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

Centocor Ortho Biotech

Status and phase: Completed; Phase 2; Phase 1

Conditions: Melanoma

Treatments: Drug: Dacarbazine; Drug: Placebo; Drug: Intetumumab

Study type: Interventional

Funder types: Industry; Other

Identifiers

NCT00246012

2004-002130-18 (EudraCT Number)

CR006004

C1034T02 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 144 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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144 participants in 9 patient groups

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

Experimental group

Description:

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.

Treatment:

Drug: Intetumumab

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

Experimental group

Description:

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.

Treatment:

Drug: Intetumumab

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

Experimental group

Description:

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.

Treatment:

Drug: Intetumumab

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

Experimental group

Description:

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.

Treatment:

Drug: Dacarbazine

Drug: Intetumumab

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

Experimental group

Description:

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.

Treatment:

Drug: Dacarbazine

Drug: Intetumumab

Dacarbazine + placebo [Phase 2]

Experimental group

Description:

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.

Treatment:

Drug: Dacarbazine

Drug: Placebo

Intetumumab 5 mg/kg [Phase 2]

Experimental group

Description:

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.

Treatment:

Drug: Intetumumab

Intetumumab 10 mg/kg [Phase 2]

Experimental group

Description:

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.

Treatment:

Drug: Intetumumab

Dacarbazine + intetumumab 10 mg/kg [Phase 2]

Experimental group

Description:

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.

Treatment:

Drug: Dacarbazine

Drug: Intetumumab