Multicenter Phase II Study of IMC-A12 in Patients With Thymoma and Thymic Carcinoma Who Have Been Previously Treated With Chemotherapy
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Detailed Description
Background:
Cisplatin-containing chemotherapy is the standard of care for advanced unresectable thymoma and thymic carcinoma. New options for treatment are necessary in patients with advanced thymoma and thymic carcinoma that have progressed on cisplatin-containing therapy. The insulin-like growth factor (IGF) pathway is being studies in various malignancies including thymoma and thymic carcinoma. IMCA12 is an anti-IGF-1R monoclonal antibody that has shown activity in patients with thymic malignancies.
Objectives:
-
To determine the objective response rate (partial response (PR)+complete response (CR)) to IMC-A12 monotherapy in patients with advanced or recurrent thymoma or thymic carcinoma.
-
To evaluate time to response, duration of response, progression-free survival (PFS) and overall survival (OS)
-
To assess safety of IMC-A12
-
To perform immunohistochemistry for IGF1R expression on tumor samples of thymoma and thymic carcinoma (exploratory)
-
To correlate response to therapy with changes in fludeoxyglucose 18F-positron emission tomography (FDG-PET) imaging at baseline and first restaging
-
To perform pharmacokinetic (PK) analysis of IMC-A12
-
To perform pharmacodynamic (PD) analysis in blood for the detection of IGF1R, AKT and pAKT in peripheral blood mononuclear cells (PBMC's) (exploratory).
-
To assess circulating endothelial cell, circulating endothelial progenitor cells, immune subset analysis and glucose transport in peripheral blood monocytes and lymphocytes (exploratory).
-
To evaluate anti-cytokine antibodies in peripheral blood (exploratory).
Eligibility:
-
Patients with histologically confirmed thymic carcinoma or thymoma who have previously been treated on at least one platinum-containing chemotherapy regimen
-
Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria
-
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 Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 until December 31, 2010, and by CTCAE Version 4.0 beginning January 1, 2011
-
Tumor response assessments by RECIST 1.0 criteria will be performed every 2 cycles
-
Correlative studies including tissue immunohistochemistry studies will be done on existing tumor blocks
-
Blood samples will be collected for for PK's, PD's, circulating endothelial cells (CEC's), circulating endothelial precursor cells (CEPC's), immune subsets, glucose transport and cytokine antibodies.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Thymoma 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
20 mg/kg intravenously once every three weeks
|
| Experimental: Thymic Carcinoma 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
20 mg/kg intravenously once every three weeks
|
Outcome Measures
Primary Outcome Measures
- Objective Response Rate (Partial Response (PR)+Complete Response (CR)) to IMC-A12 Monotherapy in Patients With Advanced or Recurrent Thymoma or Thymic Carcinoma. [Patients were assessed for response every 2 cycles (every 6 weeks) while receiving the study drug.]
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.
Secondary Outcome Measures
- Number of Participants With Adverse Events [81 months and 17 days]
Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.
- Percentage of Participants Who Respond to Treatment [39 months]
Percentage of participants who respond to treatment was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST).
- Disease Control Rate (DCR) [39 months]
Disease control rate is defined as objective response plus stable disease.
- Time to Progression [39 months]
Time between the first day of treatment to the day of disease progression.
- Overall Survival [39 months]
Time from treatment start date until date of death or date last known alive.
- Median Number of Cycles of Therapy [6 weeks]
A cycle is defined as 21 days or 6 weeks of therapy.
- Correlate Response to Therapy With Changes in FDG-PET Imaging [6 weeks after initiation of treatment]
Participants with scans that showed neither sufficient shrinkage to qualify as an objective response nor sufficient increase to qualify as disease progression, taking as reference the smallest cumulative longest dimension since start of treatment, to have stable disease.
Eligibility Criteria
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 and minorities in this study.
EXCLUSION CRITERIA:
-
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.
-
Human Immunodeficiency virus (HIV) positive patients with poorly controlled viral loads (viral load greater than 50 copies HIV/ml), and/or 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 thymic malignancies not meeting the above criteria can be considered for inclusion in the study.
-
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | National Institutes of Health Clinical Center, 9000 Rockville Pike | Bethesda | Maryland | United States | 20892 |
| 2 | Memorial Sloan Kettering Cancer Center | New York | New York | United States | 10021 |
Sponsors and Collaborators
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Arun Rajan, M.D., National Cancer Institute (NCI)
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
- 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.
- Giaccone G. Treatment of malignant thymoma. Curr Opin Oncol. 2005 Mar;17(2):140-6. Review.
- 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.
- 090212
- 09-C-0212
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | The thymic carcinoma cohort was closed after enrolment of 12 participants because of lack of activity. |
| Arm/Group Title | Thymoma | Thymic Carcinoma |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Period Title: Overall Study | ||
| STARTED | 37 | 12 |
| COMPLETED | 37 | 12 |
| NOT COMPLETED | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Thymoma | Thymic Carcinoma | Total |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | Total of all reporting groups |
| Overall Participants | 37 | 12 | 49 |
| Age (Count of Participants) | |||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
28
75.7%
|
11
91.7%
|
39
79.6%
|
| >=65 years |
9
24.3%
|
1
8.3%
|
10
20.4%
|
| Gender (Count of Participants) | |||
| Female |
18
48.6%
|
5
41.7%
|
23
46.9%
|
| Male |
19
51.4%
|
7
58.3%
|
26
53.1%
|
| Race/Ethnicity, Customized (participants) [Number] | |||
| White, non-Hispanic |
25
67.6%
|
5
41.7%
|
30
61.2%
|
| White, Hispanic |
2
5.4%
|
1
8.3%
|
3
6.1%
|
| Black |
6
16.2%
|
1
8.3%
|
7
14.3%
|
| Asian |
4
10.8%
|
5
41.7%
|
9
18.4%
|
| Region of Enrollment (participants) [Number] | |||
| United States |
37
100%
|
12
100%
|
49
100%
|
| Median age (years) [Median (Full Range) ] | |||
| Median (Full Range) [years] |
52
|
55
|
52
|
| Metastatic Sites (participants) [Number] | |||
| Intrathoracic sites only |
18
48.6%
|
0
0%
|
18
36.7%
|
| Extrathoracic sites(w/without intrathoracic sites |
11
29.7%
|
12
100%
|
23
46.9%
|
| Histological Analysis (WHO classification) (participants) [Number] | |||
| AB |
2
5.4%
|
0
0%
|
2
4.1%
|
| B1 |
4
10.8%
|
0
0%
|
4
8.2%
|
| B2 |
15
40.5%
|
0
0%
|
15
30.6%
|
| B2/B3 |
3
8.1%
|
0
0%
|
3
6.1%
|
| B3 |
9
24.3%
|
0
0%
|
9
18.4%
|
| C |
0
0%
|
12
100%
|
12
24.5%
|
| Not otherwise specified |
4
10.8%
|
0
0%
|
4
8.2%
|
| Paraneoplastic Syndromes (participants) [Number] | |||
| Myastenia gravis |
9
24.3%
|
0
0%
|
9
18.4%
|
| Shulman's syndrome |
1
2.7%
|
0
0%
|
1
2%
|
| Pure red-cell aplasia |
3
8.1%
|
0
0%
|
3
6.1%
|
| Crohn's disease |
1
2.7%
|
0
0%
|
1
2%
|
| Ulcerative colitis |
1
2.7%
|
0
0%
|
1
2%
|
| Mucocutaneous candidiasis |
1
2.7%
|
0
0%
|
1
2%
|
| Previous systemic treatment (number of regimens) (regimens) [Median (Full Range) ] | |||
| Median (Full Range) [regimens] |
3
|
2
|
2
|
| Previous systemic treatment (six or more regimens) (participants) [Number] | |||
| Number [participants] |
10
27%
|
2
16.7%
|
12
24.5%
|
| Previous chemotherapy (participants) [Number] | |||
| One line |
12
32.4%
|
7
58.3%
|
19
38.8%
|
| Two lines |
8
21.6%
|
2
16.7%
|
10
20.4%
|
| Three or more lines |
17
45.9%
|
3
25%
|
20
40.8%
|
| Previous platinum treatment (participants) [Number] | |||
| Number [participants] |
37
100%
|
12
100%
|
49
100%
|
| Previous anthracycline (participants) [Number] | |||
| Number [participants] |
27
73%
|
5
41.7%
|
32
65.3%
|
| Investigational drugs (participants) [Number] | |||
| Number [participants] |
17
45.9%
|
4
33.3%
|
21
42.9%
|
| Previous radiotherapy (participants) [Number] | |||
| Number [participants] |
23
62.2%
|
4
33.3%
|
27
55.1%
|
| Previous surgery (participants) [Number] | |||
| Radical |
28
75.7%
|
2
16.7%
|
30
61.2%
|
| Debulking |
1
2.7%
|
1
8.3%
|
2
4.1%
|
| Biopsy |
8
21.6%
|
9
75%
|
17
34.7%
|
| Eastern Cooperative Oncology Group (ECOG) Performance Status (participants) [Number] | |||
| 0 - Normal Activity |
3
8.1%
|
1
8.3%
|
4
8.2%
|
| 1 - Symptoms, but ambulatory |
29
78.4%
|
8
66.7%
|
37
75.5%
|
| 2 - In bed <50% of the time |
5
13.5%
|
3
25%
|
8
16.3%
|
Outcome Measures
| Title | Objective Response Rate (Partial Response (PR)+Complete Response (CR)) to IMC-A12 Monotherapy in Patients With Advanced or Recurrent Thymoma or Thymic Carcinoma. |
|---|---|
| Description | 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. |
| Time Frame | Patients were assessed for response every 2 cycles (every 6 weeks) while receiving the study drug. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Thymoma | Thymic Carcinoma |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 37 | 12 |
| Complete Response |
0
0%
|
0
0%
|
| Partial Response |
5
13.5%
|
0
0%
|
| Stable Disease |
28
75.7%
|
5
41.7%
|
| Progressive Disease |
4
10.8%
|
7
58.3%
|
| Title | Number of Participants With Adverse Events |
|---|---|
| Description | Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module. |
| Time Frame | 81 months and 17 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups. |
| Arm/Group Title | IMC-A12 Monotherapy in Patients |
|---|---|
| Arm/Group Description | Patients will receive IMC-A12 at a dose of 20 mg/kg intravenously once every three weeks. |
| Measure Participants | 49 |
| Number [Participants] |
49
132.4%
|
| Title | Percentage of Participants Who Respond to Treatment |
|---|---|
| Description | Percentage of participants who respond to treatment was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). |
| Time Frame | 39 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Thymoma | Thymic Carcinoma |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 37 | 12 |
| Number (95% Confidence Interval) [percentage of participants] |
14
37.8%
|
0
0%
|
| Title | Disease Control Rate (DCR) |
|---|---|
| Description | Disease control rate is defined as objective response plus stable disease. |
| Time Frame | 39 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Thymoma | Thymic Carcinoma |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 37 | 12 |
| Number (95% Confidence Interval) [percentage of participants] |
89
240.5%
|
42
350%
|
| Title | Time to Progression |
|---|---|
| Description | Time between the first day of treatment to the day of disease progression. |
| Time Frame | 39 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Thymoma | Thymic Carcinoma |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 37 | 12 |
| Median (95% Confidence Interval) [Months] |
9.9
|
1.7
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Thymoma, Thymic Carcinoma |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Kaplan Meier | |
| Comments | ||
| Title | Overall Survival |
|---|---|
| Description | Time from treatment start date until date of death or date last known alive. |
| Time Frame | 39 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Thymoma | Thymic Carcinoma |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 37 | 12 |
| Median (95% Confidence Interval) [Months] |
27.5
|
8.4
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Thymoma, Thymic Carcinoma |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Kaplan Meier | |
| Comments | ||
| Title | Median Number of Cycles of Therapy |
|---|---|
| Description | A cycle is defined as 21 days or 6 weeks of therapy. |
| Time Frame | 6 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Thymoma | Thymic Carcinoma |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 37 | 12 |
| Median (Full Range) [Cycles] |
13
|
2.5
|
| Title | Correlate Response to Therapy With Changes in FDG-PET Imaging |
|---|---|
| Description | Participants with scans that showed neither sufficient shrinkage to qualify as an objective response nor sufficient increase to qualify as disease progression, taking as reference the smallest cumulative longest dimension since start of treatment, to have stable disease. |
| Time Frame | 6 weeks after initiation of treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| We did radiological assessment ourselves, and an independent radiological assessment was not undertaken for assessment of response or progression. |
| Arm/Group Title | Thymoma | Thymic Carcinoma |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 0 | 0 |
Adverse Events
| Time Frame | ||
|---|---|---|
| Adverse Event Reporting Description | Adverse events are not separated by group because the adverse events are related to the drug which was the same in both groups. | |
| Arm/Group Title | IMC-A12 Monotherapy in Patients | |
| Arm/Group Description | Patients will receive IMC-A12 at a dose of 20 mg/kg intravenously once every three weeks. | |
All Cause Mortality |
||
| IMC-A12 Monotherapy in Patients | ||
| Affected / at Risk (%) | # Events | |
| Total | / (NaN) | |
Serious Adverse Events |
||
| IMC-A12 Monotherapy in Patients | ||
| Affected / at Risk (%) | # Events | |
| Total | 29/49 (59.2%) | |
| Cardiac disorders | ||
| Myocardial infection | 1/49 (2%) | 1 |
| Gastrointestinal disorders | ||
| Mucositis Oral | 1/49 (2%) | 1 |
| Abdominal pain | 1/49 (2%) | 1 |
| Rectal pain | 1/49 (2%) | 1 |
| Diarrhea | 1/49 (2%) | 1 |
| General disorders | ||
| Death NOS | 22/49 (44.9%) | 22 |
| Chills | 1/49 (2%) | 1 |
| Fever | 1/49 (2%) | 1 |
| Infections and infestations | ||
| Bronchial infection | 1/49 (2%) | 1 |
| Enterocolitis infection | 1/49 (2%) | 1 |
| Soft tissue infection | 1/49 (2%) | 1 |
| Metabolism and nutrition disorders | ||
| CPK increased | 1/49 (2%) | 1 |
| Hyperglycemia | 1/49 (2%) | 1 |
| Musculoskeletal and connective tissue disorders | ||
| Bone pain | 1/49 (2%) | 1 |
| Generalized muscle weakness | 1/49 (2%) | 1 |
| Myositis | 1/49 (2%) | 1 |
| Non-cardiac chest pain | 1/49 (2%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||
| Neoplasms benign, mailgnant and unspecified | 2/49 (4.1%) | 2 |
| Nervous system disorders | ||
| Seizure | 1/49 (2%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||
| Chest wall pain | 1/49 (2%) | 2 |
| Dyspnea | 3/49 (6.1%) | 3 |
| Hypoxia | 2/49 (4.1%) | 2 |
| Lung infection | 1/49 (2%) | 1 |
| Respiratory failure | 2/49 (4.1%) | 2 |
| Vascular disorders | ||
| Thromboembolic event | 1/49 (2%) | 1 |
Other (Not Including Serious) Adverse Events |
||
| IMC-A12 Monotherapy in Patients | ||
| Affected / at Risk (%) | # Events | |
| Total | 49/49 (100%) | |
| Blood and lymphatic system disorders | ||
| Activated partial thromboplastin time prolonged | 7/49 (14.3%) | 12 |
| Anemia | 35/49 (71.4%) | 105 |
| Edema: limbs | 1/49 (2%) | 2 |
| INR increased | 1/49 (2%) | 1 |
| Lymphocyte count decreased | 20/49 (40.8%) | 63 |
| lymphocyte count increased | 8/49 (16.3%) | 14 |
| Neutrophil count decreased | 8/49 (16.3%) | 29 |
| Platelet count decreased | 16/49 (32.7%) | 45 |
| White blood cell decreased | 11/49 (22.4%) | 40 |
| Bronchopulmonary hemorrhage | 3/49 (6.1%) | 4 |
| Cardiac disorders | ||
| Acute coronary syndrome | 2/49 (4.1%) | 2 |
| Hypotension | 2/49 (4.1%) | 2 |
| Palpitations | 1/49 (2%) | 1 |
| Sinus bradycardia | 1/49 (2%) | 1 |
| Ear and labyrinth disorders | ||
| Ear and labyrinth disorders - Other, specify (patient reports of diminished hearing) | 1/49 (2%) | 1 |
| Hearing impaired | 3/49 (6.1%) | 4 |
| Tinnitus | 1/49 (2%) | 1 |
| Eye disorders | ||
| Dry eye | 2/49 (4.1%) | 2 |
| Eye disorders - Other, specify (Aur; lost vision R eye) | 2/49 (4.1%) | 2 |
| Eye pain | 1/49 (2%) | 1 |
| Flashing lights | 3/49 (6.1%) | 3 |
| Floaters | 4/49 (8.2%) | 5 |
| Blurred vision | 1/49 (2%) | 1 |
| Conjunctivitis | 2/49 (4.1%) | 2 |
| Gastrointestinal disorders | ||
| Abdominal distention | 1/49 (2%) | 1 |
| Abdominal pain | 3/49 (6.1%) | 3 |
| Diarrhea | 9/49 (18.4%) | 22 |
| Dry mouth | 2/49 (4.1%) | 2 |
| Dysgeusia | 2/49 (4.1%) | 2 |
| Gastroesophageal reflux disease | 2/49 (4.1%) | 2 |
| Gastrointestinal disorders - Other, specify | 4/49 (8.2%) | 5 |
| Hemorroids | 2/49 (4.1%) | 2 |
| Lower gastrointestinal hemorrhage | 1/49 (2%) | 3 |
| Mucosal infection | 2/49 (4.1%) | 2 |
| Mucositis oral | 9/49 (18.4%) | 18 |
| Nausea | 17/49 (34.7%) | 27 |
| Oral pain | 2/49 (4.1%) | 3 |
| Rectal pain | 1/49 (2%) | 1 |
| Vomiting | 11/49 (22.4%) | 18 |
| Dyspepsia | 2/49 (4.1%) | 2 |
| Constipation | 7/49 (14.3%) | 16 |
| Anorexia | 20/49 (40.8%) | 29 |
| Bloating | 1/49 (2%) | 1 |
| General disorders | ||
| Fatigue | 18/49 (36.7%) | 44 |
| Fever | 3/49 (6.1%) | 5 |
| Flu like symptoms | 1/49 (2%) | 1 |
| Insomnia | 2/49 (4.1%) | 2 |
| Pain | 3/49 (6.1%) | 6 |
| Tumor pain | 8/49 (16.3%) | 11 |
| Weight loss | 6/49 (12.2%) | 14 |
| Immune system disorders | ||
| Allergic reaction | 2/49 (4.1%) | 2 |
| Allergic rhinitis | 7/49 (14.3%) | 7 |
| Infusion related reaction | 1/49 (2%) | 1 |
| Postnasal drip | 1/49 (2%) | 1 |
| Infections and infestations | ||
| Infections and infestations - Other, specify (Opportunistic; thrush) | 2/49 (4.1%) | 2 |
| Kidney infection | 1/49 (2%) | 1 |
| Tooth infection | 2/49 (4.1%) | 2 |
| Bladder infection | 3/49 (6.1%) | 3 |
| Bronchial infection | 6/49 (12.2%) | 7 |
| Investigations | ||
| Investigations-Other, specify (Bicarbonate, serum-low) | 1/49 (2%) | 1 |
| Metabolism and nutrition disorders | ||
| Alanine aminotransferase increased | 23/49 (46.9%) | 60 |
| Alkaline phosphatase increased | 17/49 (34.7%) | 31 |
| Hypercalcemia | 14/49 (28.6%) | 26 |
| Hyperglycemia | 37/49 (75.5%) | 182 |
| Hyperkalemia | 10/49 (20.4%) | 24 |
| Hypermagnesemia | 9/49 (18.4%) | 20 |
| Hypernatremia | 10/49 (20.4%) | 17 |
| Hyperuricemia | 22/49 (44.9%) | 57 |
| Hypoalbuminemia | 39/49 (79.6%) | 110 |
| Hypocalcemia | 7/49 (14.3%) | 20 |
| Hypoglycemia | 7/49 (14.3%) | 10 |
| Hypokalemia | 6/49 (12.2%) | 7 |
| Hypophosphatemia | 5/49 (10.2%) | 11 |
| Hypomagnesemia | 20/49 (40.8%) | 59 |
| Lipase increased | 6/49 (12.2%) | 22 |
| Serum amylase increased | 8/49 (16.3%) | 18 |
| Hyponatremia | 30/49 (61.2%) | 78 |
| Creatinine increased | 17/49 (34.7%) | 68 |
| Aspartate aminotransferase increased | 23/49 (46.9%) | 59 |
| CPK increased | 9/49 (18.4%) | 17 |
| Blood bilirubin increased | 8/49 (16.3%) | 26 |
| Glucose intolerance | 1/49 (2%) | 1 |
| Musculoskeletal and connective tissue disorders | ||
| Flank pain | 2/49 (4.1%) | 2 |
| Generalized muscle weakness | 1/49 (2%) | 1 |
| Muscle weakness lower limb | 2/49 (4.1%) | 2 |
| Musculoskeletal and connective tissue disorder-Other, specify | 13/49 (26.5%) | 15 |
| Myalgia | 5/49 (10.2%) | 7 |
| Neck pain | 1/49 (2%) | 1 |
| Non-cardiac chest pain | 3/49 (6.1%) | 3 |
| Arthralgia | 3/49 (6.1%) | 3 |
| Back pain | 2/49 (4.1%) | 2 |
| Chest wall pain | 6/49 (12.2%) | 11 |
| Facial muscle weakness | 1/49 (2%) | 1 |
| Pain in extremity | 1/49 (2%) | 1 |
| Bone pain | 1/49 (2%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||
| Neoplasms benign, mailgnant and unspecified | 1/49 (2%) | 1 |
| Nervous system disorders | ||
| Dizziness | 5/49 (10.2%) | 8 |
| Headache | 6/49 (12.2%) | 11 |
| Peripheral sensory neuropathy | 8/49 (16.3%) | 12 |
| Presyncope | 1/49 (2%) | 1 |
| Tremor | 2/49 (4.1%) | 2 |
| Vertigo | 5/49 (10.2%) | 8 |
| Ataxia | 1/49 (2%) | 1 |
| Cognitive disturbance | 1/49 (2%) | 1 |
| Confusion | 1/49 (2%) | 1 |
| Renal and urinary disorders | ||
| Renal and urinary disorders - Other, specify (urinary hesitancy) | 1/49 (2%) | 1 |
| Urinary tract infection | 4/49 (8.2%) | 4 |
| Urinary frequency | 1/49 (2%) | 1 |
| Reproductive system and breast disorders | ||
| Erectile dysfunction | 3/49 (6.1%) | 3 |
| Respiratory, thoracic and mediastinal disorders | ||
| Cough | 16/49 (32.7%) | 31 |
| Dyspnea | 13/49 (26.5%) | 20 |
| Epistaxis | 5/49 (10.2%) | 7 |
| Hiccups | 1/49 (2%) | 1 |
| Hoarseness | 4/49 (8.2%) | 9 |
| Laryngeal hemorrhage | 2/49 (4.1%) | 2 |
| Sinusitis | 3/49 (6.1%) | 3 |
| Upper respiratory infection | 8/49 (16.3%) | 9 |
| Voice alteration | 1/49 (2%) | 1 |
| Nasal congestion | 1/49 (2%) | 1 |
| Sore throat | 1/49 (2%) | 1 |
| Skin and subcutaneous tissue disorders | ||
| Alopecia | 7/49 (14.3%) | 7 |
| Dry skin | 6/49 (12.2%) | 6 |
| Nail discoloration | 1/49 (2%) | 2 |
| Nail loss | 5/49 (10.2%) | 5 |
| Rash acneiform | 1/49 (2%) | 1 |
| Rash maculo-papular | 6/49 (12.2%) | 8 |
| Skin and subcutaneous tissue disorders - Other, specify | 4/49 (8.2%) | 4 |
| Skin ulceration | 1/49 (2%) | 1 |
| Pruritis | 1/49 (2%) | 1 |
| Skin hypopigmentation | 1/49 (2%) | 1 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Dr. Arun Rajan |
|---|---|
| Organization | National Cancer Institute, National Institutes of Health |
| Phone | 301-594-5322 |
| rajana@mail.nih.gov |
- 090212
- 09-C-0212