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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00957905
First received: August 12, 2009
Last updated: November 21, 2014
Last verified: October 2014
  Purpose

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.


Condition Intervention Phase
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
Drug: Alvocidib Hydrochloride
Drug: Oxaliplatin
Drug: Leucovorin Calcium
Drug: Fluorouracil
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 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 [ Time Frame: Within 3 courses of treatment ] [ Designated as safety issue: No ]
    Evaluable patients are those patients who are able to complete at least one cycle of therapy or have progressed any time during therapy.


Secondary Outcome Measures:
  • Toxicity, graded using the NCI CTCAE version 4.0 [ Time Frame: Up to 4 years ] [ Designated as safety issue: Yes ]
    Toxicities will be summarized by maximum grade per patient across all cycles, separately for each phase if applicable.

  • Time to tumor response [ Time Frame: From treatment start until first documented CR or PR, assessed up to 4 years ] [ Designated as safety issue: No ]
  • Progression-free survival [ Time Frame: From treatment start until first documented progression or death, assessed up to 4 years ] [ Designated as safety issue: No ]
    Summarized using the methods of Kaplan and Meier.


Estimated Enrollment: 50
Study Start Date: June 2009
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part A (alvocidib and oxaliplatin)
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.
Drug: Alvocidib Hydrochloride
Given IV
Other Names:
  • FLAVO
  • HL-275
  • HMR 1275
Drug: Oxaliplatin
Given IV
Experimental: 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.
Drug: Alvocidib Hydrochloride
Given IV
Other Names:
  • FLAVO
  • HL-275
  • HMR 1275
Drug: Oxaliplatin
Given IV
Drug: Leucovorin Calcium
Given IV
Other Name: CF
Drug: Fluorouracil
Given IV

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00957905

Locations
United States, California
Tower Cancer Research Foundation
Beverly Hills, California, United States, 90211-1850
City of Hope
Duarte, California, United States, 91010
City of Hope Medical Center
Duarte, California, United States, 91010
University of Southern California/Norris Cancer Center
Los Angeles, California, United States, 90033
University of California at Davis Cancer Center
Sacramento, California, United States, 95817
United States, Illinois
University of Chicago
Chicago, Illinois, United States, 60637
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
United States, Pennsylvania
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15232
University of Pittsburgh Medical Center-Presbyterian Hospital
Pittsburgh, Pennsylvania, United States, 15213
United States, Wisconsin
University of Wisconsin Cancer Center Riverview
Wisconsin Rapids, Wisconsin, United States, 54494
Sponsors and Collaborators
Investigators
Principal Investigator: Darren Feldman Memorial Sloan-Kettering Cancer Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00957905     History of Changes
Other Study ID Numbers: NCI-2011-01405, NCI-2011-01405, MSKCC-09034, CDR0000646950, 09-034, 8258, U01CA062505, U01CA069856, U01CA062491, U01CA069912, P30CA008748, N01CM00071, U01CA099168
Study First Received: August 12, 2009
Last Updated: November 21, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Germinoma
Neoplasms
Neoplasms, Germ Cell and Embryonal
Ovarian Neoplasms
Seminoma
Testicular Neoplasms
Adnexal Diseases
Endocrine Gland Neoplasms
Endocrine System Diseases
Genital Diseases, Female
Genital Diseases, Male
Genital Neoplasms, Female
Genital Neoplasms, Male
Gonadal Disorders
Neoplasms by Histologic Type
Neoplasms by Site
Ovarian Diseases
Testicular Diseases
Urogenital Neoplasms
Alvocidib
Fluorouracil
Leucovorin
Levoleucovorin
Oxaliplatin
Antidotes
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Growth Inhibitors

ClinicalTrials.gov processed this record on November 24, 2014