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History of Changes for Study: NCT02375204
Standard-Dose Combination Chemotherapy or High-Dose Combination Chemotherapy and Stem Cell Transplant in Treating Patients With Relapsed or Refractory Germ Cell Tumors
Latest version (submitted August 2, 2022) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 February 25, 2015 None (earliest Version on record)
2 March 2, 2015 Study Status and Outcome Measures
3 March 24, 2015 Study Description, Sponsor/Collaborators and Study Status
4 August 4, 2015 Recruitment Status, Study Status, Contacts/Locations and Oversight
5 October 1, 2015 Study Status, Contacts/Locations, Outcome Measures and Sponsor/Collaborators
6 December 8, 2015 Arms and Interventions, Study Status and Contacts/Locations
7 June 2, 2016 Contacts/Locations, Study Status, Arms and Interventions and Sponsor/Collaborators
8 July 26, 2016 Study Status, Outcome Measures and Sponsor/Collaborators
9 November 16, 2016 Contacts/Locations and Study Status
10 January 24, 2017 Contacts/Locations and Study Status
11 March 6, 2017 Contacts/Locations and Study Status
12 April 19, 2017 Contacts/Locations and Study Status
13 June 20, 2017 Study Status and Contacts/Locations
14 August 15, 2017 Contacts/Locations and Study Status
15 December 4, 2017 Study Status
16 February 5, 2018 Contacts/Locations and Study Status
17 March 6, 2018 Contacts/Locations and Study Status
18 April 6, 2018 Contacts/Locations and Study Status
19 May 4, 2018 Contacts/Locations and Study Status
20 June 8, 2018 Contacts/Locations and Study Status
21 July 16, 2018 Contacts/Locations and Study Status
22 August 6, 2018 Contacts/Locations and Study Status
23 September 5, 2018 Contacts/Locations and Study Status
24 January 22, 2019 Contacts/Locations and Study Status
25 February 19, 2019 Contacts/Locations and Study Status
26 May 14, 2019 Contacts/Locations and Study Status
27 June 18, 2019 Contacts/Locations and Study Status
28 August 2, 2019 Contacts/Locations and Study Status
29 September 18, 2019 Contacts/Locations and Study Status
30 October 21, 2019 Contacts/Locations and Study Status
31 November 19, 2019 Contacts/Locations and Study Status
32 January 7, 2020 Contacts/Locations and Study Status
33 February 4, 2020 Contacts/Locations and Study Status
34 March 4, 2020 Study Status and Contacts/Locations
35 April 9, 2020 Contacts/Locations and Study Status
36 May 6, 2020 Contacts/Locations and Study Status
37 June 3, 2020 Contacts/Locations and Study Status
38 July 22, 2020 Contacts/Locations and Study Status
39 September 3, 2020 Contacts/Locations and Study Status
40 October 8, 2020 Contacts/Locations and Study Status
41 November 10, 2020 Contacts/Locations and Study Status
42 January 8, 2021 Contacts/Locations and Study Status
43 February 5, 2021 Contacts/Locations and Study Status
44 March 5, 2021 Contacts/Locations and Study Status
45 June 9, 2021 Contacts/Locations and Study Status
46 July 19, 2021 Contacts/Locations and Study Status
47 August 16, 2021 Contacts/Locations and Study Status
48 August 25, 2021 Contacts/Locations and Study Status
49 October 11, 2021 Contacts/Locations and Study Status
50 November 11, 2021 Contacts/Locations and Study Status
51 December 13, 2021 Contacts/Locations and Study Status
52 January 11, 2022 Contacts/Locations and Study Status
53 February 16, 2022 Contacts/Locations and Study Status
54 March 22, 2022 Contacts/Locations and Study Status
55 April 18, 2022 Contacts/Locations and Study Status
56 June 3, 2022 Contacts/Locations and Study Status
57 July 15, 2022 Contacts/Locations and Study Status
58 August 2, 2022 Contacts/Locations and Study Status
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Study NCT02375204
Submitted Date:  February 25, 2015 (v1)

Open or close this module Study Identification
Unique Protocol ID: A031102
Brief Title: Standard-Dose Combination Chemotherapy or High-Dose Combination Chemotherapy and Stem Cell Transplant in Treating Patients With Relapsed or Refractory Germ Cell Tumors
Official 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 IDs: U10CA180821 [U.S. NIH Grant/Contract]
NCI-2014-01696 [Registry Identifier: NCI Clinical Trial Reporting Program]
Open or close this module Study Status
Record Verification: February 2015
Overall Status: Not yet recruiting
Study Start: March 2015
Primary Completion: March 2018 [Anticipated]
Study Completion:
First Submitted: February 20, 2015
First Submitted that
Met QC Criteria:
February 25, 2015
First Posted: March 2, 2015 [Estimate]
Last Update Submitted that
Met QC Criteria:
February 25, 2015
Last Update Posted: March 2, 2015 [Estimate]
Open or close this module Sponsor/Collaborators
Sponsor: Alliance for Clinical Trials in Oncology
Responsible Party: Sponsor
Collaborators: National Cancer Institute (NCI)
Open or close this module Oversight
U.S. FDA-regulated Drug:
U.S. FDA-regulated Device:
Data Monitoring: Yes
Open or close this module Study Description
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.
Detailed Description:

The study is an international collaboration with European sites. 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.

Open or close this module Conditions
Conditions: 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
Keywords:
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 3
Interventional Study Model: Parallel Assignment
Number of Arms: 2
Masking: None (Open Label)
Allocation: Randomized
Enrollment: 420 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Active Comparator: 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.

Drug: paclitaxel
IV
Other Names:
  • Taxol
Drug: ifosfamide
IV
Other Names:
  • Ifex®, IFOS
Drug: cisplatin
IV
Other Names:
  • CDDP
Drug: pegylated G-CSF
IV
Drug: G-CSF
IV
Experimental: 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.

Drug: paclitaxel
IV
Other Names:
  • Taxol
Drug: ifosfamide
IV
Other Names:
  • Ifex®, IFOS
Drug: pegylated G-CSF
IV
Drug: G-CSF
IV
Drug: carboplatin
IV
Other Names:
  • Paraplatin®, CBDCA
Drug: etoposide phosphate
IV
Other Names:
  • VePesid®, Toposar®, VP16
Procedure: stem cell reinfusion
surgical procedure
Open or close this module Outcome Measures
Primary Outcome Measures:
1. overall survival
[ Time Frame: Up to 36 months post-treatment ]

Secondary Outcome Measures:
1. progression free survival
[ Time Frame: Up to 36 months post-treatment ]

2. proportion of patients achieving either a complete response (CR) or parital response
[ Time Frame: Up to 3 months post-registration ]

3. treatment related mortality
[ Time Frame: Up to 30 days post-treatment ]

4. toxicity
[ Time Frame: Up to 3 months post-registration ]

Open or close this module Eligibility
Minimum Age: 14 Years
Maximum Age:
Sex: Male
Gender Based:
Accepts Healthy Volunteers: No
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.
Open or close this module Contacts/Locations
Central Contact Person: Darren Feldman, MD
Telephone: 646 422-4491
Study Officials: Darren Feldman, MD
Study Chair
Memorial Sloan Kettering Cancer Center
Locations:
Open or close this module IPDSharing
Plan to Share IPD:
Open or close this module References
Links:
Available IPD/Information:

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