A Study of Pre-Operative Treatment of Newly-Diagnosed, Surgically-Resectable Osteosarcoma With Doxorubicin, Ifosfamide, Etoposide, and Cisplatin With Early Metabolic Assessment of Response

NCT01258634 | Terminated Phase 1

• 1 other identifier: 10-186-B
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

This is a pilot study that will allow investigators to collect data related to early and potentially more accurate response assessments using a chemotherapy protocol that eliminates methotrexate to maximize the dose intensity of doxorubicin. The pilot data will be used to seek funding to more fully address the hypotheses in a multi-institutional, Phase II or Phase III trial. The primary and secondary objectives are as follows: Primary:

1. 1.To evaluate the feasibility and potential usefulness of measuring early changes in tumor metabolic activity, assessed by Fludeoxyglucose-Positron Emission Tomography (FDG-PET) imaging and alkaline phosphatase activity, as early predictors of histological response rate at 12 weeks in osteosarcoma patients.
2. 2.To explore whether histological response can be assessed by a computer algorithm using virtual microscopic images of pathology material, and whether quantifying necrosis in this way correlates with microscope slide-based review.

Conditions

Osteosarcoma; Lung Metastases

Keywords

Osteosarcoma; Surgically Resectable High Grade Osteosarcoma; Lung Metastases Only

Outcome Measures

Primary Outcomes (1)

• Feasibility and usefulness of measuring early changes in tumor metabolic activity.

  The feasibility and potential usefulness of measuring early changes in tumor metabolic activity will be assessed by early Fludeoxyglucose-Positron Emission Tomography imaging and alkaline phosphatase activity.

  6 months after last subject has been enrolled

Secondary Outcomes (4)

• Gather pilot data on the histological response rate

  3 years after last enrolled subject has completed therapy

• Explore whether histological response can be measured by a computer algorithm

  1 year after last enrolled subject has completed therapy

• Gather pilot data on 3-year event-free survival

  3 years after last subject is enrolled

• Gather pilot data on toxicity

  3 years after last subject is enrolled on the study.

Study Arms (1)

Pre-op treatment

OTHER

Drug: Dexrazoxane; Drug: Doxorubicin; Drug: Cisplatin; Drug: G-CSF; Drug: PEG-filgrastim; Drug: Etoposide; Drug: Ifosfamide; Drug: Mesna; Drug: Leucovorin

Interventions

Dexrazoxane DRUG

Preoperative Chemotherapy Courses 1, 2, 3, 4: 750mg/m2; IV over 15 minutes on day 1 Postoperative Chemotherapy for Good Responders Courses 1 and 2: 750mg/m2 IV over 15 minutes on Day 1 Postoperative Chemotherapy for Poor Responders Courses 2 and 4: 750mg/m2 IV over 15 minutes on Day 1

Pre-op treatment

Doxorubicin DRUG

Preoperative Chemotherapy Courses 1 and 3: 75mg/m2; IV push day 1 Courses 2 and 4: 75mg/m2; IV push day 1, hour 0 Postoperative Chemotherapy for Good Responders Course 1: 75mg/m2; IV push day 1 Course 2: 75mg/m2; IV push day 1, hour 0 Postoperative Chemotherapy for Poor Responders Course 2: 75mg/m2; IV push day 1 Course 4: 75mg/m2; IV push day 1, hour 0

Pre-op treatment

Cisplatin DRUG

Preoperative Chemotherapy Courses 1 and 3: 60mg/m2 daily x 2 days, in 1000 ml D5W NS + 10g/m2 mannitol Postoperative Chemotherapy for Good Responders Courses 1 and 2: 60mg/m2 daily x 2 days, in 1000 ml D5W NS + 10g/m2 mannitol Postoperative Chemotherapy for Poor Responders: Course 2: 60mg/m2 daily x 2 days, in 1000 ml D5W NS + 10g/m2 mannitol

Pre-op treatment

G-CSF DRUG

Preoperative Chemotherapy Courses 1, 2, 3, and 4: 5mcg/Kg; IV/SQ starting 24 hours after chemotherapy until WBC \>10,000 Postoperative Chemotherapy for Good Responders Courses 1, 2, and 3: 5mcg/Kg; IV/SQ starting 24 hours after chemotherapy until WBC \>10,000 Postoperative Chemotherapy for Poor Responders Courses 2, 4, and 5: 5mcg/Kg; IV/SQ starting 24 hours after chemotherapy until WBC \>10,000

Pre-op treatment

PEG-filgrastim DRUG

Preoperative Chemotherapy Courses 1, 2, 3, and 4: 6mg; SQ starting 24 hours after chemotherapy Postoperative Chemotherapy for Good Responders Courses 1, 2, and 3: 6mg; SQ starting 24 hours after chemotherapy Postoperative Chemotherapy for Poor Responders Courses 2 and 4: 6mg; SQ starting 24 hours after chemotherapy

Pre-op treatment

Etoposide DRUG

Preoperative Chemotherapy Courses 2 and 4: 50mg/m2 on days 1, 2, 3, 4 Postoperative Chemotherapy for Good Responders Course 2: 50mg/m2 on days 1, 2, 3, 4 Course 3: 50mg/m2 on days, 1, 2, 3, 4 Hour 0-1 Postoperative Chemotherapy for Poor Responders Course 4: 50mg/m2 on days 1, 2, 3, 4 Course 5: 50mg/m2 on days 1, 2, 3, 4

Pre-op treatment

Ifosfamide DRUG

Preoperative Chemotherapy Courses 2 and 4: 3g/m2; IV over 1 hour Days 1, 2, 3, 4 Postoperative Chemotherapy for Good Responders Course 2: 3g/m2; IV over 1 hour Days 1, 2, 3, 4 Course 3: 3g/m2; IV over 1 hour Days 1, 2, 3, 4 Postoperative Chemotherapy for Poor Responders Course 4: 3g/m2; IV over 1 hour Days 1, 2, 3, 4 Course 5: 3g/m2; IV over 1 hour Days 1, 2, 3, 4

Pre-op treatment

Mesna DRUG

Preoperative Chemotherapy Courses 2 and 4: 600mg/m2, 1st dose in bag with ifosfamide, 2nd dose IV over 3 hours immediately post ifosfamide infusion, Subsequent doses - hour 5, 8, 11, 14 (IV push) Postoperative Chemotherapy for Good Responders Courses 2 and 3: 600mg/m2, 1st dose in bag with ifosfamide, 2nd dose IV over 3 hours immediately post ifosfamide infusion, Subsequent doses - hour 5, 8, 11, 14 (IV push) Postoperative Chemotherapy for Poor Responders Courses 4 and 5: 600mg/m2, 1st dose in bag with ifosfamide, 2nd dose IV over 3 hours immediately post ifosfamide infusion, Subsequent doses - hour 5, 8, 11, 14 (IV push)

Pre-op treatment

Leucovorin DRUG

Postoperative Chemotherapy for Poor Responders Courses 1 and 3: 15 mg/m2/dose IV or PO every 6 hours, beginning 24 hours after start of methotrexate infusion and continuing until methotrexate level is \<0.1 uM

Pre-op treatment

Eligibility Criteria

• Age: 2 Years - 35 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Must be between 2 and 35 years of age at time of diagnosis
• Must have biopsy-proven, high-grade osteosarcoma.
• Patients with metastases are eligible as long as the lung is the only site of metastatic disease.
• The primary tumor and all pulmonary metastases must be deemed to be potentially resectable. There must be a commitment by the surgical team to resect the primary tumor at week 12, and pulmonary nodules at any point, unless the clinical situation indicates these interventions are not in the patient's best interest.
• Patients must have normal laboratory values and cardiac function as defined below:
• Creatinine clearance or radioisotope GFR of \> or equal to 70ml/min/1.73 m2 OR
• A serum creatinine based on age/gender as follows:
• Age Maximum Serum Creatinine (mg/dL) Male Female
• month to \< 6 months 0.4 0.4 6 months to \< 1 year 0.5 0.5
• to \< 2 years 0.6 0.6
• to \< 6 years 0.8 0.8
• to \< 10 years 1 1 10 to \< 13 years 1.2 1.2 13 to \< 16 years 1.5 1.4
• or equal to 16 years 1.7 1.4
• Cardiac: Adequate cardiac function is defined as:
• Shortening fraction of \> or equal to 28% by echocardiogram OR Ejection fraction of \> or equal to 50% by radionuclide angiogram

You may not qualify if:

• Patients with any low-grade osteosarcoma, post-radiation osteosarcoma, and osteosarcoma associated with Paget's disease are not eligible.
• Patients with metastases other than lung metastases are not eligible.
• Patients may not have received prior chemotherapy.

Sponsors & Collaborators

• University of Chicago: lead

Study Sites (1)

University of Chicago Department of Pediatrics Hematology/Oncology

Chicago, Illinois, 60637, United States

Location

MeSH Terms

Conditions

Osteosarcoma

Interventions

Dexrazoxane; Doxorubicin; Cisplatin; Granulocyte Colony-Stimulating Factor; pegfilgrastim; Etoposide; Ifosfamide; Mesna; Leucovorin

Condition Hierarchy (Ancestors)

Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma

Intervention Hierarchy (Ancestors)

Razoxane; Diketopiperazines; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Cyclophosphamide; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Oxazines; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfhydryl Compounds; Sulfur Compounds; Sulfonic Acids; Sulfur Acids; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes

Study Officials

• Stephen X. Skapek, MD

  University of Chicago

  PRINCIPAL INVESTIGATOR

• Andres Morales, MD

  University of Chicago

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 30, 2010
• First Posted: December 13, 2010
• Study Start: July 1, 2010
• Primary Completion: November 1, 2011
• Study Completion: November 1, 2011
• Last Updated: December 10, 2013

Record last verified: 2013-12

Locations

US (1)