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

NCT00246012 | Completed Phase 1 Results DMC

• 3 other identifiers: CR006004C1034T022004-002130-18
• Study Type: interventional
• Target: 144
• Locations: 3 countries
• Sites: 32

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.

Conditions

Melanoma

Keywords

Melanoma; Neoplasm; CNTO 95; Dacarbazine; Intetumumab

Outcome Measures

Primary Outcomes (8)

• Number of Participants With Dose Limiting Toxicities (DLTs) - Phase 1

  The DLT is defined as any Grade 3 or higher adverse event identified by the safety data monitoring committee as attributable to intetumumab except for hypersensitivity reactions, which are not considered DLTs unless there are 2 or more occurrences of greater than or equal to Grade 3 hypersensitivity reaction within a group.

  Up to 21 days post-first infusion from the last treated participant in Phase 1

• Maximum Observed Serum Concentration (Cmax) of Intetumumab - Phase 1 (Part 1)

  The maximum observed analyte concentration in serum was reported.

  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

• Area Under the Serum Concentration Versus Time Curve (AUC) of Intetumumab - Phase 1 (Part 1)

  The AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption.

  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

• Half-life of Intetumumab - Phase 1 (Part 1)

  Plasma decay half-life is the time measured for the plasma concentration of the drug to decrease by one half.

  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

• Total Clearance (CL) of Intetumumab After Intravenous Administration - Phase 1 (Part 1)

  The CL is a quantitative measure of the rate at which a drug substance is removed from the body.

  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

• Volume of Distribution (Vz) of Intetumumab - Phase 1 (Part 1)

  Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.

  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

• Accumulation Ratio (R) of Intetumumab - Phase 1 (Part 1)

  The R is obtained by dividing AUC at two different time points.

  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

• Progression-Free Survival (PFS) - Phase 2

  The PFS was defined as the time from the date of randomization to the date of initial documented progressive disease (PD), or the date of initial documented symptomatic deterioration, or the date of death, whichever occurred first. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as at least a 20% increase in the sum of the longest diameter of target lesions, taking as a reference the smallest sum longest diameter recorded since the treatment started or the appearance of 1 or more new lesions.

  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 (15)

• Percentage of Participants Who Achieved a Best Overall Tumor Response as Complete Response (CR) or Partial Response (PR) - Phase 2

  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)

• Percentage of Participants Who Achieved CR - Phase 2

  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)

• Percentage of Participants Who Achieved Stable Disease (SD) - Phase 2

  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)

• Overall Survival (OS) - Phase 2

  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

• Duration of Response - Phase 2

  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

Other Outcomes (2)

• Area Under the Concentration Versus Time Curve Between Zero to Infinite Time (AUCinf) of Intetumumab - Phase 1 (Part 1)

  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

• Percentage of Participants Who Achieved a Best Overall Response as CR, PR, or SD - Phase 2

  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

Study Arms (9)

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

EXPERIMENTAL

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.

Drug: Intetumumab

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

EXPERIMENTAL

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.

Drug: Intetumumab

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

EXPERIMENTAL

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.

Drug: Intetumumab

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

EXPERIMENTAL

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.

Drug: Intetumumab; Drug: Dacarbazine

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

EXPERIMENTAL

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.

Drug: Intetumumab; Drug: Dacarbazine

Dacarbazine + placebo [Phase 2]

EXPERIMENTAL

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.

Drug: Dacarbazine; Drug: Placebo

Intetumumab 5 mg/kg [Phase 2]

EXPERIMENTAL

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.

Drug: Intetumumab

Intetumumab 10 mg/kg [Phase 2]

EXPERIMENTAL

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.

Drug: Intetumumab

Dacarbazine + intetumumab 10 mg/kg [Phase 2]

EXPERIMENTAL

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.

Drug: Intetumumab; Drug: Dacarbazine

Interventions

Intetumumab 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 1 (Part 2)]; Dacarbazine + intetumumab 10 mg/kg [Phase 2]; Dacarbazine + intetumumab 5 mg/kg [Phase 1 (Part 2)]; Intetumumab 10 mg/kg [Phase 1 (Part 1)]; Intetumumab 10 mg/kg [Phase 2]; Intetumumab 3 mg/kg [Phase 1 (Part 1)]; Intetumumab 5 mg/kg [Phase 1 (Part 1)]; Intetumumab 5 mg/kg [Phase 2]

Dacarbazine 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)]; Dacarbazine + intetumumab 10 mg/kg [Phase 2]; Dacarbazine + intetumumab 5 mg/kg [Phase 1 (Part 2)]; Dacarbazine + placebo [Phase 2]

Placebo DRUG

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

Dacarbazine + placebo [Phase 2]

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Centocor, Inc.: lead
• Janssen-Cilag Farmaceutica, S.R.L.: collaborator

Study Sites (32)

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Scottsdale, Arizona, United States

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La Jolla, California, United States

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Santa Monica, California, United States

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Walnut Creek, California, United States

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Aurora, Colorado, United States

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

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Miami, Florida, United States

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Atlanta, Georgia, United States

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Park Ridge, Illinois, United States

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Beech Grove, Indiana, United States

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Omaha, Nebraska, United States

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Buffalo, New York, United States

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New York, New York, United States

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Philadelphia, Pennsylvania, United States

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Nashville, Tennessee, United States

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Dallas, Texas, United States

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Seattle, Washington, United States

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Berlin, Germany

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Bonn, Germany

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Buxtehude, Germany

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Düsseldorf, Germany

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Essen, Germany

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Hanover, Germany

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Jena, Germany

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Kiel, Germany

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Mannheim, Germany

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Münster, Germany

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Cambridge, United Kingdom

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London, United Kingdom

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Manchester, United Kingdom

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Sheffield, United Kingdom

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Southampton, United Kingdom

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MeSH Terms

Conditions

Melanoma; Neoplasms

Interventions

intetumumab; Dacarbazine

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Senior Director
• Organization: Centocor, Inc.

908-927-2116

Study Officials

• Centocor, Inc. Clinical Trial

  Centocor, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 28, 2005
• First Posted: October 31, 2005
• Study Start: May 1, 2005
• Primary Completion: June 1, 2008
• Study Completion: February 1, 2009
• Last Updated: August 19, 2013
• Results First Posted: August 19, 2013

Record last verified: 2013-07

Locations

GB (5); US (17); DE (10)