Doxorubicin With Cisplatin, High-Dose Methotrexate, and Additional Risk-Adapted Outpatient Chemotherapy - Full Text View

Purpose

The goal of this clinical research study is to learn if giving certain combinations of chemotherapy drugs before and after surgery, mostly in the outpatient clinic instead of in the hospital, can result in fewer hospital stays during treatment for osteosarcoma. The drugs and schedules will vary depending on the status of the cancer and its level of risk for spreading, but they will include combinations of doxorubicin (non-liposomal), cisplatin, methotrexate, and ifosfamide, as described below.

Condition	Intervention
Osteosarcoma	Drug: Doxorubicin Drug: Cisplatin Drug: Methotrexate Drug: Leucovorin Drug: Dexrazoxane Drug: Ifosfamide Behavioral: Questionnaire Drug: Gemcitabine Drug: Sargramostim Procedure: Surgery Drug: Mesna

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Outpatient Chemotherapy in Pediatric Osteosarcoma: Doxorubicin With Cisplatin, High-Dose Methotrexate, and Additional Risk-Adapted Outpatient Chemotherapy

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: Methotrexate Leucovorin calcium Ifosfamide Methotrexate sodium Cisplatin Mesna Doxorubicin Dexrazoxane Doxorubicin hydrochloride Carboplatin Levoleucovorin Gemcitabine Gemcitabine hydrochloride Sargramostim Dexrazoxane hydrochloride

U.S. FDA Resources

Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:

Treatment Success (6 or fewer hospitalizations during front-line chemotherapy) [ Time Frame: Baseline to 5 Years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Quality of Life (Ped QL) Assessment [ Time Frame: Peds QL measures at week 0 (during first chemo cycle), week 6, week 20, at end of therapy, and at 3 years. ] [ Designated as safety issue: No ]

Enrollment:	7
Study Start Date:	May 2008
Study Completion Date:	November 2010
Primary Completion Date:	November 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Outpatient Chemotherapy Pre-Surgery, Arm 1: Doxorubicin intravenous (IV) 90 mg daily, Cisplatin 60 mg/m^2/day for 2 days, Methotrexate 12 gm/m^2, Leucovorin Rescue 10 mg IV, with 10 mg orally every 6 hours; Surgery; Post-Surgery, Arm 1: Methotrexate 12 gm/m^2, Doxorubicin IV 90 mg, Cisplatin 60 mg/ m^2 twice daily, Leucovorin Rescue.	Drug: Doxorubicin Pre-Surgery, Arm 1: IV Over 15 Minutes on Day 1 of Weeks 1 and 6; Post-Surgery, Arm 1: IV on Day 1 of Weeks 16, 21, and 26; Pre-Surgery, Arm 2: IV over 15 Minutes on Day 1 of Weeks 1, 4, and 7. Dose 90 mg/m^2. Other Names: AD Hydroxydaunomycin hydrochloride Drug: Cisplatin Pre-Surgery, Arm 1: IV Over 48 Hours, on Days 1 and 2 of Weeks 1 and 6; Post-Surgery, Arm 1: IV Over 48 Hours, on Days 1 and 2 of Weeks 16, 21, and 26. Pre-Surgery, Arm 2: Infusion through an artery over 4 hours on Day 1 of Weeks 1, 4, and 7. Dose 60 mg/m^2/day for 2 days continuous infusion. Other Name: Paraplatin® Drug: Methotrexate Pre-Surgery, Arm 1: IV Over 4 Hours on Day 1 of Weeks 4, 5, 9, and 10; Post-Surgery, Arm 1: IV Over 4 Hours on Day 1 of Weeks 14, 15, 19, 20, 24, 25, 29, and 30; Post-Surgery, Arm 2: IV Over 4 Hours on Day 1 of Weeks 14, 15, 20, 21, 26, 27, 32, 33, 38, and 39. Dose 12 gm/m^2, max 20 gm over 4 hours. Drug: Leucovorin Pre- and Post-Surgery, Arm 1: IV Over 5 minutes on the day after each methotrexate dose and then by mouth every 6 hours; Post-Surgery, Arm 2: IV Over 5 minutes on the day after each methotrexate dose and then by mouth every 6 hours. Dose 10 mg IV, with 10 mg orally every 6 hours. Behavioral: Questionnaire Questionnaires to be completed on 5 different days during the study. Other Name: Survey Procedure: Surgery Planned limb salvage surgery after 3 courses of doxorubicin + cisplatin (IV) and High-dose methotrexate - at approximately week 12.
Experimental: Additional Risk-Adapted Outpatient Chemotherapy Pre-Surgery, Arm 2: Dexrazoxane 900 mg/m^2 intravenous (IV) then Doxorubicin IV 90 mg daily, Cisplatin 120 mg/m^2 (intra-arterial); Surgery; Post-Surgery, Arm 2: Methotrexate 12 gm/m^2, Leucovorin Rescue 10 mg IV, with 10 mg orally every 6 hours; Ifosfamide 2.8 grams m^2/day and Mesna 2.8 gm/m^2/day continuous IV over 6 days; Lung-Directed Chemotherapy, Arm 2: Gemcitabine, Sargramostim Inhaled aerosol (5 mcg/kg, maximum dose 300 mcg).	Drug: Doxorubicin Pre-Surgery, Arm 1: IV Over 15 Minutes on Day 1 of Weeks 1 and 6; Post-Surgery, Arm 1: IV on Day 1 of Weeks 16, 21, and 26; Pre-Surgery, Arm 2: IV over 15 Minutes on Day 1 of Weeks 1, 4, and 7. Dose 90 mg/m^2. Other Names: AD Hydroxydaunomycin hydrochloride Drug: Cisplatin Pre-Surgery, Arm 1: IV Over 48 Hours, on Days 1 and 2 of Weeks 1 and 6; Post-Surgery, Arm 1: IV Over 48 Hours, on Days 1 and 2 of Weeks 16, 21, and 26. Pre-Surgery, Arm 2: Infusion through an artery over 4 hours on Day 1 of Weeks 1, 4, and 7. Dose 60 mg/m^2/day for 2 days continuous infusion. Other Name: Paraplatin® Drug: Methotrexate Pre-Surgery, Arm 1: IV Over 4 Hours on Day 1 of Weeks 4, 5, 9, and 10; Post-Surgery, Arm 1: IV Over 4 Hours on Day 1 of Weeks 14, 15, 19, 20, 24, 25, 29, and 30; Post-Surgery, Arm 2: IV Over 4 Hours on Day 1 of Weeks 14, 15, 20, 21, 26, 27, 32, 33, 38, and 39. Dose 12 gm/m^2, max 20 gm over 4 hours. Drug: Leucovorin Pre- and Post-Surgery, Arm 1: IV Over 5 minutes on the day after each methotrexate dose and then by mouth every 6 hours; Post-Surgery, Arm 2: IV Over 5 minutes on the day after each methotrexate dose and then by mouth every 6 hours. Dose 10 mg IV, with 10 mg orally every 6 hours. Drug: Dexrazoxane Dose 900 mg/m^2 IV Push with doxorubicin. Pre-Surgery, Arm 2: IV Over 15 minutes on Day 1 of Weeks 1, 4, and 7. Other Name: Zinecard Drug: Ifosfamide Post-Surgery, Arm 2: IV continuously over 5 days each time, on Weeks 16, 22, 28, and 34. Dose 2.8 gm/m^2. Dose 2.8 grams m^2/day. Other Name: Ifex Behavioral: Questionnaire Questionnaires to be completed on 5 different days during the study. Other Name: Survey Drug: Gemcitabine IV over 1 hour, every other week. Other Names: Gemzar Gemcitabine Hydrochloride Drug: Sargramostim Inhaled aerosol (5 mcg/kg, maximum dose 300 mcg) twice a day for 7 days on, 7 days off, beginning the day receive gemcitabine. Other Names: GM-CSF Leukine™ Procedure: Surgery Planned limb salvage surgery after 3 courses of doxorubicin + cisplatin (IV) and High-dose methotrexate - at approximately week 12. Drug: Mesna IV continuously over 6 days each time, on Weeks 16, 22, 28, and 34. Dose 2.8 gm/m^2/day. Other Name: Mesnex

Arms

Assigned Interventions

Experimental: Outpatient Chemotherapy

Pre-Surgery, Arm 1: Doxorubicin intravenous (IV) 90 mg daily, Cisplatin 60 mg/m^2/day for 2 days, Methotrexate 12 gm/m^2, Leucovorin Rescue 10 mg IV, with 10 mg orally every 6 hours; Surgery; Post-Surgery, Arm 1: Methotrexate 12 gm/m^2, Doxorubicin IV 90 mg, Cisplatin 60 mg/ m^2 twice daily, Leucovorin Rescue.

Drug: Doxorubicin

Pre-Surgery, Arm 1: IV Over 15 Minutes on Day 1 of Weeks 1 and 6; Post-Surgery, Arm 1: IV on Day 1 of Weeks 16, 21, and 26; Pre-Surgery, Arm 2: IV over 15 Minutes on Day 1 of Weeks 1, 4, and 7. Dose 90 mg/m^2.

Other Names:

AD
Hydroxydaunomycin hydrochloride

Drug: Cisplatin

Pre-Surgery, Arm 1: IV Over 48 Hours, on Days 1 and 2 of Weeks 1 and 6; Post-Surgery, Arm 1: IV Over 48 Hours, on Days 1 and 2 of Weeks 16, 21, and 26. Pre-Surgery, Arm 2: Infusion through an artery over 4 hours on Day 1 of Weeks 1, 4, and 7. Dose 60 mg/m^2/day for 2 days continuous infusion.

Other Name: Paraplatin®

Drug: Methotrexate

Pre-Surgery, Arm 1: IV Over 4 Hours on Day 1 of Weeks 4, 5, 9, and 10; Post-Surgery, Arm 1: IV Over 4 Hours on Day 1 of Weeks 14, 15, 19, 20, 24, 25, 29, and 30; Post-Surgery, Arm 2: IV Over 4 Hours on Day 1 of Weeks 14, 15, 20, 21, 26, 27, 32, 33, 38, and 39. Dose 12 gm/m^2, max 20 gm over 4 hours.

Drug: Leucovorin

Pre- and Post-Surgery, Arm 1: IV Over 5 minutes on the day after each methotrexate dose and then by mouth every 6 hours; Post-Surgery, Arm 2: IV Over 5 minutes on the day after each methotrexate dose and then by mouth every 6 hours. Dose 10 mg IV, with 10 mg orally every 6 hours.

Behavioral: Questionnaire

Questionnaires to be completed on 5 different days during the study.

Other Name: Survey

Procedure: Surgery

Planned limb salvage surgery after 3 courses of doxorubicin + cisplatin (IV) and High-dose methotrexate - at approximately week 12.

Experimental: Additional Risk-Adapted Outpatient Chemotherapy

Pre-Surgery, Arm 2: Dexrazoxane 900 mg/m^2 intravenous (IV) then Doxorubicin IV 90 mg daily, Cisplatin 120 mg/m^2 (intra-arterial); Surgery; Post-Surgery, Arm 2: Methotrexate 12 gm/m^2, Leucovorin Rescue 10 mg IV, with 10 mg orally every 6 hours; Ifosfamide 2.8 grams m^2/day and Mesna 2.8 gm/m^2/day continuous IV over 6 days; Lung-Directed Chemotherapy, Arm 2: Gemcitabine, Sargramostim Inhaled aerosol (5 mcg/kg, maximum dose 300 mcg).

Drug: Doxorubicin

Pre-Surgery, Arm 1: IV Over 15 Minutes on Day 1 of Weeks 1 and 6; Post-Surgery, Arm 1: IV on Day 1 of Weeks 16, 21, and 26; Pre-Surgery, Arm 2: IV over 15 Minutes on Day 1 of Weeks 1, 4, and 7. Dose 90 mg/m^2.

Other Names:

AD
Hydroxydaunomycin hydrochloride

Drug: Cisplatin

Pre-Surgery, Arm 1: IV Over 48 Hours, on Days 1 and 2 of Weeks 1 and 6; Post-Surgery, Arm 1: IV Over 48 Hours, on Days 1 and 2 of Weeks 16, 21, and 26. Pre-Surgery, Arm 2: Infusion through an artery over 4 hours on Day 1 of Weeks 1, 4, and 7. Dose 60 mg/m^2/day for 2 days continuous infusion.

Other Name: Paraplatin®

Drug: Methotrexate

Pre-Surgery, Arm 1: IV Over 4 Hours on Day 1 of Weeks 4, 5, 9, and 10; Post-Surgery, Arm 1: IV Over 4 Hours on Day 1 of Weeks 14, 15, 19, 20, 24, 25, 29, and 30; Post-Surgery, Arm 2: IV Over 4 Hours on Day 1 of Weeks 14, 15, 20, 21, 26, 27, 32, 33, 38, and 39. Dose 12 gm/m^2, max 20 gm over 4 hours.

Drug: Leucovorin

Pre- and Post-Surgery, Arm 1: IV Over 5 minutes on the day after each methotrexate dose and then by mouth every 6 hours; Post-Surgery, Arm 2: IV Over 5 minutes on the day after each methotrexate dose and then by mouth every 6 hours. Dose 10 mg IV, with 10 mg orally every 6 hours.

Drug: Dexrazoxane

Dose 900 mg/m^2 IV Push with doxorubicin. Pre-Surgery, Arm 2: IV Over 15 minutes on Day 1 of Weeks 1, 4, and 7.

Other Name: Zinecard

Drug: Ifosfamide

Post-Surgery, Arm 2: IV continuously over 5 days each time, on Weeks 16, 22, 28, and 34. Dose 2.8 gm/m^2. Dose 2.8 grams m^2/day.

Other Name: Ifex

Behavioral: Questionnaire

Questionnaires to be completed on 5 different days during the study.

Other Name: Survey

Drug: Gemcitabine

IV over 1 hour, every other week.

Other Names:

Gemzar
Gemcitabine Hydrochloride

Drug: Sargramostim

Inhaled aerosol (5 mcg/kg, maximum dose 300 mcg) twice a day for 7 days on, 7 days off, beginning the day receive gemcitabine.

Other Names:

GM-CSF
Leukine™

Procedure: Surgery

Planned limb salvage surgery after 3 courses of doxorubicin + cisplatin (IV) and High-dose methotrexate - at approximately week 12.

Drug: Mesna

IV continuously over 6 days each time, on Weeks 16, 22, 28, and 34. Dose 2.8 gm/m^2/day.

Other Name: Mesnex

Show Detailed Description

Eligibility

Ages Eligible for Study:	5 Years to 40 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Newly diagnosed high-grade osteosarcoma. Patients with unresectable or metastatic disease ARE eligible.
Age 5-40 years old on date of diagnostic biopsy.
Adequate organ function: creatinine 1.6 or lower, bilirubin <2, Hemoglobin 8 gm/dL or greater, Absolute neutrophil count (ANC) 1000 or more, platelets 100,000 or more. Cardiac ejection fraction (EF) 50% or better, hearing threshold 40 dB at 4000 Hz or better.
Signed informed consent.
Negative pregnancy test in females of child bearing potential, and if sexually active, willingness to use effective contraception during chemotherapy.

Exclusion Criteria:

Diagnosis other than osteosarcoma.
Pregnant or lactating females, or unwilling to use effective contraception during chemotherapy

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00673179

Locations

United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030

Sponsors and Collaborators

M.D. Anderson Cancer Center

Investigators

Principal Investigator:

Peter M. Anderson, MD, PhD

M.D. Anderson Cancer Center

More Information

Additional Information:

The University of Texas M.D.Anderson Cancer Center This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT00673179 History of Changes
Other Study ID Numbers:	2007-0404
Study First Received:	May 6, 2008
Last Updated:	July 9, 2012
Health Authority:	United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:

Doxorubicin
AD
Hydroxydaunomycin hydrochloride
Cisplatin
Paraplatin®
Methotrexate
Ifosfamide
Osteosarcoma
Sargramostim

Leukine™
Leucovorin
Gemcitabine
Gemzar
Gemcitabine Hydrochloride
GM-CSF
Questionnaire
Survey

Additional relevant MeSH terms:

Osteosarcoma
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Sarcoma
Mesna
Levoleucovorin
Isophosphamide mustard
Gemcitabine
Cisplatin
Doxorubicin
Ifosfamide
Methotrexate

Razoxane
Carboplatin
Leucovorin
Protective Agents
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Radiation-Sensitizing Agents
Antibiotics, Antineoplastic
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Vitamin B Complex
Vitamins

ClinicalTrials.gov processed this record on May 16, 2013