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

Recurrent Ovarian Germ Cell Tumor Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00957905
• Other study ID #: NCI-2011-01405
• Secondary ID: NCI-2011-01405MS
• Status: Completed
• Phase: Phase 2
• First received: August 12, 2009
• Last updated: May 11, 2015
• Start date: June 2009
• Est. completion date: August 2014

Study information

• Verified date: April 2015
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 37
• Est. completion date: August 2014
• Est. primary completion date: August 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Germinoma
• Neoplasms
• Neoplasms, Germ Cell and Embryonal
• Ovarian Neoplasms
• 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
• Seminoma
• Stage III Testicular Cancer
• Stage IV Extragonadal Non-Seminomatous Germ Cell Tumor
• Stage IV Extragonadal Seminoma
• Stage IV Ovarian Germ Cell Tumor
• Testicular Neoplasms

Intervention

Drug:
• Alvocidib Hydrochloride
Given IV
• Fluorouracil
Given IV
• Leucovorin Calcium
Given IV
• Oxaliplatin
Given IV

Locations

Country	Name	City	State
United States	Tower Cancer Research Foundation	Beverly Hills	California
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	USC / Norris Comprehensive Cancer Center	Los Angeles	California
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	University of Pittsburgh Cancer Institute (UPCI)	Pittsburgh	Pennsylvania
United States	UPMC-Presbyterian Hospital	Pittsburgh	Pennsylvania
United States	Mayo Clinic	Rochester	Minnesota
United States	University of California Davis Comprehensive Cancer Center	Sacramento	California
United States	Riverview Hospital	Wisconsin Rapids	Wisconsin

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Evaluable patients are those patients who are able to complete at least one cycle of therapy or have progressed any time during therapy.	Within 3 courses of treatment	No
Secondary	Progression-free survival	Summarized using the methods of Kaplan and Meier.	From treatment start until first documented progression or death, assessed up to 4 years	No
Secondary	Time to tumor response		From treatment start until first documented CR or PR, assessed up to 4 years	No
Secondary	Toxicity, graded using the NCI CTCAE version 4.0	Toxicities will be summarized by maximum grade per patient across all cycles, separately for each phase if applicable.	Up to 4 years	Yes