Brief Title
Salvage Chemotherapy for Poor Prognosis Germ Cell Tumors
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
Brief 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.
Study Phase
Phase 1/Phase 2
Study Type
Interventional
Primary Outcome
Response
Secondary Outcome
complete response rate
Condition
Germ Cell Tumor
Intervention
Bevacizumab
Study Arms / Comparison Groups
bevacizumab
Description: Two intensified treatments at 6-week intervals will start on D69 (max D76) and D111 (max J118) respectively, combining: A bevacizumab treatment: 7.5 mg/kg every 3 weeks from D1 to the first intensified treatment for a total of 4 injections. The 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
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
30
Start Date
April 2012
Completion Date
September 2020
Primary Completion Date
March 2019
Eligibility Criteria
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
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
, 33 1 56 01 64 52, [email protected]
Location Countries
France
Location Countries
France
Administrative Informations
NCT ID
NCT01966913
Organization ID
P100135
Responsible Party
Sponsor
Study Sponsor
Assistance Publique - Hôpitaux de Paris
Study Sponsor
, ,
Verification Date
February 2019