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

NCT01160458 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 10014610-C-0146
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Pleural Mesothelioma; Peritoneal Mesothelioma

Keywords

Monoclonal Antibody; Pleural Mesothelioma; Peritoneal Mesothelioma

Outcome Measures

Primary Outcomes (1)

• Clinical Response Rate (PR+CR)

  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.

  36 months

Secondary Outcomes (4)

• Safety of IMC-A12 in Patients With Mesothelioma

  Date treatment consent signed to date off study, approximately 36 months

• Duration of Overall Response

  36 months

• Progression Free Survival (PFS)

  To study completion, an average of 3 years

• Overall Survival (OS)

  To study completion, an average of 3 years

Study Arms (1)

IMC-A12 Monotherapy in Patients

EXPERIMENTAL

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)

Drug: IMC-A12

Interventions

IMC-A12 DRUG

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)

Also known as: A12 Cixutumumab

IMC-A12 Monotherapy in Patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• Patients must have had at least one prior platinum-containing chemotherapy regimen. There is no limit to the number of prior chemotherapy regimens received.
• 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) scan.
• 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.
• Age greater than or equal to 18 years. Since mesothelioma is extremely rare in children they are excluded from this study.
• Life expectancy of greater than 3 months.
• Performance status Eastern Cooperative Oncology Group (ECOG) less than or equal to 2.
• 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)

You may not qualify if:

• 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.
• 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%.
• 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 requirements.
• Patients may not be receiving any other investigational agents.
• 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.
• Prior treatment with drugs of the IGF-1R inhibitor class.
• 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.
• 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.
• 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.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to IMC-A12.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Bridda A, Padoan I, Mencarelli R, Frego M. Peritoneal mesothelioma: a review. MedGenMed. 2007 May 10;9(2):32.

  PMID: 17955087 BACKGROUND

• Vogelzang NJ, Rusthoven JJ, Symanowski J, Denham C, Kaukel E, Ruffie P, Gatzemeier U, Boyer M, Emri S, Manegold C, Niyikiza C, Paoletti P. Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol. 2003 Jul 15;21(14):2636-44. doi: 10.1200/JCO.2003.11.136.

  PMID: 12860938 BACKGROUND

• O'Byrne KJ, Edwards JG, Waller DA. Clinico-pathological and biological prognostic factors in pleural malignant mesothelioma. Lung Cancer. 2004 Aug;45 Suppl 1:S45-8. doi: 10.1016/j.lungcan.2004.04.025.

  PMID: 15261433 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Mesothelioma, Malignant

Interventions

cixutumumab

Condition Hierarchy (Ancestors)

Mesothelioma; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Pleural Neoplasms; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Dr. Raffit Hassan, M.D.
• Organization: National Cancer Institute, National Institutes of Health

hassanr@mail.nih.gov

301-451-8742

Study Officials

• Raffit Hassan, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr. Raffit Hassan

Study Record Dates

• First Submitted: July 9, 2010
• First Posted: July 12, 2010
• Study Start: June 2, 2010
• Primary Completion: August 13, 2016
• Study Completion: February 24, 2017
• Last Updated: April 10, 2018
• Results First Posted: May 14, 2013

Record last verified: 2018-03

Locations

US (1)