The primary objective of this study is to determine the first-cycle maximum tolerated dose (MTD) and recommended Phase II (RP2D) dose of Cabazitaxel when combined with Cisplatin and Follow-Up induction chemotherapy in patients with locally advanced squamous cell carcinoma of the head and neck for three cycles.
The primary study objectives are the following: * To assess the safety, the maximum tolerated dose (MTD) and the dose limiting toxicity of cabazitaxel when combined with cisplatin and Follow-Up (FU) induction chemotherapy in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). * To establish the phase II recommended dose of cabazitaxel when combined with cisplatin and Follow-Up induction in patients with locally advanced squamous cell carcinoma of the head and neck. The secondary study objectives, in regards to the combined Cabazitaxel-Platinum Fluorouracil regimen in patients with newly diagnosed squamous cell carcinoma of the head and neck, are the following: * To assess the toxicity profile * To assess best Overall Response Rate (complete and partial responses) after completion of 3 cycles of treatment * To assess Progression Free Survival (PFS) and Overall Survival (OS) after 3 years Analysis of the secondary variables will be primarily descriptive in nature due to the small sample size. All results will be considered hypothesis generating to be confirmed in a future study. Patient, for whom an informed consent has been obtained and who have met the inclusion/exclusion criteria after having the screening evaluation performed within a one-week window, will be assigned to a dose level according to the dose escalation rule described in the protocol. Treatment consists of an Induction chemotherapy period, which is the period when the patient will undergo 3 cycles of Cabazitaxel-Platinum Fluorouracil (PF). The Induction chemotherapy will be followed by Consolidation Therapy, which is 6-7 weeks of Chemoradiation treatment or Surgery + Recovery time, depending on their primary site and overall medical condition. Both treatment periods will consist of approximately 16 weeks (9 weeks of Induction and 7 weeks of Consolidation, if Chemoradiation Radiation Therapy (CRT)), or shorter than 16 weeks, if surgery. After three cycles, the patients will be assessed for clinical, radiographic, and pathologic response to Cabazitaxel-Platinum Fluorouracil before beginning Chemoradiation Radiation Therapy or surgery. Patients, who do not complete three cycles of Cabazitaxel-Platinum Fluorouracil for reasons of toxicity, progressive disease, choice, or other medical necessity, will be treated with standard Chemoradiation Radiation Therapy or surgery depending on their primary site and overall medical condition. Once the Consolidation treatment is completed, the follow-up of patients will be for 3 years.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
40
* Cabazitaxel on D1 Dose: 10mg/m2 IV x 1 Route: Intravenous infusion over 60 minutes, mixed as described in protocol over 1 hour Schedule: Day 1, every 21 days (+ 2 days) * Cisplatin on D1 Dose: 100 mg/m2 Route: Intravenous infusion over 60 minutes to 3 hours, mixed in 1000 ml of normal saline Schedule: Day 1, every 21 days (+ 2 days) * 5 Fluorouracil on D1-D4 Dose: 800 mg/m2/day Route: 24-hour continuous infusion over 4 days Schedule: Days 1, 2, 3 and 4 of Cycles 1, 2 and 3 (every 21 days) + 2 days)
* Cabazitaxel on D1 Dose: 12.5mg/m2 IV x 1 Route: Intravenous infusion over 60 minutes, mixed as described in protocol over 1 hour Schedule: Day 1, every 21 days (+ 2 days) * Cisplatin on D1 Dose: 100 mg/m2 Route: Intravenous infusion over 60 minutes to 3 hours, mixed in 1000 ml of normal saline Schedule: Day 1, every 21 days (+ 2 days) * 5 Fluorouracil on D1-D4 Dose: 800 mg/m2/day Route: 24-hour continuous infusion over 4 days Schedule: Days 1, 2, 3 and 4 of Cycles 1, 2 and 3 (every 21 days) + 2 days)
Icahn School of Medicine at Mount Sinai
New York, New York, United States
Maximum Tolerated Dose (MTD)
MTD is defined as the dose level immediately below the DLT. The study will be conducted until MTD and recommended Phase II dose are established.
Time frame: at 1 week
Maximum Tolerated Dose (MTD)
MTD is defined as the dose level immediately below the DLT. The study will be conducted until MTD and recommended Phase II dose are established.
Time frame: at 4 weeks
Maximum Tolerated Dose (MTD)
MTD is defined as the dose level immediately below the DLT. The study will be conducted until MTD and recommended Phase II dose are established.
Time frame: at 7 weeks
Maximum Tolerated Dose (MTD)
MTD is defined as the dose level immediately below the DLT. The study will be conducted until MTD and recommended Phase II dose are established.
Time frame: at 9 weeks
Dose-limiting toxicity (DLT)
DLT is defined as a grade3 toxicity lasting more than 7 days or grade 4 or 5 toxicity, with the exception of febrile neutropenia which will be considered as ½ DLT per full dose per episode. The DLT will be the basis for determining the MTD. Treatment cohorts will be dosed in escalating order only after the safety of the previous dose level is established, or until an MTD has been determined.
Time frame: at 1 week
Dose-limiting toxicity (DLT)
DLT is defined as a grade3 toxicity lasting more than 7 days or grade 4 or 5 toxicity, with the exception of febrile neutropenia which will be considered as ½ DLT per full dose per episode. The DLT will be the basis for determining the MTD. Treatment cohorts will be dosed in escalating order only after the safety of the previous dose level is established, or until an MTD has been determined.
Time frame: at 4 weeks
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
* Cabazitaxel on D1 Dose: 15mg/m2 IV x 1 Route: Intravenous infusion over 60 minutes, mixed as described in protocol over 1 hour Schedule: Day 1, every 21 days (+ 2 days) * Cisplatin on D1 Dose: 100 mg/m2 Route: Intravenous infusion over 60 minutes to 3 hours, mixed in 1000 ml of normal saline Schedule: Day 1, every 21 days (+ 2 days) * 5 Fluorouracil on D1-D4 Dose: 800 mg/m2/day Route: 24-hour continuous infusion over 4 days Schedule: Days 1, 2, 3 and 4 of Cycles 1, 2 and 3 (every 21 days) + 2 days)
* Cabazitaxel on D1 Dose: 17.5mg/m2 IV x 1 Route: Intravenous infusion over 60 minutes, mixed as described in protocol over 1 hour Schedule: Day 1, every 21 days (+ 2 days) * Cisplatin on D1 Dose: 100 mg/m2 Route: Intravenous infusion over 60 minutes to 3 hours, mixed in 1000 ml of normal saline Schedule: Day 1, every 21 days (+ 2 days) * 5 Fluorouracil on D1-D4 Dose: 800 mg/m2/day Route: 24-hour continuous infusion over 4 days Schedule: Days 1, 2, 3 and 4 of Cycles 1, 2 and 3 (every 21 days) + 2 days)
* Cabazitaxel on D1 Dose: 20mg/m2 IV x 1 Route: Intravenous infusion over 60 minutes, mixed as described in protocol over 1 hour Schedule: Day 1, every 21 days (+ 2 days) * Cisplatin on D1 Dose: 100 mg/m2 Route: Intravenous infusion over 60 minutes to 3 hours, mixed in 1000 ml of normal saline Schedule: Day 1, every 21 days (+ 2 days) * 5 Fluorouracil on D1-D4 Dose: 800 mg/m2/day Route: 24-hour continuous infusion over 4 days Schedule: Days 1, 2, 3 and 4 of Cycles 1, 2 and 3 (every 21 days) + 2 days)
Dose-limiting toxicity (DLT)
DLT is defined as a grade3 toxicity lasting more than 7 days or grade 4 or 5 toxicity, with the exception of febrile neutropenia which will be considered as ½ DLT per full dose per episode. The DLT will be the basis for determining the MTD. Treatment cohorts will be dosed in escalating order only after the safety of the previous dose level is established, or until an MTD has been determined.
Time frame: at 7 weeks
Dose-limiting toxicity (DLT)
DLT is defined as a grade3 toxicity lasting more than 7 days or grade 4 or 5 toxicity, with the exception of febrile neutropenia which will be considered as ½ DLT per full dose per episode. The DLT will be the basis for determining the MTD. Treatment cohorts will be dosed in escalating order only after the safety of the previous dose level is established, or until an MTD has been determined.
Time frame: at 9 weeks
Toxicity Profile
The toxicity profile of cabazitaxel when combined with cisplatin and FU induction chemotherapy will be assessed
Time frame: at 9 weeks
Overall Response Rate
The Best Overall Response Rate (complete and partial responses) will be assessed after completion of 3 cycles of treatment.
Time frame: at 9 weeks
Progression Free Survival/Overall Survival
The Progression Free Survival and Overall Survival will be assessed during the 3-year follow-up period. The follow-up period is every 3 months for the first 2 years post consolidation (week 16) thereafter every 6 months for the 3rd year post consolidation (week 16).
Time frame: for 3 years