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Standard-Dose Combination Che...

Standard-Dose Combination Chemotherapy or High-Dose Combination Chemotherapy and Stem Cell Transplant in Treating Patients with Relapsed or Refractory Germ Cell Tumors

Last Updated: 2025-01-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

420 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-08-06

Study Completion Date

2031-06-01

Brief Summary

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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.

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Detailed Description

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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.

Conditions

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Germ Cell Tumor Teratoma Choriocarcinoma Germinoma Mixed Germ Cell Tumor Yolk Sac Tumor Childhood Teratoma Malignant Germ Cell Neoplasm Extragonadal Seminoma Non-seminomatous Germ Cell Tumor Seminoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm A: TIP

Patients will receive treatment for 4 cycles administered every 21 days.

Cycles 1-4 (1 cycle = 21 days)

* paclitaxel 250 mg/m\^2 IV over 24 hours on Day 1 including premedication as defined in the protocol (eg, dexamethasone, diphenhydramine and H2 blocker)
* ifosfamide 1500 mg/m\^2 IV daily on Days 2-5 with mesna protection as defined in the protocol
* cisplatin 25 mg/m\^2 IV daily on Days 2-5
* pegylated G-CSF 6 mg subcutaneous on Day 6 or 7 or G-CSF as defined in the protocol on Days 6-18

Patients may commence with each Arm A cycle provided they meet the criteria as defined in the protocol.

Group Type OTHER

paclitaxel

Intervention Type DRUG

ifosfamide

Intervention Type DRUG

cisplatin

Intervention Type DRUG

pegylated G-CSF

Intervention Type DRUG

G-CSF

Intervention Type DRUG

Arm B: TI-CE

Patients will receive treatment for a total of 5 cycles.

Cycles 1-2 (1 cycle = 14 days)

* paclitaxel 200 mg/m\^2 IV over 3 hours on Day 1 including premedication as defined in the protocol (eg, dexamethasone, diphenhydramine and H2 blocker)
* ifosfamide 2000 mg/m\^2 IV daily on Days 1-3 with mesna protection as defined in the protocol
* G-CSF 10 µg/kg subcutaneously on Days 3-15 (cycle 1) and Days 3-14 (cycle 2) or pegylated G-CSF 6 mg subcutaneous on Day 4 or 6 (cycle 1) and Day 4 or 5 (cycle 2)
* leukapheresis every 14 days, if there is an inadequate number of CD34+ cells/kg collected in cycle 1

Cycles 3-5 (1 cycle = 21 days)

* carboplatin daily on Days 1-3
* etoposide 400 mg/m\^2 daily on Days 1-3
* stem cell reinfusion on day 5
* pegylated G-CSF 6 mg subcutaneously or G-CSF at approximately 5 µg/kg daily on Days 5-15

Patients may commence with each Arm B cycle provided they meet the criteria as defined in the protocol.

Group Type OTHER

paclitaxel

Intervention Type DRUG

ifosfamide

Intervention Type DRUG

pegylated G-CSF

Intervention Type DRUG

G-CSF

Intervention Type DRUG

carboplatin

Intervention Type DRUG

etoposide phosphate

Intervention Type DRUG

stem cell reinfusion

Intervention Type PROCEDURE

surgical procedure

Interventions

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paclitaxel

Intervention Type DRUG

ifosfamide

Intervention Type DRUG

cisplatin

Intervention Type DRUG

pegylated G-CSF

Intervention Type DRUG

G-CSF

Intervention Type DRUG

carboplatin

Intervention Type DRUG

etoposide phosphate

Intervention Type DRUG

stem cell reinfusion

surgical procedure

Intervention Type PROCEDURE

Other Intervention Names

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Taxol Ifex®, IFOS CDDP Paraplatin®, CBDCA VePesid®, Toposar®, VP16

Eligibility Criteria

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Inclusion Criteria

* 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.

Minimum Eligible Age

14 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Darren Feldman, MD

Role: STUDY_CHAIR

Memorial Sloan Kettering Cancer Center

Locations

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Children's Hospital of Alabama

Birmingham, Alabama, United States

Site Status

UC San Diego Moores Cancer Center

La Jolla, California, United States

Site Status

Loma Linda University Medical Center

Loma Linda, California, United States

Site Status

USC / Norris Comprehensive Cancer Center

Los Angeles, California, United States

Site Status

Kaiser Permanente-Oakland

Oakland, California, United States

Site Status

Stanford Cancer Institute Palo Alto

Palo Alto, California, United States

Site Status

UCSF Medical Center-Mission Bay

San Francisco, California, United States

Site Status

Alfred I duPont Hospital for Children

Wilmington, Delaware, United States

Site Status

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, United States

Site Status

University of Florida Health Science Center - Gainesville

Gainesville, Florida, United States

Site Status

Nemours Children's Clinic-Jacksonville

Jacksonville, Florida, United States

Site Status

Nicklaus Children's Hospital

Miami, Florida, United States

Site Status

Miami Cancer Institute

Miami, Florida, United States

Site Status

Arnold Palmer Hospital for Children

Orlando, Florida, United States

Site Status

Johns Hopkins All Children's Hospital

St. Petersburg, Florida, United States

Site Status

Saint Joseph's Hospital/Children's Hospital-Tampa

Tampa, Florida, United States

Site Status

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, United States

Site Status

Northwestern University

Chicago, Illinois, United States

Site Status

Rush University Medical Center

Chicago, Illinois, United States

Site Status

University of Illinois

Chicago, Illinois, United States

Site Status

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, United States

Site Status

Ascension Via Christi Hospitals Wichita

Wichita, Kansas, United States

Site Status

Cancer Center of Kansas - Wichita

Wichita, Kansas, United States

Site Status

Ochsner Medical Center Jefferson

New Orleans, Louisiana, United States

Site Status

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Site Status

Spectrum Health at Butterworth Campus

Grand Rapids, Michigan, United States

Site Status

University of Michigan Health - West

Wyoming, Michigan, United States

Site Status

Children's Hospitals and Clinics of Minnesota - Minneapolis

Minneapolis, Minnesota, United States

Site Status

Mayo Clinic in Rochester

Rochester, Minnesota, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Nebraska Methodist Hospital

Omaha, Nebraska, United States

Site Status

Summerlin Hospital Medical Center

Las Vegas, Nevada, United States

Site Status

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, United States

Site Status

Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, United States

Site Status

Saint Joseph's Regional Medical Center

Paterson, New Jersey, United States

Site Status

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status

Memorial Sloan Kettering Commack

Commack, New York, United States

Site Status

Memorial Sloan Kettering Westchester

East White Plains, New York, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

Memorial Sloan Kettering Nassau

Uniondale, New York, United States

Site Status

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, United States

Site Status

Carolinas Medical Center/Levine Cancer Institute

Charlotte, North Carolina, United States

Site Status

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Site Status

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Site Status

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Site Status

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

University of Pennsylvania/Abramson Cancer Center

Philadelphia, Pennsylvania, United States

Site Status

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, United States

Site Status

Rhode Island Hospital

Providence, Rhode Island, United States

Site Status

Prisma Health Cancer Institute - Spartanburg

Boiling Springs, South Carolina, United States

Site Status

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status