Germ Cell TumorPhase 1/2TAXIFIIINCT01966913
Salvage Chemotherapy for Poor Prognosis Germ Cell Tumors
A Phase 1/2 study testing Bevacizumab and ICE chemotherapy regimen in people with Germ Cell Tumor, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Germ Cell Tumor
- What is being tested?
- Bevacizumab and ICE chemotherapy regimen
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteFrance
- Study dates
- Apr 2012to Sep 2020
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 9Show fewer
- Normal laboratory tests levels usually required for intensive treatments
- Performance status < 2.
- Life expectancy ≥ 3 months.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read more
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.
- Conditions
- Germ Cell Tumor
- Being tested
- Bevacizumab, ICE chemotherapy regimen
- Keywords
- Germ Cell Tumors, Bevacizumab, salvage therapy
- Medical subject headings
- Neoplasms, Germ Cell and Embryonal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BevacizumabDrug
ICE chemotherapy regimenDrug
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
| Study group | Role | What they receive |
|---|---|---|
| bevacizumab | Experimental | 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:
1. Etoposide, 300 mg/m²/d in two daily injections at 12-h intervals,
2. Carboplatin, AUC 4/d by injections adjusted daily to the creatinine clearance,
3. Ifosfamide, 2400 mg/m²/d,
4. For 5 consecutive days followed by HSC reinjection and G-CSF (filgrastim- Neupogen) on D11 of each intensive cycle Receives: Drug: Bevacizumab; Drug: ICE chemotherapy regimen |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response
Partial response or complete response evaluated by scanography and assay for tumor marker(s) a month after the end of the 2 cycles
Measured: 3 months
Toxicity
Safety recorded according to CTCAE-v4 criteria
Measured: 6 months
Secondary outcomes (5)
complete response rate
Measured: within 2 years of inclusion
complete pathological response (pCR) or complete surgical response (sCR)
Measured: within 2 years after inclusion
overall survival
Measured: within 2 years after inclusion
response duration
Measured: within 2 years after inclusion
progression-free survival
Measured: within 2 years after inclusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Oct 2013 (estimated)
- Study startApr 2012
- Primary completionMar 2019 (estimated)
- Study completionSep 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Germ Cell TumorStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01966913
- Sponsor's protocol ID
- P100135
- Acronym
- TAXIFIII
- Status last verified
- Feb 2019
- First submitted
- 11 Oct 2013
- Last updated
- 19 Feb 2019
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 19 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01966913
- Acronym / sponsor ID
- TAXIFIII / P100135
- Conditions
- Germ Cell Tumor
- Keywords
- Germ Cell Tumors, Bevacizumab, salvage therapy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- Apr 2012
- Primary completion
- Mar 2019 (estimated)
- Study completion
- Sep 2020 (estimated)
- First posted
- 22 Oct 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| bevacizumab | Experimental | Drug: Bevacizumab, Drug: ICE chemotherapy regimenTwo 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: 1. Etoposide, 300 mg/m²/d in two daily injections at 12-h intervals, 2. Carboplatin, AUC 4/d by injections adjusted daily to the creatinine clearance, 3. Ifosfamide, 2400 mg/m²/d, 4. For 5 consecutive days followed by HSC reinjection and G-CSF (filgrastim- Neupogen) on D11 of each intensive cycle |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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:
- First extra-gonadal tumor relapse
- Normal laboratory tests levels usually required for intensive treatments
Key exclusion criteria (8 listed)
- Brain metastases
- Lesions of growing teratoma
- Cardiovascular disease, uncontrolled hypertension
- History of transient ischemic attacks
- All other contraindications to bevacizumab treatment
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Bevacizumab | Drug | bevacizumab |
| ICE chemotherapy regimenEtoposide, 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 | Drug | bevacizumab |
Primary outcome
Response
Time frame: 3 months
Partial response or complete response evaluated by scanography and assay for tumor marker(s) a month after the end of the 2 cycles
Toxicity
Time frame: 6 months
Safety recorded according to CTCAE-v4 criteria
5 secondary outcomes
complete response rate
Time frame: within 2 years of inclusion
complete pathological response (pCR) or complete surgical response (sCR)
Time frame: within 2 years after inclusion
overall survival
Time frame: within 2 years after inclusion
response duration
Time frame: within 2 years after inclusion
progression-free survival
Time frame: within 2 years after inclusion
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Feb 2019.
Related trials for Germ Cell Tumor
Active, not recruitingPhase 1/2
Selumetinib in Treating Young Patients With Recurrent or Refractory Low Grade Glioma
Low Grade Glioma, Recurrent Childhood Pilocytic Astrocytoma
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingPhase 1
IL-17 Blockade to Decrease irAEs (REPLAY)
Metastatic Melanoma
RecruitingPhase 2
A UGT1A1 Genotype-Directed Study of Belinostat Pharmacokinetics and Toxicity
Carcinoma, Neuroendocrine, Tumor, Neuroendocrine
Enrolling by invitationObservational study
Natural History Study of Early Life Exposures in Agriculture (ELEA)
Prostate Cancer, Leukemia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Bevacizumab and ICE chemotherapy regimen in people with Germ Cell Tumor, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 19 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Frédéric SELLE, MD (33 1 56 01 64 52, frederic.selle@tnn.aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Response (time frame: 3 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Feb 2019.