Alvocidib and Oxaliplatin With or Without Fluorouracil and Leucovorin Calcium in Treating Patients With Relapsed or Refractory Germ Cell Tumors

PRIMARY OBJECTIVES:

I. To evaluate the antitumor efficacy of alvocidib and oxaliplatin with or without
fluorouracil and leucovorin calcium in patients with relapsed or refractory germ cell
tumors.

SECONDARY OBJECTIVES:

I. To further evaluate the safety of these regimens in these patients. II. To evaluate the
time to tumor response and progression-free survival of patients treated with these
regimens.

III. To explore the association between treatment response and p21, p53, and apoptotic
markers.

OUTLINE: Patients are initially enrolled in part A (closed to accrual as of 11/15/2010).
Depending on response to treatment, additional patients may be enrolled in part B.

PART A (alvocidib and oxaliplatin) (closed to accrual as of 11/15/2010): Patients receive
alvocidib IV over 1 hour and oxaliplatin IV over 2 hours on days 1, 15, and 29. Courses
repeat every 42 days in the absence of disease progression or unacceptable toxicity.

PART B (alvocidib and FOLFOX): Patients receive alvocidib IV over 1 hour, oxaliplatin IV
over 2 hours, and leucovorin calcium IV over 2 hours followed by fluorouracil IV
continuously over 48 hours on days 1, 15, and 29. Courses repeat every 42 days in the
absence of disease progression or unacceptable toxicity. Tumor tissue samples may be
collected periodically for further laboratory analysis.

After completion of study treatment, patients are followed up every 4-8 weeks.

Inclusion Criteria:

- Histologically confirmed germ cell tumor (GCT)

- Seminoma or non-seminoma

- Progressive disease after prior cisplatin-based therapy AND meets 1 of the following
criteria:

- Not considered to be a candidate for potentially curative therapy

- Previously treated with high-dose chemotherapy regimens

- Does not wish to undergo potentially curative high-dose therapy

- Measurable or evaluable disease, as defined by 1 of the following criteria:

- Unidimensionally measurable metastatic disease, defined as ≥ 1 malignant tumor
mass that can be accurately measured in ≥ 1 dimension as ≥ 20 mm by conventional
CT scan or MRI or as ≥ 10 mm by spiral CT scan

- Bone lesions, ascites, peritoneal carcinomatosis, miliary lesions, pleural
or pericardial effusions, lymphangitis of the skin or lung, cystic lesions,
or irradiated lesions are not considered measurable disease

- Patients with measurable disease only (i.e., normal tumor markers) must
have ≥ 1 site of disease that has not been previously irradiated

- Elevation of alpha-fetoprotein > 15 ng/mL and/or elevation of beta-human
chorionic gonadotropin > 2.2 mIU/L

- If tumor markers are not elevated, ≥ 1 site of measurable disease must be
present

- No known untreated CNS metastasis or primary CNS tumor

- Patients who have undergone local treatment for brain metastases and whose brain
metastases are demonstrated to be stable by repeat imaging studies performed ≥ 4
weeks after treatment are eligible

- Karnofsky performance status 70-100%

- ANC ≥ 1,000/mm^3

- Platelet count ≥ 100,000/mm^3

- Hemoglobin ≥ 8.0 g/dL

- Serum creatinine ≤ 2.0 times upper limit of normal (ULN)

- Total serum bilirubin ≤ 1.5 times ULN

- AST and ALT ≤ 2.5 times ULN (unless elevation is due to underlying malignancy)

- Not pregnant or nursing

- Negative pregnancy test by ultrasound

- Fertile patients must use effective contraception

- Willing and able to comply with scheduled study visits, treatment plans, laboratory
tests, follow-up tests for safety or effectiveness, and other study procedures

- Mediport or Broviac access required for patients enrolled in part B of the study

- No serious active infections

- No significant (≥ grade 2) or persistent ongoing toxicity, including peripheral
neuropathy, from prior therapy

- None of the following within the past 6 months:

- Myocardial infarction

- Severe/unstable angina

- Coronary/peripheral artery bypass graft

- Symptomatic congestive heart failure

- Cerebrovascular accident or transient ischemic attack

- Pulmonary embolism

- No contraindication to any of the study drugs

- No other severe acute or chronic medical or psychiatric condition or laboratory
abnormality that may increase the risk associated with study participation or study
drug administration, interfere with the interpretation of study results, and, in the
judgement of the investigator, may make the patient inappropriate for study entry

- No concurrent anti-retroviral therapy for HIV-positive patients

- Recovered from prior radiotherapy or surgery

- Residual grade 1 toxicities allowed

- No prior alvocidib

- At least 2 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C),
immunotherapy, or radiotherapy

- More than 4 weeks since prior major surgery

- No other concurrent approved or investigational anticancer treatment, including
surgery, radiotherapy, chemotherapy, biologic-response modifiers, hormone therapy, or
immunotherapy

- No concurrent participation in another investigational treatment clinical trial

- Concurrent participation in supportive care trials or non-treatment trials
(e.g., quality of life or laboratory analysis studies) allowed

- No concurrent vitamins, antioxidants, herbal preparations, or supplements, except for
a single-tablet multivitamin