Salvage Chemotherapy for Poor Prognosis Germ Cell Tumors

Germ Cell Tumor Clinical Trial

— TAXIFIII  

Official title:

Salvage Chemotherapy for Poor Prognosis Germ Cell Tumors - A Phase I-II Sequential Chemotherapy Protocol of Bevacizumab (Avastin) Plus High-dose ICE (Ifosfamide - Carboplatin - Etoposide) Intensification

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01966913
• Other study ID #: P100135
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: April 2012
• Est. completion date: September 2020

Study information

• Verified date: February 2019
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Frédéric SELLE, MD
• Phone: 33 1 56 01 64 52
• Email: frederic.selle[@]tnn.aphp.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

High-dose chemotherapy with autologous hematopoietic stem-cell transplantation is a standard salvage treatment used in adults with germ cell tumors (Einhorn et al, J Clin Oncol 2007).

Disease prognosis following 1 to 2 intensified combinations of etoposide - carboplatin +/- ifosfamide depends on the patient's performance status (PS) at inclusion and the prior sensitivity of the disease to cisplatin. A poor PS and/or being refractory to cisplatin suggest a higher toxicity and a bad prognosis.

However, predictive factors of response to high-dose chemotherapy do not include a chemo-sensitivity phase with a semi-intensive chemotherapy excluding a platinum compound (epirubicin - paclitaxel), which still allows stem-cell harvest. The use of this chemotherapy combination induced a response in more than one third of the patients treated during disease progression in the TAXIF I study. The same strategy was tested in the TAXIF II study, which completed the inclusion of 45 patients and was closed in May 2008. Results of the TAXIF II study, are currently being analyzed; they support the hypothesis to prioritarily treat patients with a sensitive relapsed disease at the time of the high-dose administration.

A combination of a semi-intensive sequential ICE type chemotherapy plus bevacizumab was used on a highly refractory patient. A 5 months nearly complete response was achieved. Indeed, the overexpression of VEGF (Vascular Endothelial Growth Factor) has been identified as an independent risk factor in patients with germ cell tumor. Therefore, a treatment strategy using an inductive chemotherapy followed, in case of response, by a double intensification therapy in combination with a VEGF treatment, could be an interesting approach in patients with poor prognosis germ cell tumors.

The aim of this phase I/II trial is to assess the feasibility of a Bevacizumab - ICE (Ifosfamide-Carboplatin-Etoposide) high dose combination with the support of autologous hematopoietic stem cell for two intensive consecutive cycles ("tandem" intensification) in patients with a poor prognosis germ cell tumor non refractory to a front-line mobilization chemotherapy using two half intensified consecutive combinations of Epirubicin-Paclitaxel.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: September 2020
• Est. primary completion date: March 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patient aged 18 years or older having signed an informed consent form.

• Germ cell tumor of gonadal origin, extra-gonadal, retro-peritoneal or primary mediastinal, excluding CNS tumors.

• Relapsed, refractory or completely refractory disease. The patients must have received:

• For relapsed patients, two lines of a standard chemotherapy (BEP or EP in first-line treatment, VeIP or VIP in second-line treatment)

• For refractory or completely refractory patients, one line of a standard chemotherapy (BEP or EP)

• First extra-gonadal tumor relapse

• Normal laboratory tests levels usually required for intensive treatments

• Performance status < 2.

• Life expectancy = 3 months.

Exclusion Criteria:

• Brain metastases

• Lesions of growing teratoma

• Cardiovascular disease, uncontrolled hypertension

• History of transient ischemic attacks

• All other contraindications to bevacizumab treatment

• Non-healing wound, active peptic ulcer or bone fracture

• known allergy to bevacizumab or any of its excipients

• known allergy to chemotherapy including Cremophor

Related Conditions & MeSH terms

• Germ Cell Tumor
• Neoplasms, Germ Cell and Embryonal

Intervention

Drug:
• Bevacizumab

• ICE chemotherapy regimen
Etoposide, 300 mg/m²/d in two daily injections at 12-h intervals, Carboplatin, AUC 4/d by injections adjusted daily to the creatinine clearance, Ifosfamide, 2400 mg/m²/d, For 5 consecutive days followed by HSC reinjection and G-CSF (filgrastim- Neupogen) on D11 of each intensive cycle

Locations

Country	Name	City	State
France	Hopital Tenon	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response	Partial response or complete response evaluated by scanography and assay for tumor marker(s) a month after the end of the 2 cycles	3 months
Primary	Toxicity	Safety recorded according to CTCAE-v4 criteria	6 months
Secondary	complete response rate		within 2 years of inclusion
Secondary	complete pathological response (pCR) or complete surgical response (sCR)		within 2 years after inclusion
Secondary	overall survival		within 2 years after inclusion
Secondary	response duration		within 2 years after inclusion
Secondary	progression-free survival		within 2 years after inclusion