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A Non-Randomized Phase 2 Study of Alvocidib (Flavopiridol) Plus Oxaliplatin With or Without 5-FU and Leucovorin for Relapsed or Refractory Germ-Cell Tumors


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Recurrent Extragonadal Germ Cell Tumor, Recurrent Extragonadal Non-seminomatous Germ Cell Tumor, Recurrent Extragonadal Seminoma, Recurrent Malignant Testicular Germ Cell Tumor, Recurrent Ovarian Germ Cell Tumor, Stage III Malignant Testicular Germ Cell Tumor, Stage IV Extragonadal Non-seminomatous Germ Cell Tumor, Stage IV Extragonadal Seminoma, Stage IV Ovarian Germ Cell Tumor

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Trial Information

A Non-Randomized Phase 2 Study of Alvocidib (Flavopiridol) Plus Oxaliplatin With or Without 5-FU and Leucovorin for Relapsed or Refractory Germ-Cell Tumors


PRIMARY OBJECTIVES:

I. To evaluate the antitumor efficacy of the combination of flavopiridol and oxaliplatin
with or without 5-FU and leucovorin in patients with relapsed or refractory GCT. The
necessity of 5-FU and leucovorin to the combination will also be indirectly tested in this
study.

SECONDARY OBJECTIVES:

I. To further evaluate the safety of flavopiridol in combination with oxaliplatin with or
without 5-fluorouracil and leucovorin in patients with refractory or relapsed GCT.

II. To evaluate the time to tumor response (TTR) and progression-free survival for patients
with refractory or relapsed GCT treated with flavopiridol in combination with oxaliplatin
with or without 5-fluorouracil and leucovorin.

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

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Objective response rate defined as the ratio of the number of patients who achieve a CR or PR divided by the number of evaluable patients, as assessed by RECIST criteria

Outcome Description:

Evaluable patients are those patients who are able to complete at least one cycle of therapy or have progressed any time during therapy.

Outcome Time Frame:

Within 3 courses of treatment

Safety Issue:

No

Principal Investigator

Darren Feldman

Investigator Role:

Principal Investigator

Investigator Affiliation:

Memorial Sloan-Kettering Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2011-01405

NCT ID:

NCT00957905

Start Date:

June 2009

Completion Date:

Related Keywords:

  • Recurrent Extragonadal Germ Cell Tumor
  • Recurrent Extragonadal Non-seminomatous Germ Cell Tumor
  • Recurrent Extragonadal Seminoma
  • Recurrent Malignant Testicular Germ Cell Tumor
  • Recurrent Ovarian Germ Cell Tumor
  • Stage III Malignant Testicular Germ Cell Tumor
  • Stage IV Extragonadal Non-seminomatous Germ Cell Tumor
  • Stage IV Extragonadal Seminoma
  • Stage IV Ovarian Germ Cell Tumor
  • Seminoma
  • Testicular Neoplasms
  • Neoplasms, Germ Cell and Embryonal
  • Germinoma
  • Ovarian Neoplasms

Name

Location

Memorial Sloan Kettering Cancer CenterNew York, New York  10021
Mayo ClinicRochester, Minnesota  55905
City of Hope Medical CenterDuarte, California  91010
University of PittsburghPittsburgh, Pennsylvania  15261
Tower Cancer Research FoundationBeverly Hills, California  90211
UC Davis Comprehensive Cancer CenterSacramento, California  95817
University of Chicago Comprehensive Cancer CenterChicago, Illinois  60637-1470
University of Southern CaliforniaLos Angeles, California  90033
University of Wisconsin Cancer Center RiverviewWisconsin Rapids, Wisconsin  54494