Platinum-Cetuximab Combined With Docetaxel or With 5FU in Patients With Recurrent/Metastatic HNSCC (TPExtreme)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02268695|
Recruitment Status : Active, not recruiting
First Posted : October 20, 2014
Last Update Posted : April 10, 2020
|Condition or disease||Intervention/treatment||Phase|
|Head and Neck Squamous Cell Carcinoma||Drug: Cisplatin Drug: 5-Fluorouracile Drug: Docetaxel Drug: Cetuximab Drug: granulocyte colony-stimulating factor (G-CSF)||Phase 2|
The EXTREME regimen, i.e. cetuximab added to platinum (100 mg/m² every 3 weeks ) and 5FU (96h continuous infusion at 1000 mg/m²/day every 3 weeks) during 6 cycles of treatment and continued as maintenance in patients with stable disease, is currently the standard of care in first line recurrent metastatic HNSCC.
From our previous experience (phase II GORTEC "TPEx" study), the TPEx regimen of 4 cycles of docetaxel-cisplatin-cetuximab followed by maintenance with cetuximab every 2 weeks seems more efficient (overall survival) compared to EXTREME regiment. Docetaxel combined with cisplatine (each administered at 75mg/m² every 3 weeks) also appeared more convenient than the standard Cisplatin-5FU-Cetuximab EXTREME regimen (4 cycles of chemotherapy instead of 6 cycles and no i.v. continuous infusion). Toxicity was manageable with G-CSF support. In addition the toxicity / efficacy profile also seems favourable as suggested by the excellent dose intensity achieved and the high rate of patients (78%) who were able to start maintenance therapy.
Taking together all these considerations, the TPEx regimen might be a good substitute for EXTREME as first-line treatment in patients with recurrent metastatic HNSCC, and it is justified and necessary to perform a direct comparison in a randomized trial to further test this hypothesis.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||416 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||TPExtreme: Randomized, Controlled Trial of Platinum-Cetuximab Combined Either With Docetaxel (TPEx) or With 5FU (Extreme) in Patients With Recurrent/Metastatic Squamous Cell Cancer of the Head and Neck|
|Actual Study Start Date :||October 10, 2014|
|Actual Primary Completion Date :||January 2019|
|Estimated Study Completion Date :||September 2020|
Active Comparator: EXTREME: Cisplatin, 5-FU and Cetuximab
Chemotherapy: 6 cycles (every 3 weeks) of Cisplatin (100 mg/m² iv on Day1), 5FU (4000 mg/m² total dose starting on day 1 and during 96h in continuous infusion), and Cetuximab (loading dose of 400 mg/m² iv on Day1, then 250 mg/m² iv weekly).
If cisplatin is not tolerated and/or when the total cumulative dose of cisplatin (including prior administration) reaches 600 mg/m², cisplatin has to be replaced by carboplatin, AUC 5 (but not exceeding 750 mg), except in the case of bleeding tumor.
Cetuximab maintenance : cetuximab continuation (250 mg/m² iv weekly) will begin only if at least disease stabilization is observed at the end of chemotherapy, and will be continued until PD or unacceptable toxicity.
Experimental: TPEx: Cisplatin, Docetaxel and Cetuximab
Chemotherapy: 4 cycles (every 3 weeks) of Cisplatin (75 mg/m² iv on Day1), Docetaxel (75 mg/m² iv on Day1), and Cetuximab (loading dose of 400 mg/m² iv on Day1, then 250 mg/m² iv weekly).
If Cisplatin is not tolerated, cisplatin is replaced by carboplatin, AUC 5 (but not exceeding 750 mg), except in the case of bleeding tumor.
Primary prophylactic administration of GCSF must be administered systematically after each cycle of chemotherapy.
Cetuximab maintenance : cetuximab continuation (500 mg/m² iv every two weeks) will begin only if at least disease stabilization is observed at the end of chemotherapy, and will be continued until PD or unacceptable toxicity.
Drug: granulocyte colony-stimulating factor (G-CSF)
- Overall survival [ Time Frame: Until patient death or at least one year after the end of the treatment ]Overall survival is defined as the time to death from any cause measured from randomization. Patients with disease progression may be treated with off protocol therapy but will be followed for overall survival evaluation.
- Objective response rate [ Time Frame: At 12 weeks ]Objective response rate (complete response (CR) or partial response (PR) according to RECIST 1.1 criteria and assessed by central imaging review) at 12 weeks. For the statistical analysis patients not evaluable (whatever the reason, including death) will be considered as failure (i.e. no CR, no PR).
- Best overall tumor response rate [ Time Frame: until progression or at least one year after the end of the treatment ]Best overall tumor response rate (RECIST 1.1 criteria) during chemotherapy and maintenance: CR or PR or SD confirmed for CR or PR by a second assessment 6 weeks later
- Progression free survival [ Time Frame: until progression or death or at least one year after the end of the treatment ]Progression free survival (PFS): minimum time from randomization to progression as defined by RECIST 1.1 criteria or to death from any cause. Patients who don't have any of these events are censored at the date of last follow-up.
- Time to Progression [ Time Frame: until progression or death or at least one year after the end of the treatment ]Time to Progression (TTP): minimum time from randomization to progression as defined by RECIST 1.1 criteria. In case of death from other cause than cancer and no prior progression, the patient will be censored at the time of death. In case of death related to cancer without an accurate date of progression before death, the patient will be considered in progression at the time of death. In the event of no progression and no death, the patient will be censored at the date of last follow-up.
- Toxicity [ Time Frame: until the end of the maintenance, an expected average of 4 months of maintenance ]Toxicity (according to CTC-NCI V4): all grades
- Compliance [ Time Frame: until the end of the maintenance, an expected average of 4 months of maintenance ]Compliance: Insufficient compliance for cetuximab is defined as a patient missing more than 2 consecutive infusions of cetuximab, even if the missed infusions are due to toxicity. Insufficient compliance for chemotherapy is defined as a patient missing more than 2 consecutive infusions of chemotherapy, even if the missed infusions are due to toxicity.
- EORTC QLQ-C30 [ Time Frame: At baseline before treatment, at Week 12, Week 18 and at Week 26 ]Health related quality of life (QoL) assessed by EORTC QLQ-C30. The primary endpoint of the QoL study is the global health status/quality of-life scale of the QLQ-C30 questionnaire
- EuroQol-5D [ Time Frame: At baseline before treatment, at Week 12, at Week 26 and then every 2 months.until death or at least one year after the end of the treatment ]Quality-adjusted life-years (QALYs) based on Euroqol EQ-5D measurements
- Net monetary benefit [ Time Frame: until death or at least one year after the end of the treatment ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02268695
|Study Chair:||Joel GUIGAY, MD||Centre Antoine Lacassagne, Nice, France|
|Study Director:||Jean BOURHIS, MD, PhD||GORTEC President|
|Principal Investigator:||Ricardo MESIA, MD||Instituto Catalá de Oncologia (ICO), Barcelona, Spain|
|Principal Investigator:||Ulrich KEILHOLZ, MD||Charité Campus Benjamin Franklin, Berlin, Germany|