An Open-Label, Dose-Escalation Study of IMC-20D7S In Patients With Malignant Melanoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
ImClone LLC
ClinicalTrials.gov Identifier:
NCT01137006
First received: June 2, 2010
Last updated: September 26, 2012
Last verified: September 2012
  Purpose

A dose escalation study designed to determine the safety, maximum tolerated dose, anti-melanoma activity, antibody blood levels and progression-free survival in patients with malignant melanoma receiving IMC-20D7S either every two weeks or every three weeks.


Condition Intervention Phase
Malignant Melanoma
Biological: IMC-20D7S (Cohort 1A)
Biological: IMC-20D7S (Cohort 2A )
Biological: IMC-20D7S (Cohort 3A )
Biological: IMC-20D7S (Cohort 4A )
Biological: IMC-20D7S (Cohort 1B)
Biological: IMC-20D7S (Cohort 2B )
Biological: Biological/Vaccine: IMC-20D7S (Cohort 3B )
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Label, Dose-Escalation Phase 1/1b Study of the Anti-gp75 Monoclonal Antibody IMC-20D7S In Patients With Malignant Melanoma Who Have Progressed After or During at Least One Treatment With Standard Cytotoxic Treatment or/and Immunotherapy Therapy or For Whom Standard Therapy is Not Indicated

Resource links provided by NLM:


Further study details as provided by ImClone LLC:

Primary Outcome Measures:
  • Maximum tolerated dose (MTD) [ Time Frame: 22 months ] [ Designated as safety issue: Yes ]
    The MTD population will include all patients who complete Cycle 1, die during Cycle 1, or discontinue due to a DLT. Patients who do not complete Cycle 1 for reasons other than a DLT will be replaced.

  • Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: 22 months ] [ Designated as safety issue: Yes ]
    All patients who receive any amount of IMC-20D7S will be included in the safety population.


Secondary Outcome Measures:
  • Maximum concentration (Cmax) cycle 1 [ Time Frame: Week 1, Day 1 ] [ Designated as safety issue: No ]
  • Minimal concentration (Cmin) cycle 1 [ Time Frame: Week 1, Day 1 ] [ Designated as safety issue: No ]
  • Halflife (t½), cycle 1 [ Time Frame: Week 1, Day 1 ] [ Designated as safety issue: No ]
  • Clearance (Cl), cycle 1 [ Time Frame: Week 1, Day 1 ] [ Designated as safety issue: No ]
  • Area under the curve (AUC), cycle 1 [ Time Frame: Week 1, Day 1 ] [ Designated as safety issue: No ]
  • Volume of distribution at steady state (Vd), cycle 1 [ Time Frame: Week 1, Day 1 ] [ Designated as safety issue: No ]
  • Maximum concentration (Cmax) cycle 3 (Arm A) [ Time Frame: Week 1, Day 57 ] [ Designated as safety issue: No ]
  • Minimal concentration (Cmin) cycle 3, (Arm A) [ Time Frame: Week 1, Day 57 ] [ Designated as safety issue: No ]
  • Halflife (t½), cycle 3, (Arm A) [ Time Frame: Week 1, Day 57 ] [ Designated as safety issue: No ]
  • Clearance (Cl), cycle 3, (Arm A) [ Time Frame: Week 1, Day 57 ] [ Designated as safety issue: No ]
  • Area under the curve (AUC), cycle 3, (Arm A) [ Time Frame: Week 1, Day 57 ] [ Designated as safety issue: No ]
  • Volume of distribution at steady state (Vd), cycle 3, (Arm A) [ Time Frame: Week 1, Day 57 ] [ Designated as safety issue: No ]
  • Maximum concentration (Cmax) cycle 3 (Arm B) [ Time Frame: Week 1, Day 85 ] [ Designated as safety issue: No ]
  • Minimal concentration (Cmin) cycle 3, (Arm B) [ Time Frame: Week 1, Day 85 ] [ Designated as safety issue: No ]
  • Halflife (t½), cycle 3, (Arm B) [ Time Frame: Week 1, Day 85 ] [ Designated as safety issue: No ]
  • Clearance (Cl), cycle 3, (Arm B) [ Time Frame: Week 1, Day 85 ] [ Designated as safety issue: No ]
  • Area under the curve (AUC), cycle 3, (Arm B) [ Time Frame: Week 1, Day 85 ] [ Designated as safety issue: No ]
  • Volume of distribution at steady state (Vd), cycle 3, (Arm B) [ Time Frame: Week 1, Day 85 ] [ Designated as safety issue: No ]
  • Maximum concentration (Cmax) cycles 2 and 4 [ Time Frame: Week 1, Day 1 ] [ Designated as safety issue: No ]
  • Minimal concentration (Cmin) cycles 2 and 4 [ Time Frame: Week 1, Day 1 ] [ Designated as safety issue: No ]
  • Halflife (t½), cycles 2 and 4 [ Time Frame: Week 1, Day 1 ] [ Designated as safety issue: No ]
  • Clearance (Cl), cycles 2 and 4 [ Time Frame: Week 1, Day 1 ] [ Designated as safety issue: No ]
  • Area under the curve (AUC), cycles 2 and 4 [ Time Frame: Week 1, Day 1 ] [ Designated as safety issue: No ]
  • Volume of distribution at steady state (Vd), cycles 2 and 4 [ Time Frame: Week 1, Day 1 ] [ Designated as safety issue: No ]
  • Development of antibodies (immunogenicity) [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    Screening for the development of circulating antibodies against IMC-20D7S.

  • Measure the progression-free survival (PFS) [ Time Frame: 22 months ] [ Designated as safety issue: No ]
    PFS is defined as the time from the first day of treatment until progression of disease or death is first reported.

  • Recommend doses for Phase 2/3 studies based on MTD [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    Dosage and regime


Enrollment: 27
Study Start Date: June 2010
Study Completion Date: August 2012
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: IMC-20D7S (A) Biological: IMC-20D7S (Cohort 1A)

5 mg/kg i.v. every 2 weeks

Administered every other week on days 1 and 15 of each treatment cycle.

If 0 dose-limiting toxicity (DLT) in first 3 participants or 1 DLT in 6 participants, then enrollment into cohort 2A.

Other Name: LY3012215
Biological: IMC-20D7S (Cohort 2A )

10 mg/kg i.v. every 2 weeks

Administered every other week on days 1 and 15 of each treatment cycle.

If no DLT in first 3 participants or 1 DLT in 6 participants in Cohort 2A then enrollment into Cohort 3A.

Other Name: LY3012215
Biological: IMC-20D7S (Cohort 3A )

20 mg/kg i.v. every 2 weeks

Administered every other week on days 1 and 15 of each treatment cycle.

If no DLT in first 3 participants or 1 DLT in 6 participants in Cohort 3A then enrollment into Cohort 4A.

Other Name: LY3012215
Biological: IMC-20D7S (Cohort 4A )

30 mg/kg i.v. every 2 weeks

Administered every other week on days 1 and 15 of each treatment cycle.

Other Name: LY3012215
Experimental: IMC-20D7S (B) Biological: IMC-20D7S (Cohort 1B)

10 mg/kg i.v. every 3 weeks

Administered every 3 weeks on days 1 and 22 of each treatment cycle.

If 0 dose-limiting toxicity (DLT) in first 3 participants or 1 DLT in 6 participants in Cohort 1B, then enrollment into cohort 2B.

Other Name: LY3012215
Biological: IMC-20D7S (Cohort 2B )

20 mg/kg i.v. every 3 weeks

Administered every 3 weeks on days 1 and 22 of each treatment cycle.

If no DLT in first 3 participants or 1 DLT in 6 participants in Cohort 2B then enrollment into Cohort 3B.

Other Name: LY3012215
Biological: Biological/Vaccine: IMC-20D7S (Cohort 3B )

30 mg/kg i.v. every 3 weeks

Administered every 3 weeks on days 1 and 22 of each treatment cycle.

Other Name: LY3012215

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient has histologically or cytologically confirmed cutaneous, mucosal, or uveal malignant melanoma which has progressed after or during at least 1 treatment with standard cytotoxic treatment or/and immunotherapy (eg, treatment with cytokines, monoclonal antibodies, and vaccines) and is not regarded to be a candidate for a potentially curative, higher priority treatment for melanoma
  • Patient is ≥ 18 years of age
  • Patient has either measurable disease as defined by RECIST 1.1 or evaluable disease
  • At least 21 days must have elapsed from major surgery, prior chemotherapy, prior treatment with an investigational agent or device, or prior radiation therapy. Relative to patient's treatment with non-approved biological products (eg, monoclonal antibodies), a minimum of 2 half-lives must have passed for eligibility to be considered
  • Patient has resolution of all clinically significant toxic effects of prior cancer therapy to Grade ≤ 1 according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.02
  • Patient has adequate hematological function, hepatic function, and renal function

Exclusion Criteria:

  • Patient has undergone major surgery (eg, laparotomy, thoracotomy, removal of organ[s]) within 21 days prior to study entry
  • Patient has elective or planned surgery to be conducted during the trial
  • Patient has documented and/or symptomatic brain or leptomeningeal metastases
  • Patient is receiving systemic steroids or other immunosuppressive medications.(Intermittent use of steroid-containing medications, eg, for asthma exacerbation or for skin lesions, is permitted)
  • Patient has an uncontrolled undercurrent illness
  • Patient has a concurrent active malignancy other than adequately treated nonmelanomatous skin cancer or other noninvasive carcinoma or in situ neoplasm
  • Patient has a known allergy to any of the treatment components (monoclonal antibodies or other therapeutic proteins such as fresh frozen plasma, human serum albumin, cytokines, or interleukins). In the event that there is suspicion the patient may have allergies, the patient should be excluded
  • Patient is pregnant or lactating
  • Patient has known HIV or AIDS infection
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01137006

Locations
United States, Massachusetts
ImClone Investigational Site
Boston, Massachusetts, United States, 02114
United States, New York
ImClone Investigational Site
New York, New York, United States, 10021
Sponsors and Collaborators
ImClone LLC
Investigators
Study Director: E-mail: ClinicalTrials@ ImClone.com ImClone LLC
  More Information

No publications provided

Responsible Party: ImClone LLC
ClinicalTrials.gov Identifier: NCT01137006     History of Changes
Other Study ID Numbers: 13945, CP22-0901, I4Z-IE-JDEA
Study First Received: June 2, 2010
Last Updated: September 26, 2012
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by ImClone LLC:
Melanoma
Phase I
antibody
melanin
tyrosinase related protein 1
glycoprotein
20D7S

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas

ClinicalTrials.gov processed this record on September 18, 2014