Anti-TGF Monoclonal Antibody (GC1008) in Relapsed Malignant Pleural Mesothelioma
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|ClinicalTrials.gov Identifier: NCT01112293|
Recruitment Status : Completed
First Posted : April 28, 2010
Results First Posted : April 10, 2020
Last Update Posted : April 10, 2020
|Condition or disease||Intervention/treatment||Phase|
|Pleural Malignant Mesothelioma||Drug: GC1008||Phase 2|
Primary: - To assess progression-free survival rate at three months.
Secondary: - To determine the toxicity and safety of systemic infusion of anti-TGF beta antibody at three-week dosing intervals. - To assess time to progression and overall survival - to assess response rate using Modified RECIST Criteria for Mesothelioma Additional Objectives: - To assess efficacy using serial measurements of serum [and intrapleural, if indwelling catheter in place] biomarkers, including serum-mesothelin related peptide (SMRP/Mesomark®) and osteopontin. - To assess systemic [and intrapleural if indwelling catheter in place] humoral anti-tumor immune responses after repeated anti-TGF beta antibody instillation. - To assess systemic [and intrapleural, if indwelling catheter in place] TGF beta, and other cytokine levels after repeated anti-TGF beta antibody instillation. - To assess biologic response measurements of TGF beta blockade from serum tests and from pleural fluid or biopsy tissue if this is available.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||14 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Trial of Anti-TGF Monoclonal Antibody (GC1008) in Relapsed Malignant Pleural Mesothelioma (MPM))|
|Study Start Date :||April 2010|
|Actual Primary Completion Date :||October 2012|
|Actual Study Completion Date :||December 2014|
Experimental: Investigational drug infusion-for safety and effectiveness
Phase II, Single-Arm, Multi-Site study. All subjects will receive the investigational agent, GC1008 in 3 week cycles of treatment
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.
Other Name: IgG4 kappa monoclonal antibody
- 3-month Progression Free Survival Rate [ Time Frame: 3 months ]The fraction of subjects surviving 3 months without disease progression.
- Toxicity and Safety of Systemic Infusion of Anti-TGF Antibody [ Time Frame: 18 months ]The toxicity and safety of systemic infusion of anti-TGF antibody at three-week dosing intervals. Number subjects with Grade 2 and Grade 3/4 treatment related toxicities.
- Time to Progression and Overall Survival [ Time Frame: 18 months ]Assessment of time to disease progression and overall survival
- Response Rate Using Modified RECIST Criteria for Mesothelioma [ Time Frame: 18 months ]Response and progression will be evaluated in this study using the international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). Changes in the largest diameter (unidimensional measurement) of the tumor lesions and the shortest diameter in the case of malignant lymph nodes are used in RECIST. The response assessment is based on the presence, absence, or unequivocal progression of the lesions.
- Number of Participants With a Change of Serum Biomarkers After Therapy [ Time Frame: 18 months ]Evaluation of changes after treatment therapy to a number of potential blood biomarkers of TGF-β effect (serum osteopontin, serum hyaluronan, serum MMP-1, serum MMP-7, serum IL-6, plasma CCL18, plasma VEGF, and plasma PAI-1). Animal models predict acute changes in TGF-β levels in blood associated with changes in serum biomarkers.
- Number of Participants With Systemic Humoral Anti-tumor Immune Response After Repeated Anti-TGFβ Antibody Instillation [ Time Frame: 18 months ]Comparing antibody bands in pre-treatment versus post-treatment serum
- Assessment of Systemic TGFβ After Repeated Anti-TGFβ Antibody Installation [ Time Frame: 18 months ]The number of participants with significant change in percentage of circulating CD4+ T regulatory cells, marked by expression of FOXP3 after treatment. TGFβ has been implicated in the formation of T regulatory cells, and the blockade of TGFβ in animal models can inhibit the formation of T regulatory cells.
- Biologic Response Measurements of TGFβ Blockade [ Time Frame: 3 weeks ]Number of participants who demonstrated upregulation of NK cell receptors 3 weeks after treatment. There are data that show anti-TGFβ antibodies can upregulate NK cell receptors in patients with chronic viral infections. TGFβ blockade was measured in samples of serum tests and from pleural fluid or biopsy if available.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01112293
|United States, Pennsylvania|
|Abramson Cancer Center of the University of Pennsylvania|
|Philadelphia, Pennsylvania, United States, 19104|
|Principal Investigator:||James Stevenson, MD||Abramson Cancer Center of the University of Pennsylvania|