Phase II Study of IMC-A12 in Patients With Mesothelioma Who Have Been Previously Treated With Chemotherapy

Phase 2

Completed

Conditions: Pleural Mesothelioma
Peritoneal Mesothelioma

Interventions: Drug: IMC-A12

Registration Number: NCT01160458

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: Background:

Background:

- IMC-A12, a new cancer treatment that has not yet been approved by the U.S. Food and Drug Administration, is an antibody that is designed to block the effects of a protein called Type I Insulin-Like Growth Factor (IGF-1R). IMC-A12 blocks the receptors in cells that respond to IGF-1R, which are thought to play an important role in helping cancer cells to grow and divide. Researchers are interested in determining whether IMC-A12 is an effective treatment for individuals who have mesothelioma that has not responded to standard chemotherapy.

Objectives:

- To evaluate the safety and effectiveness of IMC-A12 treatment in individuals with mesothelioma who have previously had chemotherapy.

Eligibility:

- Individuals at least 18 years of age who have been diagnosed with mesothelioma that has not responded to chemotherapy.

Design:

* Eligible participants will be screened with a full physical examination and medical history, blood and urine samples, and imaging studies.

* Participants will receive IMC-A12 once every 3 weeks (21-day cycle), and will be evaluated before the start of each new cycle with blood tests and imaging studies if needed.

* Treatment cycles will continue for as long as needed, unless severe side effects develop or the disease progresses.

Detailed Description: Background:

Platinum-based chemotherapy is the standard of care for advanced unresectable malignant mesothelioma. New options for treatment are necessary in patients with advanced disease that have progressed on platinum-based therapy. The insulin-like growth factor (IGF) pathway is being studies in various malignancies including mesothelioma. IMC-A12 is an anti-IGF-1R monoclonal antibody that has shown activity in patients with various malignancies.

Objectives:

Primary Objective:

- To determine the clinical response rate (partial response (PR)+complete response (CR)) to IMC-A12 monotherapy in patients with advanced mesothelioma.

Secondary Objectives:

* To determine response duration, progression free survival (PFS) and overall survival (OS).

* To assess safety of IMC-A12 in patients with mesothelioma

Exploratory Objectives:

* To evaluate tumor IGF-1R expression and correlation with response

* To correlate response to therapy with changes in fludeoxyglucose 18F-positron emission tomography (FDG-PET) imaging.

* To monitor serum mesothelin and cancer antigen 125 or carbohydrate antigen 125 (CA-125) levels prior to and during therapy.

Eligibility:

* Patients with histologically confirmed malignant pleural or peritoneal mesothelioma who have previously been treated on at least one platinum-containing chemotherapy regimen with progressive disease documented prior to study entry, or have refused cytotoxic chemotherapy.

* Measurable disease by modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria for pleural mesothelioma or by RECIST criteria for peritoneal mesothelioma.

* Adequate renal, hepatic and hematopoietic function.

* No major surgery, radiotherapy, chemotherapy or biologic therapy within 28 days of IMC-A12 therapy

Design:

* Patients will receive IMC-A12 at a dose of 20 mg/kg intravenously once every three weeks.

* Treatment with IMC-A12 alone will continue until disease progression.

* Toxicity will be assessed every cycle by the Cancer Therapy Evaluation Program (CTEP) Version 4.0 of Common Terminology Criteria for Adverse Events (CTCAE).

* Tumor response assessments will be performed every 2 cycles.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 20

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
IMC-A12 Monotherapy in Patients	IMC-A12	20 mg/kg intravenous over 60 minutes or not to exceed 25 mg/minute once every 3 weeks (+ or -1 day cycle 3 and beyond)

Primary Outcome Measures

Name	Time	Method
Clinical Response Rate (PR+CR)	36 months	Clinical response is assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response is complete disappearance of all target lesions. Partial response is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.

Secondary Outcome Measures

Name	Time	Method
Safety of IMC-A12 in Patients With Mesothelioma	Date treatment consent signed to date off study, approximately 36 months	Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.
Duration of Overall Response	36 months	Duration of Overall Response is assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) and is measured from the time measurement criteria are met for complete response (CR) or partial response (PR) (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started). Complete response is complete disappearance of all target lesions. Partial response is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Progressive disease is at least a 20% increase in the sum of the longest diameter of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm. (Note: the appearance of one or more new lesions is also considered progression).
Progression Free Survival (PFS)	To study completion, an average of 3 years	Progression Free Survival is defined as the time interval from the start of treatment to documented evidence of disease progression. Progressive disease is at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum on study longest diameter (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm. (Note: the appearance of one or more new lesions is also considered progression).
Overall Survival (OS)	To study completion, an average of 3 years	Overall survival is the time interval from the start of treatment to the date of death.