A Randomized Phase II trial of Carboplatin-Paclitaxel with or without Ramucirumab in Patients with Unresectable Locally Advanced, Recurrent, or Metastatic Thymic Carcinoma

Patients must:

be >/= 18 years of age;
have histologically or cytologically confirmed thymic carcinoma;
have unresectable thymic carcinoma that is either locally advanced, recurrent, or metastatic ("thymic carcinoma" includes "thymic epithelial malignancy, consistent with thymic carcinoma", "WHO Type C thymic epithelial tumor", and "thymic epithelial malignancy" with radiographic imaging consistent with thymic carcinoma");
not be candidates for localized surgery;
have measurable disease (see Section 10.1) documented by CT or MRI within 28 calendar days prior to randomization. The CT from a combined PET/CT may be used only if it is of diagnostic quality as defined in Section 10.1a. 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 (RECIST 1.1);
have a Zubrod performance status of 0 to 2 (See Section 10.4);
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;
not have elective or planned major surgery to be performed during the course of the clinical trial;
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);
have a CT or MRI scan of the brain to evaluate for CNS disease within 42 calendar days prior to registration;
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;
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;
have adequate hematologic function, as evidenced by an absolute neutrophil count (ANC) >/= 1500/mcL, hemoglobin >/= 9 g/dL (5.58 mmol/L), and platelets >/= 100,000/mcL documented within 28 calendar days prior to randomization;
have adequate coagulation function as defined by International Normalized Ratio (INR) </= 1.5, and a 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;
be switched to low molecular weight heparin and have achieved stable coagulation profile 14 days prior to randomization (for patients receiving warfarin);
not have experienced any Grade 3 or above GI bleeding within 84 calendar days prior to randomization;
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;
have adequate hepatic function as defined by a total bilirubin </= 1.5 x the institutional upper limit normal (IULN), and aspartate transaminase (AST) and alanine transaminase (ALT) </= 3.0 x IULN. For patients with liver metastases, total bilirubin and AST or ALT must be </= 5.0 x IULN These tests must be documented within 28 calendar days prior to randomization;
not have cirrhosis at a level of Child-Pugh B (or worse) (See Appendix 18.1);
not have cirrhosis (any degree) and a history of hepatic encephalopathy;
not have clinically meaningful ascites resulting from cirrhosis. Clinically meaningful ascites is defined as ascites from cirrhosis requiring diuretics or paracentesis;
adequate renal function as defined by a 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 IULN, a 24-hour urine collection to calculate creatinine clearance must be performed) documented within 28 calendar days prior to randomization;
Have urinary protein </= 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;
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;
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;
not be pregnant or nursing due to the risk of harming fetus or infant. 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;
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;
not have a prior history of gastrointestinal perforation/fistula (within 6 months of randomization) or risk factors for perforation;
not have a serious or nonhealing wound, ulcer, or bone fracture within 28 calendar days prior to randomization;
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;
be offered the opportunity to participate in banking of specimens for future research as described in Section 15.1.