A Safety and Efficacy Study of Intetumumab, Alone and in Combination With Dacarbazine, in Participants With Stage 4 Melanoma

NCT ID: NCT00246012

Last Updated: 2013-08-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 144 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-05-31
• Study Completion Date: 2009-02-28

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.

Conditions

Melanoma

Keywords

Melanoma; Neoplasm; CNTO 95; Dacarbazine; Intetumumab

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Intetumumab 3 mg/kg [Phase 1 (Part 1)]

Intetumumab will be administered at the dose of 3 milligram per kilogram (mg/kg) as intravenous infusion (a fluid or a medicine delivered into a vein by way of a needle) over a period of 2 hours (hr) (± 15 minutes) once every 3 weeks until the occurrence of dose limiting toxicities (DLTs). If after an evaluation of the preliminary single-dose pharmacokinetics, receptor saturation is not observed at the 3 mg/kg or 5 mg/kg dose level, that dose of intetumumab will be discontinued in Part 1 and participants will be treated at the highest, documented safe dose level at which receptor saturation is observed.

Group Type: EXPERIMENTAL

Intetumumab

Intervention Type: DRUG

Intetumumab will be administered at the dose of 3 milligram per kilogram (mg/kg) as intravenous infusion (a fluid or a medicine delivered into a vein by way of a needle) over a period of 2 hours (hr) (± 15 minutes) once every 3 weeks until the occurrence of dose limiting toxicities (DLTs). In Phase 2, intetumumab (5 mg/kg or 10 mg/kg) will be administered for 8 cycles until no evidence of disease progression or unacceptable toxicity. If a participant responds to therapy with stable disease (SD) or better, the participant will be eligible to receive up to 8 cycles of extended administrations.

Intetumumab 5 mg/kg [Phase 1 (Part 1)]

Intetumumab will be administered at the dose of 5 mg/kg as intravenous infusion over a period of 2 hr (± 15 minutes) once every 3 weeks until the occurrence of DLTs. If after an evaluation of the preliminary single-dose pharmacokinetics, receptor saturation is not observed at the 3 mg/kg or 5 mg/kg dose level, that dose of intetumumab will be discontinued in Part 1 and participants will be treated at the highest, documented safe dose level at which receptor saturation is observed.

Group Type: EXPERIMENTAL

Intetumumab

Intervention Type: DRUG

Intetumumab will be administered at the dose of 3 milligram per kilogram (mg/kg) as intravenous infusion (a fluid or a medicine delivered into a vein by way of a needle) over a period of 2 hours (hr) (± 15 minutes) once every 3 weeks until the occurrence of dose limiting toxicities (DLTs). In Phase 2, intetumumab (5 mg/kg or 10 mg/kg) will be administered for 8 cycles until no evidence of disease progression or unacceptable toxicity. If a participant responds to therapy with stable disease (SD) or better, the participant will be eligible to receive up to 8 cycles of extended administrations.

Intetumumab 10 mg/kg [Phase 1 (Part 1)]

Intetumumab will be administered at the dose of 10 mg/kg as intravenous infusion over a period of 2 hr (± 15 minutes) once every 3 weeks until the occurrence of DLTs.

Group Type: EXPERIMENTAL

Intetumumab

Intervention Type: DRUG

Intetumumab will be administered at the dose of 3 milligram per kilogram (mg/kg) as intravenous infusion (a fluid or a medicine delivered into a vein by way of a needle) over a period of 2 hours (hr) (± 15 minutes) once every 3 weeks until the occurrence of dose limiting toxicities (DLTs). In Phase 2, intetumumab (5 mg/kg or 10 mg/kg) will be administered for 8 cycles until no evidence of disease progression or unacceptable toxicity. If a participant responds to therapy with stable disease (SD) or better, the participant will be eligible to receive up to 8 cycles of extended administrations.

Dacarbazine + intetumumab 5 mg/kg [Phase 1 (Part 2)]

Intetumumab will be administered at the dose of 5 mg/kg as intravenous infusion over a period of 2 hr (± 15 minutes) once every 3 weeks for 8 cycles until no evidence of disease progression or unacceptable toxicity. If participants respond to therapy with stable disease (SD) or better, they will be considered eligible to receive up to 8 cycles of extended administrations. Commercially available dacarbazine will be administered at the dose of 1000 milligram per meter-square (mg/m\^2) intravenously over a period of 60 minutes (± 30 minutes) prior to intetumumab infusion.

Group Type: EXPERIMENTAL

Intetumumab

Intervention Type: DRUG

Intetumumab will be administered at the dose of 3 milligram per kilogram (mg/kg) as intravenous infusion (a fluid or a medicine delivered into a vein by way of a needle) over a period of 2 hours (hr) (± 15 minutes) once every 3 weeks until the occurrence of dose limiting toxicities (DLTs). In Phase 2, intetumumab (5 mg/kg or 10 mg/kg) will be administered for 8 cycles until no evidence of disease progression or unacceptable toxicity. If a participant responds to therapy with stable disease (SD) or better, the participant will be eligible to receive up to 8 cycles of extended administrations.

Dacarbazine

Intervention Type: DRUG

Commercially available dacarbazine will be administered intravenously over a 60-minute period (+30 minutes/-30 minutes) and prior to the intetumumab/placebo infusion. In case participants are unable to tolerate dacarbazine even after 2 dose reductions, they will be given the option to continue on intetumumab alone.

Dacarbazine + intetumumab 10 mg/kg [Phase 1 (Part 2)]

Intetumumab will be administered at the dose of 10 mg/kg as intravenous infusion over a period of 2 hr (± 15 minutes) once every 3 weeks for 8 cycles until no evidence of disease progression or unacceptable toxicity. If participants respond to therapy with SD or better, they will be considered eligible to receive up to 8 cycles of extended administrations. Commercially available dacarbazine will be administered at the dose of 1000 mg/m\^2 intravenously over a period of 60 minutes (± 30 minutes) prior to intetumumab infusion.

Group Type: EXPERIMENTAL

Intetumumab

Intervention Type: DRUG

Intetumumab will be administered at the dose of 3 milligram per kilogram (mg/kg) as intravenous infusion (a fluid or a medicine delivered into a vein by way of a needle) over a period of 2 hours (hr) (± 15 minutes) once every 3 weeks until the occurrence of dose limiting toxicities (DLTs). In Phase 2, intetumumab (5 mg/kg or 10 mg/kg) will be administered for 8 cycles until no evidence of disease progression or unacceptable toxicity. If a participant responds to therapy with stable disease (SD) or better, the participant will be eligible to receive up to 8 cycles of extended administrations.

Dacarbazine

Intervention Type: DRUG

Commercially available dacarbazine will be administered intravenously over a 60-minute period (+30 minutes/-30 minutes) and prior to the intetumumab/placebo infusion. In case participants are unable to tolerate dacarbazine even after 2 dose reductions, they will be given the option to continue on intetumumab alone.

Dacarbazine + placebo [Phase 2]

Placebo will be administered intravenously over a period of 2 hr (±15 minutes). Commercially available dacarbazine will be administered at the dose of 1000 mg/m\^2 intravenously over a period of 60 minutes (± 30 minutes) prior to placebo infusion. In case participants are unable to tolerate dacarbazine even after 2 dose reductions, they will be given the option to continue with 10 mg/kg intetumumab alone.

Group Type: EXPERIMENTAL

Dacarbazine

Intervention Type: DRUG

Commercially available dacarbazine will be administered intravenously over a 60-minute period (+30 minutes/-30 minutes) and prior to the intetumumab/placebo infusion. In case participants are unable to tolerate dacarbazine even after 2 dose reductions, they will be given the option to continue on intetumumab alone.

Placebo

Intervention Type: DRUG

Placebo will be administered intravenously over a period of 2 hours (+15 minutes/-15 minutes).

Intetumumab 5 mg/kg [Phase 2]

Intetumumab will be administered at the dose of 5 mg/kg as intravenous infusion over a period of 2 hr (± 15 minutes) once every 3 weeks for 8 cycles until no evidence of disease progression or unacceptable toxicity. If participants respond to therapy with SD or better, they are considered eligible to receive up to 8 cycles of extended administrations.

Group Type: EXPERIMENTAL

Intetumumab

Intervention Type: DRUG

Intetumumab will be administered at the dose of 3 milligram per kilogram (mg/kg) as intravenous infusion (a fluid or a medicine delivered into a vein by way of a needle) over a period of 2 hours (hr) (± 15 minutes) once every 3 weeks until the occurrence of dose limiting toxicities (DLTs). In Phase 2, intetumumab (5 mg/kg or 10 mg/kg) will be administered for 8 cycles until no evidence of disease progression or unacceptable toxicity. If a participant responds to therapy with stable disease (SD) or better, the participant will be eligible to receive up to 8 cycles of extended administrations.

Intetumumab 10 mg/kg [Phase 2]

Intetumumab will be administered at the dose of 10 mg/kg as intravenous infusion over a period of 2 hr (± 15 minutes) once every 3 weeks for 8 cycles until no evidence of disease progression or unacceptable toxicity. If participants respond to therapy with SD or better, they are considered eligible to receive up to 8 cycles of extended administrations.

Group Type: EXPERIMENTAL

Intetumumab

Intervention Type: DRUG

Intetumumab will be administered at the dose of 3 milligram per kilogram (mg/kg) as intravenous infusion (a fluid or a medicine delivered into a vein by way of a needle) over a period of 2 hours (hr) (± 15 minutes) once every 3 weeks until the occurrence of dose limiting toxicities (DLTs). In Phase 2, intetumumab (5 mg/kg or 10 mg/kg) will be administered for 8 cycles until no evidence of disease progression or unacceptable toxicity. If a participant responds to therapy with stable disease (SD) or better, the participant will be eligible to receive up to 8 cycles of extended administrations.

Dacarbazine + intetumumab 10 mg/kg [Phase 2]

Intetumumab will be administered at the dose of 10 mg/kg as intravenous infusion over a period of 2 hr (± 15 minutes) once every 3 weeks for 8 cycles until no evidence of disease progression or unacceptable toxicity. If participants respond to therapy with SD or better, they are considered eligible to receive up to 8 cycles of extended administrations. Commercially available dacarbazine will be administered at the dose of 1000 mg/m\^2 intravenously over a period of 60 minutes (± 30 minutes) prior to intetumumab infusion.

Group Type: EXPERIMENTAL

Intetumumab

Intervention Type: DRUG

Intetumumab will be administered at the dose of 3 milligram per kilogram (mg/kg) as intravenous infusion (a fluid or a medicine delivered into a vein by way of a needle) over a period of 2 hours (hr) (± 15 minutes) once every 3 weeks until the occurrence of dose limiting toxicities (DLTs). In Phase 2, intetumumab (5 mg/kg or 10 mg/kg) will be administered for 8 cycles until no evidence of disease progression or unacceptable toxicity. If a participant responds to therapy with stable disease (SD) or better, the participant will be eligible to receive up to 8 cycles of extended administrations.

Dacarbazine

Intervention Type: DRUG

Commercially available dacarbazine will be administered intravenously over a 60-minute period (+30 minutes/-30 minutes) and prior to the intetumumab/placebo infusion. In case participants are unable to tolerate dacarbazine even after 2 dose reductions, they will be given the option to continue on intetumumab alone.

Interventions

Intetumumab

Intetumumab will be administered at the dose of 3 milligram per kilogram (mg/kg) as intravenous infusion (a fluid or a medicine delivered into a vein by way of a needle) over a period of 2 hours (hr) (± 15 minutes) once every 3 weeks until the occurrence of dose limiting toxicities (DLTs). In Phase 2, intetumumab (5 mg/kg or 10 mg/kg) will be administered for 8 cycles until no evidence of disease progression or unacceptable toxicity. If a participant responds to therapy with stable disease (SD) or better, the participant will be eligible to receive up to 8 cycles of extended administrations.

Intervention Type: DRUG

Dacarbazine

Commercially available dacarbazine will be administered intravenously over a 60-minute period (+30 minutes/-30 minutes) and prior to the intetumumab/placebo infusion. In case participants are unable to tolerate dacarbazine even after 2 dose reductions, they will be given the option to continue on intetumumab alone.

Intervention Type: DRUG

Placebo

Placebo will be administered intravenously over a period of 2 hours (+15 minutes/-15 minutes).

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen-Cilag Farmaceutica, S.R.L.

UNKNOWN

Sponsor Role: collaborator

Centocor, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Centocor, Inc. Clinical Trial

Role: STUDY_DIRECTOR

Centocor, Inc.

Locations

Scottsdale, Arizona, United States

La Jolla, California, United States

Santa Monica, California, United States

Walnut Creek, California, United States

Aurora, Colorado, United States

Washington D.C., District of Columbia, United States

Miami, Florida, United States

Atlanta, Georgia, United States

Park Ridge, Illinois, United States

Beech Grove, Indiana, United States

Omaha, Nebraska, United States

Buffalo, New York, United States

New York, New York, United States

Philadelphia, Pennsylvania, United States

Nashville, Tennessee, United States

Dallas, Texas, United States

Seattle, Washington, United States

Berlin, , Germany

Bonn, , Germany

Buxtehude, , Germany

Düsseldorf, , Germany

Essen, , Germany

Hanover, , Germany

Jena, , Germany

Kiel, , Germany

Mannheim, , Germany

Münster, , Germany

Cambridge, , United Kingdom

London, , United Kingdom

Manchester, , United Kingdom

Sheffield, , United Kingdom

Southampton, , United Kingdom

Countries

Austria; Belgium; United States; Germany; United Kingdom

Other Identifiers

C1034T02

Identifier Type: OTHER

Identifier Source: secondary_id

2004-002130-18

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR006004

Identifier Type: -

Identifier Source: org_study_id