Combination Chemotherapy and Peripheral Stem Cell Transplantation in Treating Patients With Sarcoma

NCT00002601 | Completed Phase 2 Results

• 5 other identifiers: 94072P30CA033572CHNMC-IRB-94072NCI-V94-0545CDR0000063845
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug and combining chemotherapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of high-dose combination chemotherapy and peripheral stem cell transplantation in treating patients who have advanced or recurrent sarcoma.

Conditions

Sarcoma

Keywords

metastatic osteosarcoma; recurrent childhood rhabdomyosarcoma; recurrent adult soft tissue sarcoma; recurrent osteosarcoma; adult rhabdomyosarcoma; metastatic childhood soft tissue sarcoma; recurrent childhood soft tissue sarcoma; previously treated childhood rhabdomyosarcoma; metastatic Ewing sarcoma/peripheral primitive neuroectodermal tumor; recurrent Ewing sarcoma/peripheral primitive neuroectodermal tumor; stage IV adult soft tissue sarcoma

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Grade 3 Bilirubin

  Criteria for early termination of this feasibility study: \> 2 patients experience grade 4 or 5 hematologic toxicity or more that 3 patients experience grade 3 hematologic toxicity; \> 2 patients experience grade 3 hepatic or gastrointestinal toxicity or \> 3 patients are unable to receive the second cycle of treatment; \> 2 patients experience grade 5 toxicity related to treatment regimen.

  2 years after completion of treatment

• Toxicities Counts

  Number of patients with grade 3 and 4 toxicities observed during cycles 1 \& 2 using the Common Toxicity Criteria Version for Chemotherapy.

  2 months after completion of second cycle of treatment.

Secondary Outcomes (2)

• 5-year Progression-free Survival

  Until disease progression, up to 5 Years

• 5-year Overall Survival

  Until death from any cause, up to 5 years

Study Arms (1)

Doxorubicin/Ifosfamide + Melphalan/CDDP + PSCT

EXPERIMENTAL

Cycle 1 Day -8 through Day -4 (96h) Doxorubicin 150 mg/m2 (CI) + Ifosfamide 14 g/m2 mixed with mesna (CI) Day -3 Mesna 3.5 g/m2 over 24 h Day -2 12.5% of stem cell reinfused. Cycle2 Day -11 Melphalan 75 mg/m2 + Cisplatin 100 mg/m2 Day -10 thru Day -6 G-CSF 5ug/kg Day -4 Melphalan 75 mg/m2 + Cisplatin 100 mg/m2 Day -3 12.5% if stem cell reinfused Day 0 37.5% of stem cell reinfused

Biological: filgrastim; Drug: cisplatin; Drug: doxorubicin hydrochloride; Drug: ifosfamide; Drug: melphalan; Procedure: peripheral blood stem cell transplantation

Interventions

filgrastim BIOLOGICAL

5 ug/kg daily following stem cell reinfusion

Doxorubicin/Ifosfamide + Melphalan/CDDP + PSCT

cisplatin DRUG

Course 2 - 100 mg/m2 at an infusion rate of 25 mg/hr

Doxorubicin/Ifosfamide + Melphalan/CDDP + PSCT

doxorubicin hydrochloride DRUG

Course 1 - 150 mg/m2 by continuous intravenous infusion for 96 hours.

Doxorubicin/Ifosfamide + Melphalan/CDDP + PSCT

ifosfamide DRUG

Course 1 - 14 gm/M2 by continuous intravenous infusion for 96 hours.

Doxorubicin/Ifosfamide + Melphalan/CDDP + PSCT

melphalan DRUG

Course 2 - 75 mg/m2 infused at a rate of 5 mg/minute

Doxorubicin/Ifosfamide + Melphalan/CDDP + PSCT

peripheral blood stem cell transplantation PROCEDURE

Administered on Day 0 following high-dose chemotherapy in both courses 1 and 2

Doxorubicin/Ifosfamide + Melphalan/CDDP + PSCT

Eligibility Criteria

• Age: 10 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

DISEASE CHARACTERISTICS: Histologically confirmed sarcomas in the following categories: Soft tissue sarcoma (STS) High-grade STS of the extremities Primary extending to fascia or locally recurrent At least 10 cm in greatest dimension or multifocal on surgical pathology Primary site controlled by surgery and/or radiotherapy High-grade truncal or head and neck sarcoma At least 10 cm in greatest dimension or any size with no surgical options for clear margins Primary site controlled by surgery and/or radiotherapy Locally recurrent disease in CR or PR after surgery, chemotherapy, or radiotherapy Metastatic STS in CR or PR after surgery, chemotherapy, or radiotherapy Osteosarcoma (OS) Extremity OS after neoadjuvant chemotherapy and surgical resection provided: Less than 50% necrosis in the surgical specimen LDH or alkaline phosphatase greater than 2 times normal at presentation Axial OS in CR or PR after chemotherapy and/or surgery Primary or recurrent metastatic OS in CR or PR after chemotherapy, surgery, and/or radiotherapy Ewing's sarcoma or primitive neuroectodermal tumor Primary site in CR or PR after chemotherapy, radiotherapy, or surgery Rib, pelvic, or axial skeleton primary Bulky tumor (at least 10 cm in greatest diameter) Primary or recurrent metastatic disease in CR or PR after surgery, chemotherapy, or radiotherapy Rhabdomyosarcoma Gross residual disease after primary treatment with surgery, chemotherapy, and radiotherapy Primary group IV or recurrent metastatic disease in CR or PR after chemotherapy and radiotherapy with or without surgery No brain metastasis No histologically confirmed bone marrow metastasis Prior metastases allowed with clearing of bone marrow at entry No contraindication to collection of mobilized stem cells or, if needed, autologous bone marrow PATIENT CHARACTERISTICS: Age: 10 to 55 Performance status: Karnofsky 80-100% Hematopoietic: Absolute neutrophil count greater than 2,000/mm3 Platelet count greater than 150,000/mm3 Hemoglobin greater than 10 g/dL Hepatic: See Disease Characteristics Bilirubin less than 1.5 mg/dL AST and ALT less than 3 times normal Hepatitis B surface antigen negative Negative hepatitis C antigen test required in patients with hepatitis C antibody Renal: Creatinine less than 1.4 mg/dL Creatinine clearance greater than 75 mL/min Cardiovascular: LVEF at least 55% by MUGA or echocardiogram No history of significant cardiac disease Pulmonary: FEV1 greater than 2 liters PaO2 greater than 70 mm Hg on room air PaCO2 less than 42 mm Hg on room air DLCO greater than 60% predicted Other: No hearing loss of greater than 40 decibels HIV negative No organic or psychiatric CNS dysfunction that would preclude study No other medical or psychosocial problems that would place patient at unacceptable risk No history of other malignancy except nonmelanoma skin cancer or carcinoma in situ of the cervix Not pregnant Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: More than 2 weeks since treatment to control primary or recurrent tumor Biologic therapy: Not specified Chemotherapy: See Disease Characteristics No more than 2 prior chemotherapy regimens (including adjuvant therapy) Prior cumulative cisplatin dose less than 400 mg/m2 Prior cumulative doxorubicin dose less than 240 mg/m2 Endocrine therapy: Not specified Radiotherapy: See Disease Characteristics No prior radiotherapy to more than 20% of the bone marrow-containing axial skeleton No prior radiotherapy to the left chest wall Surgery: See Disease Characteristics

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Cancer Center and Beckman Research Institute, City of Hope

Duarte, California, 91010-3000, United States

Location

MeSH Terms

Conditions

Sarcoma; Osteosarcoma; Rhabdomyosarcoma; Neuroectodermal Tumors, Primitive, Peripheral

Interventions

Filgrastim; Cisplatin; Doxorubicin; Ifosfamide; Melphalan; Peripheral Blood Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Myosarcoma; Neoplasms, Muscle Tissue; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Cyclophosphamide; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Results Point of Contact

• Title: Paul Frankel, Ph.D.
• Organization: City of Hope

pfrankel@och.org

(626)256-4673

Study Officials

• George Somlo, MD

  City of Hope Comprehensive Cancer Center

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 1, 1999
• First Posted: March 11, 2004
• Study Start: September 1, 1994
• Primary Completion: September 1, 2014
• Study Completion: September 1, 2014
• Last Updated: March 3, 2017
• Results First Posted: January 19, 2017

Record last verified: 2017-01

Locations

US (1)