A Safety and MORAb-028 Dose Determination Study in Subjects With Metastatic Melanoma

July 15, 2014 updated by: Morphotek

A Phase 1 Study of the Safety, Tolerability, Pharmacokinetics and Radiologic Distribution of Ascending Single-Dose Radiolabeled MORAb-028 in Subjects With Metastatic Melanoma

The purpose of this study is to evaluate whether therapy with MORAb-028 is safe, effective, and to determine the appropriate dose of MORAb-028 in the treatment of metastatic melanoma.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Melanoma is a serious form of skin cancer. If untreated, the melanoma can spread beyond the original affected tissue and invade distant tissue and organs. Treatment for metastatic melanoma includes medical treatments (chemotherapy or immunotherapy), surgery, or radiation therapy. MORAb-028 is a recombinant human immunoglobulin M (IgM) monoclonal antibody that recognizes a cell surface diacyl ganglioside named disialoganglioside (GD2). GD2 is overexpressed in tumors of neuro-ectodermal origin such as melanomas, neuroblastomas, small-cell lung carcinomas, and many sarcomas, while absent in most normal tissues. GD2 expression has been demonstrated in human melanoma and small cell lung cancer by thin layer chromatography and radiolabeled anti-GD2 antibody detection. It is hypothesized that one mode of action of MORAb-028 is complement-dependent cytotoxicity. Complement-dependent cytotoxicity is a mechanism for killing tumor cells in which an antibody bound to the target cell surface fixes complement, which results in assembly of the complement membrane attack complex that punches holes in the target cell membrane resulting in subsequent cell lysis. IgMs strongly bind to C1Q and robustly activate complement-dependent cytotoxicity. MORAb-028 is being developed as a potential therapy for GD2-positive tumors.

Study Type

Interventional

Enrollment (Actual)

18

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10022
        • Memorial Sloan-Kettering Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Measurable metastatic melanoma that has failed standard therapy
  • Males and females greater than or equal to 18 years of age
  • Life expectancy of greater than or equal to 3 months

Exclusion Criteria:

  • Significant cardiovascular impairment
  • Clinically significant illness, medical condition, surgical history, or laboratory abnormality that could affect the safety of the subject or negatively impact the study results
  • Chemotherapy, radiotherapy, or immunotherapy within 3 weeks prior to administration to MORAb-028

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cohort 1
MORAb-028 0.1 mg/kg intravenous
Drug: MORAb-028
Cohort 1: 0.1 mg/kg IV on study day 1 only Cohort 2: 0.2 mg/kg IV on study day 1 only Cohort 3: 0.5 mg/kg IV on study day 1 only Cohort 4: 1.0 mg/kg IV on study day 1 only
Experimental: Cohort 2
MORAb-028 0.2 mg/kg intravenous
Drug: MORAb-028
Cohort 1: 0.1 mg/kg IV on study day 1 only Cohort 2: 0.2 mg/kg IV on study day 1 only Cohort 3: 0.5 mg/kg IV on study day 1 only Cohort 4: 1.0 mg/kg IV on study day 1 only
Experimental: Cohort 3
MORAb-028 0.5 mg/kg intravenous
Drug: MORAb-028
Cohort 1: 0.1 mg/kg IV on study day 1 only Cohort 2: 0.2 mg/kg IV on study day 1 only Cohort 3: 0.5 mg/kg IV on study day 1 only Cohort 4: 1.0 mg/kg IV on study day 1 only
Experimental: Cohort 4
MORAb-028 1.0 mg/kg intravenous
Drug: MORAb-028
Cohort 1: 0.1 mg/kg IV on study day 1 only Cohort 2: 0.2 mg/kg IV on study day 1 only Cohort 3: 0.5 mg/kg IV on study day 1 only Cohort 4: 1.0 mg/kg IV on study day 1 only

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Safety of single dose radio labeled MORAb-028 in subjects with metastatic melanoma
Time Frame: Daily for 7 days followed by weekly for 2 weeks, then biweekly for 4 weeks
Daily for 7 days followed by weekly for 2 weeks, then biweekly for 4 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
Radiologic distribution of a single i.v. infusion of MORAb-028
Time Frame: Daily for 1 week post study drug administration
Daily for 1 week post study drug administration
Pharmacokinetic parameters of labeled and unlabeled MORAb-028
Time Frame: Daily for 7 days followed by weekly for 2 weeks, then biweekly for 4 weeks
Daily for 7 days followed by weekly for 2 weeks, then biweekly for 4 weeks
The incidence of human antihuman antibody formation
Time Frame: Week 2 and Week 8
Week 2 and Week 8

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Morphotek

Investigators

  • Study Director: Christina Coughlin, MD, PhD, Morphotek

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2010

Primary Completion (Actual)

June 1, 2012

Study Completion (Actual)

September 1, 2012

Study Registration Dates

First Submitted

September 29, 2010

First Submitted That Met QC Criteria

September 29, 2010

First Posted (Estimate)

September 30, 2010

Study Record Updates

Last Update Posted (Estimate)

July 16, 2014

Last Update Submitted That Met QC Criteria

July 15, 2014

Last Verified

July 1, 2014

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MORAb-028-001

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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