Alvocidib and Oxaliplatin With or Without Fluorouracil and Leucovorin Calcium in Treating Patients With Relapsed or Refractory Germ Cell Tumors
Condition: Recurrent Extragonadal Seminoma; Recurrent Malignant Extragonadal Germ Cell Tumor; Recurrent Malignant Extragonadal Non-Seminomatous Germ Cell Tumor; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Ovarian Germ Cell Tumor; Stage III Testicular Cancer; Stage IV Extragonadal Non-Seminomatous Germ Cell Tumor; Stage IV Extragonadal Seminoma; Stage IV Ovarian Germ Cell Tumor
MeSH terms: Neoplasms; Neoplasms, Germ Cell and Embryonal; Germinoma; Ovarian Neoplasms; Testicular Neoplasms; Seminoma; Recurrence
Intervention: Alvocidib Hydrochloride; Fluorouracil; Leucovorin Calcium; Oxaliplatin
Intervention description: Given IV; Given IV; Given IV; Given IV
Intervention MeSH terms: Calcium, Dietary; Leucovorin; Folic Acid; Fluorouracil; Oxaliplatin; Alvocidib; Calcium; Levoleucovorin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 36.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial is studying alvocidib and oxaliplatin to see how well they work when
      given with or without fluorouracil and leucovorin calcium in treating patients with relapsed
      or refractory germ cell tumors. Drugs used in chemotherapy, such as alvocidib, oxaliplatin,
      fluorouracil, and leucovorin calcium, work in different ways to stop the growth of tumor
      cells, either by killing the cells or by stopping them from dividing. Giving alvocidib
      together with oxaliplatin with or without fluorouracil and leucovorin calcium may kill more
      tumor cells.
    

Eligibility criteria:

        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