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

NCT00957905 | Completed Phase 2 Results

• 13 other identifiers: NCI-2011-01405MSKCC-09034CDR000064695009-0348258N01CM00071N01CM62206P30CA008748U01CA062491U01CA062505U01CA069856U01CA069912U01CA099168
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 10

Brief 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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate

  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

  Within 3 courses of treatment

Other Outcomes (3)

• Toxicity

  Up to 4 years

• Progression-free Survival

  From treatment start until first documented progression or death, assessed up to 4 years

• Time to Tumor Response

  From treatment start until first documented CR or PR, assessed up to 4 years

Study Arms (2)

Part A (alvocidib and oxaliplatin)

EXPERIMENTAL

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; Drug: Oxaliplatin

Part B (alvocidib and FOLFOX)

EXPERIMENTAL

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; Drug: Fluorouracil; Drug: Leucovorin Calcium; Drug: Oxaliplatin

Interventions

Alvocidib Hydrochloride DRUG

Given IV

Also known as: 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

Part A (alvocidib and oxaliplatin); Part B (alvocidib and FOLFOX)

Fluorouracil DRUG

Given IV

Also known as: 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

Part B (alvocidib and FOLFOX)

Leucovorin Calcium DRUG

Given IV

Also known as: 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

Part B (alvocidib and FOLFOX)

Oxaliplatin DRUG

Given IV

Also known as: 1-OHP, Dacotin, Dacplat, Diaminocyclohexane Oxalatoplatinum, Eloxatin, Eloxatine, JM-83, Oxalatoplatin, Oxalatoplatinum, RP 54780, RP-54780, SR-96669

Part A (alvocidib and oxaliplatin); Part B (alvocidib and FOLFOX)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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%

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (10)

Tower Cancer Research Foundation

Beverly Hills, California, 90211-1850, United States

Location

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

UPMC-Presbyterian Hospital

Pittsburgh, Pennsylvania, 15213, United States

Location

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, 15232, United States

Location

Riverview Hospital

Wisconsin Rapids, Wisconsin, 54494, United States

Location

MeSH Terms

Conditions

Testicular Neoplasms

Interventions

cytokine inducible SH2-containing protein; alvocidib; Fluorouracil; dehydroftorafur; Leucovorin; Oxaliplatin

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Male Urogenital Diseases; Endocrine System Diseases; Testicular Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Coordination Complexes; Organic Chemicals

Results Point of Contact

• Title: Dr. Darren Feldman
• Organization: Memorial Sloan Kettering Cancer Center

feldmand@mskcc.org

646-422-4491

Study Officials

• Darren Feldman

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 12, 2009
• First Posted: August 13, 2009
• Study Start: June 1, 2009
• Primary Completion: August 1, 2014
• Study Completion: August 1, 2014
• Last Updated: March 10, 2017
• Results First Posted: March 10, 2017

Record last verified: 2017-01

Locations

US (10)