Carboplatin and Paclitaxel With or Without Ramucirumab in Treating Patients With Locally Advanced, Recurrent, or Metastatic Thymic Cancer That Cannot Be Removed by Surgery

PRIMARY OBJECTIVES:

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.

TERTIARY OBJECTIVES:

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 courses 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 courses 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.

Inclusion Criteria:

- Patients must have histologically or cytologically confirmed 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