Locally Advanced Thymic Carcinoma, Metastatic Thymic Carcinoma, Recurrent Thymic Carcinoma, Unresectable Thymic Carcinoma
Conditions
Brief summary
This randomized phase II trial studies how well carboplatin and paclitaxel with or without ramucirumab work in treating patients with thymic cancer that has spread to other places in the body, has come back, or cannot be removed by surgery. Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as ramucirumab, may interfere with the ability of tumor cells to grow and spread. It is not yet known if giving carboplatin and paclitaxel with or without ramucirumab will work better in treating patients with thymic cancer.
Detailed description
PRIMARY OBJECTIVE: I. To compare progression-free survival between patients with incurable unresectable locally advanced, or recurrent, or metastatic thymic carcinoma randomized to carboplatin-paclitaxel with or without ramucirumab. SECONDARY OBJECTIVES: I. To evaluate the frequency and severity of toxicity of carboplatin-paclitaxel with or without ramucirumab in this patient population. II. To compare the response rate (complete response, partial response, confirmed and unconfirmed) between treatment arms. III. To compare disease control rate (complete response, partial response, confirmed or unconfirmed, stable disease) between treatment arms. IV. To compare overall survival between treatment arms. ADDITIONAL OBJECTIVE: I. To bank specimens for future research. OUTLINE: Patients are randomized to 1 of 2 arms. ARM A: Patients receive ramucirumab intravenously (IV) over 60 minutes, carboplatin IV, and paclitaxel IV on day 1. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients who have not progressed may continue to receive ramucirumab for up to 1 year. ARM B: Patients receive carboplatin IV and paclitaxel IV on day 1. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 1 year, and then every 6 months for 1 year.
Interventions
DRUGCarboplatin
Given IV
DRUGPaclitaxel
Given IV
BIOLOGICALRamucirumab
Given IV
Sponsors
National Cancer Institute (NCI)
SWOG Cancer Research Network
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients must have histologically or cytologically confirmed thymic carcinoma; thymic carcinoma may be defined as thymic epithelial malignancy, consistent with thymic carcinoma, or World Health Organization (WHO) type C thymic epithelial tumor, or thymic epithelial malignancy with radiographic imaging consistent with thymic carcinoma * Patients must have unresectable thymic carcinoma, that is either locally advanced, recurrent, or metastatic * Patients must not be candidates for localized surgery * Patients must have measurable disease documented by computed tomography (CT) or magnetic resonance imaging (MRI) within 28 calendar days prior to randomization; the CT from a combined positron emission tomography (PET)/CT may be used only if it is of diagnostic quality; non-measurable disease must be assessed within 42 calendar days prior to randomization; all known sites of disease must be assessed and documented on the baseline tumor assessment form (Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1) * Patients must have a Zubrod performance status of 0 to 2 * Patients must not have undergone major surgery within 28 calendar days prior to randomization, or minor surgery/subcutaneous venous access device placement within 7 calendar days prior to randomization; the patient must not have elective or planned major surgery to be performed during the course of the clinical trial * Patients must not have had prior systemic anti-cancer therapy for locally advanced or metastatic unresectable thymic carcinoma * If patients have recurrent unresectable thymic carcinoma, patients may have had prior neoadjuvant or adjuvant chemotherapy if treatment concluded \>= 6 months prior to randomization * Patients must have a CT or MRI scan of the brain to evaluate for central nervous system (CNS) disease within 42 calendar days prior to registration; patient must not have brain metastases unless: (1) metastases have been treated and have remained controlled for at least two weeks following treatment, AND (2) patient has no residual neurological dysfunction off corticosteroids for at least 1 day * Patients must not be candidates for radiation therapy with curative intent; prior palliative radiation therapy is allowed as long as a period of 7 days has passed since the last dose was received and the patient has recovered from any associated toxicity at the time of randomization * Absolute neutrophil count (ANC) \>= 1500/mcL documented within 28 calendar days prior to randomization * Hemoglobin \>= 9 g/dL (5.58 mmol/L) documented within 28 calendar days prior to randomization * Platelets \>= 100,000/mcL documented within 28 calendar days prior to randomization * International normalized ratio (INR) =\< 1.5 documented within 28 calendar days prior to randomization * Partial thromboplastin time (PTT) =\< 5 seconds above the institutional upper limit of normal (IULN) (unless receiving anticoagulation therapy) documented within 28 calendar days prior to randomization * Patients receiving warfarin must be switched to low molecular weight heparin and have achieved stable coagulation profile 14 days prior to randomization * Patients must not have experienced any grade 3 or above gastrointestinal (GI) bleeding within 84 calendar days prior to randomization * Patients must not have a history of deep vein thrombosis (DVT), pulmonary embolism (PE), or any other significant thromboembolism (venous port or catheter thrombosis or superficial venous thrombosis are not considered significant) during the 84 calendar days prior to randomization * Total bilirubin =\< 1.5 x the institutional upper limit normal (IULN) documented within 28 calendar days prior to randomization * Aspartate aminotransferase (aspartate transaminase \[AST\]) and alanine aminotransferase (alanine transaminase \[ALT\]) =\< 3.0 x IULN; for patients with liver metastases, total bilirubin and AST or ALT must be =\< 5.0 x IULN documented within 28 calendar days prior to randomization * Patients must not have any of following: * Cirrhosis at a level of Child-Pugh B (or worse) * Cirrhosis (any degree) and a history of hepatic encephalopathy; or * Clinically meaningful ascites resulting from cirrhosis; clinically meaningful ascites is defined as ascites from cirrhosis requiring diuretics or paracentesis * Serum creatinine =\< 1.5 x IULN, or creatinine clearance (measured via 24-hour urine collection) \>= 40 mL/minute (that is, if serum creatinine is \> 1.5 x ULN, a 24-hour urine collection to calculate creatinine clearance must be performed) documented within 28 calendar days prior to randomization * Patient urinary protein must be =\< 1+ on dipstick or routine urinalysis (UA); if urine dipstick or routine analysis is \>= 2+, a 24-hour urine collection for protein must demonstrate \< 1000 mg of protein in 24 hours); these tests must be documented within 28 calendar days prior to randomization * Patients must not have experienced any arterial thromboembolic events, including but not limited to myocardial infarction, transient ischemic attack, cerebrovascular accident, or unstable angina, within 6 months prior to randomization * Patients must not have a history of uncontrolled or poorly-controlled hypertension (defined as \> 160 mmHg systolic or \> 100 mmHg diastolic for \> 4 weeks) despite standard medical management * Patients must not be pregnant or nursing; women/men of reproductive potential must have agreed to use an effective contraceptive method (hormonal or barrier method of birth control; abstinence) prior to randomization, during the study participation and for 4 months after the last dose of protocol treatment; a woman is considered to be of reproductive potential if she has had menses at any time in the preceding 12 consecutive months; in addition to routine contraceptive methods, effective contraception also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation; however, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures * Patients must not have experienced hemoptysis (defined as bright red blood or \>= 1/2 teaspoon) within 2 months prior to randomization or with radiographic evidence of intratumor cavitation or has radiologically documented evidence of major blood vessel invasion or encasement by cancer * Patients must not have a prior history of gastrointestinal perforation/fistula (within 6 months of randomization) or risk factors for perforation * Patients must not have a serious or nonhealing wound, ulcer, or bone fracture within 28 calendar days prior to randomization * Patients must not be receiving chronic antiplatelet therapy, including aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs, including ibuprofen, naproxen, and others), dipyridamole or clopidogrel, or similar agents within 7 days prior to randomization; once-daily aspirin use (maximum dose 325 mg/day) is permitted * Patients must be offered the opportunity to participate in banking of specimens for future research * Patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines * As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival | up to 2 years after registration | Compare progression-free survival between patients with incurable unresectable locally advanced, or recurrent, or metastatic thymic carcinoma randomized to carboplatin-paclitaxel with or without ramucirumab. Progression-free survival is defined as: From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause. Progression is defined as: 20% increase in the sum of appropriate diameters of target measurable lesions over smallest sum observed, as well as an absolute increase of at least 0.5 cm. Unequivocal progression of non-measurable disease in the opinion of the treating physician (an explanation must be provided). Appearance of any new lesion/site. Death due to disease without prior documentation of progression and without symptomatic deterioration |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Frequency and Severity of Adverse Events | Up to 2 years post randomization | Only adverse events that are possibly, probably or definitely related to study drug are reported. |
| Response Rate | Up to 2 years after registration | To compare the response rate (complete response, partial response, confirmed and unconfirmed) between treatment arms in the subset of this patient population with measurable disease. Complete response - Complete disappearance of all target and non-target lesions (with the exception of lymph nodes mentioned below). No new lesions. No disease related symptoms. Any lymph nodes (whether target or non-target) must have reduction in short axis to \< 1.0 cm. Partial response - Applies only to patients with at least 1 measurable lesion. Greater than or equal to 30% decrease under baseline of the sum of appropriate diameters of all targets measurable lesions. No unequivocal progression of non-measurable disease. No new lesions. |
| Disease Control Rate | Up to 2 years after registration | To compare disease control rate (complete response, partial response, confirmed or unconfirmed, stable disease) between treatment arms in the subset of this patient population with measurable disease. |
| Overall Survival | Up to 2 years after registration | To compare overall survival between treatment arms. Overall survival is defined as time from date of registration to date of death due to any cause. Because of low accrual, and too few participant deaths, we do not plan to analyze or report with outcome. |
Countries
United States
Participant flow
Recruitment details
21 participant enrolled, 20 of which were eligible. 3 participants withdrew consent before treatment start.
Participants by arm
| Arm | Count |
|---|---|
| Experimental: Arm A (Ramucirumab, Carboplatin, Paclitaxel) Patients receive ramucirumab IV over 60 minutes, carboplatin IV, and paclitaxel IV on day 1. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients who have not progressed may continue to receive ramucirumab for up to 1 year. | 8 |
| Active Comparator: Arm B (Carboplatin, Paclitaxel) Patients receive carboplatin IV and paclitaxel IV on day 1. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. | 12 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 |
| Overall Study | Ineligible | 0 | 1 |
| Overall Study | Other not protocol specified | 1 | 0 |
| Overall Study | Progression | 4 | 2 |
| Overall Study | Withdrew consent before starting treatment | 0 | 3 |
Baseline characteristics
| Characteristic | Total | Experimental: Arm A (Ramucirumab, Carboplatin, Paclitaxel) | Active Comparator: Arm B (Carboplatin, Paclitaxel) |
|---|---|---|---|
| Adjuvant chemotherapy No | 18 Participants | 7 Participants | 11 Participants |
| Adjuvant chemotherapy Yes | 2 Participants | 1 Participants | 1 Participants |
| Age, Continuous | 66.8 Years | 68.2 Years | 65.7 Years |
| Hispanic No | 15 Participants | 5 Participants | 10 Participants |
| Hispanic Unknown | 1 Participants | 0 Participants | 1 Participants |
| Hispanic Yes | 4 Participants | 3 Participants | 1 Participants |
| Histologic subtype Lymphoepithelioma like | 1 Participants | 0 Participants | 1 Participants |
| Histologic subtype Squamous cell | 16 Participants | 6 Participants | 10 Participants |
| Histologic subtype Undifferentiated | 3 Participants | 2 Participants | 1 Participants |
| Neoadjuvant chemotherapy No | 19 Participants | 7 Participants | 12 Participants |
| Neoadjuvant chemotherapy Yes | 1 Participants | 1 Participants | 0 Participants |
| Palliative radiation therapy No | 19 Participants | 8 Participants | 11 Participants |
| Palliative radiation therapy Yes | 1 Participants | 0 Participants | 1 Participants |
| Pathologic cancer type Thymic carcinoma, not otherwise specified | 15 Participants | 5 Participants | 10 Participants |
| Pathologic cancer type Thymic epithelial malignancy | 3 Participants | 1 Participants | 2 Participants |
| Pathologic cancer type Unknown | 2 Participants | 2 Participants | 0 Participants |
| Performance Status 0 | 13 Participants | 5 Participants | 8 Participants |
| Performance Status 1 | 7 Participants | 3 Participants | 4 Participants |
| Race/Ethnicity, Customized Asian | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Black | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Unknown | 3 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 13 Participants | 6 Participants | 7 Participants |
| Sex: Female, Male Female | 5 Participants | 1 Participants | 4 Participants |
| Sex: Female, Male Male | 15 Participants | 7 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 8 | 2 / 9 |
| other Total, other adverse events | 8 / 8 | 9 / 9 |
| serious Total, serious adverse events | 3 / 8 | 0 / 9 |
Outcome results
Primary
Progression-free Survival
Compare progression-free survival between patients with incurable unresectable locally advanced, or recurrent, or metastatic thymic carcinoma randomized to carboplatin-paclitaxel with or without ramucirumab. Progression-free survival is defined as: From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause. Progression is defined as: 20% increase in the sum of appropriate diameters of target measurable lesions over smallest sum observed, as well as an absolute increase of at least 0.5 cm. Unequivocal progression of non-measurable disease in the opinion of the treating physician (an explanation must be provided). Appearance of any new lesion/site. Death due to disease without prior documentation of progression and without symptomatic deterioration
Time frame: up to 2 years after registration
Population: All eligible participants who received at least one cycle of treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Experimental: Arm A (Ramucirumab, Carboplatin, Paclitaxel) | Progression-free Survival | 8 Months |
| Active Comparator: Arm B (Carboplatin, Paclitaxel) | Progression-free Survival | 7 Months |
Secondary
Disease Control Rate
To compare disease control rate (complete response, partial response, confirmed or unconfirmed, stable disease) between treatment arms in the subset of this patient population with measurable disease.
Time frame: Up to 2 years after registration
Population: Participants with measurable disease and achieved a response. 2 participants in the active comparator arm had non-measurable disease. 6 participants in the active comparator arm had no response and 1 participants in the experimental arm had no response.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Experimental: Arm A (Ramucirumab, Carboplatin, Paclitaxel) | Disease Control Rate | 2.92 months |
| Active Comparator: Arm B (Carboplatin, Paclitaxel) | Disease Control Rate | 1.67 months |
Secondary
Frequency and Severity of Adverse Events
Only adverse events that are possibly, probably or definitely related to study drug are reported.
Time frame: Up to 2 years post randomization
Population: Participants who received any protocol treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Experimental: Arm A (Ramucirumab, Carboplatin, Paclitaxel) | Frequency and Severity of Adverse Events | Diarrhea | 1 Participants |
| Experimental: Arm A (Ramucirumab, Carboplatin, Paclitaxel) | Frequency and Severity of Adverse Events | Fatigue | 1 Participants |
| Experimental: Arm A (Ramucirumab, Carboplatin, Paclitaxel) | Frequency and Severity of Adverse Events | Anemia | 1 Participants |
| Experimental: Arm A (Ramucirumab, Carboplatin, Paclitaxel) | Frequency and Severity of Adverse Events | Lymphocyte count decreased | 1 Participants |
| Experimental: Arm A (Ramucirumab, Carboplatin, Paclitaxel) | Frequency and Severity of Adverse Events | Dyspnea | 1 Participants |
| Experimental: Arm A (Ramucirumab, Carboplatin, Paclitaxel) | Frequency and Severity of Adverse Events | Neutrophil count decreased | 0 Participants |
| Experimental: Arm A (Ramucirumab, Carboplatin, Paclitaxel) | Frequency and Severity of Adverse Events | Thromboembolic event | 0 Participants |
| Experimental: Arm A (Ramucirumab, Carboplatin, Paclitaxel) | Frequency and Severity of Adverse Events | Ejection fraction decreased | 1 Participants |
| Experimental: Arm A (Ramucirumab, Carboplatin, Paclitaxel) | Frequency and Severity of Adverse Events | White blood cell decreased | 1 Participants |
| Experimental: Arm A (Ramucirumab, Carboplatin, Paclitaxel) | Frequency and Severity of Adverse Events | Resp, thoracic and mediastinal disorders - Other | 1 Participants |
| Active Comparator: Arm B (Carboplatin, Paclitaxel) | Frequency and Severity of Adverse Events | White blood cell decreased | 1 Participants |
| Active Comparator: Arm B (Carboplatin, Paclitaxel) | Frequency and Severity of Adverse Events | Resp, thoracic and mediastinal disorders - Other | 0 Participants |
| Active Comparator: Arm B (Carboplatin, Paclitaxel) | Frequency and Severity of Adverse Events | Anemia | 0 Participants |
| Active Comparator: Arm B (Carboplatin, Paclitaxel) | Frequency and Severity of Adverse Events | Diarrhea | 0 Participants |
| Active Comparator: Arm B (Carboplatin, Paclitaxel) | Frequency and Severity of Adverse Events | Dyspnea | 0 Participants |
| Active Comparator: Arm B (Carboplatin, Paclitaxel) | Frequency and Severity of Adverse Events | Ejection fraction decreased | 0 Participants |
| Active Comparator: Arm B (Carboplatin, Paclitaxel) | Frequency and Severity of Adverse Events | Fatigue | 0 Participants |
| Active Comparator: Arm B (Carboplatin, Paclitaxel) | Frequency and Severity of Adverse Events | Lymphocyte count decreased | 0 Participants |
| Active Comparator: Arm B (Carboplatin, Paclitaxel) | Frequency and Severity of Adverse Events | Neutrophil count decreased | 1 Participants |
| Active Comparator: Arm B (Carboplatin, Paclitaxel) | Frequency and Severity of Adverse Events | Thromboembolic event | 1 Participants |
Secondary
Overall Survival
To compare overall survival between treatment arms. Overall survival is defined as time from date of registration to date of death due to any cause. Because of low accrual, and too few participant deaths, we do not plan to analyze or report with outcome.
Time frame: Up to 2 years after registration
Population: Only one death has been reported - so this outcome can not be completed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Experimental: Arm A (Ramucirumab, Carboplatin, Paclitaxel) | Overall Survival | NA months |
| Active Comparator: Arm B (Carboplatin, Paclitaxel) | Overall Survival | NA months |
Secondary
Response Rate
To compare the response rate (complete response, partial response, confirmed and unconfirmed) between treatment arms in the subset of this patient population with measurable disease. Complete response - Complete disappearance of all target and non-target lesions (with the exception of lymph nodes mentioned below). No new lesions. No disease related symptoms. Any lymph nodes (whether target or non-target) must have reduction in short axis to \< 1.0 cm. Partial response - Applies only to patients with at least 1 measurable lesion. Greater than or equal to 30% decrease under baseline of the sum of appropriate diameters of all targets measurable lesions. No unequivocal progression of non-measurable disease. No new lesions.
Time frame: Up to 2 years after registration
Population: Participants who had measurable disease. 2 participants in the active comparator arm did not have measurable disease.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Experimental: Arm A (Ramucirumab, Carboplatin, Paclitaxel) | Response Rate | Complete response | 0 Participants |
| Experimental: Arm A (Ramucirumab, Carboplatin, Paclitaxel) | Response Rate | Partial repsonse | 7 Participants |
| Experimental: Arm A (Ramucirumab, Carboplatin, Paclitaxel) | Response Rate | No response | 1 Participants |
| Active Comparator: Arm B (Carboplatin, Paclitaxel) | Response Rate | No response | 6 Participants |
| Active Comparator: Arm B (Carboplatin, Paclitaxel) | Response Rate | Complete response | 0 Participants |
| Active Comparator: Arm B (Carboplatin, Paclitaxel) | Response Rate | Partial repsonse | 4 Participants |