- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00112684
Alvocidib in Treating Patients With Locally Advanced or Metastatic Solid Tumors
A Pilot Study of Flavopiridol in Patients With Advanced Solid Tumors
Study Overview
Status
Intervention / Treatment
Detailed Description
PRIMARY OBJECTIVES:
I. Determine the toxicity profile and dose-limiting toxicity of flavopiridol (alvocidib) in patients with locally advanced or metastatic solid tumors.
II. Determine the maximum tolerated dose of this drug in these patients.
SECONDARY OBJECTIVES:
I. Determine the pharmacokinetics and pharmacodynamics of this drug in these patients.
II. Determine the immunomodulatory effects of this drug in these patients. III. Determine pharmacogenomics of this drug, using peripheral blood mononuclear cells, in patients who experience clinical response.
OUTLINE: This is a pilot, dose-escalation study.
Patients receive alvocidib intravenously (IV) over 4½ hours once weekly in weeks 1-4. Treatment repeats every 6 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients achieving stable disease after 4 courses of therapy discontinue study treatment. Patients who achieve complete remission (CR) receive 1 additional course of therapy beyond documentation of CR. Cohorts of 3-6 patients receive escalating doses of alvocidib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. A total of 10 patients are treated at the MTD.
After completion of study treatment, patients are followed within 4 weeks.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Ohio
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Columbus, Ohio, United States, 43210
- Ohio State University Medical Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
Histologically or cytologically confirmed solid tumor
- Locally advanced or metastatic disease for which curative treatment does not exist or is no longer effective
Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan
- No previously irradiated* measurable lesion unless lesion demonstrates progressive disease OR there are other measurable lesions outside the irradiated* field
The following are not considered measurable disease:
- Bone lesions
- Leptomeningeal disease
- Ascites
- Pleural or pericardial effusion
- Lymphangitis cutis/pulmonis
- Abdominal masses that are not confirmed and followed by imaging techniques
- Cystic lesions
- No uncontrolled brain metastases
- Performance status - ECOG 0-1
- At least 6 months
- Absolute neutrophil count ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- AST and ALT ≤ 2.5 times upper limit of normal (ULN)
- Bilirubin ≤ 1.5 times ULN
- Creatinine ≤ 1.5 times ULN
- No symptomatic congestive heart failure
- No unstable angina pectoris
- No uncontrolled cardiac arrhythmia
- No uncontrolled hypertension
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No history of allergic reaction attributed to compounds of similar chemical or biological composition to flavopiridol
- No ongoing or active infection
- No uncontrolled illness
- No psychiatric illness or social situation that would preclude study compliance
- More than 12 weeks since prior hepatic arterial chemoembolization
- More than 4 weeks since prior systemic chemotherapy
- No prior flavopiridol
- See Disease Characteristics
- More than 12 weeks since prior radioactive metaiodobenzylguanidine (MIBG)
- More than 4 weeks since prior external beam radiotherapy
- Recovered from all prior tumor-specific therapy
- More than 4 weeks since prior investigational tumor-specific therapy
- Concurrent octreotide for control of carcinoid syndrome allowed
- No concurrent combination anti-retroviral therapy for HIV-positive patients
- No other concurrent tumor-specific therapy
- No other concurrent investigational therapy
- No other concurrent anticancer therapy
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment (chemotherapy, biological therapy)
Patients receive alvocidib IV over 4½ hours once weekly in weeks 1-4.
Treatment repeats every 6 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.
|
Correlative studies
Given IV
Other Names:
Correlative studies
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Adverse events of dose escalated alvocidib administered in patients with advanced solid tumors
Time Frame: At weeks 1-4, 7-10, 11 or 12, and within 4 weeks after the completion of study treatment
|
Graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.
|
At weeks 1-4, 7-10, 11 or 12, and within 4 weeks after the completion of study treatment
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Pharmacokinetics of alvocidib administered in this schedule
Time Frame: After the first dose of treatment drug
|
The pharmacokinetic parameters include Cmax, Css, Clearance, t1/2 α, t1/2 β, central volume of distribution and steady state volume of distribution.
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After the first dose of treatment drug
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Immunomodulatory effects of alvocidib
Time Frame: Baseline, days 1 and 15 of courses 1 and 2, and within 4 weeks after the completion of study treatment
|
Gene expression quantified using Real Time PCR; type 1 and type 2 cytokines, co-stimulatory molecules, and adhesion molecules in PBMCs.
Activation of lymphocyte subsets and presence of co-stimulatory and adhesion molecules assessed using multicolor flow cytometry.
IL-6 levels in plasma will be measured by ELISA.
T-cells will be enriched from PBMCs using mAb-coated immunomagnetic beads and activated with anti-CD3/anti-CD28 mAbs, inomycin or PMA.
Cytokine production will be measured using cytometric bead array.
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Baseline, days 1 and 15 of courses 1 and 2, and within 4 weeks after the completion of study treatment
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Pharmacogenomics studies on procured PBMCs if clinical responses are observed
Time Frame: Baseline, and within 4 weeks after the completion of study treatment
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Performed if clinical responses are observed.
Examine for selected polymorphisms of genes influencing alvocidib metabolism and/or resistance genes that may predict response or toxicity.
These changes will be correlated with AUC, toxicity and clinical response to therapy.
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Baseline, and within 4 weeks after the completion of study treatment
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Measurement of serum tumor markers depending on the tumor type
Time Frame: Baseline, week 11 or 12, and within 4 weeks after the completion of study treatment
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Markers include CEA, CA 19-9, CA 15-3, PSA, LDH, AFP, b-HCG, pancreastatin, gastrin, pancreatic polypeptide, glucagon, substance-P, neurotensin, calcitonin, somatostatin, vasoactive intestinal peptide, gastrin releasing polypeptide, ACTH, and chromogranin-A.
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Baseline, week 11 or 12, and within 4 weeks after the completion of study treatment
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Manisha Shah, Ohio State University
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- NCI-2009-00135 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- P30CA016058 (U.S. NIH Grant/Contract)
- U01CA076576 (U.S. NIH Grant/Contract)
- OSU-2005C0009
- CDR0000429582
- NCI-7204
- OSU-04111
- OSU 04111 (Other Identifier: Ohio State University Medical Center)
- 7204 (Other Identifier: CTEP)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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