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A Phase II Trial of Anti-TGF Monoclonal Antibody (GC1008) in Relapsed Malignant Pleural Mesothelioma (MPM))

Phase 2
18 Years
Not Enrolling
Pleural Malignant Mesothelioma

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Trial Information

A Phase II Trial of Anti-TGF Monoclonal Antibody (GC1008) in Relapsed Malignant Pleural Mesothelioma (MPM))

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.

Inclusion Criteria:

- Pathologically [histologically or cytologically] documented pleural malignant

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.

Type of Study:


Study Design:

Primary Purpose: Treatment

Outcome Measure:

3-month PFS rate

Outcome Description:

Will estimate the fraction of subjects surviving 3 months without disease progression. The first stage will involve enrolling, treating and following 13 patients. If no more than one of the first 13 patients is alive without progression at 3 months, the study will be terminated for the lack of efficacy

Outcome Time Frame:

3 months

Safety Issue:


Principal Investigator

James Stevenson, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Abramson Cancer Center of the University of Pennsylvania


United States: Food and Drug Administration

Study ID:

UPCC 03510



Start Date:

April 2010

Completion Date:

October 2012

Related Keywords:

  • Pleural Malignant Mesothelioma
  • Subjects who have pleural malignant mesothelioma
  • Mesothelioma



Abramson Cancer Center of the University of PennsylvaniaPhiladelphia, Pennsylvania  19104-4283