Invasive Thymoma and Thymic Carcinoma, Recurrent Thymoma and Thymic Carcinoma, Stage III Thymoma, Stage IVA Thymoma, Stage IVB Thymoma
Conditions
Brief summary
This phase II trial is studying how well saracatinib works in treating patients with relapsed or refractory thymoma or thymic cancer. Saracatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth
Detailed description
PRIMARY OBJECTIVES: I. To evaluate the objective response rate (complete response and partial response) in patients with relapsed or refractory thymoma or thymic carcinoma treated with AZD0530. SECONDARY OBJECTIVES: I. To evaluate the toxicity of AZD0530 in these patients. II. To evaluate the progression-free survival of these patients. III. To evaluate the overall survival of these patients. IV. To evaluate the disease control rate, defined as complete response, partial response, and stable disease, in these patients. OUTLINE: This is a multicenter study. Patients receive oral saracatinib once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically for 5 years.
Interventions
DRUGsaracatinib
Given orally
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed invasive thymoma or thymic carcinoma, meeting the following criteria: * Relapsed or refractory disease * Metastatic, unresectable disease * Locally invasive disease allowed provided it is not resectable and has been previously treated * Progressive disease * Measurable disease, defined as \>= 1 unidimensionally measurable lesion \>= 20 mm by conventional techniques or \>= 10 mm by spiral CT scan * Must have received \>= 1 prior chemotherapy regimen * No active brain metastases * Patients with previously treated brain metastases (surgical resection or radiotherapy) are eligible provided they have documented stable brain disease for \>= 1 month after completion of therapy and are asymptomatic * ECOG performance status 0-2 * Leukocytes \>= 3,000/mm\^3 * ANC \>= 1,500/mm\^3 * Platelet count \>= 100,000/mm\^3 * Hemoglobin \> 9 g/dL * Serum bilirubin \< 2.0 times upper limit of normal (ULN) * Transaminases =\< 2.5 times ULN (\< 5.0 times ULN if liver metastasis is present) * Serum creatinine \< 1.5 times ULN OR creatinine clearance \> 50 mL/min * Urine protein:creatinine ratio \< 0.5 OR urine protein \< 1,000 mg by 24-hour urine collection * QTc \< 460 msec * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for 30 days after completion of study treatment * No known history of allergic reactions attributed to compounds of similar chemical or biological composition to AZD0530 * No other malignancies within the past 3 years, except curatively treated in situ carcinoma of the cervix or completely resected nonmelanoma skin cancer * No concurrent active malignancies other than thymic malignancy * No condition that impairs the ability to swallow AZD0350 tablets (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease) * No cardiac dysfunction including, but not limited to, any of the following: * Symptomatic congestive heart failure * Unstable angina pectoris * Cardiac arrhythmia * History of ischemic heart disease * Myocardial infarction within the past year * No QTc prolongation or other significant ECG abnormalities * No poorly controlled hypertension (i.e., systolic blood pressure \[BP\] ≥ 150 mm Hg or diastolic BP ≥ 95 mm Hg) * No evidence of severe or uncontrolled systemic conditions that would make it undesirable to participate in the study or that would jeopardize compliance with the study, including any of the following: * Severe hepatic impairment * Interstitial lung disease (bilateral, diffuse, or parenchymal lung disease) * Unstable or uncompensated respiratory condition * Unstable or uncompensated cardiac condition * No uncontrolled illness including, but not limited to, any of the following: * Ongoing or active infection * Mental health issues or social circumstances that would limit compliance with study requirements * No prior src inhibitors * At least 4 weeks since prior systemic therapy (6 weeks for carmustine or mitomycin C) * At least 8 weeks since prior immunotherapy * At least 4 weeks since prior octreotide * Concurrent octreotide for pure red cell aplasia allowed provided patient continues on the same dose and schedule, has had a response to this drug, and has demonstrated progressive thymoma by radiography or physical exam * At least 4 weeks since prior surgery and recovered * At least 4 weeks since prior investigational agents * At least 4 weeks since prior radiotherapy to measurable disease sites (2 weeks for palliative radiotherapy to metastatic sites) and recovered * At least 7 days since prior and no concurrent active CYP3A4 agents or substances * No other concurrent investigational or anticancer agents * No concurrent combination antiretroviral therapy for HIV-positive patients * Concurrent steroids allowed for treatment of a pre-existing autoimmune disorder or as antiemetic therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (Complete and Partial Response) | Up to 5 years | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. The objective response rate will be reported by each disease classification. The percent of patients having an objective response (complete or partial response) will be estimated with a 95% exact binomial confidence interval for the percent of patients receiving drug. Note: there were no objective responses in this trial. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival | Time from the date of registration to the first reported outcome event, assessed up to 5 years | Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. This will be examined in an exploratory fashion using Kaplan-Meier estimates. Time until progression, death or last evaluation will be calculated. If a patient did not progress or die, they will be censored at their last evaluation in the analysis. |
| Overall Survival | Time from the date of registration to last reported date of survival, assessed up to 5 years | Will be examined in an exploratory fashion using Kaplan-Meier estimates. Time until death or last evaluation will be calculated. If a patient did not die, they will be censored in the analysis. |
| Disease Control Rate | Up to 5 years | Will be examined in an exploratory fashion using Kaplan-Meier estimates. Disease control rate defined as complete response (CR) + partial response (PR) + stable disease (SD). The length of time until progression or until last evaluation will be calculated. For patients who did not progress, they will be censored in the analysis. |
| Expected Toxicities Including Skin Rashes and Diarrhea | Up to 5 years | Number of patients who had toxicities classified as skin rashes and diarrhea within the adverse events. |
Countries
United States
Participant flow
Recruitment details
This protocol was based on getting at least 12 eligible patients with thymoma to complete stage one. There are 12 eligible thymoma patients and also 9 thymic carcinoma patients. Since no patients in the thymoma group had a response of Complete or Partial response, the study ended without going to stage two.
Participants by arm
| Arm | Count |
|---|---|
| Thymoma Patients classified as having Thymoma. Patients receive 175 mg oral saracatinib once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. | 12 |
| Thymic Carcinoma Patients classified as having Thymic carcinoma. Patients receive 175 mg oral saracatinib once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. | 9 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
| Overall Study | Disease progression | 9 | 7 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Noncompliance | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Thymoma | Thymic Carcinoma | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical >=65 years | 1 Participants | 2 Participants | 3 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants | 6 Participants | 17 Participants |
| Age, Continuous | 49.2 years STANDARD_DEVIATION 12.25 | 54.2 years STANDARD_DEVIATION 17.94 | 51.3 years STANDARD_DEVIATION 14.76 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants | 9 Participants | 20 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 8 Participants | 7 Participants | 15 Participants |
| Sex: Female, Male Female | 7 Participants | 3 Participants | 10 Participants |
| Sex: Female, Male Male | 5 Participants | 6 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 12 / 12 | 9 / 9 |
| serious Total, serious adverse events | 2 / 12 | 1 / 9 |
Outcome results
Primary
Objective Response Rate (Complete and Partial Response)
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. The objective response rate will be reported by each disease classification. The percent of patients having an objective response (complete or partial response) will be estimated with a 95% exact binomial confidence interval for the percent of patients receiving drug. Note: there were no objective responses in this trial.
Time frame: Up to 5 years
Population: All patients with at least one post baseline measurement.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Thymoma | Objective Response Rate (Complete and Partial Response) | 0 percentage of participants |
| Thymic Carcinoma | Objective Response Rate (Complete and Partial Response) | 0 percentage of participants |
Secondary
Disease Control Rate
Will be examined in an exploratory fashion using Kaplan-Meier estimates. Disease control rate defined as complete response (CR) + partial response (PR) + stable disease (SD). The length of time until progression or until last evaluation will be calculated. For patients who did not progress, they will be censored in the analysis.
Time frame: Up to 5 years
Population: All patients who enrolled and received treatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Thymoma | Disease Control Rate | 5.72 months |
| Thymic Carcinoma | Disease Control Rate | 3.55 months |
Secondary
Expected Toxicities Including Skin Rashes and Diarrhea
Number of patients who had toxicities classified as skin rashes and diarrhea within the adverse events.
Time frame: Up to 5 years
Population: All patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Thymoma | Expected Toxicities Including Skin Rashes and Diarrhea | 10 participants |
| Thymic Carcinoma | Expected Toxicities Including Skin Rashes and Diarrhea | 3 participants |
Secondary
Overall Survival
Will be examined in an exploratory fashion using Kaplan-Meier estimates. Time until death or last evaluation will be calculated. If a patient did not die, they will be censored in the analysis.
Time frame: Time from the date of registration to last reported date of survival, assessed up to 5 years
Population: All patients who enrolled and received treatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Thymoma | Overall Survival | 37.47 months |
| Thymic Carcinoma | Overall Survival | 6.68 months |
Secondary
Progression-free Survival
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. This will be examined in an exploratory fashion using Kaplan-Meier estimates. Time until progression, death or last evaluation will be calculated. If a patient did not progress or die, they will be censored at their last evaluation in the analysis.
Time frame: Time from the date of registration to the first reported outcome event, assessed up to 5 years
Population: All patients who enrolled and received treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Thymoma | Progression-free Survival | 5.30 months |
| Thymic Carcinoma | Progression-free Survival | 0.89 months |