Clinical trial NCT00441337: A Study of MDX-1106 in Patients With Selected Refractory or Relapsed Malignancies
Official title: A Phase 1, Open Label, Dose-escalation, Safety and Pharmacokinetic Study of MDX-1106 in Patients With Selected or Relapsed Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Carcinoma, Non-Small-Cell Lung
Colorectal Cancer
Malignant Melanoma
Renal Cancer
Prostate Cancer
Keywords: malignancies
cancer
non small cell lung cancer
lung cancer
colorectal cancer
adenocarcinoma
melanoma
malignant melanoma
renal cancer
renal carcinoma
carcinoma
prostate cancer
prostate adenocarcinoma
Recurrent or treatment refractory malignancies
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2007-02-28
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: To evaluate the safety, tolerability, efficacy, and pharmacokinetics of MDX-1106 when administered to patients with advanced non-small cell lung cancer, colorectal cancer, malignant melanoma, clear cell renal cell cancer or hormone refractory prostate cancer

Detailed description: Six patients enrolled at each dose level of 0.3, 1.0, 3.0 and 10mg/kg; the remaining 10 to 15 patients may subsequently be enrolled at a dose at or below the maximum tolerated dose (MTD) during the dose-escalation portion of the study. Patients who respond may receive additional doses of drug.

Eligibility criteria: Inclusion Criteria:

* Relapsed/refractory non-small cell lung cancer, colorectal adenocarcinoma, malignant melanoma, renal (clear) cell carcinoma, or hormone-refractory prostate adenocarcinoma
* Prior treatment must have been completed at least 4 weeks prior to enrollment
* No untreated primary or metastatic brain or meningeal tumors
* ECOG PS 0 or 1
* Meet all screening laboratory values

Exclusion Criteria:

* History of severe hypersensitivity reactions to other monoclonal antibodies
* Active autoimmune disease or a documented history of autoimmune disease
* Prior therapy with an anti-PD-1 or anti-CTLA-4 antibody
* Active infection
* Concurrent medical condition requiring the use of immunosuppressive medications

Primary outcomes:
measure: Number of Participants With Severe Adverse Events (AEs), Serious Adverse Events (SAEs), Drug-Related AEs, Deaths, Discontinuation of Study Drug Due to AE, Dose-Limiting Toxicity (DLT) AE and Immune-related AEs (irAEs) in Safety Population
timeFrame: Day 1 to 70 days post last dose of study drug; 28 days past study discontinuation
measure: Geometric Mean Maximum Serum Concentration (Cmax) Observed Post-Single Dose
timeFrame: Day 1 to Day 85
measure: Median Time at Which the Maximum Serum Concentration Occurred (Tmax) Post-Single Dose
timeFrame: Day 1 to Day 85
measure: Geometric Mean Area Under the Curve (AUC) From Time of Dosing to Time of Last Observation (0-T) and Extrapolated to Infinity (INF) Observed Post-Single Dose
timeFrame: Day 1 to Day 85
measure: Mean Elimination Half-life (T-HALF) Post-Single Dose
timeFrame: Day 1 to Day 85
measure: Geometric Mean Total Body Clearance of Drug From Serum (CLT) Post-Single Dose
timeFrame: Day 1 to Day 85
measure: Mean Volume of Distribution (Vz) Post-Single Dose
timeFrame: Day 1 to Day 85
measure: Percent of Participants With Best Overall Response Rate in Safety Population and in Tumor Evaluable Population
timeFrame: Day 1 up to 2 Years.
measure: Percent of Participants With Prostate-Specific Antigen (PSA) Response After the First Dose by Day 85 In Participants With Hormone-Refractory Prostate Adenocarcinoma (HRPC)
timeFrame: Day 1 to Day 85
Secondary outcomes:
measure: Number of Participants With Best Overall Response (BOR) by Category in Safety Population
timeFrame: Day 1 to Day 85
measure: Percentage of Participants With Disease Control and Major Durable Disease Control
timeFrame: Day 1 to 2 Years
measure: Median Time to Tumor Response and Duration of Tumor Response
timeFrame: Day 1 to 2 Years
measure: Time to Tumor Progression and Tumor Progression Free Survival
timeFrame: Day 1 to 2 Years
measure: Median Time to PSA Progression in Days and Median PSA Progression Free Survival in Days in PSA Evaluable Population
timeFrame: Day 1 to 2 Years
measure: Mean Change From Baseline in PSA Relative Velocity at Days 29, 57, and 85 With Cycle 1 in PSA Evaluable Population
timeFrame: Day 29, Day 57, Day 85
measure: Mean Change From Baseline in Electrocardiogram Parameters PR, QRS and QT in Safety Population
timeFrame: Baseline, Day 2, Day 85, Day 113
measure: Mean Diastolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in 0.3 mg Cohort - Safety Population
timeFrame: Baseline, Day 1
measure: Mean Systolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in 0.3 mg Cohort - Safety Population
timeFrame: Baseline, Day 1
measure: Mean Diastolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in 1mg, 3mg, and 10 mg Cohorts - Safety Population
timeFrame: Baseline, Day 1
measure: Mean Systolic Blood Pressure at Baseline and Post-Infusion Day 1 (Cycle 1) in in 1mg, 3mg, and 10 mg Cohorts - Safety Population
timeFrame: Baseline, Day 1
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins Unv., School of Medicine
state: Maryland
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: St. Louis
country: United States
facility: Washington University School of Medicine - Barnes Jewish Hospital
state: Missouri
city: Huntersville
country: United States
facility: Carolina BioOncology Institute, PLLC
state: North Carolina
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: George S, Pili R, Carducci MA, Kim JJ. Role of immunotherapy for renal cell cancer in 2011. J Natl Compr Canc Netw. 2011 Sep 1;9(9):1011-8. doi: 10.6004/jnccn.2011.0085.