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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02375204




Registration number
NCT02375204
Ethics application status
Date submitted
20/02/2015
Date registered
25/02/2015
Date last updated
22/01/2019

Titles & IDs
Public title
Standard-Dose Combination Chemotherapy or High-Dose Combination Chemotherapy and Stem Cell Transplant in Treating Patients With Relapsed or Refractory Germ Cell Tumors
Scientific title
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
Secondary ID [1] 0 0
U10CA180821
Secondary ID [2] 0 0
A031102
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Germ Cell Tumor 0 0
Teratoma 0 0
Choriocarcinoma 0 0
Germinoma 0 0
Mixed Germ Cell Tumor 0 0
Yolk Sac Tumor 0 0
Childhood Teratoma 0 0
Malignant Germ Cell Neoplasm 0 0
Extragonadal Seminoma 0 0
Non-seminomatous Germ Cell Tumor 0 0
Seminoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Ovarian and primary peritoneal
Cancer 0 0 0 0
Testicular
Cancer 0 0 0 0
Other cancer types
Cancer 0 0 0 0
Womb (Uterine or endometrial cancer)
Reproductive Health and Childbirth 0 0 0 0
Fetal medicine and complications of pregnancy

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - paclitaxel
Treatment: Drugs - ifosfamide
Treatment: Drugs - cisplatin
Treatment: Drugs - pegylated G-CSF
Treatment: Drugs - G-CSF
Treatment: Drugs - carboplatin
Treatment: Drugs - etoposide phosphate
Treatment: Surgery - stem cell reinfusion

Other: 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.

Other: 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.


Treatment: Drugs: paclitaxel
IV

Treatment: Drugs: ifosfamide
IV

Treatment: Drugs: cisplatin
IV

Treatment: Drugs: pegylated G-CSF
IV

Treatment: Drugs: G-CSF
IV

Treatment: Drugs: carboplatin
IV

Treatment: Drugs: etoposide phosphate
IV

Treatment: Surgery: stem cell reinfusion
surgical procedure

Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Surgery
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
overall survival
Timepoint [1] 0 0
Up to 36 months post-treatment
Secondary outcome [1] 0 0
progression free survival
Timepoint [1] 0 0
Up to 36 months post-treatment
Secondary outcome [2] 0 0
proportion of patients achieving either a complete response (CR) or partial response
Timepoint [2] 0 0
Up to 3 months post-registration
Secondary outcome [3] 0 0
treatment related mortality
Timepoint [3] 0 0
Up to 30 days post-treatment
Secondary outcome [4] 0 0
number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Timepoint [4] 0 0
Up to 3 months post-registration
Secondary outcome [5] 0 0
Validation of International Prognostic Factor Study Group stratification system (eg, primary site, prior response, progression free interval)
Timepoint [5] 0 0
Up to 3 years post-registration

Eligibility
Key inclusion criteria
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.
Minimum age
14 Years
Maximum age
No limit
Gender
Males
Can healthy volunteers participate?
No
Key exclusion criteria

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [3] 0 0
Box Hill Hospital - Box Hill
Recruitment hospital [4] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [3] 0 0
3128 - Box Hill
Recruitment postcode(s) [4] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Kansas
Country [6] 0 0
United States of America
State/province [6] 0 0
Massachusetts
Country [7] 0 0
United States of America
State/province [7] 0 0
Michigan
Country [8] 0 0
United States of America
State/province [8] 0 0
Minnesota
Country [9] 0 0
United States of America
State/province [9] 0 0
Missouri
Country [10] 0 0
United States of America
State/province [10] 0 0
Nebraska
Country [11] 0 0
United States of America
State/province [11] 0 0
New Jersey
Country [12] 0 0
United States of America
State/province [12] 0 0
New York
Country [13] 0 0
United States of America
State/province [13] 0 0
North Carolina
Country [14] 0 0
United States of America
State/province [14] 0 0
Ohio
Country [15] 0 0
United States of America
State/province [15] 0 0
Oklahoma
Country [16] 0 0
United States of America
State/province [16] 0 0
Pennsylvania
Country [17] 0 0
United States of America
State/province [17] 0 0
South Carolina
Country [18] 0 0
United States of America
State/province [18] 0 0
Tennessee
Country [19] 0 0
United States of America
State/province [19] 0 0
Texas
Country [20] 0 0
United States of America
State/province [20] 0 0
Wisconsin
Country [21] 0 0
Belgium
State/province [21] 0 0
Brussels
Country [22] 0 0
Belgium
State/province [22] 0 0
Bruxelles
Country [23] 0 0
Denmark
State/province [23] 0 0
Copenhagen
Country [24] 0 0
France
State/province [24] 0 0
Lyon
Country [25] 0 0
France
State/province [25] 0 0
Marseille
Country [26] 0 0
France
State/province [26] 0 0
Paris
Country [27] 0 0
France
State/province [27] 0 0
Strasbourg
Country [28] 0 0
France
State/province [28] 0 0
Toulouse
Country [29] 0 0
France
State/province [29] 0 0
Villejuif
Country [30] 0 0
Germany
State/province [30] 0 0
Saxony
Country [31] 0 0
Germany
State/province [31] 0 0
Dusseldorf
Country [32] 0 0
Germany
State/province [32] 0 0
Essen
Country [33] 0 0
Germany
State/province [33] 0 0
Hamburg
Country [34] 0 0
Germany
State/province [34] 0 0
Koblenz
Country [35] 0 0
Germany
State/province [35] 0 0
Marburg
Country [36] 0 0
Germany
State/province [36] 0 0
Munich
Country [37] 0 0
Germany
State/province [37] 0 0
Ulm
Country [38] 0 0
Ireland
State/province [38] 0 0
Dublin
Country [39] 0 0
Italy
State/province [39] 0 0
Busto Arsizio
Country [40] 0 0
Italy
State/province [40] 0 0
Meldola
Country [41] 0 0
Italy
State/province [41] 0 0
Milano
Country [42] 0 0
Italy
State/province [42] 0 0
Pavia
Country [43] 0 0
Netherlands
State/province [43] 0 0
Amsterdam
Country [44] 0 0
Netherlands
State/province [44] 0 0
Groningen
Country [45] 0 0
Netherlands
State/province [45] 0 0
Nijmegen
Country [46] 0 0
Spain
State/province [46] 0 0
Barcelona
Country [47] 0 0
Spain
State/province [47] 0 0
Murcia
Country [48] 0 0
Switzerland
State/province [48] 0 0
Bern
Country [49] 0 0
Switzerland
State/province [49] 0 0
Geneva
Country [50] 0 0
Switzerland
State/province [50] 0 0
Zurich
Country [51] 0 0
United Kingdom
State/province [51] 0 0
England
Country [52] 0 0
United Kingdom
State/province [52] 0 0
Scotland
Country [53] 0 0
United Kingdom
State/province [53] 0 0
Surrey

Funding & Sponsors
Primary sponsor type
Other
Name
Alliance for Clinical Trials in Oncology
Address
Country
Other collaborator category [1] 0 0
Government body
Name [1] 0 0
National Cancer Institute (NCI)
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
European Organisation for Research and Treatment of Cancer - EORTC
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
Movember Foundation
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Other
Name [4] 0 0
Institute of Cancer Research (ICR), United Kingdom
Address [4] 0 0
Country [4] 0 0
Other collaborator category [5] 0 0
Other
Name [5] 0 0
Cancer Research UK
Address [5] 0 0
Country [5] 0 0
Other collaborator category [6] 0 0
Other
Name [6] 0 0
UNICANCER
Address [6] 0 0
Country [6] 0 0
Other collaborator category [7] 0 0
Other
Name [7] 0 0
Irish Group CTI
Address [7] 0 0
Country [7] 0 0

Ethics approval
Ethics application status

Summary
Brief 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.
Trial website
https://clinicaltrials.gov/show/NCT02375204
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Darren Feldman, MD
Address 0 0
Memorial Sloan Kettering Cancer Center
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Darren Feldman, MD
Address 0 0
Country 0 0
Phone 0 0
646 422-4491
Fax 0 0
Email 0 0
Contact person for scientific queries

No data has been provided for results reporting
Summary results
Not applicable