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Hematopoietic/Lymphoid CancerPhase 1NCT00070239

Alvocidib in Treating Patients With Metastatic or Unresectable Refractory Solid Tumors or Hematologic Malignancies

A Phase 1 study testing alvocidib, pharmacological study and fludeoxyglucose F 18 in people with Hematopoietic/Lymphoid Cancer and Unspecified Adult Solid Tumor, Protocol Specific, run by National Cancer Institute (NCI) at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This phase I trial is studying the side effects and best dose of alvocidib in treating patients with metastatic or unresectable refractory solid tumors or hematologic malignancies. Drugs used in chemotherapy, such as alvocidib, work in different ways to stop cancer cells from dividing so they stop growing or die. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
alvocidib, pharmacological study and fludeoxyglucose F 18
Could I receive a placebo?
No, everyone receives an active treatment
How many people
100 participants
Where
1 siteUnited States
Study dates
Aug 2003to Jun 2006
Phase
Phase 1
Are there results?
None posted in the registry

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 malignancy, including the following types:
  • Hematologic malignancy, including any of the following: (Accrual for patients with hematologic malignancies temporarily closed as of 11/30/04)
  • Mantle cell lymphoma
  • Morphologically confirmed disease
  • CD20 and CD5 positive
  • Any other refractory lymphoma
Show all 96Show fewer
  • Chronic lymphocytic leukemia
  • Rai stage III or IV and meeting at least 1 of the following criteria for active disease:
  • Weight loss > 10% in the last 6 months
  • Fatigue
  • Fever or night sweats with no evidence of infection
  • Progressive anemia or thrombocytopenia
  • Progressive lymphocytosis with a lymphocyte doubling time of < 6 months
  • Marked hypogammaglobulinemia or paraproteinemia
  • Progressive splenomegaly and/or lymphadenopathy
  • Multiple myeloma
  • Disease confirmed by bone marrow aspirate and/or biopsy
  • Relapsed or refractory disease after the most recent treatment regimen
  • Quantifiable monoclonal immunoglobulin in serum and/or urine
  • Solid tumor, including but not limited to any of the following:
  • Breast cancer
  • Histologically or cytologically confirmed stage IV invasive disease
  • HER-2 positivity not required for study enrollment
  • Tumor overexpressing HER-2 should be confirmed by immunohistochemistry OR fluorescence in situ hybridization
  • Small cell lung cancer
  • Extensive stage or limited stage disease in relapse
  • Extrapulmonary small cell carcinoma allowed
  • Squamous cell carcinoma of the head and neck
  • Metastatic, recurrent, or refractory disease
  • Renal cell carcinoma
  • Mesothelioma
  • Pleural or peritoneal disease of epithelial, sarcomatoid, or mixed subtype
  • Melanoma
  • Kaposi's sarcoma
  • Metastatic or unresectable disease for which standard therapy does not exist or is no longer effective
  • Measurable or nonmeasurable disease (solid tumor patients)
  • Measurable disease defined as at least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques or 10 mm by spiral CT scan
  • Nonmeasurable disease includes any of the following:
  • All other lesions, including lesions < 20 mm by conventional techniques or 10 mm by spiral CT scan
  • Bone lesions
  • Cytologically positive pleural or peritoneal disease
  • Elevated tumor marker (e.g., CEA, CA 125, CA 19-9, or other tumor marker)
  • Multinodular or confluent nonmeasurable pulmonary, hepatic, adrenal, intra-abdominal, or skin metastases
  • Previously treated with at least 1 chemotherapy regimen*
  • Prior therapy may have included combined modality treatment (e.g., full-dose chemotherapy and radiotherapy with radiosensitizing chemotherapy)
  • Prior therapy with flavopiridol allowed provided the patient was enrolled in a flavopiridol clinical trial employing a different schedule NOTE: *Except in cases where chemotherapy is not known to be effective (e.g., renal cell carcinoma, chondrosarcoma, or gastrointestinal stromal tumor)
  • No active CNS metastases
  • History of CNS metastases allowed provided all of the following criteria are met:
  • Previously treated and stable and asymptomatic for at least 4 weeks since the completion of treatment
  • Image documentation required
  • Off steroids or on a stable dose of steroids for at least 1 week
  • Hormone receptor status:
  • Not specified
  • Age
  • 18 and over
  • Sex
  • Male or female
  • Menopausal status
  • Not specified
  • Performance status
  • ECOG 0-1 OR
  • Karnofsky 70-100%
  • Life expectancy
  • More than 12 weeks
  • Hematopoietic
  • Absolute neutrophil count > 1,000/mm^3*
  • Platelet count > 75,000/mm^3 (50,000 for hematologic malignancies)* (Accrual for patients with hematologic malignancies temporarily closed as of 11/30/04) NOTE: *Unless abnormality is caused by tumor burden and not cumulative prior chemotherapy
  • Hepatic
  • Bilirubin normal
  • AST/ALT ≤ 2.5 times upper limit of normal (ULN) (5 times ULN if liver metastases are present)
  • Renal
  • Creatinine ≤ 2.0 mg/dL OR
  • Creatinine clearance ≥ 60 mL/min
  • Cardiovascular
  • No myocardial infarction within the past 6 months
  • No unstable angina within the past 6 months
  • No transient ischemic attack or cerebrovascular accident within the past 6 months
  • No history of arterial vascular events
  • No new cardiac arrhythmias likely to be related to cardiac ischemia within the past 6 months
  • No symptomatic congestive heart failure
  • Pulmonary
  • No history of pulmonary embolism within the past 6 months
  • Gastrointestinal
  • No chronic diarrheal disease within the past 6 months
  • No severe malnutrition
  • No intractable emesis
  • Other
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective hormonal or barrier contraception
  • No ongoing or active infection
  • No other concurrent uncontrolled illness
  • No psychiatric illness or social situation that would preclude study compliance
  • At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
  • At least 3 weeks since prior radiotherapy No prior radiotherapy to 50% or more of bone marrow
  • Recovered from all prior therapy No other concurrent investigational agents No concurrent combination antiretroviral therapy for HIV-positive patients

Who cannot join

None listed.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02115

Other trials in United States

About this study

Official title: A Phase I Clinical, Pharmacokinetic and Pharmacodynamic Study of Flavopiridol in Patients With Refractory Solid Tumors and Hematologic Malignancies

This phase I trial is studying the side effects and best dose of alvocidib in treating patients with metastatic or unresectable refractory solid tumors or hematologic malignancies. Drugs used in chemotherapy, such as alvocidib, work in different ways to stop cancer cells from dividing so they stop growing or die.

Read the detailed description

PRIMARY OBJECTIVE:

  1. Determine the maximum tolerated dose of flavopiridol in patients with metastatic or unresectable refractory solid tumors or hematologic malignancies. (Accrual for patients with hematologic malignancies temporarily closed as of 11/30/04)

SECONDARY OBJECTIVES:

  1. Determine the safety profile and toxic effects of this drug in these patients.

II. Determine the pharmacokinetics of this drug in these patients. III. Determine, by pharmacodynamic assays, the ability of this drug to inhibit cyclin-dependent kinase activity in tumor tissue, normal proliferating tissues, circulating tumor cells, and in plasma in these patients.

IV. Determine, preliminarily, the antitumor activity of this drug in these patients.

OUTLINE: This is a 2-part, dose-escalation, multicenter study.

PART 1 (closed to accrual as of 8/2005): Patients receive alvocidib IV over 1 hour on days 1, 8, and 15.

Cohorts of 3-6 patients receive escalating doses of alvocidib until the maximum tolerated dose (MTD)* is determined.

PART 2: Patients receive alvocidib IV over 1 hour at or below the MTD determined in part 1 and then receive a maintenance dose of alvocidib IV over 1-6 hours on days 1, 8, and 15. Cohorts of 3-6 patients receive escalating durations of the maintenance dose of alvocidib until the MTD* is determined. An additional cohort of 10-20 patients receives alvocidib over 1 hour on days 1 and 15 at the MTD.

NOTE: *The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

In both parts, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients are followed at 1 month and then every 2 months thereafter.

Being tested
alvocidib, pharmacological study, fludeoxyglucose F 18, fluorine F 18 fluorothymidine, positron emission tomography
Medical subject headings
Hematologic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • alvocidibDrug

    Also called FLAVO, flavopiridol, HMR 1275, L-868275

    Given IV

  • pharmacological studyOther

    Also called pharmacological studies

    Correlative studies

  • fludeoxyglucose F 18Radiation

    Also called 18FDG, FDG

    Correlative studies

  • fluorine F 18 fluorothymidineOther

    Also called 18F-FLT, 3'-deoxy-3'-[18F]fluorothymidine, fluorothymidine F-18

    Correlative studies

  • positron emission tomographyProcedure or surgery

    Also called FDG-PET, PET, PET scan, tomography, emission computed

    Correlative studies

Study groups in NCT00070239
Study groupRoleWhat they receive
TreatmentExperimentalPART 1 (closed to accrual as of 8/2005): Patients receive alvocidib IV over 1 hour on days 1, 8, and 15. Cohorts of 3-6 patients receive escalating doses of alvocidib until the MTD* is determined. PART 2: Patients receive alvocidib IV over 1 hour at or below the MTD determined in part 1 and then receive a maintenance dose of alvocidib IV over 1-6 hours on days 1, 8, and 15. Cohorts of 3-6 patients receive escalating durations of the maintenance dose of alvocidib until the MTD* is determined. An additional cohort of 10-20 patients receives alvocidib over 1 hour on days 1 and 15 at the MTD. NOTE: *The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. In both parts, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: alvocidib; Other: pharmacological study; Radiation: fludeoxyglucose F 18; Other: fluorine F 18 fluorothymidine; Procedure: positron emission tomography

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dose-limiting toxicity (DLT)

    Measured: 28 days

  2. MTD (or recommended phase II dose), defined as one dose level below that which produces two instances of DLT during the first 28-day course and the level at which no more than one of six patients experiences DLT during course 1

    Measured: 28 days

Secondary outcomes (3)

  1. Pharmacokinetic parameters, including maximum concentration (Cmax), half-life, area under the curve (AUC), clearance, and volume of distribution

    Determined by nonlinear regression analysis of geometric mean plasma profile. Cmax in patients w/stable disease or response at 8 weeks compared to those who progressed using Mann-Whitney test. Wilcoxon signed-rank test to compare concentration and metabolic ratios directly following infusion and 24, 48, 72 hrs later. Concentration and metabolic ratios compared in patients w/ and w/o toxicities of diarrhea, neutropenia, and asthenia using Mann- Whitney test. Fisher's exact test to assess association of flavopiridol systemic metabolism (low vs. high metabolic ratio) w/development of toxicity.

    Measured: 24 hours, 48 hours, 72 hours, and 8 weeks

  2. Potency of alvocidib in plasma based on change in proliferation of stimulated peripheral blood mononuclear cells (PBMCs)

    Measured: Baseline to up to 72 hours of day 1 course 1

  3. Change in tumor metabolism and proliferation assessed by fludeoxyglucose F 18 (FDG) and fluorine F 18 fluorothymidine (FLT) positron emission tomography (PET)

    Each type of pre- and post-treatment scans may be analyzed as paired data. The FDG and FLT data will be correlated to explore the relationship between tumor metabolism and tumor proliferation, for example, using Pearson or Spearman correlation coefficient.

    Measured: Baseline to up to day 19 of course 2

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Oct 2003 (estimated)
  2. Study startAug 2003
  3. Primary completionJun 2006

Resources

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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
100 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00070239
Sponsor's protocol ID
NCI-2009-00039
Other IDs
NCI-2009-00039, 03-082, P 6052, CDR0000331689, 03-082, 6052, U01CA062490
Status last verified
Dec 2013
First submitted
3 Oct 2003
Last updated
16 Dec 2013
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing alvocidib, pharmacological study and fludeoxyglucose F 18 in people with Hematopoietic/Lymphoid Cancer and Unspecified Adult Solid Tumor, Protocol Specific, run by National Cancer Institute (NCI) at 1 site 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 96 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: stopped early, as of the sponsor's last update on 16 Dec 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early. Results are not available in the source record.

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?

Dose-limiting toxicity (DLT) (time frame: 28 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00070239.

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 16 Dec 2013; AzTrials last refreshed its copy on 7 Nov 2026.

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