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

NCT ID: NCT00957905

Last Updated: 2017-03-10

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

36 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-06-30

Study Completion Date

2014-08-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

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

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

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.

Group Type EXPERIMENTAL

Alvocidib Hydrochloride

Intervention Type DRUG

Given IV

Oxaliplatin

Intervention Type DRUG

Given IV

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.

Group Type EXPERIMENTAL

Alvocidib Hydrochloride

Intervention Type DRUG

Given IV

Fluorouracil

Intervention Type DRUG

Given IV

Leucovorin Calcium

Intervention Type DRUG

Given IV

Oxaliplatin

Intervention Type DRUG

Given IV

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Alvocidib Hydrochloride

Given IV

Intervention Type DRUG

Fluorouracil

Given IV

Intervention Type DRUG

Leucovorin Calcium

Given IV

Intervention Type DRUG

Oxaliplatin

Given IV

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

4H-1-Benzopyran-4-one, 2-(2-chlorophenyl)-5, 7-dihydroxy-8-(3-hydroxy-1-methyl-4-piperidinyl)-, hydrochloride, (-)-cis- Flavopiridol Hydrochloride HL-275 HMR 1275 L-86-8275 L-868275 MDL 107,826A MDL-107826A 5-Fluoro-2,4(1H, 3H)-pyrimidinedione 5-Fluorouracil 5-Fluracil 5-FU AccuSite Actino-Hermal Adrucil Arumel Cytosafe Efudex Efurix Fiverocil Fluoro Uracil Fluoroplex Fluouracil Flurablastin Fluracedyl Fluracil Fluril Fluroblastin Flurox Ribofluor Ro 2-9757 Ro-2-9757 Timazin Adinepar Calcifolin Calcium (6S)-Folinate Calcium Folinate Calcium Leucovorin Calfolex Calinat Cehafolin Citofolin Citrec Citrovorum Factor Cromatonbic Folinico Dalisol Disintox Divical Ecofol Emovis Factor, Citrovorum Flynoken A Folaren Folaxin FOLI-cell Foliben Folidan Folidar Folinac Folinate Calcium folinic acid Folinic Acid Calcium Salt Pentahydrate Folinoral Folinvit Foliplus Folix Imo Lederfolat Lederfolin Leucosar leucovorin Rescufolin Rescuvolin Tonofolin Wellcovorin 1-OHP Dacotin Dacplat Diaminocyclohexane Oxalatoplatinum Eloxatin Eloxatine JM-83 Oxalatoplatin Oxalatoplatinum RP 54780 RP-54780 SR-96669

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

National Cancer Institute (NCI)

NIH

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Darren Feldman

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Tower Cancer Research Foundation

Beverly Hills, California, United States

Site Status

City of Hope Comprehensive Cancer Center

Duarte, California, United States

Site Status

USC / Norris Comprehensive Cancer Center

Los Angeles, California, United States

Site Status

University of California Davis Comprehensive Cancer Center

Sacramento, California, United States

Site Status

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Site Status

UPMC-Presbyterian Hospital

Pittsburgh, Pennsylvania, United States

Site Status

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, United States

Site Status

Riverview Hospital

Wisconsin Rapids, Wisconsin, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

NCI-2011-01405

Identifier Type: REGISTRY

Identifier Source: secondary_id

MSKCC-09034

Identifier Type: -

Identifier Source: secondary_id

CDR0000646950

Identifier Type: -

Identifier Source: secondary_id

09-034

Identifier Type: OTHER

Identifier Source: secondary_id

8258

Identifier Type: OTHER

Identifier Source: secondary_id

N01CM00071

Identifier Type: NIH

Identifier Source: secondary_id

View Link

N01CM62206

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P30CA008748

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01CA062491

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01CA062505

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01CA069856

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01CA069912

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01CA099168

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2011-01405

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.