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



Status:Recruiting
Conditions:Cancer, Cancer
Therapuetic Areas:Oncology
Healthy:No
Age Range:14 - Any
Updated:2/23/2019
Start Date:March 2015
Contact:Darren Feldman, MD
Phone:646 422-4491

Use our guide to learn which trials are right for you!

A Randomized Phase III Trial Comparing Conventional-Dose Chemotherapy Using Paclitaxel, Ifosfamide, and Cisplatin (TIP) With High-Dose Chemotherapy Using Mobilizing Paclitaxel Plus Ifosfamide Followed by High-Dose Carboplatin and Etoposide (TI-CE) as First Salvage Treatment in Relapsed or Refractory Germ Cell Tumors

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.

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.

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.
We found this trial at
55
sites
Greenville, South Carolina 29605
Principal Investigator: Jeffrey K. Giguere
Phone: 864-241-6251
?
mi
from
Greenville, SC
Click here to add this to my saved trials
666 Elm Street
Buffalo, New York 14263
(716) 845-2300
Principal Investigator: Ellis G. Levine
Phone: 800-767-9355
Roswell Park Cancer Institute Welcome to Roswell Park Cancer Institute (RPCI), America's first cancer center...
?
mi
from
Buffalo, NY
Click here to add this to my saved trials
3333 Burnet Avenue # Mlc3008
Cincinnati, Ohio 45229
 1-513-636-4200 
Principal Investigator: James I. Geller
Phone: 888-823-5923
Cincinnati Children's Hospital Medical Center Patients and families from across the region and around the...
?
mi
from
Cincinnati, OH
Click here to add this to my saved trials
262 Danny Thomas Pl
Memphis, Tennessee 38105
(901) 495-3300
Principal Investigator: Alberto S. Pappo
Phone: 888-823-5923
St. Jude Children's Research Hospital St. Jude is unlike any other pediatric treatment and research...
?
mi
from
Memphis, TN
Click here to add this to my saved trials
South 34th Street
Philadelphia, Pennsylvania 19104
 215-590-1000
Principal Investigator: Frank M. Balis
Phone: 888-823-5923
Children's Hospital of Philadelphia Since its start in 1855 as the nation's first hospital devoted...
?
mi
from
Philadelphia, PA
Click here to add this to my saved trials
1500 East Medical Center Drive
Ann Arbor, Michigan 48109
800-865-1125
Principal Investigator: David C. Smith
University of Michigan Comprehensive Cancer Center The U-M Comprehensive Cancer Center's mission is the conquest...
?
mi
from
Ann Arbor, MI
Click here to add this to my saved trials
Atlanta, Georgia 30322
Principal Investigator: Bradley C. Carthon
Phone: 404-778-1868
?
mi
from
Atlanta, GA
Click here to add this to my saved trials
Basking Ridge, New Jersey 07920
Principal Investigator: Darren R. Feldman
Phone: 212-639-5007
?
mi
from
Basking Ridge, NJ
Click here to add this to my saved trials
450 Brookline Ave
Boston, Massachusetts 2215
617-632-3000
Principal Investigator: A. L. Frazier
Phone: 877-442-3324
Dana-Farber Cancer Institute Since it’s founding in 1947, Dana-Farber has been committed to providing adults...
?
mi
from
Boston, MA
Click here to add this to my saved trials
Camperdown, New South Wales 2050
Principal Investigator: Peter S. Grimison
Phone: 61 (02) 9515 6766
?
mi
from
Camperdown,
Click here to add this to my saved trials
Chapel Hill, North Carolina 27599
Principal Investigator: Matthew I. Milowsky
Phone: 877-668-0683
?
mi
from
Chapel Hill, NC
Click here to add this to my saved trials
171 Ashley Avenue
Charleston, South Carolina 29425
843-792-1414
Principal Investigator: Jacqueline M. Kraveka
Phone: 843-792-9321
Medical University of South Carolina The Medical University of South Carolina (MUSC) has grown from...
?
mi
from
Charleston, SC
Click here to add this to my saved trials
Charlotte, North Carolina 28204
Principal Investigator: Joel A. Kaplan
Phone: 800-804-9376
?
mi
from
Charlotte, NC
Click here to add this to my saved trials
1653 W. Congress Parkway
Chicago, Illinois 60612
(312) 942-5000
Principal Investigator: Mary L. Schmidt
Phone: 312-942-5498
Rush University Medical Center Rush University Medical Center encompasses a 664-bed hospital serving adults and...
?
mi
from
Chicago, IL
Click here to add this to my saved trials
5841 S Maryland Ave
Chicago, Illinois 60637
1-773-702-6180
Principal Investigator: Walter M. Stadler
Phone: 773-702-8222
University of Chicago Comprehensive Cancer Center The University of Chicago Comprehensive Cancer Center (UCCCC) is...
?
mi
from
Chicago, IL
Click here to add this to my saved trials
303 East Superior Street
Chicago, Illinois 60611
Phone: 312-472-1234
?
mi
from
Chicago, IL
Click here to add this to my saved trials
Columbus, Ohio 43210
Principal Investigator: J. P. Monk
Phone: 800-293-5066
?
mi
from
Columbus, OH
Click here to add this to my saved trials
Commack, New York 11725
Principal Investigator: Darren R. Feldman
Phone: 631-623-4000
?
mi
from
Commack, NY
Click here to add this to my saved trials
Easley, South Carolina 29640
Principal Investigator: Jeffrey K. Giguere
Phone: 864-241-6251
?
mi
from
Easley, SC
Click here to add this to my saved trials
1600 Southwest Archer Road
Gainesville, Florida 32610
Principal Investigator: William B. Slayton
Phone: 352-273-8010
?
mi
from
Gainesville, FL
Click here to add this to my saved trials
100 Michigan St NE
Grand Rapids, Michigan 49503
(616) 391-1774
Principal Investigator: Kathleen J. Yost
Phone: 616-391-1230
Spectrum Health at Butterworth Campus Butterworth Hospital is one of four facilities that make up...
?
mi
from
Grand Rapids, MI
Click here to add this to my saved trials
Greenville, South Carolina 29607
Principal Investigator: Robert D. Siegel
Phone: 864-603-6213
?
mi
from
Greenville, SC
Click here to add this to my saved trials
1 St. Francis Drive
Greenville, South Carolina 29601
864-255-1000
Principal Investigator: Robert D. Siegel
Phone: 864-603-6213
Saint Francis Hospital This 245-bed, all-private-room facility is located near downtown Greenville, South Carolina. Formerly...
?
mi
from
Greenville, SC
Click here to add this to my saved trials
Greenville, South Carolina 29605
Principal Investigator: Jeffrey K. Giguere
Phone: 864-241-6251
?
mi
from
Greenville, SC
Click here to add this to my saved trials
Greenville, South Carolina 29615
Principal Investigator: Jeffrey K. Giguere
Phone: 864-241-6251
?
mi
from
Greenville, SC
Click here to add this to my saved trials
701 Grove Rd
Greenville, South Carolina 29605
(864) 455-7000
Principal Investigator: Jeffrey K. Giguere
Phone: 864-241-6251
Greenville Memorial Hospital Greenville Memorial Medical Campus is a regional referral center for the diagnosis...
?
mi
from
Greenville, SC
Click here to add this to my saved trials
Greer, South Carolina 29650
Principal Investigator: Jeffrey K. Giguere
Phone: 864-241-6251
?
mi
from
Greer, SC
Click here to add this to my saved trials
30 Prospect Ave
Hackensack, New Jersey 07601
(201) 996-2000
Principal Investigator: Burton E. Appel
Phone: 201-996-2879
Hackensack University Medical Center Hackensack University Medical Center, part of the Hackensack University Health Network,...
?
mi
from
Hackensack, NJ
Click here to add this to my saved trials
500 Westchester Avenue
Harrison, New York 10604
Principal Investigator: Darren R. Feldman
Phone: 212-639-7592
?
mi
from
Harrison, NY
Click here to add this to my saved trials
Houston, Texas 77030
Principal Investigator: Matthew T. Campbell
Phone: 877-312-3961
?
mi
from
Houston, TX
Click here to add this to my saved trials
3855 Health Sciences Dr,
La Jolla, California 92093
(858) 822-6100
Principal Investigator: Divya T. Koura
Phone: 858-822-5354
UC San Diego Moores Cancer Center Established in 1978, UC San Diego Moores Cancer Center...
?
mi
from
La Jolla, CA
Click here to add this to my saved trials
11234 Anderson St
Loma Linda, California 92354
(909) 558-4000
Principal Investigator: Albert Kheradpour
Phone: 909-558-3375
Loma Linda University Medical Center An outgrowth of the original Sanitarium on the hill in...
?
mi
from
Loma Linda, CA
Click here to add this to my saved trials
1441 Eastlake Ave
Los Angeles, California 90033
(323) 865-3000
Principal Investigator: James S. Hu
Phone: 323-865-0451
U.S.C./Norris Comprehensive Cancer Center The USC Norris Comprehensive Cancer Center, located in Los Angeles, is...
?
mi
from
Los Angeles, CA
Click here to add this to my saved trials
Miami, Florida 33155
Principal Investigator: Enrique A. Escalon
Phone: 888-823-5923
?
mi
from
Miami, FL
Click here to add this to my saved trials
Middletown, New Jersey 07748
?
mi
from
Middletown, NJ
Click here to add this to my saved trials
9200 W Wisconsin Ave
Milwaukee, Wisconsin 53226
(414) 805-3666
Principal Investigator: Deepak Kilari
Phone: 414-805-4380
Froedtert and the Medical College of Wisconsin Froedtert Health combines with the Medical College of...
?
mi
from
Milwaukee, WI
Click here to add this to my saved trials
2525 Chicago Ave
Minneapolis, Minnesota 55404
(612) 813-6000
Principal Investigator: Michael K. Richards
Phone: 888-823-5923
Children's Hospitals and Clinics of Minnesota - Minneapolis Children's Hospitals and Clinics of Minnesota is...
?
mi
from
Minneapolis, MN
Click here to add this to my saved trials
Nashville, Tennessee 37232
Principal Investigator: Scott C. Borinstein
Phone: 800-811-8480
?
mi
from
Nashville, TN
Click here to add this to my saved trials
Nashville, Tennessee 37203
Principal Investigator: Haydar A. Frangoul
Phone: 888-823-5923
?
mi
from
Nashville, TN
Click here to add this to my saved trials
1275 York Ave
New York, New York 10021
(212) 639-2000
Principal Investigator: Darren R. Feldman
Phone: 212-639-7592
Memorial Sloan Kettering Cancer Center Memorial Sloan Kettering Cancer Center — the world's oldest and...
?
mi
from
New York, NY
Click here to add this to my saved trials
940 NE 13th St
Oklahoma City, Oklahoma 73190
(405) 271-6458
Principal Investigator: Abhishek Tripathi
Phone: 405-271-8777
University of Oklahoma Health Sciences Center The OU Health Sciences Center is composed of seven...
?
mi
from
Oklahoma City, OK
Click here to add this to my saved trials
8303 Dodge Street
Omaha, Nebraska 68114
(402) 354–4000
Principal Investigator: Ralph J. Hauke
Phone: 402-354-5144
Nebraska Methodist Hospital Methodist Hospital is a general medical and surgical hospital in Omaha, NE....
?
mi
from
Omaha, NE
Click here to add this to my saved trials
875 Blake Wilbur Drive
Palo Alto, California 94304
Principal Investigator: Sandy Srinivas
Phone: 650-498-7061
?
mi
from
Palo Alto, CA
Click here to add this to my saved trials
Philadelphia, Pennsylvania 19104
Principal Investigator: David J. Vaughn
Phone: 800-474-9892
?
mi
from
Philadelphia, PA
Click here to add this to my saved trials
Pittsburgh, Pennsylvania 15232
Principal Investigator: Leonard J. Appleman
Phone: 412-647-8073
?
mi
from
Pittsburgh, PA
Click here to add this to my saved trials
Rochester, Minnesota 55905
Principal Investigator: Brian A. Costello
Phone: 855-776-0015
?
mi
from
Rochester, MN
Click here to add this to my saved trials
Rockville Centre, New York 11570
Principal Investigator: Darren R. Feldman
Phone: 516-256-3651
?
mi
from
Rockville Centre, NY
Click here to add this to my saved trials
660 S Euclid Ave
Saint Louis, Missouri 63110
(314) 362-5000
Principal Investigator: Joel Picus
Phone: 800-600-3606
Washington University School of Medicine Washington University Physicians is the clinical practice of the School...
?
mi
from
Saint Louis, MO
Click here to add this to my saved trials
Saint Petersburg, Florida 33701
Principal Investigator: Jennifer L. Mayer
Phone: 888-823-5923
?
mi
from
Saint Petersburg, FL
Click here to add this to my saved trials
San Francisco, California 94158
Principal Investigator: Terence W. Friedlander
Phone: 877-827-3222
?
mi
from
San Francisco, CA
Click here to add this to my saved trials
Seneca, South Carolina 29672
Principal Investigator: Jeffrey K. Giguere
Phone: 864-241-6251
?
mi
from
Seneca, SC
Click here to add this to my saved trials
Spartanburg, South Carolina 29307
Principal Investigator: Jeffrey K. Giguere
Phone: 864-241-6251
?
mi
from
Spartanburg, SC
Click here to add this to my saved trials
929 N St Francis St
Wichita, Kansas 67214
(316) 268-5775
Principal Investigator: Shaker R. Dakhil
Phone: 800-362-0070
Via Christi Regional Medical Center Via Christi Health's rich history of serving the people of...
?
mi
from
Wichita, KS
Click here to add this to my saved trials
Wichita, Kansas 67214
Principal Investigator: Shaker R. Dakhil
Phone: 316-268-5374
?
mi
from
Wichita, KS
Click here to add this to my saved trials
5900 Byron Center Ave SW
Wyoming, Michigan 49519
(616) 252-7200
Principal Investigator: Kathleen J. Yost
Phone: 616-391-1230
Metro Health Hospital Metro Health is an integrated healthcare system offering expert, award-winning care that
?
mi
from
Wyoming, MI
Click here to add this to my saved trials