Anti-TGF Monoclonal Antibody (GC1008) in Relapsed Malignant Pleural Mesothelioma

NCT01112293 | Completed Phase 2 Results DMC

• 1 other identifier: UPCC 03510
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

This study is being conducted to evaluate the overall safety and effectiveness of an investigational drug, GC1008, in patients with mesothelioma. An investigational drug is one that has not been approved by the FDA. Approximately 40 people will be enrolled on this study at the University of Pennsylvania (Main Institution/Coordinating Site) and the University of Chicago (Participating Institution). We expect about 20 subjects to be enrolled at each institution.

Conditions

Pleural Malignant Mesothelioma

Keywords

Subjects who have pleural malignant mesothelioma

Outcome Measures

Primary Outcomes (1)

• 3-month Progression Free Survival Rate

  The fraction of subjects surviving 3 months without disease progression.

  3 months

Secondary Outcomes (1)

• Toxicity and Safety of Systemic Infusion of Anti-TGF Antibody

  18 months

Other Outcomes (6)

• Time to Progression and Overall Survival

  18 months

• Response Rate Using Modified RECIST Criteria for Mesothelioma

  18 months

• Number of Participants With a Change of Serum Biomarkers After Therapy

  18 months

Study Arms (1)

Investigational drug infusion-for safety and effectiveness

EXPERIMENTAL

Phase II, Single-Arm, Multi-Site study. All subjects will receive the investigational agent, GC1008 in 3 week cycles of treatment

Drug: GC1008

Interventions

GC1008 DRUG

GC1008 is a human IgG4 kappa monoclonal antibody capable of neutralizing all mammalian isoforms of TGFbeta (i.e., beta1, beta 2 and beta 3). GC1008 is a high affinity antibody with dissociation constants (Kds) of 1.8 nM, 2.8 nM and 1.4 nM for TGF1,2,and 3, respectively.

Also known as: IgG4 kappa monoclonal antibody

Investigational drug infusion-for safety and effectiveness

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Pathologically \[histologically or cytologically\] documented pleural malignant mesothelioma.
• Patients must have had at least one, but no more than two prior systemic therapies, at least one of which contained pemetrexed.

You may not qualify if:

• ECOG Performance status of 0 or 1.
• Greater or equal to 18 years of age.
• Male and female patients of child-producing potential must agree to use effective contraception while enrolled on study and receiving the experimental drug, and for at least 3 months after the last treatment.
• Women of childbearing potential must have a negative serum or urine pregnancy test within 1 week prior to beginning treatment on this trial.
• Must be able and willing to give written informed consent. Patients may not be consented by a durable power of attorney.
• Serum albumin greater or equal to 2.5
• Adequate organ function
• Patients must have negative tests for human immunodeficiency virus (HIV) and for hepatitis viruses B and C (antibody and/or antigen) unless the result is consistent with prior vaccination or prior infection with full recovery.
• At the time of enrollment, patients must be greater than 3 weeks since major surgery, radiotherapy, chemotherapy (greater or equal to 6 weeks if they were treated with a nitrosourea, mitomycin or monoclonal antibody), immunotherapy, or biotherapy/targeted therapies and recovered from the toxicity of prior treatment to less than or equal to Grade 1, exclusive of alopecia. Concurrent non-protocol cancer therapy is not permitted. (In patients who received long acting agents, a treatment free interval of 2 half lives should be considered.) Note: Although a patient can be entered by these criteria, if a patient is less than 3-6 months from radiotherapy or talc pleurodesis, FDG-PET scanning will not be useful. 12).
• Known central nervous system (CNS) metastases, meningeal carcinomatosis, malignant seizures, or a disease that either causes or threatens neurologic compromise (e.g., unstable vertebral metastases).
• Presence of pericardial effusion
• Rapidly re-accumulating, symptomatic malignant pleural effusions status-post thoracentesis or pleural catheter insertion that requires immediate mechanical or chemical pleurodesis for adequate palliation.
• Active thrombophlebitis, thromboembolism, hypercoagulability states, bleeding, or use of anti-coagulation therapy (including lovenox, warfarin, or anti platelet agents such as aspirin \[with the exception of low dose ASA \~ 81 mg/d\] , clopidogrel, ticlopidine, dipyridamole, and other agents used to induce long-acting platelet dysfunction). Patients with a history of deep venous thrombosis may participate if successfully treated, completely resolved, and no treatment has been given for greater than 4 months.
• Pregnant or nursing women, due to the unknown effects of GC1008 on the developing fetus or newborn infant.
• Other active invasive malignancy requiring ongoing therapy.

Sponsors & Collaborators

• Abramson Cancer Center at Penn Medicine: lead

Study Sites (1)

Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Mesothelioma, Malignant

Interventions

fresolimumab

Condition Hierarchy (Ancestors)

Mesothelioma; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Pleural Neoplasms; Lung Diseases; Respiratory Tract Diseases

Limitations and Caveats

Limitations of the trial include small sample size and lack of post-tumor treatment samples.

Results Point of Contact

• Title: James Robinson
• Organization: AbramsonCC

jamesrobinson2@pennmedicine.upenn.edu

215-662-8758

Study Officials

• James Stevenson, MD

  Abramson Cancer Center at Penn Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 27, 2010
• First Posted: April 28, 2010
• Study Start: April 1, 2010
• Primary Completion: October 1, 2012
• Study Completion: December 1, 2014
• Last Updated: April 10, 2020
• Results First Posted: April 10, 2020

Record last verified: 2020-03

Locations

US (1)