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

This study has been terminated.
(Sponsor terminated protocol)
Sponsor:
Information provided by (Responsible Party):
Morphotek
ClinicalTrials.gov Identifier:
NCT01212276
First received: September 29, 2010
Last updated: July 15, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Metastatic Melanoma
Malignant Metastatic Melanoma
Advanced Melanoma
Melanoma
Drug: MORAb-028
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1 Study of the Safety, Tolerability, Pharmacokinetics and Radiologic Distribution of Ascending Single-Dose Radiolabeled MORAb-028 in Subjects With Metastatic Melanoma

Resource links provided by NLM:


Further study details as provided by Morphotek:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Radiologic distribution of a single i.v. infusion of MORAb-028 [ Time Frame: Daily for 1 week post study drug administration ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
  • The incidence of human antihuman antibody formation [ Time Frame: Week 2 and Week 8 ] [ Designated as safety issue: Yes ]

Enrollment: 18
Study Start Date: December 2010
Study Completion Date: September 2012
Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

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

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
  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: NCT01212276

Locations
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10022
Sponsors and Collaborators
Morphotek
Investigators
Study Director: Christina Coughlin, MD, PhD Morphotek
Principal Investigator: Jorge Carrasquillo, MD Memorial Sloan-Kettering Cancer Center
  More Information

No publications provided

Responsible Party: Morphotek
ClinicalTrials.gov Identifier: NCT01212276     History of Changes
Other Study ID Numbers: MORAb-028-001
Study First Received: September 29, 2010
Last Updated: July 15, 2014
Health Authority: United States: Food and Drug Administration

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 July 29, 2014