Alvocidib in Treating Patients With Locally Advanced or Metastatic Solid Tumors

Unspecified Adult Solid Tumor, Protocol Specific Clinical Trial

Official title:

A Pilot Study of Flavopiridol in Patients With Advanced Solid Tumors

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00112684
• Other study ID #: NCI-2009-00135
• Secondary ID: NCI-2009-00135OS
• Status: Terminated
• Phase: Phase 1
• First received: June 2, 2005
• Last updated: February 21, 2014
• Start date: February 2006

Study information

• Verified date: November 2011
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Other known NCT identifiers

• NCT01645540

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 25
• Est. primary completion date: July 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Unspecified Adult Solid Tumor, Protocol Specific

Intervention

Drug:
• alvocidib
Given IV

Other:
• pharmacological study
Correlative studies
• laboratory biomarker analysis
Correlative studies

Locations

Country	Name	City	State
United States	Ohio State University Medical Center	Columbus	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse events of dose escalated alvocidib administered in patients with advanced solid tumors	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	Yes
Secondary	Pharmacokinetics of alvocidib administered in this schedule	The pharmacokinetic parameters include Cmax, Css, Clearance, t1/2 a, t1/2 ß, central volume of distribution and steady state volume of distribution.	After the first dose of treatment drug	No
Secondary	Immunomodulatory effects of alvocidib	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.	Baseline, days 1 and 15 of courses 1 and 2, and within 4 weeks after the completion of study treatment	No
Secondary	Pharmacogenomics studies on procured PBMCs if clinical responses are observed	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.	Baseline, and within 4 weeks after the completion of study treatment	No
Secondary	Measurement of serum tumor markers depending on the tumor type	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.	Baseline, week 11 or 12, and within 4 weeks after the completion of study treatment	No