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

Purpose

Primary Objectives:

1. Develop an outpatient thoracic treatment paradigm by reducing the number of hospitalizations during front-line osteosarcoma therapy and to improve Quality of Life (QOL) and quality of care by providing state-of the art osteosarcoma treatment in the pediatric outpatient clinic (e.g. Pediatric Ambulatory Therapy Center, PATC) except for intra-arterial chemotherapy, surgery, significant illness, or if requested by the patient and/or caregiver.

Secondary Objectives:

To document incidence of lung metastases on therapy and after completion of therapy.
Monitor safety profile and determine efficacy (PFS) of a lung-directed therapy in higher-risk patients using gemcitabine and aerosol GM-CSF.
Collect data on local control including: type of procedure(s) for control of primary tumor, type of procedure(s) for control of metastases, time interval from start of chemotherapy to achieve no evidence of disease (NED) status, wound complications and infections, and percent necrosis of surgical specimens.
Compare PFS for non-metastatic extremity (standard-risk) and higher-risk cohorts.
Analyze FAS expression on surgical specimens (lung metastases and primary tumors).
Monitor incidence of ototoxicity (>40 dB loss at 4000 Hz and/or >30dB at 2000Hz) and cardiotoxicity (EF decrease>10 % or <50% EF).

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

MedlinePlus related topics:

Cancer

Drug Information available for:

Doxorubicin Doxorubicin hydrochloride Ifosfamide Cisplatin Leucovorin Calcium Citrovorum factor Folinic acid calcium salt pentahydrate Leucovorin Methotrexate Gemcitabine hydrochloride Gemcitabine Sargramostim Granulocyte-macrophage colony-stimulating factor Dexrazoxane Dexrazoxane hydrochloride ICRF 159 Razoxane

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Parallel Assignment, Safety/Efficacy Study

Official Title:	Outpatient Chemotherapy in Pediatric Osteosarcoma: Doxorubicin With Cisplatin, High-Dose Methotrexate, and Additional Risk-Adapted Outpatient Chemotherapy

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

Primary Outcome Measures:

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. [ Time Frame: 20 Months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To find out if giving lung-directed chemotherapy with gemcitabine and inhaled (breathed in) aerosol GM-CSF (sargramostim) to pts. who are at high risk for osteosarcoma spreading to the lungs, can help to prevent the disease from spreading to the lungs. [ Time Frame: 20 Months ] [ Designated as safety issue: No ]
The safety of this continuation therapy will also be studied. [ Time Frame: 20 Months ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	40
Study Start Date:	May 2008
Estimated Primary Completion Date:	January 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Pre-Surgery, Arm 1: Doxorubicin, Cisplatin, Methotrexate, Leucovorin; Post-Surgery, Arm 1: Methotrexate, Doxorubicin, Cisplatin, Leucovorin.	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. 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. 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. 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. Behavioral: Questionnaire Questionnaires to be completed on 5 different days during the study.
2: Experimental Pre-Surgery, Arm 2: Dexrazoxane, Doxorubicin, Cisplatin; Post-Surgery, Arm 2: Methotrexate, Leucovorin, Ifosfamide; Lung-Directed Chemotherapy, Arm 2: Gemcitabine, Sargramostim.	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. 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. 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. 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. Drug: Dexrazoxane Pre-Surgery, Arm 2: IV Over 15 minutes on Day 1 of Weeks 1, 4, and 7. Drug: Ifosfamide Post-Surgery, Arm 2: IV continuously over 5 days each time, on Weeks 16, 22, 28, and 34. Behavioral: Questionnaire Questionnaires to be completed on 5 different days during the study. Drug: Gemcitabine IV over 1 hour, every other week. Drug: Sargramostim Inhaled aerosol twice a day for 7 days on, 7 days off, beginning the day you receive gemcitabine.

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, ANC 1000 or more, platelets 100,000 or more. Cardiac 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

Contacts


Contact: Peter M. Anderson, MD, PhD	713-563-0893

Locations


United States, Texas
	U.T.M.D. Anderson Cancer Center	Recruiting
	Houston, Texas, United States, 77030
	Principal Investigator: Peter M. Anderson, MD,PhD

Sponsors and Collaborators

M.D. Anderson Cancer Center

Investigators


Principal Investigator:	Peter M. Anderson, MD, PhD	U.T.M.D. Anderson Cancer Center

More Information

Responsible Party:	U.T.M.D. Anderson Cancer Center ( Peter M. Anderson, MD, PhD/Professor )
Study ID Numbers:	2007-0404
First Received:	May 6, 2008
Last Updated:	May 6, 2008
ClinicalTrials.gov Identifier:	NCT00673179
Health Authority:	United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:

Doxorubicin

Cisplatin

Methotrexate

Ifosfamide

Osteosarcoma

Sargramostim

Leucovorin

Gemcitabine

Gemzar

GM-CSF

Questionnaire

Survey

Study placed in the following topic categories:

Malignant mesenchymal tumor

Osteosarcoma

Leucovorin

Osteogenic sarcoma

Soft tissue sarcomas

Doxorubicin

Razoxane

Folic Acid

Neoplasms, Connective and Soft Tissue

Ifosfamide

Cisplatin

Mechlorethamine

Sarcoma

Methotrexate

Gemcitabine

Isophosphamide mustard

Additional relevant MeSH terms:

Antimetabolites

Anti-Infective Agents

Antimetabolites, Antineoplastic

Immunologic Factors

Molecular Mechanisms of Pharmacological Action

Antineoplastic Agents

Physiological Effects of Drugs

Reproductive Control Agents

Antibiotics, Antineoplastic

Therapeutic Uses

Vitamins

Abortifacient Agents

Micronutrients

Alkylating Agents

Dermatologic Agents

Nucleic Acid Synthesis Inhibitors

Neoplasms by Histologic Type

Vitamin B Complex

Growth Substances

Enzyme Inhibitors

Cardiovascular Agents

Abortifacient Agents, Nonsteroidal

Folic Acid Antagonists

Antiviral Agents

Immunosuppressive Agents

Pharmacologic Actions

Neoplasms

Neoplasms, Bone Tissue

Radiation-Sensitizing Agents

Chelating Agents

ClinicalTrials.gov processed this record on October 24, 2008

Sponsored by:	M.D. Anderson Cancer Center
Information provided by:	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT00673179