AzTrials
AzTrials

Gastrointestinal Stromal TumorPhase 1NCT00098579

Doxorubicin Hydrochloride and Alvocidib in Treating Patients With Metastatic or Recurrent Sarcoma That Cannot Be Removed By Surgery

A Phase 1 study testing alvocidib and doxorubicin hydrochloride in people with Gastrointestinal Stromal Tumor and Recurrent Adult Soft Tissue Sarcoma, run by National Cancer Institute (NCI) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This phase I trial is studying the side effects and best dose of alvocidib when given with doxorubicin hydrochloride in treating patients with metastatic or recurrent sarcoma that cannot be removed by surgery. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
alvocidib and doxorubicin hydrochloride
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
36 participants
Where
1 siteUnited States
Study dates
Oct 2004to Jul 2011
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 or cytologically confirmed soft-tissue sarcoma*
  • Unresectable disease
  • Locally recurrent or metastatic disease
  • Disease amenable to biopsy (patients treated at the maximum tolerated dose only)
  • No known prior or concurrent brain metastases
  • Performance status - Karnofsky 60-100%
Show all 47Show fewer
  • Performance status - ECOG 0-2
  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Bilirubin ≤ 1.5 mg/dL
  • AST and ALT ≤ 2.5 times upper limit of normal
  • Creatinine ≤ 1.5 mg/dL
  • Creatinine clearance ≥ 60 mL/min
  • Ejection fraction ≥ 50% by MUGA or echocardiogram
  • No uncontrolled hypertension
  • No myocardial infarction
  • No New York Heart Association class II-IV congestive heart failure
  • No unstable angina
  • No serious cardiac arrhythmia requiring medication
  • No peripheral vascular disease ≥ grade 2 within the past year
  • No other clinically significant cardiac disease
  • No prior deep vein thrombosis
  • No other prior vascular thrombus
  • No prior pulmonary embolism
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No symptomatic peripheral neuropathy ≥ grade 2
  • No other malignancy within the past 5 years except adequately treated basal cell skin cancer or carcinoma in situ of the cervix
  • Carcinoma in situ not considered a second malignancy
  • No history of allergic reaction attributed to compounds of similar chemical or biologic composition to study drugs
  • No psychiatric illness or social situation that would preclude study compliance
  • No ongoing or active infection
  • No other uncontrolled illness
  • See Chemotherapy
  • At least 3 weeks since prior immunotherapy and recovered
  • At least 3 weeks since prior chemotherapy (6 weeks for carmustine or mitomycin) and recovered
  • No more than 2 prior cytotoxic chemotherapy regimens
  • Peroxisome proliferator-activated receptor (PPAR)-gamma agonists, thalidomide, or targeted therapy (i.e., tyrosine kinase inhibitors including imatinib mesylate, sorafenib, or sunitinib malate) do not count as a prior chemotherapy regimen
  • No prior anthracyclines
  • At least 3 weeks since prior radiotherapy and recovered
  • No prior extensive radiotherapy to bone marrow-producing sites (e.g., radiotherapy to both the pelvis and spine)
  • At least a 1 week washout period since prior tyrosine kinase inhibitors or other targeted therapy
  • Concurrent low-dose warfarin (1 mg per day) to prevent thrombus of a central line allowed
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • No other concurrent investigational agents
  • No other concurrent anticancer therapy

Who cannot join

None listed.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

Other trials in United States

About this study

Official title: Phase I Trial of Doxorubicin and Alvocidib (Flavopiridol; NCI Supplied Agent, NSC 649890) in the Treatment of Metastatic Sarcoma

This phase I trial is studying the side effects and best dose of alvocidib when given with doxorubicin hydrochloride in treating patients with metastatic or recurrent sarcoma that cannot be removed by surgery. Drugs used in chemotherapy, such as doxorubicin hydrochloride and 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 help doxorubicin hydrochloride work better by making tumor cells more sensitive to the drug. Giving more than one drug may kill more tumor cells

Read the detailed description

PRIMARY OBJECTIVE:

  1. 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.

SECONDARY OBJECTIVES:

  1. 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.

Being tested
alvocidib, doxorubicin hydrochloride
Medical subject headings
Gastrointestinal Stromal Tumors, Sarcoma

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

  • doxorubicin hydrochlorideDrug

    Also called ADM, ADR, Adria, Adriamycin PFS

    Given IV

Study groups in NCT00098579
Study groupRoleWhat they receive
Treatment (chemotherapy)ExperimentalPatients 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.
Receives: Drug: alvocidib; Drug: doxorubicin hydrochloride

What is being measured

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

  1. MTD of alvocidib when given every three weeks in conjunction with doxorubicin hydrochloride

    Defined as the dose level immediately preceding the dose where 2 or more patients experienced DLT.

    Measured: Course 1

Secondary outcomes (3)

  1. Dose limiting toxicity

    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.

    Measured: Weekly during course 1 at initiation of each course thereafter

  2. Clinical pharmacokinetics of the regimen

    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).

    Measured: Week 1

  3. Therapeutic activity of alvocidib in combination with doxorubicin hydrochloride in patients with advanced solid tumors

    Evaluated using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee.

    Measured: Every 2 courses for the first 6 courses and every 3 courses thereafter

Timeline

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

  1. First posted8 Dec 2004 (estimated)
  2. Study startOct 2004
  3. Primary completionJul 2011

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
36 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00098579
Sponsor's protocol ID
NCI-2009-00048
Other IDs
04-075A, U01CA069856
Status last verified
Mar 2013
First submitted
7 Dec 2004
Last updated
19 Mar 2013
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing alvocidib and doxorubicin hydrochloride in people with Gastrointestinal Stromal Tumor and Recurrent Adult Soft Tissue Sarcoma, 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 47 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: finished, as of the sponsor's last update on 19 Mar 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

MTD of alvocidib when given every three weeks in conjunction with doxorubicin hydrochloride (time frame: Course 1). 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 NCT00098579.

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 19 Mar 2013.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in