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

Melanoma Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01212276
• Other study ID #: MORAb-028-001
• Status: Terminated
• Phase: Phase 1
• First received: September 29, 2010
• Last updated: July 15, 2014
• Start date: December 2010
• Est. completion date: September 2012

Study information

• Verified date: July 2014
• Source: Morphotek
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 18
• Est. completion date: September 2012
• Est. primary completion date: June 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Advanced Melanoma
• Malignant Metastatic Melanoma
• Melanoma
• Metastatic Melanoma

Intervention

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

Locations

Country	Name	City	State
United States	Memorial Sloan-Kettering Cancer Center	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Morphotek

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety of single dose radio labeled MORAb-028 in subjects with metastatic melanoma		Daily for 7 days followed by weekly for 2 weeks, then biweekly for 4 weeks	Yes
Secondary	Radiologic distribution of a single i.v. infusion of MORAb-028		Daily for 1 week post study drug administration	Yes
Secondary	Pharmacokinetic parameters of labeled and unlabeled MORAb-028		Daily for 7 days followed by weekly for 2 weeks, then biweekly for 4 weeks	Yes
Secondary	The incidence of human antihuman antibody formation		Week 2 and Week 8	Yes