Vincristine, Doxorubicin, Cyclophosphamide and Dexrazoxane (VACdxr) in High Risk Ewing's Sarcoma Patients

January 17, 2020 updated by: M.D. Anderson Cancer Center

Randomized Phase II Study of Vincristine, Doxorubicin, Cyclophosphamide and Dexrazoxane (VACdxr) With or Without ImmTher for Newly Diagnosed High Risk Ewing's Sarcoma

Objectives:

  1. To determine if dose intensive Vincristine, Doxorubicin, Cyclophosphamide and Dexrazoxane (VACdxr) with or without ImmTherTM can improve the 2-year disease-free survival seen with standard VAC therapy.
  2. To evaluate the feasibility and describe the toxicity associated with VACdxr.
  3. To evaluate the feasibility and describe the toxicity of administering ImmTherTM on a weekly basis for 50- 52 weeks.
  4. To determine which therapy (VACdxr+ or VACdxr-) is worthy of further evaluation.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Patients will be assigned at random (as by the toss of a coin) to receive 1 of 2 treatments.

Arm A: VACdxr will be given over 2 days through a needle in a vein. On day 1, vincristine will be given over 15 minutes, and doxorubicin will be given over 30 minutes.

Dexrazoxane will be given 30 minutes before doxorubicin; this drug protects the heart from damage by doxorubicin. Cyclophosphamide will be given once a day on days 1 and 2. This will make up 1 cycle of VACdxr treatment; the cycle will be repeated every 3 weeks for up to 6 cycles.

To prevent some side effects of VACdxr, the drugs Mesna and Neupogen/or Neulasta will also be given. Mesna helps prevent bladder damage. Neupogen is a growth factor that stimulates the body to make more white blood cells. Neulasta is a growth factor related to Neupogen.

After cycle 3, surgery may be done to remove any tumor that remains. The principal investigator will also decide whether radiation treatment should be done. If so, patients will receive radiation therapy.

Starting 1 month after all treatment is done, patients will receive ImmTher. ImmTher stimulates the body's white blood cells to attack and kill tumor cells. The drug will be given through a needle in a vein over 1 hour, every week for 1 year.

Arm B: Patients will be treated the same as patients in Arm A, except that they will not receive ImmTher.

Patients may have to stay in the hospital during VACdxr treatment and after surgery. Patients will receive ImmTher in the outpatient clinic.

Before treatment starts, patients will have a complete exam including blood and urine tests and an EKG and ECHO or multiple gated acquisition scan (MUGA) (heart function tests). X-rays and CT, MRI, bone marrow aspiration, and bone scans will be done. Women will have a pregnancy test.

After each treatment with drugs, after surgery, and after radiation treatment, patients will have checkups. These will include blood and urine tests and sometimes x-rays.

After cycle 3 of VACdxr, patients will have chest x-ray and x-ray of primary tumor. CT chest, MRI, bone marrow aspiration and bone scans will be done after 3 cycles as indicated. These tests will be done to record and measure tumors.

After treatment stops, patients will return for checkups every 3 months for 2 years.

This is an investigational study. ImmTher is an investigational agent. All other study drugs are approved by the U.S. Food and Drug Administration. As many as 104 patients will take part in the study; about 95 of these will be treated at M.D. Anderson.

Study Type

Interventional

Enrollment (Actual)

46

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • Houston, Texas, United States, 77030
        • University of Texas MD Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

3 years to 60 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • High risk Ewing's Family of tumors (metastatic disease at diagnosis, humerus, femur or trunk primary, bulky primary (greater than 8 cm)), or LDH greater or equal to 900 IU/ml prior to biopsy.
  • No prior chemotherapy.
  • Written informed consent
  • Normal cardiac function (ejection fraction greater or equal to 50%).
  • Males and non pregnant females.
  • Biologic age 3-60 years old.
  • Adequate bone marrow function (defined as an absolute peripheral granulocyte count of>500/mm3, platelet count of >75,000/mm3, and hemoglobin >8g/dl with transfusion if required).
  • Adequate renal function defined as blood urea nitrogen (BUN) <30mg% and serum creatinine <1.5 x normal for age or creatinine clearance >70.
  • Patients of child bearing potential must agree to use an effective method of contraception.
  • Normal hepatic function (bilirubin <1.5mg/dl, serum glutamate oxaloacetate transaminase (SGOT) or serum glutamate pyruvate transaminase (SGPT) <3x normal).

Exclusion Criteria: N/A

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm A: VACdxr With ImmTher
Chemotherapy repeated every 3 weeks for 6 cycles: Vincristine 2.0 mg/m^2 (max 2.0 mg) intravenous (IV), Doxorubicin 90 mg/m^2 IV over 30 minutes, Cyclophosphamide 2.0 g/m^2 IV daily for 2 days. Dexrazoxane 900 mg/m^2 IV (30 minutes prior to doxorubicin). ImmTher 900 mcg/m^2 IV over 1 hour every week x 50-52 weeks.
Drug: Vincristine
2.0 mg/m^2 (max 2.0 mg) IV x 1 repeated every 3 weeks X 6.
Drug: Doxorubicin
90 mg/m^2 IV over 30 min x 1 repeated every 3 weeks X 6.
Other Names:
  • Adriamycin
  • Rubex
Drug: Cyclophosphamide
2.0 g/m^2 IV daily x 2 days repeated every 3 weeks X 6.
Other Names:
  • Cytoxan
  • Neosar
Drug: Dexrazoxane
900 mg/m^2 IV (30 min prior to doxorubicin) repeated every 3 weeks X 6.
Other Names:
  • Zinecard
  • DXR
Biological: ImmTher
900 mcg/m^2 IV over 1 hour every week x 50-52 weeks.
Active Comparator: Arm B: VACdxr
Chemotherapy repeated every 3 weeks for 6 cycles: Vincristine 2.0 mg/m^2 (max 2.0 mg) IV. Doxorubicin 90 mg/m^2 IV over 30 minutes, Cyclophosphamide 2.0 g/m^2 IV daily for 2 days, Dexrazoxane 900 mg/m^2 IV (30 minutes prior to doxorubicin).
Drug: Vincristine
2.0 mg/m^2 (max 2.0 mg) IV x 1 repeated every 3 weeks X 6.
Drug: Doxorubicin
90 mg/m^2 IV over 30 min x 1 repeated every 3 weeks X 6.
Other Names:
  • Adriamycin
  • Rubex
Drug: Cyclophosphamide
2.0 g/m^2 IV daily x 2 days repeated every 3 weeks X 6.
Other Names:
  • Cytoxan
  • Neosar
Drug: Dexrazoxane
900 mg/m^2 IV (30 min prior to doxorubicin) repeated every 3 weeks X 6.
Other Names:
  • Zinecard
  • DXR

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
2-year Disease-free Survival (DFS): Effect of Treatment With Combination Drugs in VACdxr Given in High Doses With or Without ImmTher to Help Participants With Ewing's Sarcoma Live Longer
Time Frame: 2 years
DFS defined as survival of participants to two years post study entry without relapse.
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

M.D. Anderson Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 1997

Primary Completion (Actual)

March 1, 2016

Study Completion (Actual)

March 1, 2016

Study Registration Dates

First Submitted

May 29, 2002

First Submitted That Met QC Criteria

May 29, 2002

First Posted (Estimate)

May 30, 2002

Study Record Updates

Last Update Posted (Actual)

January 29, 2020

Last Update Submitted That Met QC Criteria

January 17, 2020

Last Verified

January 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ID97-198
  • NCI-2012-01285 (Registry Identifier: NCI CTRP)

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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