Alvocidib in Treating Patients With Locally Advanced or Metastatic Solid Tumors

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00112684
First received: June 2, 2005
Last updated: February 21, 2014
Last verified: November 2011
  Purpose

This phase I trial is studying the side effects and best dose of alvocidib in treating patients with locally advanced or metastatic solid tumors. Drugs used in chemotherapy, such as alvocidib, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Alvocidib may also stimulate the immune system in different ways and stop tumor cells from growing. It may also stop the growth of solid tumors by blocking blood flow to the tumor.


Condition Intervention Phase
Unspecified Adult Solid Tumor, Protocol Specific
Drug: alvocidib
Other: pharmacological study
Other: laboratory biomarker analysis
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Study of Flavopiridol in Patients With Advanced Solid Tumors

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
    Graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.


Secondary Outcome Measures:
  • Pharmacokinetics of alvocidib administered in this schedule [ Time Frame: After the first dose of treatment drug ] [ Designated as safety issue: No ]
    The pharmacokinetic parameters include Cmax, Css, Clearance, t1/2 α, t1/2 β, central volume of distribution and steady state volume of distribution.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • Pharmacogenomics studies on procured PBMCs if clinical responses are observed [ Time Frame: Baseline, and within 4 weeks after the completion of study treatment ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.


Enrollment: 25
Study Start Date: February 2006
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: alvocidib
Given IV
Other Names:
  • FLAVO
  • flavopiridol
  • HMR 1275
  • L-868275
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: laboratory biomarker analysis
Correlative studies

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00112684

Locations
United States, Ohio
Ohio State University Medical Center
Columbus, Ohio, United States, 43210
Sponsors and Collaborators
Investigators
Principal Investigator: Manisha Shah Ohio State University
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00112684     History of Changes
Obsolete Identifiers: NCT01645540
Other Study ID Numbers: NCI-2009-00135, NCI-2009-00135, OSU-2005C0009, CDR0000429582, NCI-7204, OSU-04111, OSU 04111, 7204, U01CA076576, P30CA016058
Study First Received: June 2, 2005
Last Updated: February 21, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms
Flavopiridol
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Growth Inhibitors
Growth Substances
Physiological Effects of Drugs
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 23, 2014