Phase 2
N=49
Multicenter Phase II Study of IMC-A12 in Patients With Thymoma and Thymic Carcinoma Who Have Been Previously Treated With Chemotherapy
Thymoma · Thymic Carcinoma · Thymic Carcinoid · Thymic Neuroendocrine Tumors
Bottom Line
View on ClinicalTrials.gov: NCT00965250 ↗Enrolled (actual)
49
Serious AEs
59.2%
Results posted
Nov 2012
Primary outcome: Primary: Objective Response Rate (Partial Response (PR)+Complete Response (CR)) to IMC-A12 Monotherapy in Patients With Advanced or Recurrent Thymoma or Thymic Carcinoma. — 0; 0; 5; 0 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- IMC-12 (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- National Cancer Institute (NCI)
- Primary completion
- Mar 2012
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Objective Response Rate (Partial Response (PR)+Complete Response (CR)) to IMC-A12 Monotherapy in Patients With Advanced or Recurrent Thymoma or Thymic Carcinoma. |
0; 0; 5; 0; 28; 5 | — |
| SECONDARY Number of Participants With Adverse Events |
49 | — |
| SECONDARY Percentage of Participants Who Respond to Treatment |
14; 0 | — |
| SECONDARY Disease Control Rate (DCR) |
89; 42 | — |
| SECONDARY Time to Progression |
9.9; 1.7 | <0.0001 sig |
| SECONDARY Overall Survival |
27.5; 8.4 | <0.0001 sig |
| SECONDARY Median Number of Cycles of Therapy |
13; 2.5 | — |
| SECONDARY Correlate Response to Therapy With Changes in FDG-PET Imaging |
— | — |
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.
Eligibility Criteria
- INCLUSION CRITERIA:
- 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)
- aspartate aminotransferase (AST)(SGOT)/alanine aminotransferase (ALT)(SGPT) less than or equal to 3 times the institutional ULN
(5x if LFT elevations due to liver metastases)
- creatinine less than or equal to 1.5 times the institutional ULN
OR
--creatinine clearance greater than or equal to 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
- Patients may be transfused to obtain a hemoglobin of 9.0.
- The patient must have fasting serum glucose less than 120 mg/dL or below the institutional ULN
- 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 (hormonal or 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.
- 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
Data sourced from ClinicalTrials.gov (NCT00965250). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.