Back to resultsA Safety and Efficacy Study of Intetumumab, Alone and in Combination With Dacarbazine, in Participants With Stage 4 Melanoma
Primary Purpose
Melanoma
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Intetumumab
Dacarbazine
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Melanoma focused on measuring Melanoma, Neoplasm, CNTO 95, Dacarbazine, Intetumumab
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Arm 9
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
Intetumumab 3 mg/kg [Phase 1 (Part 1)]
Intetumumab 5 mg/kg [Phase 1 (Part 1)]
Intetumumab 10 mg/kg [Phase 1 (Part 1)]
Dacarbazine + intetumumab 5 mg/kg [Phase 1 (Part 2)]
Dacarbazine + intetumumab 10 mg/kg [Phase 1 (Part 2)]
Dacarbazine + placebo [Phase 2]
Intetumumab 5 mg/kg [Phase 2]
Intetumumab 10 mg/kg [Phase 2]
Dacarbazine + intetumumab 10 mg/kg [Phase 2]
Arm 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.
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.
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.
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.
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.
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.
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.
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.
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.
Outcomes
Primary Outcome Measures
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.
Maximum Observed Serum Concentration (Cmax) of Intetumumab - Phase 1 (Part 1)
The maximum observed analyte concentration in serum was reported.
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.
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.
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.
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.
Accumulation Ratio (R) of Intetumumab - Phase 1 (Part 1)
The R is obtained by dividing AUC at two different time points.
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.
Secondary Outcome Measures
Percentage of Participants Who Achieved a Best Overall Tumor Response as Complete Response (CR) or Partial Response (PR) - Phase 2
The CR: complete disappearance of all measurable and non-measurable target lesions and PR: 50 percent (%) or more decrease in sum of the longest diameters of target lesion(s), with at least stable disease (SD) in all other evaluable disease in the absence of treatment failure. The best response achieved among all the evaluated time points was reported.
Percentage of Participants Who Achieved CR - Phase 2
The CR: complete disappearance of all measurable and non-measurable target lesions. The participants who achieved CR as the best response were reported.
Percentage of Participants Who Achieved Stable Disease (SD) - Phase 2
The SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Progressive disease (PD), taking as a reference the smallest sum longest diameter since the treatment started. The participants who achieved SD as the best response were reported.
Overall Survival (OS) - Phase 2
The OS is defined as the time from the date of randomization to the date of death due to any cause and was to be censored at the date that the subject is last known to be alive.
Duration of Response - Phase 2
Time duration required to achieve a CR or PR.
Time to Worsening in Eastern Cooperative Oncology Group (ECOG) Performance Status - Phase 2
Eastern Cooperative Oncology (ECOG) performance status: Participants will be graded from 0 (Fully active, able to carry on all pre-disease activities without restriction) to 4 (Completely disabled, cannot carry on any self-care, totally confined to bed or chair). Worsening in ECOG score was defined as ≥ 1 point increase in ECOG score from baseline.
Maximum Observed Serum Concentration (Cmax) of Intetumumab - Phase 2
The maximum observed analyte concentration in serum was reported.
Change From Baseline in Functional Assessment of Cancer Therapy-Melanoma Subscale (FACT-MS) Score - Phase 2
The FACT-MS subscale is used to evaluate health related quality of life. It consists of 16 items: 12 items related to physical well-being, 3 to emotional well-being and 1 to social well-being. Scores for all items will range from 0 to 4. Total score ranges from 0-64; higher score indicates a more positive quality of life.
Change From Baseline in Brief Pain Inventory (BPI) Score - Phase 2
The BPI questionnaire is used to evaluate heath related quality of life. BPI allows participants to rate the severity of their pain on a scale of 0 (no pain) to 10 (pain as bad as you can imagine).
Maximum Observed Serum Concentration (Cmax) of Intetumumab - Phase 1 (Part 2)
The maximum observed analyte concentration in serum was reported.
Area Under the Serum Concentration Versus Time Curve (AUC) of Intetumumab - Phase 1 (Part 2)
The AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption.
Half-life of Intetumumab - Phase 1 (Part 2)
Plasma decay half-life is the time measured for the plasma concentration of the drug to decrease by one half.
Total Clearance (CL) of Intetumumab After Intravenous Administration - Phase 1 (Part 2)
The CL is a quantitative measure of the rate at which a drug substance is removed from the body.
Volume of Distribution (Vz) of Intetumumab - Phase 1 (Part 2)
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.
Accumulation Ratio (R) of Intetumumab - Phase 1 (Part 2)
The R is obtained by dividing AUC at two different time points.
Full Information
NCT ID
NCT00246012
First Posted
October 28, 2005
Last Updated
July 17, 2013
Sponsor
Centocor, Inc.
Collaborators
Janssen-Cilag Farmaceutica, S.R.L.
1. Study Identification
Unique Protocol Identification Number
NCT00246012
Brief Title
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
2. Study Status
Record Verification Date
July 2013
Overall Recruitment Status
Completed
Study Start Date
May 2005 (undefined)
Primary Completion Date
June 2008 (Actual)
Study Completion Date
February 2009 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Centocor, Inc.
Collaborators
Janssen-Cilag Farmaceutica, S.R.L.
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Melanoma
Keywords
Melanoma, Neoplasm, CNTO 95, Dacarbazine, Intetumumab
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
144 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Intetumumab 3 mg/kg [Phase 1 (Part 1)]
Arm Type
Experimental
Arm 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.
Arm Title
Intetumumab 5 mg/kg [Phase 1 (Part 1)]
Arm Type
Experimental
Arm 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.
Arm Title
Intetumumab 10 mg/kg [Phase 1 (Part 1)]
Arm Type
Experimental
Arm 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.
Arm Title
Dacarbazine + intetumumab 5 mg/kg [Phase 1 (Part 2)]
Arm Type
Experimental
Arm 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.
Arm Title
Dacarbazine + intetumumab 10 mg/kg [Phase 1 (Part 2)]
Arm Type
Experimental
Arm 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.
Arm Title
Dacarbazine + placebo [Phase 2]
Arm Type
Experimental
Arm 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.
Arm Title
Intetumumab 5 mg/kg [Phase 2]
Arm Type
Experimental
Arm 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.
Arm Title
Intetumumab 10 mg/kg [Phase 2]
Arm Type
Experimental
Arm 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.
Arm Title
Dacarbazine + intetumumab 10 mg/kg [Phase 2]
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
Intetumumab
Intervention 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). 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
Intervention Name(s)
Dacarbazine
Intervention Description
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
Intervention Name(s)
Placebo
Intervention Description
Placebo will be administered intravenously over a period of 2 hours (+15 minutes/-15 minutes).
Primary Outcome Measure Information:
Title
Number of Participants With Dose Limiting Toxicities (DLTs) - Phase 1
Description
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.
Time Frame
Up to 21 days post-first infusion from the last treated participant in Phase 1
Title
Maximum Observed Serum Concentration (Cmax) of Intetumumab - Phase 1 (Part 1)
Description
The maximum observed analyte concentration in serum was reported.
Time Frame
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
Title
Area Under the Serum Concentration Versus Time Curve (AUC) of Intetumumab - Phase 1 (Part 1)
Description
The AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption.
Time Frame
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
Title
Half-life of Intetumumab - Phase 1 (Part 1)
Description
Plasma decay half-life is the time measured for the plasma concentration of the drug to decrease by one half.
Time Frame
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
Title
Total Clearance (CL) of Intetumumab After Intravenous Administration - Phase 1 (Part 1)
Description
The CL is a quantitative measure of the rate at which a drug substance is removed from the body.
Time Frame
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
Title
Volume of Distribution (Vz) of Intetumumab - Phase 1 (Part 1)
Description
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.
Time Frame
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
Title
Accumulation Ratio (R) of Intetumumab - Phase 1 (Part 1)
Description
The R is obtained by dividing AUC at two different time points.
Time Frame
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
Title
Progression-Free Survival (PFS) - Phase 2
Description
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.
Time Frame
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 Outcome Measure Information:
Title
Percentage of Participants Who Achieved a Best Overall Tumor Response as Complete Response (CR) or Partial Response (PR) - Phase 2
Description
The CR: complete disappearance of all measurable and non-measurable target lesions and PR: 50 percent (%) or more decrease in sum of the longest diameters of target lesion(s), with at least stable disease (SD) in all other evaluable disease in the absence of treatment failure. The best response achieved among all the evaluated time points was reported.
Time Frame
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)
Title
Percentage of Participants Who Achieved CR - Phase 2
Description
The CR: complete disappearance of all measurable and non-measurable target lesions. The participants who achieved CR as the best response were reported.
Time Frame
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)
Title
Percentage of Participants Who Achieved Stable Disease (SD) - Phase 2
Description
The SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Progressive disease (PD), taking as a reference the smallest sum longest diameter since the treatment started. The participants who achieved SD as the best response were reported.
Time Frame
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)
Title
Overall Survival (OS) - Phase 2
Description
The OS is defined as the time from the date of randomization to the date of death due to any cause and was to be censored at the date that the subject is last known to be alive.
Time Frame
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
Title
Duration of Response - Phase 2
Description
Time duration required to achieve a CR or PR.
Time Frame
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
Title
Time to Worsening in Eastern Cooperative Oncology Group (ECOG) Performance Status - Phase 2
Description
Eastern Cooperative Oncology (ECOG) performance status: Participants will be graded from 0 (Fully active, able to carry on all pre-disease activities without restriction) to 4 (Completely disabled, cannot carry on any self-care, totally confined to bed or chair). Worsening in ECOG score was defined as ≥ 1 point increase in ECOG score from baseline.
Time Frame
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
Title
Maximum Observed Serum Concentration (Cmax) of Intetumumab - Phase 2
Description
The maximum observed analyte concentration in serum was reported.
Time Frame
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
Title
Change From Baseline in Functional Assessment of Cancer Therapy-Melanoma Subscale (FACT-MS) Score - Phase 2
Description
The FACT-MS subscale is used to evaluate health related quality of life. It consists of 16 items: 12 items related to physical well-being, 3 to emotional well-being and 1 to social well-being. Scores for all items will range from 0 to 4. Total score ranges from 0-64; higher score indicates a more positive quality of life.
Time Frame
Day 1 (pre-dose) of Cycles 1, 2, 3; and final visit (3 weeks post-last dose of study medication)
Title
Change From Baseline in Brief Pain Inventory (BPI) Score - Phase 2
Description
The BPI questionnaire is used to evaluate heath related quality of life. BPI allows participants to rate the severity of their pain on a scale of 0 (no pain) to 10 (pain as bad as you can imagine).
Time Frame
Day 1 (pre-dose) of Cycles 1, 2, 3; and final visit (3 weeks post-last dose of study medication)
Title
Maximum Observed Serum Concentration (Cmax) of Intetumumab - Phase 1 (Part 2)
Description
The maximum observed analyte concentration in serum was reported.
Time Frame
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
Title
Area Under the Serum Concentration Versus Time Curve (AUC) of Intetumumab - Phase 1 (Part 2)
Description
The AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption.
Time Frame
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
Title
Half-life of Intetumumab - Phase 1 (Part 2)
Description
Plasma decay half-life is the time measured for the plasma concentration of the drug to decrease by one half.
Time Frame
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
Title
Total Clearance (CL) of Intetumumab After Intravenous Administration - Phase 1 (Part 2)
Description
The CL is a quantitative measure of the rate at which a drug substance is removed from the body.
Time Frame
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
Title
Volume of Distribution (Vz) of Intetumumab - Phase 1 (Part 2)
Description
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.
Time Frame
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
Title
Accumulation Ratio (R) of Intetumumab - Phase 1 (Part 2)
Description
The R is obtained by dividing AUC at two different time points.
Time Frame
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 Pre-specified Outcome Measures:
Title
Area Under the Concentration Versus Time Curve Between Zero to Infinite Time (AUCinf) of Intetumumab - Phase 1 (Part 1)
Description
The AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞).
Time Frame
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
Title
Percentage of Participants Who Achieved a Best Overall Response as CR, PR, or SD - Phase 2
Description
The CR: complete disappearance of all measurable and non-measurable target lesions and PR: 50% or more decrease in sum of the longest diameters of target lesion(s), with at least stable disease (SD) in all other evaluable disease in the absence of treatment failure.
Time Frame
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Centocor, Inc. Clinical Trial
Organizational Affiliation
Centocor, Inc.
Official's Role
Study Director
Facility Information:
City
Scottsdale
State/Province
Arizona
Country
United States
City
La Jolla
State/Province
California
Country
United States
City
Santa Monica
State/Province
California
Country
United States
City
Walnut Creek
State/Province
California
Country
United States
City
Aurora
State/Province
Colorado
Country
United States
City
Washington
State/Province
District of Columbia
Country
United States
City
Miami
State/Province
Florida
Country
United States
City
Atlanta
State/Province
Georgia
Country
United States
City
Park Ridge
State/Province
Illinois
Country
United States
City
Beech Grove
State/Province
Indiana
Country
United States
City
Omaha
State/Province
Nebraska
Country
United States
City
Buffalo
State/Province
New York
Country
United States
City
New York
State/Province
New York
Country
United States
City
Philadelphia
State/Province
Pennsylvania
Country
United States
City
Nashville
State/Province
Tennessee
Country
United States
City
Dallas
State/Province
Texas
Country
United States
City
Seattle
State/Province
Washington
Country
United States
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
12. IPD Sharing Statement
Learn more about this trial
A Safety and Efficacy Study of Intetumumab, Alone and in Combination With Dacarbazine, in Participants With Stage 4 Melanoma
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