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Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT02375204
Other study ID # A031102
Secondary ID U10CA180821NCI-2
Status Active, not recruiting
Phase Phase 3
First received
Last updated
Start date August 5, 2015
Est. completion date June 2024

Study information

Verified date March 2023
Source Alliance for Clinical Trials in Oncology
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This randomized phase III trial studies how well standard-dose combination chemotherapy works compared to high-dose combination chemotherapy and stem cell transplant in treating patients with germ cell tumors that have returned after a period of improvement or did not respond to treatment. Drugs used in chemotherapy, such as paclitaxel, ifosfamide, cisplatin, carboplatin, and etoposide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving chemotherapy before a stem cell transplant stops the growth of cancer cells by stopping them from dividing or killing them. Giving colony-stimulating factors, such as filgrastim or pegfilgrastim, and certain chemotherapy drugs, helps stem cells move from the bone marrow to the blood so they can be collected and stored. Chemotherapy is then given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy. It is not yet known whether high-dose combination chemotherapy and stem cell transplant are more effective than standard-dose combination chemotherapy in treating patients with refractory or relapsed germ cell tumors.


Description:

The study is an international collaboration with European sites. Collaborators on the study include the National Cancer Institute, the European Organization for Research and Treatment of Cancer and the Movember Foundation. Randomization will be stratified by region (North America and Europe) and by modified IPFSG (International Prognostic Factor Study Group) risk classification (low, intermediate and high). The primary and secondary objectives are described below. Primary Objective: 1. To compare the overall survival in patients treated with conventional-dose chemotherapy using the TIP regimen with high-dose chemotherapy (HDCT) plus autologous stem cell transplant (ASCT) using the TI-CE regimen as initial salvage treatment of patients with relapsed or refractory germ cell tumors (GCT) Secondary Objectives: 1. To compare the progression-free survival (PFS) of patients treated with initial salvage HDCT with TI-CE versus initial salvage CDCT with TIP 2. To compare the favorable response rate (FRR) of patients treated with initial salvage HDCT with TI-CE versus initial salvage CDCT with TIP 3. To compare the toxicity, including treatment-related mortality, associated with high-dose chemotherapy and ASCT using TI-CE compared with conventional-dose chemotherapy using TIP as initial salvage treatment for patients with relapsed or refractory GCT 4. To prospectively evaluate the IPFSG scoring system as a predictor of outcome to initial salvage therapy in patients with relapsed or refractory GCT. In this trial, randomization will be stratified by a modification of their IPFSG category and we will prospectively evaluate whether or not actual outcomes vary by risk group in the appropriate manner (low risk patients have higher OS than high-risk group). 5. To evaluate the association between tumor marker decline rates of Alpha-Fetoprotein (AFP) and Human Chorionic Gonadotropin (HCG) with OS and PFS. Treatment is to continue until disease progression, unacceptable toxicity or completion of all protocol treatment.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 420
Est. completion date June 2024
Est. primary completion date June 2024
Accepts healthy volunteers No
Gender Male
Age group 14 Years and older
Eligibility 1. Documentation of Disease - Histologic Documentation: Confirmation of GCT histology (both seminoma and nonseminoma) on pathologic review at the center of enrollment. - Tumor may have originated in any primary site. NOTE: In rare circumstances, patients will be allowed to enroll even if a pathologic diagnosis may not have been established. - This would require a clinical situation consistent with the diagnosis of GCT (testicular, peritoneal, retroperitoneal or mediastinal mass, elevated tumor marker levels {HCG = 500; AFP = 500} and typical pattern of metastases) 2. Evidence of Disease - Must have evidence of progressive or recurrent GCT (measurable or non-measurable) following one line of cisplatin-based chemotherapy, defined as meeting at least one of the following criteria: - Tumor biopsy of new or growing or unresectable lesions demonstrating viable non-teratomatous GCT (enrollment on this study for adjuvant treatment after macroscopically complete resection of viable GCT is not allowed). In the event of an incomplete gross resection where viable GCT is found, patients will be considered eligible for the study. - Consecutive elevated serum tumor markers (HCG or AFP) that are increasing. Increase of an elevated LDH alone does not constitute progressive disease. - Development of new or enlarging lesions in the setting of persistently elevated HCG or AFP, even if the HCG and AFP are not continuing to increase. 3. Prior Treatment - Must have received 3-6 cycles of cisplatin-based chemotherapy as part of first-line (initial) chemotherapy. - Prior POMBACE, CBOP-BEP, or GAMEC are allowed. - Note: For patients requiring immediate treatment, 1 cycle of conventional-dose salvage chemotherapy is allowed. Therefore, these patients may have received 7 prior cycles of chemotherapy. 6 cycles as part of first-line chemotherapy and 1 cycle of salvage conventional chemotherapy. - No more than one prior line of chemotherapy for GCT (other than the 1 cycle of salvage chemotherapy as defined in the protocol) - Definition of one line of chemotherapy: One line of therapy can in some cases consist of 2 different cisplatin-based treatment combinations, provided there is no disease progression between these two regimens. - Prior treatment with carboplatin as adjuvant therapy is allowed, provided patients meet other eligibility criteria (e.g., the patient has also received 3-4 cycles of cisplatin-based chemotherapy). - Prior treatment with 1-2 cycles of BEP or EP as adjuvant chemotherapy for early stage GCT is allowed, provided the patient also received 3-4 cycles of BEP or EP again at relapse. Patients treated with 3-4 cycles of VIP at relapse following 1-2 cycles of BEP/EP are not eligible as this would be considered more than 1 line of prior therapy. - No prior treatment with high-dose chemotherapy (defined as treatment utilizing stem cell rescue) - No prior treatment with TIP with the exception when given as a bridge to treatment on protocol for patients with rapidly progressive disease who cannot wait to complete the eligibility screening process. Only one cycle is allowed. - No concurrent treatment with other cytotoxic drugs or targeted therapies. - No radiation therapy (other than to the brain) within 14 days of day 1 of protocol chemotherapy except radiation to brain metastases, which must be completed 7 days prior to start of chemotherapy. - No previous chemotherapy within 17 days prior to enrollment. A minimum of three weeks after the last day of the start of the previous chemotherapy regimen before the first day of chemotherapy on study protocol. - Must have adequate recovery from prior surgery (eg, healed scar, resumption of diet) 4. Age = 14 years (= 18 years in Germany) 5. ECOG Performance Status 0 to 2 6. Male gender 7. Required Initial Laboratory Values: - Absolute Neutrophil Count (ANC) = 1,500/mm^3 - Platelet Count = 100,000/mm^3 - Calculated creatinine clearance = 50 mL/min - Bilirubin = 2.0 x upper limits of normal (ULN) - AST/ALT = 2.5 x upper limits of normal (ULN) 8. No concurrent malignancy other than non-melanoma skin cancer, superficial noninvasive (pTa or pTis) TCC of the bladder, contralateral GCT, or intratubular germ cell neoplasia. Patients with a prior malignancy, but at least 2 years since any evidence of disease are allowed. 9. Negative Serology (antibody test) for the following infectious diseases: - Human Immunodeficiency Virus (HIV) type 1 and 2 - Human T-cell Leukemia Virus (HTLV) type 1 and 2 (mandatory in US but optional in Canada and Europe) - Hepatitis B surface antigen - Hepatitis C antibody 10. No late relapse with completely surgically resectable disease. Patients with late relapses (defined as relapse = 2 years from the date of completion of the last chemotherapy regimen) whose disease is completely surgically resectable are not eligible. Patients with late relapses who have unresectable disease are eligible. 11. No large (= 2 cm) hemorrhagic or symptomatic brain metastases until local treatment has been administered (radiation therapy or surgery). Treatment may begin = 7 days after completion of local treatment. Patients with small (< 2 cm) and asymptomatic brain metastases are allowed and may be treated with radiation therapy and/or surgery concurrently with Arm A or cycles 1 and 2 of Arm B if deemed medically indicated. Radiation therapy should not be given concurrently with high-dose carboplatin or etoposide. 12. No secondary somatic malignancy arising from teratoma (e.g., teratoma with malignant transformation) when it is actively part of the disease recurrence or progression.

Study Design


Intervention

Drug:
paclitaxel
IV
ifosfamide
IV
cisplatin
IV
pegylated G-CSF
IV
G-CSF
IV
carboplatin
IV
etoposide phosphate
IV
Procedure:
stem cell reinfusion
surgical procedure

Locations

Country Name City State
Australia Box Hill Hospital Box Hill Victoria
Australia Royal Prince Alfred Hospital Camperdown New South Wales
Australia Peter MacCallum Cancer Centre Melbourne Victoria
Australia Princess Alexandra Hospital Woolloongabba Queensland
Belgium Institut Jules Bordet Anderlecht
Belgium University Hospital Saint Luc Brussels
Denmark Rigshospitalet University Hospital Copenhagen
France Centre Leon Berard Lyon
France Institut Paoli Calmettes Marseille
France Hopital Tenon/Assistance Publique - Hopitaux de Paris Paris
France CHRU Strasbourg - Hospital Civil Strasbourg
France Center Claudius Regaud Toulouse
France Centre Alexis Vautrin Vandoeuvre-les-Nancy
France Gustave Roussy Villejuif
Germany University of Berlin Charite Campus Benjamin Franklin Berlin
Germany Technical University Dresden Dresden Saxony
Germany University of Dusseldorf Dusseldorf
Germany University of Essen Essen
Germany University Medical Center Hamburg-Eppendorf Hamburg
Germany UniversitaetsKlinikum Heidelberg Heidelberg
Germany GK-Mittelrhein Saint Martin's Koblenz
Germany Philipps University Marburg Marburg
Germany Rotkreuzklinikum Munchen Munich
Germany Klinikum Nurnberg Nord Nurnberg
Germany University Hospital Ulm Ulm
Ireland Saint James Hospital Dublin
Italy Ospedale di Circolo di Busto Arsizio Busto Arsizio
Italy Istituto Scientifico Romagnolo Meldola
Italy Istituto Nazionale Tumori Milano
Italy San Matteo Hospital Pavia
Netherlands The Netherlands Cancer Institute Amsterdam
Netherlands University Medical Center Groningen Groningen
Netherlands Radboud University Nijmegen Medical Centre Nijmegen
Spain Duran i Reynals Hospital-Catalan Institute of Oncology Barcelona
Spain Hospital De La Santa Creu I Sant Pau Barcelona
Spain Hospital Universitario 12 de Octubre Madrid
Spain Hospital General Universitario Morales Meseguer Murcia
Switzerland Inselspital Bern
Switzerland Hopitaux Universitaires de Geneve Geneva
Switzerland University Hospital Zurich Zurich
United Kingdom Beatson Oncology Center Glasgow Scotland
United Kingdom Saint Bartholomew's Hospital London England
United Kingdom Christie Hospital Manchester England
United Kingdom Nottingham City Hospital Nottingham
United Kingdom Weston Park Hospital Sheffield England
United Kingdom Southampton General Hospital Southampton England
United Kingdom The Royal Marsden NHS Foundation Trust - Sutton Surrey
United Kingdom Saint James's University Hospital West Yorkshire England
United States University of Michigan Comprehensive Cancer Center Ann Arbor Michigan
United States Emory University Hospital/Winship Cancer Institute Atlanta Georgia
United States Memorial Sloan Kettering Basking Ridge Basking Ridge New Jersey
United States Children's Hospital of Alabama Birmingham Alabama
United States Prisma Health Cancer Institute - Spartanburg Boiling Springs South Carolina
United States Dana-Farber Cancer Institute Boston Massachusetts
United States Roswell Park Cancer Institute Buffalo New York
United States UNC Lineberger Comprehensive Cancer Center Chapel Hill North Carolina
United States Medical University of South Carolina Charleston South Carolina
United States Carolinas Medical Center/Levine Cancer Institute Charlotte North Carolina
United States Northwestern University Chicago Illinois
United States Rush University Medical Center Chicago Illinois
United States University of Chicago Comprehensive Cancer Center Chicago Illinois
United States University of Illinois Chicago Illinois
United States Cincinnati Children's Hospital Medical Center Cincinnati Ohio
United States Ohio State University Comprehensive Cancer Center Columbus Ohio
United States Memorial Sloan Kettering Commack Commack New York
United States Prisma Health Cancer Institute - Easley Easley South Carolina
United States Marshfield Medical Center-EC Cancer Center Eau Claire Wisconsin
United States El Paso Children's Hospital El Paso Texas
United States University of Florida Health Science Center - Gainesville Gainesville Florida
United States Spectrum Health at Butterworth Campus Grand Rapids Michigan
United States BI-LO Charities Children's Cancer Center Greenville South Carolina
United States Prisma Health Cancer Institute - Butternut Greenville South Carolina
United States Prisma Health Cancer Institute - Eastside Greenville South Carolina
United States Prisma Health Cancer Institute - Faris Greenville South Carolina
United States Prisma Health Greenville Memorial Hospital Greenville South Carolina
United States Saint Francis Cancer Center Greenville South Carolina
United States Saint Francis Hospital Greenville South Carolina
United States Prisma Health Cancer Institute - Greer Greer South Carolina
United States Hackensack University Medical Center Hackensack New Jersey
United States Memorial Sloan Kettering Westchester Harrison New York
United States M D Anderson Cancer Center Houston Texas
United States Nemours Children's Clinic-Jacksonville Jacksonville Florida
United States UC San Diego Moores Cancer Center La Jolla California
United States Summerlin Hospital Medical Center Las Vegas Nevada
United States Loma Linda University Medical Center Loma Linda California
United States USC / Norris Comprehensive Cancer Center Los Angeles California
United States Marshfield Medical Center-Marshfield Marshfield Wisconsin
United States Saint Jude Children's Research Hospital Memphis Tennessee
United States Miami Cancer Institute Miami Florida
United States Nicklaus Children's Hospital Miami Florida
United States Memorial Sloan Kettering Monmouth Middletown New Jersey
United States Medical College of Wisconsin Milwaukee Wisconsin
United States Children's Hospitals and Clinics of Minnesota - Minneapolis Minneapolis Minnesota
United States Marshfield Clinic-Minocqua Center Minocqua Wisconsin
United States The Children's Hospital at TriStar Centennial Nashville Tennessee
United States Vanderbilt University/Ingram Cancer Center Nashville Tennessee
United States Ochsner Medical Center Jefferson New Orleans Louisiana
United States Memorial Sloan Kettering Cancer Center New York New York
United States Kaiser Permanente-Oakland Oakland California
United States University of Oklahoma Health Sciences Center Oklahoma City Oklahoma
United States Nebraska Methodist Hospital Omaha Nebraska
United States Arnold Palmer Hospital for Children Orlando Florida
United States Stanford Cancer Institute Palo Alto Palo Alto California
United States Saint Joseph's Regional Medical Center Paterson New Jersey
United States Children's Hospital of Philadelphia Philadelphia Pennsylvania
United States University of Pennsylvania/Abramson Cancer Center Philadelphia Pennsylvania
United States University of Pittsburgh Cancer Institute (UPCI) Pittsburgh Pennsylvania
United States Rhode Island Hospital Providence Rhode Island
United States Marshfield Medical Center-Rice Lake Rice Lake Wisconsin
United States Mayo Clinic in Rochester Rochester Minnesota
United States Washington University School of Medicine Saint Louis Missouri
United States Johns Hopkins All Children's Hospital Saint Petersburg Florida
United States UCSF Medical Center-Mission Bay San Francisco California
United States Seattle Children's Hospital Seattle Washington
United States Prisma Health Cancer Institute - Seneca Seneca South Carolina
United States Spartanburg Medical Center Spartanburg South Carolina
United States Marshfield Medical Center-River Region at Stevens Point Stevens Point Wisconsin
United States Saint Joseph's Hospital/Children's Hospital-Tampa Tampa Florida
United States Memorial Sloan Kettering Nassau Uniondale New York
United States MedStar Georgetown University Hospital Washington District of Columbia
United States Marshfield Medical Center - Weston Weston Wisconsin
United States Ascension Via Christi Hospitals Wichita Wichita Kansas
United States Cancer Center of Kansas - Wichita Wichita Kansas
United States Alfred I duPont Hospital for Children Wilmington Delaware
United States University of Michigan Health - West Wyoming Michigan

Sponsors (8)

Lead Sponsor Collaborator
Alliance for Clinical Trials in Oncology Cancer Research UK, European Organisation for Research and Treatment of Cancer - EORTC, Institute of Cancer Research (ICR), United Kingdom, Irish Group CTI, Movember Foundation, National Cancer Institute (NCI), UNICANCER

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Denmark,  France,  Germany,  Ireland,  Italy,  Netherlands,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary overall survival Up to 36 months post-treatment
Secondary progression free survival Up to 36 months post-treatment
Secondary proportion of patients achieving either a complete response (CR) or partial response Up to 3 months post-registration
Secondary treatment related mortality Up to 30 days post-treatment
Secondary number of participants with treatment-related adverse events as assessed by CTCAE v4.0 Up to 3 months post-registration
Secondary Validation of International Prognostic Factor Study Group stratification system (eg, primary site, prior response, progression free interval) Up to 3 years post-registration
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