Doxorubicin Hydrochloride and Alvocidib in Treating Patients With Metastatic or Recurrent Sarcoma That Cannot Be Removed By Surgery
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|ClinicalTrials.gov Identifier: NCT00098579|
Recruitment Status : Completed
First Posted : December 8, 2004
Last Update Posted : March 19, 2013
|Condition or disease||Intervention/treatment||Phase|
|Gastrointestinal Stromal Tumor Recurrent Adult Soft Tissue Sarcoma Stage IV Adult Soft Tissue Sarcoma||Drug: alvocidib Drug: doxorubicin hydrochloride||Phase 1|
I. Determine the maximum tolerated dose of flavopiridol (alvocidib) when administered with a fixed dose of doxorubicin (doxorubicin hydrochloride) in patients with unresectable metastatic or locally recurrent sarcoma.
I. Determine the clinical pharmacokinetics of this regimen in these patients. II. Determine, preliminarily, the therapeutic activity of this regimen in these patients.
III. Correlate pRb, p53, and p21 protein levels with treatment response and apoptosis in patients treated with this regimen.
IV. Correlate NMR biochemical patterns with response in patients treated with this regimen.
OUTLINE: This is an open-label, dose-escalation study of alvocidib.
Patients receive doxorubicin hydrochloride intravenously (IV) over 5-10 minutes and alvocidib IV over 1 hour on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients reaching a cumulative doxorubicin dose of 600 mg/m^2 or experiencing cardiotoxicity may receive alvocidib alone at the discretion of the investigator. 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. Ten additional patients receive treatment at the MTD. Patients are followed every 3 months for 1 year.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||36 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I Trial of Doxorubicin and Alvocidib (Flavopiridol; NCI Supplied Agent, NSC 649890) in the Treatment of Metastatic Sarcoma|
|Study Start Date :||October 2004|
|Actual Primary Completion Date :||July 2011|
Experimental: Treatment (chemotherapy)
Patients receive doxorubicin hydrochloride IV over 5-10 minutes and alvocidib IV over 1 hour on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients reaching a cumulative doxorubicin dose of 600 mg/m^2 or experiencing cardiotoxicity may receive alvocidib alone at the discretion of the investigator. Cohorts of 3-6 patients receive escalating doses of alvocidib until the 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. Ten additional patients receive treatment at the MTD. Patients are followed every 3 months for 1 year.
Other Names:Drug: doxorubicin hydrochloride
- MTD of alvocidib when given every three weeks in conjunction with doxorubicin hydrochloride [ Time Frame: Course 1 ]Defined as the dose level immediately preceding the dose where 2 or more patients experienced DLT.
- Dose limiting toxicity [ Time Frame: Weekly during course 1 at initiation of each course thereafter ]Defined as the occurrence of Grade 4 hematologic toxicity 21 days after treatment, Grade 4 hematologic toxicity lasting 7 days or longer, Grade 3 or 4 non-hematologic toxicity, or any delay in treatment of more than two weeks. Evaluated using the National Cancer Institute (NCI) Common Toxicity Criteria. Graded using the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.
- Clinical pharmacokinetics of the regimen [ Time Frame: Week 1 ]Biopsies will be performed by Tru-Cut or CT guidance. The material obtained will be examined for p21, p53 and pRb expression by immunohistochemistry (IHC) as well as measurements of apoptosis by terminal deoxynucleotidyl transferase (TdT)- mediated dUTP nick end labeling (TUNEL).
- Therapeutic activity of alvocidib in combination with doxorubicin hydrochloride in patients with advanced solid tumors [ Time Frame: Every 2 courses for the first 6 courses and every 3 courses thereafter ]Evaluated using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00098579
|United States, New York|
|Memorial Sloan Kettering Cancer Center|
|New York, New York, United States, 10065|
|Principal Investigator:||David D'Adamo||Memorial Sloan Kettering Cancer Center|