Alvocidib and Oxaliplatin With or Without Fluorouracil and Leucovorin Calcium in Treating Patients With Relapsed or Refractory Germ Cell Tumors
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ClinicalTrials.gov Identifier: NCT00957905 |
Recruitment Status :
Completed
First Posted : August 13, 2009
Results First Posted : March 10, 2017
Last Update Posted : March 10, 2017
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Condition or disease | Intervention/treatment | Phase |
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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: Fluorouracil Drug: Leucovorin Calcium Drug: Oxaliplatin | Phase 2 |
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.
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 36 participants |
Allocation: | Non-Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (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 |
Study Start Date : | June 2009 |
Actual Primary Completion Date : | August 2014 |
Actual Study Completion Date : | August 2014 |

Arm | Intervention/treatment |
---|---|
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.
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Drug: Alvocidib Hydrochloride
Given IV
Other Names:
Drug: Oxaliplatin Given IV
Other Names:
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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.
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Drug: Alvocidib Hydrochloride
Given IV
Other Names:
Drug: Fluorouracil Given IV
Other Names:
Drug: Leucovorin Calcium Given IV
Other Names:
Drug: Oxaliplatin Given IV
Other Names:
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- Objective Response Rate [ Time Frame: Within 3 courses of treatment ]Number of Participants with Partial Response (PR), Stable Disease (SD), Progression of Disease (POD) Per Response Evaluation Criteria In Solid Tumors Criteria" (RECIST v1.0) for target lesions and assessed by MRI and/or CT: Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for a Partial Response nor sufficient increase to qualify for Progression of Disease (POD); POD, 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
- Toxicity [ Time Frame: Up to 4 years ]graded using the NCI CTCAE version 4.0.See adverse event section
- Progression-free Survival [ Time Frame: From treatment start until first documented progression or death, assessed up to 4 years ]
- Time to Tumor Response [ Time Frame: From treatment start until first documented CR or PR, assessed up to 4 years ]

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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
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Histologically confirmed germ cell tumor (GCT)
- Seminoma or non-seminoma
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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
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Measurable or evaluable disease, as defined by 1 of the following criteria:
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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
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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
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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
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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
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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
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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

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00957905
United States, California | |
Tower Cancer Research Foundation | |
Beverly Hills, California, United States, 90211-1850 | |
City of Hope Comprehensive Cancer Center | |
Duarte, California, United States, 91010 | |
USC / Norris Comprehensive Cancer Center | |
Los Angeles, California, United States, 90033 | |
University of California Davis Comprehensive Cancer Center | |
Sacramento, California, United States, 95817 | |
United States, Illinois | |
University of Chicago Comprehensive Cancer Center | |
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 | |
UPMC-Presbyterian Hospital | |
Pittsburgh, Pennsylvania, United States, 15213 | |
University of Pittsburgh Cancer Institute (UPCI) | |
Pittsburgh, Pennsylvania, United States, 15232 | |
United States, Wisconsin | |
Riverview Hospital | |
Wisconsin Rapids, Wisconsin, United States, 54494 |
Principal Investigator: | Darren Feldman | Memorial Sloan Kettering Cancer Center |
Responsible Party: | National Cancer Institute (NCI) |
ClinicalTrials.gov Identifier: | NCT00957905 |
Other Study ID Numbers: |
NCI-2011-01405 NCI-2011-01405 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) MSKCC-09034 CDR0000646950 09-034 ( Other Identifier: Memorial Sloan-Kettering Cancer Center ) 8258 ( Other Identifier: CTEP ) N01CM00071 ( U.S. NIH Grant/Contract ) N01CM62206 ( U.S. NIH Grant/Contract ) P30CA008748 ( U.S. NIH Grant/Contract ) U01CA062491 ( U.S. NIH Grant/Contract ) U01CA062505 ( U.S. NIH Grant/Contract ) U01CA069856 ( U.S. NIH Grant/Contract ) U01CA069912 ( U.S. NIH Grant/Contract ) U01CA099168 ( U.S. NIH Grant/Contract ) |
First Posted: | August 13, 2009 Key Record Dates |
Results First Posted: | March 10, 2017 |
Last Update Posted: | March 10, 2017 |
Last Verified: | January 2017 |
Neoplasms Neoplasms, Germ Cell and Embryonal Germinoma Ovarian Neoplasms Testicular Neoplasms Seminoma Neoplasms by Histologic Type Endocrine Gland Neoplasms Neoplasms by Site Ovarian Diseases Adnexal Diseases Genital Neoplasms, Female Urogenital Neoplasms Endocrine System Diseases Gonadal Disorders |
Genital Neoplasms, Male Testicular Diseases Calcium, Dietary Leucovorin Folic Acid Fluorouracil Oxaliplatin Alvocidib Calcium Levoleucovorin Calcium-Regulating Hormones and Agents Physiological Effects of Drugs Bone Density Conservation Agents Antimetabolites Molecular Mechanisms of Pharmacological Action |