NCT01112293 · REGISTRY CONDITION SEARCH

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

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE2
Status at capture: COMPLETED
Registry last update: 2020-04-10

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

3-month Progression Free Survival Rate

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outcome · POSTED

Toxicity and Safety of Systemic Infusion of Anti-TGF Antibody

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outcome · POSTED

Time to Progression and Overall Survival

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outcome · POSTED

Response Rate Using Modified RECIST Criteria for Mesothelioma

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outcome · POSTED

Number of Participants With a Change of Serum Biomarkers After Therapy

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outcome · POSTED

Number of Participants With Systemic Humoral Anti-tumor Immune Response After Repeated Anti-TGFβ Antibody Instillation

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outcome · POSTED

Assessment of Systemic TGFβ After Repeated Anti-TGFβ Antibody Installation

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outcome · POSTED

Biologic Response Measurements of TGFβ Blockade

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: Inclusion Criteria: * 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. * Documented progressive disease evaluable by Modified RECIST criteria. \[Progressive symptoms after 1st line therapy in the absence of objective progression are acceptable as a criterion for enrollment\]. Patients who have had previous extrapleural pneumonectomy and disease recurrence will be eligible if they have no other exclusion criteria. * 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). Exclusion Criteria: * 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. * Patients with an organ transplant, including those that have received an allogeneic bone marrow transplant. * Use of investigational agents within 4 weeks prior to study enrollment (within 6 weeks if the treatment was with a long-acting agent such as a monoclonal antibody). * Patients on immunosuppressive therapy * Significant or uncontrolled medical illness, such as congestive heart failure (CHF), myocardial infarction, symptomatic coronary artery disease, significant ventricular arrhythmias within the last 6 months, or significant pulmonary dysfunction. Patients with a remote history of asthma or active mild asthma may participate. * Active infection, including active herpes zoster, as well as unexplained fever (temperature 38.1C), or antibiotic therapy within 1 week prior to enrollment. * Systemic autoimmune disease (e.g., systemic lupus erythematosus, active rheumatoid arthritis, etc.). * Positive stool fecal occult blood test (patients who are positive will need a standard GI work-up consisting of an Esophagogastroduodenoscopy (EGD) and Colonoscopy) prior to enrollment to rule out possible reasons for bleeding. A patient will be eligible with negative results for both exams. * Active GI bleeding within past 5 years other than due to benign anorectal causes such as hemorrhoids, fissures and stricture. * A known allergy to any component of GC1008. * Patients who, in the opinion of the Investigator, have significant medical or psychosocial problems that warrant exclusion.
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Phase II, Single-Arm, Multi-Site study. All subjects will receive the investigational agent, GC1008 in 3 week cycles of treatment
intervention Names
Drug: GC1008
label
Investigational drug infusion-for safety and effectiveness
type
EXPERIMENTAL

interventions

arm Group Labels
Investigational drug infusion-for safety and effectiveness
description
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.
name
GC1008
other Names
IgG4 kappa monoclonal antibody
type
DRUG

Study design

allocation

intervention Model

SINGLE_GROUP

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 14
type: ACTUAL

Registered outcome plans (not posted results)

other Outcomes

description
Assessment of time to disease progression and overall survival
measure
Time to Progression and Overall Survival
time Frame
18 months
description
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.
measure
Response Rate Using Modified RECIST Criteria for Mesothelioma
time Frame
18 months
description
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.
measure
Number of Participants With a Change of Serum Biomarkers After Therapy
time Frame
18 months
description
Comparing antibody bands in pre-treatment versus post-treatment serum
measure
Number of Participants With Systemic Humoral Anti-tumor Immune Response After Repeated Anti-TGFβ Antibody Instillation
time Frame
18 months
description
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.
measure
Assessment of Systemic TGFβ After Repeated Anti-TGFβ Antibody Installation
time Frame
18 months
description
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.
measure
Biologic Response Measurements of TGFβ Blockade
time Frame
3 weeks

primary Outcomes

description
The fraction of subjects surviving 3 months without disease progression.
measure
3-month Progression Free Survival Rate
time Frame
3 months

secondary Outcomes

description
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.
measure
Toxicity and Safety of Systemic Infusion of Anti-TGF Antibody
time Frame
18 months

Full study description

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.
detailed Description: 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.

Source references

Source notices and limitations

Discovery and provenance

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Preserved source evidence · Not medical advice