MelanomaPhase 1/2NCT00246012
A Safety and Efficacy Study of Intetumumab, Alone and in Combination With Dacarbazine, in Participants With Stage 4 Melanoma
A Phase 1/2 study testing Intetumumab and Dacarbazine in people with Melanoma, run by Centocor, Inc. at 32 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma
- What is being tested?
- Intetumumab and Dacarbazine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 144 participants
- Where
- 32 sitesin 3 countries
- Study dates
- May 2005to Feb 2009
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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 locations and contacts
32 sites in 3 countries.
32 sites in 3 countries
United States17 sites
Study site
Atlanta, Georgia
Study site
Aurora, Colorado
Study site
Beech Grove, Indiana
Study site
Buffalo, New York
Study site
Dallas, Texas
Study site
La Jolla, California
Study site
Miami, Florida
Study site
Nashville, Tennessee
Study site
New York, New York
Study site
Omaha, Nebraska
Study site
Park Ridge, Illinois
Study site
Philadelphia, Pennsylvania
Study site
Santa Monica, California
Study site
Scottsdale, Arizona
Study site
Seattle, Washington
Study site
Walnut Creek, California
Study site
Washington D.C., District of Columbia
Germany10 sites
Study site
Berlin
Study site
Bonn
Study site
Buxtehude
Study site
Düsseldorf
Study site
Essen
Study site
Hanover
Study site
Jena
Study site
Kiel
Study site
Mannheim
Study site
Münster
United Kingdom5 sites
Study site
Cambridge
Study site
London
Study site
Manchester
Study site
Sheffield
Study site
Southampton
About this study
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
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.
Read the 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
- Being tested
- Intetumumab, Dacarbazine, Placebo
- Keywords
- Melanoma, Neoplasm, CNTO 95, Dacarbazine, Intetumumab
- Medical subject headings
- Melanoma, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IntetumumabDrug
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.
DacarbazineDrug
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.
PlaceboDrug
Placebo will be administered intravenously over a period of 2 hours (+15 minutes/-15 minutes).
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: Intetumumab; Drug: Dacarbazine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
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.
Measured: 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
The CR: complete disappearance of all measurable and non-measurable target lesions. The participants who achieved CR as the best response were reported.
Measured: 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
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.
Measured: 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
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.
Measured: 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
Time duration required to achieve a CR or PR.
Measured: 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
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.
Measured: 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
Maximum Observed Serum Concentration (Cmax) of Intetumumab - Phase 2
The maximum observed analyte concentration in serum was reported.
Measured: 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
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.
Measured: Day 1 (pre-dose) of Cycles 1, 2, 3; and final visit (3 weeks post-last dose of study medication)
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).
Measured: Day 1 (pre-dose) of Cycles 1, 2, 3; and final visit (3 weeks post-last dose of study medication)
Maximum Observed Serum Concentration (Cmax) of Intetumumab - Phase 1 (Part 2)
The maximum observed analyte concentration in serum was reported.
Measured: 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 2)
The AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption.
Measured: 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 2)
Plasma decay half-life is the time measured for the plasma concentration of the drug to decrease by one half.
Measured: 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 2)
The CL is a quantitative measure of the rate at which a drug substance is removed from the body.
Measured: 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 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.
Measured: 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 2)
The R is obtained by dividing AUC at two different time points.
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Oct 2005 (estimated)
- Study startMay 2005
- Primary completionJun 2008
- Study completionFeb 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for MelanomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 144 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centocor, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Janssen-Cilag Farmaceutica, S.R.L.
- Responsible party
- Sponsor
- Investigators
- Centocor, Inc. Clinical Trial, Study director, Centocor, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00246012
- Sponsor's protocol ID
- CR006004
- Other IDs
- C1034T02, 2004-002130-18, 2004
- Status last verified
- Jul 2013
- First submitted
- 28 Oct 2005
- Last updated
- 19 Aug 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 19 Aug 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00246012
- Acronym / sponsor ID
- CR006004
- Conditions
- Melanoma
- Keywords
- Melanoma, Neoplasm, CNTO 95, Dacarbazine, Intetumumab
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 144 participants (actual)
- Lead sponsor
- Centocor, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Janssen-Cilag Farmaceutica, S.R.L.
- Study start
- May 2005
- Primary completion
- Jun 2008 (actual)
- Study completion
- Feb 2009 (actual)
- First posted
- 31 Oct 2005 (estimated)
- Results
- Posted 19 Aug 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 9
| Arm | Type | Receives |
|---|---|---|
| Intetumumab 3 mg/kg [Phase 1 (Part 1)] | Experimental | Drug: IntetumumabIntetumumab 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 5 mg/kg [Phase 1 (Part 1)] | Experimental | Drug: IntetumumabIntetumumab 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 10 mg/kg [Phase 1 (Part 1)] | Experimental | Drug: IntetumumabIntetumumab 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. |
| Dacarbazine + intetumumab 5 mg/kg [Phase 1 (Part 2)] | Experimental | Drug: Intetumumab, Drug: DacarbazineIntetumumab 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. |
| Dacarbazine + intetumumab 10 mg/kg [Phase 1 (Part 2)] | Experimental | Drug: Intetumumab, Drug: DacarbazineIntetumumab 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. |
| Dacarbazine + placebo [Phase 2] | Experimental | Drug: Dacarbazine, Drug: PlaceboPlacebo 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 5 mg/kg [Phase 2] | Experimental | Drug: IntetumumabIntetumumab 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 10 mg/kg [Phase 2] | Experimental | Drug: IntetumumabIntetumumab 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. |
| Dacarbazine + intetumumab 10 mg/kg [Phase 2] | Experimental | Drug: Intetumumab, Drug: DacarbazineIntetumumab 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IntetumumabIntetumumab 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. | Drug | 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] |
| DacarbazineCommercially 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. | Drug | 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] |
| PlaceboPlacebo will be administered intravenously over a period of 2 hours (+15 minutes/-15 minutes). | Drug | Dacarbazine + placebo [Phase 2] |
Primary outcome
Number of Participants With Dose Limiting Toxicities (DLTs) - Phase 1
Time frame: Up to 21 days post-first infusion from the last treated participant in 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)
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
The maximum observed analyte concentration in serum was reported.
Area Under the Serum Concentration Versus Time Curve (AUC) of Intetumumab - Phase 1 (Part 1)
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
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)
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
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)
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
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)
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
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)
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
The R is obtained by dividing AUC at two different time points.
Progression-Free Survival (PFS) - Phase 2
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
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.
15 secondary outcomes
Percentage of Participants Who Achieved a Best Overall Tumor Response as Complete Response (CR) or Partial Response (PR) - Phase 2
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)
Percentage of Participants Who Achieved CR - Phase 2
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)
Percentage of Participants Who Achieved Stable Disease (SD) - Phase 2
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)
Overall Survival (OS) - Phase 2
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
Duration of Response - Phase 2
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
Time to Worsening in Eastern Cooperative Oncology Group (ECOG) Performance Status - Phase 2
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
Maximum Observed Serum Concentration (Cmax) of Intetumumab - Phase 2
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
Change From Baseline in Functional Assessment of Cancer Therapy-Melanoma Subscale (FACT-MS) Score - Phase 2
Time frame: Day 1 (pre-dose) of Cycles 1, 2, 3; and final visit (3 weeks post-last dose of study medication)
Change From Baseline in Brief Pain Inventory (BPI) Score - Phase 2
Time frame: Day 1 (pre-dose) of Cycles 1, 2, 3; and final visit (3 weeks post-last dose of study medication)
Maximum Observed Serum Concentration (Cmax) of Intetumumab - Phase 1 (Part 2)
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
Area Under the Serum Concentration Versus Time Curve (AUC) of Intetumumab - Phase 1 (Part 2)
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
Half-life of Intetumumab - Phase 1 (Part 2)
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
Total Clearance (CL) of Intetumumab After Intravenous Administration - Phase 1 (Part 2)
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
Volume of Distribution (Vz) of Intetumumab - Phase 1 (Part 2)
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
Accumulation Ratio (R) of Intetumumab - Phase 1 (Part 2)
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Aug 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Centocor, Inc. Clinical Trial study director
Centocor, Inc.
32 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Intetumumab and Dacarbazine in people with Melanoma, run by Centocor, Inc. at 32 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Aug 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 32 sites in United States, Germany, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Aug 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Dose Limiting Toxicities (DLTs) - Phase 1 (time frame: Up to 21 days post-first infusion from the last treated participant in Phase 1). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Aug 2013.