Clinical trial NCT00246012: A Safety and Efficacy Study of Intetumumab, Alone and in Combination With Dacarbazine, in Participants With Stage 4 Melanoma
Official title: A Phase 1/2, Multi-Center, Blinded, Randomized, Controlled Study of the Safety and Efficacy of the Human Monoclonal Antibody to Human α ν Integrins (CNTO 95), Alone and in Combination With Dacarbazine, in Subjects With Stage IV Melanoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Melanoma
Keywords: Melanoma
Neoplasm
CNTO 95
Dacarbazine
Intetumumab
Lead sponsor: Centocor, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Janssen-Cilag Farmaceutica, S.R.L.
First posted: 2005-10-30
Enrollment: 144
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety and effectiveness of the intetumumab, alone and in combination with dacarbazine, in patients with stage 4 melanoma.

Detailed description: This is a Phase 1/2, multi-center, randomized (the study medication is assigned by chance) study. This study will be conducted in 2 Phases (Phase 1 and Phase 2). Phase 1 of this study will be non-randomized, open-label (all people know the identity of the intervention) and dose-escalation phase. It includes screening period and treatment period, which consists of 2 parts (Part 1 and Part 2). In Part 1, participants will receive 1 of 3 single dose levels of intetumumab \[3 milligram per kilogram (mg/kg), 5 mg/kg or 10 mg/kg\]. Part 2 will include 2 dose cohorts: dacarbazine plus intetumumab (5 mg/kg) or dacarbazine plus intetumumab (10 mg/kg). Phase 2 of this study will be randomized, blinded (neither physician nor participant knows the intervention which the participant will receive) and controlled (an inactive substance and other medication is compared with a study medication to test whether the medication has a real effect in this clinical study). This phase of the study will include screening period, treatment period (8 cycles of treatment with every cycle once in 3 weeks) and follow-up period (24 weeks). During the treatment period, participants will be randomly assigned to 1 of 4 treatment groups, Group 1: dacarbazine plus placebo, Group 2: intetumumab (5 mg/kg), Group 3: intetumumab (10 mg/kg) and Group 4: dacarbazine plus intetumumab. Randomization will be further based on the site of metastases and Eastern Cooperative Oncology Group performance status at Baseline. Single-medication intetumumab treatment groups will be open-label, while the dacarbazine plus intetumumab or placebo groups will be blinded. The total duration of the Phase 2 of this study will be up to 52 weeks or up to 76 weeks in case of extended dosing (extended administrations \[up to 8 additional cycles\] of the same assigned treatment will be allowed for participants that are responding to therapy with stable disease or better). Participants will be assessed for incidence of dose limiting toxicities, pharmacokinetics and tumor responses. Participants' safety will be monitored throughout the study.

Eligibility criteria: Inclusion Criteria:

* Histologically confirmed melanoma including ocular and mucosal
* Documented AJCC (American Joint Committee on Cancer) Stage 3 unresectable or Stage 4 melanoma (Phase 1); AJCC Stage 4 melanoma (Phase 2)
* Radiographically measurable disease or measurable skin lesions
* Prior chemotherapy for metastatic melanoma will be allowed for Phase 1, while previously untreated for melanoma by chemotherapy will be allowed for Phase 2
* Agrees to protocol-defined use of effective contraception

Exclusion Criteria:

* History of receiving murine or human/murine recombination products of human αν integrins
* Known human immunodeficiency virus (HIV) positivity and clinically important active infection
* Presence of bone metastases or malignant effusions (non-measurable lesions) and central nervous system metastases
* Prior radiation to target lesions
* Concurrent immunotherapy, biotherapy, radiotherapy, chemotherapy, or investigational therapy and therapeutic use of anticoagulation

Primary outcomes:
measure: Number of Participants With Dose Limiting Toxicities (DLTs) - Phase 1
timeFrame: Up to 21 days post-first infusion from the last treated participant in Phase 1
measure: Maximum Observed Serum Concentration (Cmax) of Intetumumab - Phase 1 (Part 1)
timeFrame: Pre-infusion, post-infusion at 2, 4, 8, 24 hour, Day 8, Day 15, post-last dose (3 weeks or 1 week) and 3 months post-last dose
measure: Area Under the Serum Concentration Versus Time Curve (AUC) of Intetumumab - Phase 1 (Part 1)
timeFrame: Pre-infusion, post-infusion at 2, 4, 8, 24 hour, Day 8, Day 15, post-last dose (3 weeks or 1 week) and 3 months post-last dose
measure: Half-life of Intetumumab - Phase 1 (Part 1)
timeFrame: Pre-infusion, post-infusion at 2, 4, 8, 24 hour, Day 8, Day 15, post-last dose (3 weeks or 1 week) and 3 months post-last dose
measure: Total Clearance (CL) of Intetumumab After Intravenous Administration - Phase 1 (Part 1)
timeFrame: Pre-infusion, post-infusion at 2, 4, 8, 24 hour, Day 8, Day 15, post-last dose (3 weeks or 1 week) and 3 months post-last dose
measure: Volume of Distribution (Vz) of Intetumumab - Phase 1 (Part 1)
timeFrame: Pre-infusion, post-infusion at 2, 4, 8, 24 hour, Day 8, Day 15, post-last dose (3 weeks or 1 week) and 3 months post-last dose
measure: Accumulation Ratio (R) of Intetumumab - Phase 1 (Part 1)
timeFrame: Pre-infusion, post-infusion at 2, 4, 8, 24 hour, Day 8, Day 15, post-last dose (3 weeks or 1 week) and 3 months post-last dose
measure: Progression-Free Survival (PFS) - Phase 2
timeFrame: From the date of randomization to date of initial documented progressive disease or death, whichever occured first, as assessed upto 6 months after last dose of study medication
Secondary outcomes:
measure: Percentage of Participants Who Achieved a Best Overall Tumor Response as Complete Response (CR) or Partial Response (PR) - Phase 2
timeFrame: Screening, within 1 week of the end of Cycles 2, 4, 6, 8 (but prior to the next cycle dose), and follow-up (3 and 6 months post-last dose where applicable)
measure: Percentage of Participants Who Achieved CR - Phase 2
timeFrame: Screening, within 1 week of the end of Cycles 2, 4, 6, 8 (but prior to the next cycle dose), and follow-up (3 and 6 months post-last dose where applicable)
measure: Percentage of Participants Who Achieved Stable Disease (SD) - Phase 2
timeFrame: Screening, within 1 week of the end of Cycles 2, 4, 6, 8 (but prior to the next cycle dose), and follow-up (3 and 6 months post-last dose where applicable)
measure: Overall Survival (OS) - Phase 2
timeFrame: Every 3 months until death, until lost to follow-up, until withdrawal of consent, or until the Sponsor ends the study, as assessed up to 6 months post-last dose of study medication
measure: Duration of Response - Phase 2
timeFrame: From the time of initial documented response (CR or PR) to the first documented sign of progression, assessed up to 6 months post-last dose of study medication
measure: Time to Worsening in Eastern Cooperative Oncology Group (ECOG) Performance Status - Phase 2
timeFrame: Baseline (within 7 days of first infusion of study medication), Day 1 of all 8 cycles, 3 weeks or 1 week post-last dose, 3 months and 6 months post-last dose of study medication
measure: Maximum Observed Serum Concentration (Cmax) of Intetumumab - Phase 2
timeFrame: Pre-infusion, post-infusion at 2, 4, 8, 24 hour, Day 8, Day 15, post-last dose (3 weeks or 1 week) and 3 months post-last dose
measure: Change From Baseline in Functional Assessment of Cancer Therapy-Melanoma Subscale (FACT-MS) Score - Phase 2
timeFrame: Day 1 (pre-dose) of Cycles 1, 2, 3; and final visit (3 weeks post-last dose of study medication)
measure: Change From Baseline in Brief Pain Inventory (BPI) Score - Phase 2
timeFrame: Day 1 (pre-dose) of Cycles 1, 2, 3; and final visit (3 weeks post-last dose of study medication)
measure: Maximum Observed Serum Concentration (Cmax) of Intetumumab - Phase 1 (Part 2)
timeFrame: Pre-infusion, post-infusion at 2, 4, 8, 24 hour, Day 8, Day 15, post-last dose (3 weeks or 1 week) and 3 months post-last dose
measure: Area Under the Serum Concentration Versus Time Curve (AUC) of Intetumumab - Phase 1 (Part 2)
timeFrame: Pre-infusion, post-infusion at 2, 4, 8, 24 hour, Day 8, Day 15, post-last dose (3 weeks or 1 week) and 3 months post-last dose
measure: Half-life of Intetumumab - Phase 1 (Part 2)
timeFrame: Pre-infusion, post-infusion at 2, 4, 8, 24 hour, Day 8, Day 15, post-last dose (3 weeks or 1 week) and 3 months post-last dose
measure: Total Clearance (CL) of Intetumumab After Intravenous Administration - Phase 1 (Part 2)
timeFrame: Pre-infusion, post-infusion at 2, 4, 8, 24 hour, Day 8, Day 15, post-last dose (3 weeks or 1 week) and 3 months post-last dose
measure: Volume of Distribution (Vz) of Intetumumab - Phase 1 (Part 2)
timeFrame: Pre-infusion, post-infusion at 2, 4, 8, 24 hour, Day 8, Day 15, post-last dose (3 weeks or 1 week) and 3 months post-last dose
measure: Accumulation Ratio (R) of Intetumumab - Phase 1 (Part 2)
timeFrame: Pre-infusion, post-infusion at 2, 4, 8, 24 hour, Day 8, Day 15, post-last dose (3 weeks or 1 week) and 3 months post-last dose
Other outcomes:
measure: Area Under the Concentration Versus Time Curve Between Zero to Infinite Time (AUCinf) of Intetumumab - Phase 1 (Part 1)
timeFrame: Pre-infusion, post-infusion at 2, 4, 8, 24 hour, Day 8, Day 15, post-last dose (3 weeks or 1 week) and 3 months post-last dose
measure: Percentage of Participants Who Achieved a Best Overall Response as CR, PR, or SD - Phase 2
timeFrame: Within 28 days of first infusion of study medication, within 1 week of the end of Cycles 2, 4, 6, 8; 3 months and 6 months post-last dose of study medication
Locations:
city: Scottsdale
country: United States
state: Arizona
city: La Jolla
country: United States
state: California
city: Santa Monica
country: United States
state: California
city: Walnut Creek
country: United States
state: California
city: Aurora
country: United States
state: Colorado
city: Washington
country: United States
state: District of Columbia
city: Miami
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Park Ridge
country: United States
state: Illinois
city: Beech Grove
country: United States
state: Indiana
city: Omaha
country: United States
state: Nebraska
city: Buffalo
country: United States
state: New York
city: New York
country: United States
state: New York
city: Philadelphia
country: United States
state: Pennsylvania
city: Nashville
country: United States
state: Tennessee
city: Dallas
country: United States
state: Texas
city: Seattle
country: United States
state: Washington
city: Berlin N/A
country: Germany
city: Bonn
country: Germany
city: Buxtehude
country: Germany
city: Düsseldorf
country: Germany
city: Essen
country: Germany
city: Hannover
country: Germany
city: Jena
country: Germany
city: Kiel
country: Germany
city: Mannheim
country: Germany
city: Munster
country: Germany
city: Cambridge
country: United Kingdom
city: London
country: United Kingdom
city: Manchester
country: United Kingdom
city: Sheffield
country: United Kingdom
city: Southampton
country: United Kingdom
Study officials:
affiliation: Centocor, Inc.
name: Centocor, Inc. Clinical Trial
role: STUDY_DIRECTOR
References: