWHO) Criteria and by Immune-related Response Criteria (irRC)
timeFrame: From Day 1, first dose to last tumor assessment up to 18.2 months
measure: Progression-free Survival (PFS) by Modified World Health Organization (mWHO) Criteria and by Immune-related Response Criteria (irRC)
timeFrame: From Day 1, first dose to the date of progression or death, whichever occurred first up to 22 months
measure: Number of Participants Surviving at 6, 12, 18, 24, and 36 Months (Overall Survival [OS] Rate)
timeFrame: From first dose to Months 6, 12, 18, 24, and 36 months
measure: Number of Participants Who Died or Had a Treatment-related Adverse Event (AE), Immune-related AE, Immune-related Serious Adverse Event (SAE), Nervous System Disorder, Treatment-related Nervous System Disorder, SAE, and AE Leading to Discontinuation
timeFrame: Continuously from Day 1, first dose, to 70 days following last dose of ipilimumab
measure: Onset of Response by Modified World Health Organization (mWHO) Criteria and Immune-related Response Criteria (irRC)
timeFrame: From Day 1, first dose to a maximum of 4.2 months
measure: Overall Survival (OS)
timeFrame: From first dose to 24 months
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic Arizona
state: Arizona
city: Duarte
country: United States
facility: City Of Hope
state: California
city: Los Angeles
country: United States
facility: The Angeles Clinic & Research Institute
state: California
city: New Haven
country: United States
facility: Yale University School Of Medicine
state: Connecticut
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Park Ridge
country: United States
facility: Oncology Specialists, S.C.
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Cancer Center
state: Indiana
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: Bronx
country: United States
facility: Local Institution
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Portland
country: United States
facility: Providence Portland Med Ctr
state: Oregon
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Ctr
state: Tennessee
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.