EORTC-1407-GUCG: 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 (TIGER)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Europese Organisatie Voor Onderzoek En Behandeling Van Kanker Organisation Europeenne Pour La Recherche Et Le Traitement Du Cancer European Organi

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

11 Jan 2016 → ongoing

Decision date (initial)

2024-08-28

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Movember · Orchid · EORTC

External identifiers

EU CT number

2024-513509-30-00

EudraCT number

2014-003930-17

ClinicalTrials.gov

NCT02375204

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy

To compare the overall survival in patients treated with conventionaldose chemotherapy using the TIP regimen with high-dose chemotherapy (HDCT) plus ASCT using the TI-CE regimen as initial salvage treatment of patients with relapsed or refractory GCT.

Secondary objectives 5

1. To compare PFS of patients treated with initial salvage HDCT with TICE vs. initial salvage CDCT with TIP.
2. To compare FRR of patients treated with initial salvage HDCT with TICE vs. initial salvage CDCT with TIP.
3. To compare 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 AFP and HCG with OS and PFS.

Conditions and MedDRA coding

Progressive or recurrent germ cell tumor (measurable or non-measurable)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Confirmation of GCT histology (both seminoma and nonseminoma) on pathologic review at the center of enrollment. Tumor may have originated in any primary site.
2. 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. 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.
4. No more than one prior line of chemotherapy for GCT (other than the 1 cycle of salvage chemotherapy).
5. Must have adequate recovery from prior surgery (e.g., healed scar, resumption of diet, etc.).
6. Age ≥ 14 years (≥ 15 years in France, ≥ 16 years in Ireland, ≥ 18 years in Germany, Denmark, Switzerland, the Netherlands, Slovenia and Italy)
7. ECOG Performance Status 0 to 2
8. Male gender
9. Required Initial Laboratory Values: Absolute Neutrophil Count (ANC) ≥ 1,500/mm3; Platelet Count ≥ 100,000/mm3; Calc. Creatinine Clearance ≥ 50 mL/min; Bilirubin ≤ 2.0 x upper limits of normal (ULN); AST/ALT ≤ 2.5 x upper limits of normal (ULN)
10. Negative Serology (antibody test) for the following infectious diseases: a. Human Immunodeficiency Virus (HIV) type 1 and 2; b. Human T-cell Leukemia Virus (HTLV) type 1 and 2 (mandatory in US but optional in Canada and Europe); c. Hepatitis B surface antigen; d. Hepatitis C antibody
11. Reproductive risk: patient must not father a baby while in this study. The treatment could affect sperm or semen. Therefore, patient and his partner must use an appropriate and effective contraceptive method during the study period and for approximately 6 months after taking the last dose of study drug. A highly effective method of birth control is defined as those which result in low failure rate (i.e. less than 1% per year) when used consistently.
12. Before patient registration/randomization, written informed consent must be given according to ICH/GCP, and national/local regulations.

Exclusion criteria 10

1. Prior treatment with high-dose chemotherapy (defined as treatment utilizing stem cell rescue).
2. 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.
3. Concurrent treatment with other cytotoxic drugs or targeted therapies.
4. 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.
5. Previous chemotherapy within 16 days prior to enrollment except for bleomycin which cannot have been given within 5 days prior to enrollment.
6. 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.
7. 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.
8. 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 highdose carboplatin or etoposide.
9. Secondary somatic malignancy arising from teratoma (e.g., teratoma with malignant transformation) when it is actively part of the disease recurrence or progression.
10. Contraindications to the use of paclitaxel, ifosfamide, cisplatine, carboplatine and etoposide as per summary of product characteristics (SPC).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Overall survival (OS)

Secondary endpoints 4

1. Progression Free Survival (PFS)
2. Favorable Response Rate (FRR)
3. Treatment-related mortality
4. Toxicity

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Europese Organisatie Voor Onderzoek En Behandeling Van Kanker Organisation Europeenne Pour La Recherche Et Le Traitement Du Cancer European Organi

Sponsor organisation

Europese Organisatie Voor Onderzoek En Behandeling Van Kanker Organisation Europeenne Pour La Recherche Et Le Traitement Du Cancer European Organi

Address

Emmanuel Mounierlaan 83 Bus 11

City

Sint-Lambrechts-Woluwe

Postcode

1200

Country

Belgium

Scientific contact point

Organisation

Europese Organisatie Voor Onderzoek En Behandeling Van Kanker Organisation Europeenne Pour La Recherche Et Le Traitement Du Cancer European Organi

Contact name

Stéphanie Kromar

Public contact point

Organisation

Europese Organisatie Voor Onderzoek En Behandeling Van Kanker Organisation Europeenne Pour La Recherche Et Le Traitement Du Cancer European Organi

Contact name

Vassilis Golfinopoulos

Third parties 7

Locations

8 EU/EEA countries · 25 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 69 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications