Multicenter Phase II Study of IMC-A12 in Patients With Thymoma and Thymic Carcinoma Who Have Been Previously Treated With Chemotherapy

NCT00965250 | Completed Phase 2 Results DMC

• 2 other identifiers: 09021209-C-0212
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 2

Brief Summary

Background:

• Cisplatin-containing chemotherapy is the standard of care for advanced thymoma and thymic carcinoma that cannot be treated with surgery. New options for treatment are necessary in patients with advanced thymoma and thymic carcinoma that have progressed on cisplatin-containing therapy.
• IMC-A12 is a new (experimental) agent that has not yet been approved by the Food and Drug Administration. IMC-A12 blocks the Insulin-like Growth Factor 1 receptor (IGF-1R). IGF-1R is found on many types of cancer cells, including cancer of the thymus, and is thought to play an important role in helping these cells to grow and divide. Objectives:
• To determine if IMC-A12 has an effect on tumor growth in patients with cancer of the thymus.
• To evaluate the safety and tolerability of IMC-A12 in treatment for cancer of the thymus. Eligibility: \- Individuals older than 18 years of age who have cancer of the thymus (thymoma, thymic carcinoma, or thymic carcinoid tumors) that has progressed in spite of standard treatment. Design:
• Treatment will take place in 21-day cycles. Patients will receive one dose of IMC-A12 intravenously once every 3 weeks at the Clinical Center. During the Clinical Center visits, researchers will perform study tests and procedures to see how the study drugs are affecting the body.
• Patients will undergo a number of tests and procedures during the treatment cycle, including physical examinations, blood and urine samples for standard tests, imaging studies (ultrasound, magnetic resonance imaging (MRI) or computed tomography (CT) scans) to evaluate tumor growth, and blood and urine samples to evaluate the amount of IMC-A12 in the body.
• Patients may continue to take the drug as long as there are no adverse side effects and as long as the tumor does not grow.

Conditions

Thymoma; Thymic Carcinoma; Thymic Carcinoid; Thymic Neuroendocrine Tumors

Keywords

Thymic Malignancies; IMC-A12; Insulin-Like Growth Factor

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (Partial Response (PR)+Complete Response (CR)) to IMC-A12 Monotherapy in Patients With Advanced or Recurrent Thymoma or Thymic Carcinoma.

  Objective response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Complete response (CR) is the disappearance of all target lesions. Partial response (PR) 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 (PD) is at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.

  Patients were assessed for response every 2 cycles (every 6 weeks) while receiving the study drug.

Secondary Outcomes (7)

• Number of Participants With Adverse Events

  81 months and 17 days

• Percentage of Participants Who Respond to Treatment

  39 months

• Disease Control Rate (DCR)

  39 months

• Time to Progression

  39 months

• Overall Survival

  39 months

Study Arms (2)

Thymoma

EXPERIMENTAL

Patients will receive IMC-A12 at a dose of 20 mg/kg intravenously once every three weeks. The most common tumors of the thymus are thymomas (well differentiated neoplasms and moderately differentiated neoplasms) and thymic (poorly differentiated neoplasms) carcinomas.

Drug: IMC-12

Thymic Carcinoma

EXPERIMENTAL

Patients will receive IMC-A12 at a dose of 20 mg/kg intravenously once every three weeks. The most common tumors of the thymus are thymomas (well differentiated neoplasms and moderately differentiated neoplasms) and thymic (poorly differentiated neoplasms) carcinomas.

Drug: IMC-12

Interventions

IMC-12 DRUG

20 mg/kg intravenously once every three weeks

Thymic Carcinoma; Thymoma

Eligibility Criteria

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

You may qualify if:

• Histologically confirmation of invasive recurrent or metastatic thymoma or thymic carcinoma by the pathology department / Center for Cancer Research (CCR) / National Cancer Institute (NCI), or the pathology department of participating institutions.
• Patients must have had at least one prior platinum-containing chemotherapy regimen. There is no limit to the number of prior chemotherapy regimens received. Progressive disease should have been documented before entry into the study.
• 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 greater than 20 mm with conventional techniques or as greater than 10 mm with spiral CT scan. See section 11 for the evaluation of measurable disease.
• Target lesions cannot be selected within previously irradiated areas, if not newly arising or clearly progressing after irradiation as proven by repeat scanning.
• Patients must have recovered from toxicity related to prior therapy to at least to grade 1 (defined by CTCAE 3.0 until December 31, 2010, and by CTCAE 4.0 beginning January 1, 2011) and 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.
• Concurrent corticosteroids for myasthenia gravis, or other paraneoplastic syndromes which often accompany thymic malignancies are allowed. Inhaled steroids are also allowed. However since steroids might occasionally induce responses in thymic malignancies patients should be on a stable dose of steroids for greater than or equal to 8 weeks before enrollment in order not to confound the efficacy assessment.
• Age greater than 18 years. Because no dosing or adverse event data are currently available on the use of IMC-A12 in patients less than 16 years of age, children are excluded from this study but will be eligible for future pediatric phase 1 single-agent trials.
• 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). Patients must have returned to baseline or grade 1 from any acute toxicity related to prior therapy:
• 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 the institutional upper limit of normal (ULN)

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 within the normal range (fasting less than 120 mg/dL or below institutional upper limit of normal) and if they are on a stable dietary or therapeutic regimen for this condition.
• 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, in situ carcinoma of the cervix, and surgically-removed papillary thyroid cancer 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.
• 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. IgG antibody may also potentially be secreted in milk and therefore breastfeeding women should be excluded.
• 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 (2)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10021, United States

Location

Related Publications (4)

• Giaccone G, Wilmink H, Paul MA, van der Valk P. Systemic treatment of malignant thymoma: a decade experience at a single institution. Am J Clin Oncol. 2006 Aug;29(4):336-44. doi: 10.1097/01.coc.0000227481.36109.e7.

  PMID: 16891859 BACKGROUND

• Giaccone G. Treatment of malignant thymoma. Curr Opin Oncol. 2005 Mar;17(2):140-6. doi: 10.1097/01.cco.0000152628.43867.8e.

  PMID: 15725919 BACKGROUND

• Okumura M, Ohta M, Tateyama H, Nakagawa K, Matsumura A, Maeda H, Tada H, Eimoto T, Matsuda H, Masaoka A. The World Health Organization histologic classification system reflects the oncologic behavior of thymoma: a clinical study of 273 patients. Cancer. 2002 Feb 1;94(3):624-32. doi: 10.1002/cncr.10226.

  PMID: 11857293 BACKGROUND

• Rajan A, Carter CA, Berman A, Cao L, Kelly RJ, Thomas A, Khozin S, Chavez AL, Bergagnini I, Scepura B, Szabo E, Lee MJ, Trepel JB, Browne SK, Rosen LB, Yu Y, Steinberg SM, Chen HX, Riely GJ, Giaccone G. Cixutumumab for patients with recurrent or refractory advanced thymic epithelial tumours: a multicentre, open-label, phase 2 trial. Lancet Oncol. 2014 Feb;15(2):191-200. doi: 10.1016/S1470-2045(13)70596-5. Epub 2014 Jan 15.

  PMID: 24439931 RESULT

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Thymoma

Condition Hierarchy (Ancestors)

Neoplasms, Complex and Mixed; Neoplasms by Histologic Type; Neoplasms; Thymus Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lymphatic Diseases; Hemic and Lymphatic Diseases

Results Point of Contact

• Title: Dr. Arun Rajan
• Organization: National Cancer Institute, National Institutes of Health

rajana@mail.nih.gov

301-594-5322

Study Officials

• Arun Rajan, 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: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 24, 2009
• First Posted: August 25, 2009
• Study Start: August 1, 2009
• Primary Completion: March 1, 2012
• Study Completion: June 1, 2016
• Last Updated: December 23, 2016
• Results First Posted: November 14, 2012

Record last verified: 2016-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)