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

Phase 2
18 Years
Open (Enrolling)
Pleural Mesothelioma, Peritoneal Mesothelioma

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Trial Information

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


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.


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

- 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.


- 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

- 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


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

- 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.

Inclusion Criteria


1. Subjects must have histologically confirmed pleural or peritoneal mesothelioma not
amenable to potentially curative surgical resection. The diagnosis will be confirmed
by the pathology department / Center for Cancer Research (CCR) / National Cancer
Institute (NCI).

2. Patients must have had at least one prior platinum-containing chemotherapy regimen.
There is no limit to the number of prior chemotherapy regimens received.

3. Patients must have measurable disease, defined as at least one lesion that can be
accurately measured in at least one dimension (longest diameter to be recorded) as >
20 mm with conventional techniques or as > 10 mm with spiral computed tomography (CT)

4. Patients must not have had major surgery, radiation therapy, chemotherapy, biologic
therapy (including any investigational agents), or hormonal therapy (other than
replacement), within 4 weeks prior to entering the study and must have evidence of
stable or progressive disease to be eligible.

5. Age greater than or equal to 18 years. Since mesothelioma is extremely rare in
children they are excluded from this study.

6. Life expectancy of greater than 3 months.

7. Performance status Eastern Cooperative Oncology Group (ECOG) less than or equal to 2.

8. Patients must have adequate organ and marrow function (as defined below).

- leukocytes greater than or equal to 3,000/mm^3

- absolute neutrophil count greater than or equal to 1,500/mm^3

- hemoglobin greater than or equal to 9 g/dL

- platelets greater than or equal to 100,000/ mm^3

- total bilirubin less than or equal to 1.5 times institutional upper limit of
normal (ULN)

- Aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase
(SGOT)/alanine aminotransferase (ALT) serum glutamic pyruvic transaminase(SGPT)
less than or equal to 3 times institutional ULN

(5 times if liver function test (LFT) elevations due to liver metastases)

- creatinine less than or equal to 1.5 times institutional ULN


- creatinine clearance greater than or equal to 60 mL/min/1.73 m^2 for patients with

levels above institutional normal

Patients may be transfused to obtain a hemoglobin of greater than or equal to 9 g/Dl.

9. The patient must have fasting serum glucose < 160 mg/dL

10. The effects of IMC-A12 on the developing human fetus are unknown. For this reason,
women of child-bearing potential and men must agree to use adequate contraception
(barrier method of birth control; abstinence) for the duration of study therapy and
for 3 months after the last dose of IMC-A12. Should a woman become pregnant or
suspect she is pregnant while participating in this study, she should inform her
treating physician immediately. While hormonal methods of birth control are
effective, we ask that female patients who are participating in the study cease
hormonal forms of birth control, as these methods of birth control (birth control
pills, injections, or implants) may affect the study drug. Patients must be off
hormonal forms of birth control for at least 4 weeks prior to initiating the study.

11. Ability to comply with intravenous administration schedule, and the ability to
understand and the willingness to sign a written informed consent document.

Inclusion of Women and Minorities

Both men and women and members of all races and ethnic groups are eligible for this trial.
Every effort will be made to recruit women and minorities in this study.


1. Patients with symptomatic brain metastases should be excluded from this clinical
trial because of their poor prognosis and because they often develop progressive
neurologic dysfunction that would confound the evaluation of neurologic and other
adverse events. However, patients who have had treatment for their brain metastases
and whose brain metastatic disease status has remained stable for at least 3 months
without steroids may be enrolled at the discretion of the principal investigator.

2. Patients with poorly controlled diabetes mellitus. Patients with a history of
diabetes mellitus are allowed to participate, provided their blood glucose is below
160 mg/dL when fasting and if they are on a stable dietary or therapeutic regimen for
this condition with their HbA1C of less than 7%.

3. Uncontrolled medical illness including, but not limited to, ongoing or uncontrolled,
symptomatic congestive heart failure (American Heart Association (AHA) Class II or
worse), uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, or
psychiatric illness/social situations that would limit compliance with study

4. Human immunodeficiency virus (HIV) positive patients with poorly controlled viral
loads (viral load > 50 copies HIV/ml), and/or acquired immune deficiency syndrome
(AIDS)-defining illnesses will be excluded due to the possibility that IMC-A12 may
worsen their condition and the likelihood that the underlying condition may obscure
the attribution of adverse events with respect to IMC-A12. HIV positive patients with
mesothelioma not meeting the above criteria can be considered for inclusion in the

5. Patients may not be receiving any other investigational agents.

6. History of another invasive malignancy in the last five years. Adequately treated
non-invasive, non-melanoma skin cancers as well as in situ carcinoma of the cervix
will be allowed.

7. Prior treatment with drugs of the IGF-1R inhibitor class.

8. Patients with tumor amenable to potentially curative therapy as assessed by the
investigator. In patients with peritoneal mesothelioma who have had no prior surgery,
a surgical consultation will be obtained to see if the patient is a candidate for
debulking surgery.

9. Pregnant women are excluded from this study because IMC-A12 is a monoclonal antibody
to IGF-1R with the potential for teratogenic or abortifacient effects. Immunoglobulin
G (IgG) antibody may also potentially be secreted in milk and therefore breastfeeding
women should be excluded. Because of the potential of teratogenic or abortifacient
effects women of childbearing potential and men must agree to use adequate
contraception (barrier methods) before, during the study and for a period of 3 months
after the last dose of the investigational agent.

10. Patients must not be on hormonal forms of birth control or hormone replacement
therapy, as this may affect the study drug. Patients must be off hormonal forms of
birth control or hormone replacement therapy for at least 4 weeks prior to initiating
the study.

11. History of allergic reactions attributed to compounds of similar chemical or biologic
composition to IMC-A12.

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Clinical Response Rate (PR+CR)

Outcome Description:

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.

Outcome Time Frame:

36 months

Safety Issue:


Principal Investigator

Raffit Hassan, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Cancer Institute (NCI)


United States: Federal Government

Study ID:




Start Date:

June 2010

Completion Date:

July 2013

Related Keywords:

  • Pleural Mesothelioma
  • Peritoneal Mesothelioma
  • Monoclonal Antibody
  • Pleural Mesothelioma
  • Peritoneal Mesothelioma
  • Mesothelioma



National Institutes of Health Clinical Center, 9000 Rockville Pike Bethesda, Maryland  20892