Recurrent Extragonadal SeminomaPhase 2NCT00957905
Alvocidib and Oxaliplatin With or Without Fluorouracil and Leucovorin Calcium in Treating Patients With Relapsed or Refractory Germ Cell Tumors
A Phase 2 study testing Alvocidib Hydrochloride, Fluorouracil and Leucovorin Calcium in people with Recurrent Extragonadal Seminoma and Recurrent Malignant Extragonadal Germ Cell Tumor, run by National Cancer Institute (NCI) at 10 sites in United States.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Recurrent Extragonadal Seminoma, Recurrent Malignant Extragonadal Germ Cell Tumor, Recurrent Malignant Extragonadal Non-Seminomatous Germ Cell Tumor
- What is being tested?
- Alvocidib Hydrochloride, Fluorouracil and Leucovorin Calcium
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 10 sitesUnited States
- Study dates
- Jun 2009to Aug 2014
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 47Show fewer
- 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
Who cannot join
None listed.
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
United States10 sites
Tower Cancer Research Foundation
Beverly Hills, California, 90211-1850
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637
City of Hope Comprehensive Cancer Center
Duarte, California, 91010
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065
UPMC-Presbyterian Hospital
Pittsburgh, Pennsylvania, 15213
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232
Mayo Clinic
Rochester, Minnesota, 55905
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817
Riverview Hospital
Wisconsin Rapids, Wisconsin, 54494
About this study
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
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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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
- 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
- Being tested
- Alvocidib Hydrochloride, Fluorouracil, Leucovorin Calcium, Oxaliplatin
- Medical subject headings
- Testicular Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Alvocidib HydrochlorideDrug
Also called 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
Given IV
FluorouracilDrug
Also called 5-Fluoro-2,4(1H, 3H)-pyrimidinedione, 5-Fluorouracil, 5-Fluracil, 5-FU
Given IV
Also called Adinepar, Calcifolin, Calcium (6S)-Folinate, Calcium Folinate
Given IV
OxaliplatinDrug
Also called 1-OHP, Dacotin, Dacplat, Diaminocyclohexane Oxalatoplatinum
Given IV
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Alvocidib Hydrochloride; Drug: Fluorouracil; Drug: Leucovorin Calcium; Drug: Oxaliplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Within 3 courses of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Aug 2009 (estimated)
- Study startJun 2009
- Primary completionAug 2014
- Study completionAug 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Recurrent Extragonadal SeminomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Darren Feldman, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00957905
- Sponsor's protocol ID
- NCI-2011-01405
- Other IDs
- NCI-2011-01405, MSKCC-09034, CDR0000646950, 09-034, 8258, N01CM00071, N01CM62206, P30CA008748
- Status last verified
- Jan 2017
- First submitted
- 12 Aug 2009
- Last updated
- 10 Mar 2017
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 10 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00957905
- Acronym / sponsor ID
- NCI-2011-01405
- 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
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Jun 2009
- Primary completion
- Aug 2014 (actual)
- Study completion
- Aug 2014 (actual)
- First posted
- 13 Aug 2009 (estimated)
- Results
- Posted 10 Mar 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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:
- 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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Part A (alvocidib and oxaliplatin) | Experimental | Drug: Alvocidib Hydrochloride, Drug: OxaliplatinPatients 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) | Experimental | Drug: Alvocidib Hydrochloride, Drug: Fluorouracil, Drug: Leucovorin Calcium, Drug: OxaliplatinPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (47 listed)
- Histologically confirmed germ cell tumor (GCT)
- Progressive disease after prior cisplatin-based therapy AND meets 1 of the following criteria:
- Measurable or evaluable disease, as defined by 1 of the following criteria:
- No known untreated CNS metastasis or primary CNS tumor
- Karnofsky performance status 70-100%
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Alvocidib HydrochlorideAlso: 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 1275Given IV | Drug | Part A (alvocidib and oxaliplatin), Part B (alvocidib and FOLFOX) |
| FluorouracilAlso: 5-Fluoro-2,4(1H, 3H)-pyrimidinedione, 5-Fluorouracil, 5-Fluracil, 5-FUGiven IV | Drug | Part B (alvocidib and FOLFOX) |
| Leucovorin CalciumAlso: Adinepar, Calcifolin, Calcium (6S)-Folinate, Calcium FolinateGiven IV | Drug | Part B (alvocidib and FOLFOX) |
| OxaliplatinAlso: 1-OHP, Dacotin, Dacplat, Diaminocyclohexane OxalatoplatinumGiven IV | Drug | Part A (alvocidib and oxaliplatin), Part B (alvocidib and FOLFOX) |
Primary outcome
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Mar 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Darren Feldman principal investigator
Memorial Sloan Kettering Cancer Center
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Alvocidib Hydrochloride, Fluorouracil and Leucovorin Calcium in people with Recurrent Extragonadal Seminoma and Recurrent Malignant Extragonadal Germ Cell Tumor, run by National Cancer Institute (NCI) at 10 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 47 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Mar 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (time frame: Within 3 courses of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Mar 2017.