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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
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Tracking Information
First Submitted Date  ICMJE August 12, 2009
First Posted Date  ICMJE August 13, 2009
Results First Submitted Date  ICMJE March 9, 2016
Results First Posted Date  ICMJE March 10, 2017
Last Update Posted Date March 10, 2017
Study Start Date  ICMJE June 2009
Actual Primary Completion Date August 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 20, 2017)		 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
Original Primary Outcome Measures  ICMJE
 (submitted: August 12, 2009)		 Objective response rate as assessed RECIST criteria
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: August 12, 2009)
  • Toxicity
  • Time to tumor response
  • Progression-free survival
Current Other Pre-specified Outcome Measures
 (submitted: January 20, 2017)
  • 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 ]
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Alvocidib and Oxaliplatin With or Without Fluorouracil and Leucovorin Calcium in Treating Patients With Relapsed or Refractory Germ Cell Tumors
Official Title  ICMJE 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
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.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • 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
Intervention  ICMJE
  • Drug: Alvocidib Hydrochloride
    Given IV
    Other Names:
    • 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
  • Drug: Fluorouracil
    Given IV
    Other Names:
    • 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
  • Drug: Leucovorin Calcium
    Given IV
    Other Names:
    • 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
  • Drug: Oxaliplatin
    Given IV
    Other Names:
    • 1-OHP
    • Dacotin
    • Dacplat
    • Diaminocyclohexane Oxalatoplatinum
    • Eloxatin
    • Eloxatine
    • JM-83
    • Oxalatoplatin
    • Oxalatoplatinum
    • RP 54780
    • RP-54780
    • SR-96669
Study Arms  ICMJE
  • 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.
    Interventions:
    • Drug: Alvocidib Hydrochloride
    • Drug: Oxaliplatin
  • 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.
    Interventions:
    • Drug: Alvocidib Hydrochloride
    • Drug: Fluorouracil
    • Drug: Leucovorin Calcium
    • Drug: Oxaliplatin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 20, 2017)		 36
Original Estimated Enrollment  ICMJE
 (submitted: August 12, 2009)		 50
Actual Study Completion Date  ICMJE August 2014
Actual Primary Completion Date August 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00957905
Other Study ID Numbers  ICMJE 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 )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Cancer Institute (NCI)
Study Sponsor  ICMJE National Cancer Institute (NCI)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Darren Feldman Memorial Sloan Kettering Cancer Center
PRS Account National Cancer Institute (NCI)
Verification Date January 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP