search
Back to results

Cabazitaxel - PF Induction Chemotherapy

Primary Purpose

Squamous Cell Carcinoma of the Head and Neck

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Cabazitaxel 10mg/m2
Cabazitaxel 12.5mg/m2
Cabazitaxel 15mg/m2
Cabazitaxel 17.5mg/m2
Cabazitaxel 20mg/m2
Sponsored by
Krzysztof Misiukiewicz
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Squamous Cell Carcinoma of the Head and Neck focused on measuring Cabazitaxel, Cabazitaxel and Cisplatin, Phase I, PF Induction Chemotherapy, Squamous Cell Carcinoma, Head and Neck, Sanofi-Aventis Oncology, Locally Advanced

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients with stage IV only, previously untreated, locally advanced SCCHN (patients may have had previous surgery, but not chemotherapy or radiotherapy).
  • During the dose escalation phase before the MTD and DLT are established for cabazitaxel combined with cisplatin and FU induction chemotherapy primary sites allowed include the oral cavity, oropharynx, larynx, hypopharynx, nasopharynx, and unknown primary regardless of Human Papilloma Virus (HPV) status. Metastatic SCCHN will be allowed in escalation phase.
  • Once MTD and DLT for cabazitaxel combined with cisplatin and FU induction chemotherapy are established (expansion cohort) primary sites allowed include the oral cavity, oropharynx (HPV negative only), larynx, hypopharynx, nasopharynx, and unknown primary (HPV negative only). No patients with metastases will be allowed in this phase (expansion cohort).
  • Age >/= 18 years
  • Eastern Cooperative Oncology Group PS 0-1
  • Predicted life expectancy >/= 12 weeks
  • Absolute Neutrophilic Count (ANC) >/= 1.5 x 10^9/L, Platelets >/= 100 x 10^9/L; bilirubin </= 1.5 x Upper Limit of Normal (ULN), Aspartate Aminotransferase (AST) and/or Alanine Aminotransferase (ALT) </= 2.5 x ULN or </= 5 x ULN if patient has documented liver metastases; serum creatinine </= 1.5 x ULN
  • Patients in the expansion cohorts must have measurable disease per Response Evaluation Criteria in Solid Tumors(RECIST)
  • Patients must be accessible for repeat dosing and follow-up
  • Patients - both males and females - with reproductive potential must agree to practice effective contraceptive measures throughout the study. Women of childbearing potential must provide a negative pregnancy test at baseline and on Day 1
  • Patients must provide verbal and written informed consent to participate in the study

Exclusion Criteria:

  • Locally advanced HPV positive oropharyngeal or unknown primary SCCHN for the expansion cohort only (Once MTD and DLT for cabazitaxel combined with cisplatin and FU induction chemotherapy established).
  • History of significant cardiac disease unless the disease is well-controlled
  • Grade 2 peripheral neuropathy
  • No excessive alcohol consumption will be allowed
  • Serious comorbid illness, and involuntary weight loss of more than 20% of body weight in the 3 months preceding study entry
  • History of cerebrovascular accident (CVA) within 12 months prior to registration or that is not stable
  • History of any psychiatric condition that might impair the patient's ability to understand or to comply with the requirements of the study or to provide informed consent
  • Pregnant or breast-feeding females Gastrointestinal (GI) abnormalities including inability to take oral medication, requirement for IV alimentation, active peptic ulcer, or prior surgical procedures affecting absorption
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to the study drug
  • Any type of active seizure disorder
  • Use of drugs that have a risk of causing QT interval prolongation within 14 days prior to Day 1 dosing
  • Use of strong or moderate CYP3A4 or CYP1A2 inhibitors/inducers, with the exception of low-dose steroids, within 14 days prior to Day 1 dosing
  • Symptomatic brain metastases that are not stable, require steroids, or that have required radiation within the last 28 days
  • Active or uncontrolled infections or serious illnesses or medical conditions that could interfere with the patient's ongoing participation in the study
  • History of Hepatitis C or Human Immunodeficiency Virus (HIV) infection, autoimmune disease, or major organ transplant.
  • Surgery, irradiation or chemotherapy within the previous 4 weeks
  • Any other concomitant anticancer therapies
  • Patients will be excluded if they received any prior chemotherapy, radiotherapy, or treatment with biologic response modifiers (except curatively treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix)
  • History of colitis or chronic diarrheal illness
  • History of, or active, co-morbid medical condition, which in the opinion of the investigator, would raise significant risk to the patient.

Sites / Locations

  • Icahn School of Medicine at Mount Sinai

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Cabazitaxel 10mg/m2

Cabazitaxel 12.5mg/m2

Cabazitaxel 15mg/m2

Cabazitaxel 17.5mg/m2

Cabazitaxel 20mg/m2

Arm Description

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)

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)

Outcomes

Primary Outcome Measures

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.
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.
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.
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.
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.
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.
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.
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.

Secondary Outcome Measures

Toxicity Profile
The toxicity profile of cabazitaxel when combined with cisplatin and FU induction chemotherapy will be assessed
Overall Response Rate
The Best Overall Response Rate (complete and partial responses) will be assessed after completion of 3 cycles of treatment.
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).

Full Information

First Posted
June 15, 2011
Last Updated
February 9, 2015
Sponsor
Krzysztof Misiukiewicz
Collaborators
Sanofi, Icahn School of Medicine at Mount Sinai
search

1. Study Identification

Unique Protocol Identification Number
NCT01379339
Brief Title
Cabazitaxel - PF Induction Chemotherapy
Official Title
Phase I Study of Cabazitaxel - Platinum Fluorouracil Induction Chemotherapy in Patients With Locally Advanced Squamous Cell Carcinoma of the Head and Neck
Study Type
Interventional

2. Study Status

Record Verification Date
February 2015
Overall Recruitment Status
Completed
Study Start Date
April 2011 (undefined)
Primary Completion Date
January 2015 (Actual)
Study Completion Date
January 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Krzysztof Misiukiewicz
Collaborators
Sanofi, Icahn School of Medicine at Mount Sinai

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
Detailed Description
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Squamous Cell Carcinoma of the Head and Neck
Keywords
Cabazitaxel, Cabazitaxel and Cisplatin, Phase I, PF Induction Chemotherapy, Squamous Cell Carcinoma, Head and Neck, Sanofi-Aventis Oncology, Locally Advanced

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Factorial Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
40 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cabazitaxel 10mg/m2
Arm Type
Experimental
Arm Description
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)
Arm Title
Cabazitaxel 12.5mg/m2
Arm Type
Experimental
Arm Description
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)
Arm Title
Cabazitaxel 15mg/m2
Arm Type
Experimental
Arm Description
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)
Arm Title
Cabazitaxel 17.5mg/m2
Arm Type
Experimental
Arm Description
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)
Arm Title
Cabazitaxel 20mg/m2
Arm Type
Experimental
Arm Description
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)
Intervention Type
Drug
Intervention Name(s)
Cabazitaxel 10mg/m2
Other Intervention Name(s)
Cabazitaxel-PF Induction Chemotherapy
Intervention Description
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)
Intervention Type
Drug
Intervention Name(s)
Cabazitaxel 12.5mg/m2
Other Intervention Name(s)
Cabazitaxel-PF Induction Chemotherapy
Intervention Description
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)
Intervention Type
Drug
Intervention Name(s)
Cabazitaxel 15mg/m2
Other Intervention Name(s)
Cabazitaxel-PF Induction Chemotherapy
Intervention Description
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)
Intervention Type
Drug
Intervention Name(s)
Cabazitaxel 17.5mg/m2
Other Intervention Name(s)
Cabazitaxel-PF Induction Chemotherapy
Intervention Description
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)
Intervention Type
Drug
Intervention Name(s)
Cabazitaxel 20mg/m2
Other Intervention Name(s)
Cabazitaxel-PF Induction Chemotherapy
Intervention Description
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)
Primary Outcome Measure Information:
Title
Maximum Tolerated Dose (MTD)
Description
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
Title
Maximum Tolerated Dose (MTD)
Description
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
Title
Maximum Tolerated Dose (MTD)
Description
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
Title
Maximum Tolerated Dose (MTD)
Description
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
Title
Dose-limiting toxicity (DLT)
Description
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
Title
Dose-limiting toxicity (DLT)
Description
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
Title
Dose-limiting toxicity (DLT)
Description
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
Title
Dose-limiting toxicity (DLT)
Description
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
Secondary Outcome Measure Information:
Title
Toxicity Profile
Description
The toxicity profile of cabazitaxel when combined with cisplatin and FU induction chemotherapy will be assessed
Time Frame
at 9 weeks
Title
Overall Response Rate
Description
The Best Overall Response Rate (complete and partial responses) will be assessed after completion of 3 cycles of treatment.
Time Frame
at 9 weeks
Title
Progression Free Survival/Overall Survival
Description
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients with stage IV only, previously untreated, locally advanced SCCHN (patients may have had previous surgery, but not chemotherapy or radiotherapy). During the dose escalation phase before the MTD and DLT are established for cabazitaxel combined with cisplatin and FU induction chemotherapy primary sites allowed include the oral cavity, oropharynx, larynx, hypopharynx, nasopharynx, and unknown primary regardless of Human Papilloma Virus (HPV) status. Metastatic SCCHN will be allowed in escalation phase. Once MTD and DLT for cabazitaxel combined with cisplatin and FU induction chemotherapy are established (expansion cohort) primary sites allowed include the oral cavity, oropharynx (HPV negative only), larynx, hypopharynx, nasopharynx, and unknown primary (HPV negative only). No patients with metastases will be allowed in this phase (expansion cohort). Age >/= 18 years Eastern Cooperative Oncology Group PS 0-1 Predicted life expectancy >/= 12 weeks Absolute Neutrophilic Count (ANC) >/= 1.5 x 10^9/L, Platelets >/= 100 x 10^9/L; bilirubin </= 1.5 x Upper Limit of Normal (ULN), Aspartate Aminotransferase (AST) and/or Alanine Aminotransferase (ALT) </= 2.5 x ULN or </= 5 x ULN if patient has documented liver metastases; serum creatinine </= 1.5 x ULN Patients in the expansion cohorts must have measurable disease per Response Evaluation Criteria in Solid Tumors(RECIST) Patients must be accessible for repeat dosing and follow-up Patients - both males and females - with reproductive potential must agree to practice effective contraceptive measures throughout the study. Women of childbearing potential must provide a negative pregnancy test at baseline and on Day 1 Patients must provide verbal and written informed consent to participate in the study Exclusion Criteria: Locally advanced HPV positive oropharyngeal or unknown primary SCCHN for the expansion cohort only (Once MTD and DLT for cabazitaxel combined with cisplatin and FU induction chemotherapy established). History of significant cardiac disease unless the disease is well-controlled Grade 2 peripheral neuropathy No excessive alcohol consumption will be allowed Serious comorbid illness, and involuntary weight loss of more than 20% of body weight in the 3 months preceding study entry History of cerebrovascular accident (CVA) within 12 months prior to registration or that is not stable History of any psychiatric condition that might impair the patient's ability to understand or to comply with the requirements of the study or to provide informed consent Pregnant or breast-feeding females Gastrointestinal (GI) abnormalities including inability to take oral medication, requirement for IV alimentation, active peptic ulcer, or prior surgical procedures affecting absorption History of allergic reactions attributed to compounds of similar chemical or biologic composition to the study drug Any type of active seizure disorder Use of drugs that have a risk of causing QT interval prolongation within 14 days prior to Day 1 dosing Use of strong or moderate CYP3A4 or CYP1A2 inhibitors/inducers, with the exception of low-dose steroids, within 14 days prior to Day 1 dosing Symptomatic brain metastases that are not stable, require steroids, or that have required radiation within the last 28 days Active or uncontrolled infections or serious illnesses or medical conditions that could interfere with the patient's ongoing participation in the study History of Hepatitis C or Human Immunodeficiency Virus (HIV) infection, autoimmune disease, or major organ transplant. Surgery, irradiation or chemotherapy within the previous 4 weeks Any other concomitant anticancer therapies Patients will be excluded if they received any prior chemotherapy, radiotherapy, or treatment with biologic response modifiers (except curatively treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix) History of colitis or chronic diarrheal illness History of, or active, co-morbid medical condition, which in the opinion of the investigator, would raise significant risk to the patient.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Krzysztof Misiukiewicz, M.D.
Organizational Affiliation
Icahn School of Medicine at Mount Sinai
Official's Role
Principal Investigator
Facility Information:
Facility Name
Icahn School of Medicine at Mount Sinai
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
14645636
Citation
Forastiere AA, Goepfert H, Maor M, Pajak TF, Weber R, Morrison W, Glisson B, Trotti A, Ridge JA, Chao C, Peters G, Lee DJ, Leaf A, Ensley J, Cooper J. Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. N Engl J Med. 2003 Nov 27;349(22):2091-8. doi: 10.1056/NEJMoa031317.
Results Reference
background
PubMed Identifier
12506176
Citation
Adelstein DJ, Li Y, Adams GL, Wagner H Jr, Kish JA, Ensley JF, Schuller DE, Forastiere AA. An intergroup phase III comparison of standard radiation therapy and two schedules of concurrent chemoradiotherapy in patients with unresectable squamous cell head and neck cancer. J Clin Oncol. 2003 Jan 1;21(1):92-8. doi: 10.1200/JCO.2003.01.008.
Results Reference
background
PubMed Identifier
11189100
Citation
Domenge C, Hill C, Lefebvre JL, De Raucourt D, Rhein B, Wibault P, Marandas P, Coche-Dequeant B, Stromboni-Luboinski M, Sancho-Garnier H, Luboinski B; French Groupe d'Etude des Tumeurs de la Tete et du Cou (GETTEC). Randomized trial of neoadjuvant chemotherapy in oropharyngeal carcinoma. French Groupe d'Etude des Tumeurs de la Tete et du Cou (GETTEC). Br J Cancer. 2000 Dec;83(12):1594-8. doi: 10.1054/bjoc.2000.1512.
Results Reference
background
PubMed Identifier
17960013
Citation
Posner MR, Hershock DM, Blajman CR, Mickiewicz E, Winquist E, Gorbounova V, Tjulandin S, Shin DM, Cullen K, Ervin TJ, Murphy BA, Raez LE, Cohen RB, Spaulding M, Tishler RB, Roth B, Viroglio Rdel C, Venkatesan V, Romanov I, Agarwala S, Harter KW, Dugan M, Cmelak A, Markoe AM, Read PW, Steinbrenner L, Colevas AD, Norris CM Jr, Haddad RI; TAX 324 Study Group. Cisplatin and fluorouracil alone or with docetaxel in head and neck cancer. N Engl J Med. 2007 Oct 25;357(17):1705-15. doi: 10.1056/NEJMoa070956.
Results Reference
background
PubMed Identifier
15057285
Citation
Jordan MA, Wilson L. Microtubules as a target for anticancer drugs. Nat Rev Cancer. 2004 Apr;4(4):253-65. doi: 10.1038/nrc1317. No abstract available.
Results Reference
background
PubMed Identifier
19147780
Citation
Mita AC, Denis LJ, Rowinsky EK, Debono JS, Goetz AD, Ochoa L, Forouzesh B, Beeram M, Patnaik A, Molpus K, Semiond D, Besenval M, Tolcher AW. Phase I and pharmacokinetic study of XRP6258 (RPR 116258A), a novel taxane, administered as a 1-hour infusion every 3 weeks in patients with advanced solid tumors. Clin Cancer Res. 2009 Jan 15;15(2):723-30. doi: 10.1158/1078-0432.CCR-08-0596.
Results Reference
background
PubMed Identifier
20888992
Citation
de Bono JS, Oudard S, Ozguroglu M, Hansen S, Machiels JP, Kocak I, Gravis G, Bodrogi I, Mackenzie MJ, Shen L, Roessner M, Gupta S, Sartor AO; TROPIC Investigators. Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial. Lancet. 2010 Oct 2;376(9747):1147-54. doi: 10.1016/S0140-6736(10)61389-X.
Results Reference
background
PubMed Identifier
4038469
Citation
Rooney M, Kish J, Jacobs J, Kinzie J, Weaver A, Crissman J, Al-Sarraf M. Improved complete response rate and survival in advanced head and neck cancer after three-course induction therapy with 120-hour 5-FU infusion and cisplatin. Cancer. 1985 Mar 1;55(5):1123-8. doi: 10.1002/1097-0142(19850301)55:53.0.co;2-8.
Results Reference
background
PubMed Identifier
7037180
Citation
Kish J, Drelichman A, Jacobs J, Hoschner J, Kinzie J, Loh J, Weaver A, Al-Sarraf M. Clinical trial of cisplatin and 5-FU infusion as initial treatment for advanced squamous cell carcinoma of the head and neck. Cancer Treat Rep. 1982 Mar;66(3):471-4.
Results Reference
background
PubMed Identifier
10793107
Citation
Gillison ML, Koch WM, Capone RB, Spafford M, Westra WH, Wu L, Zahurak ML, Daniel RW, Viglione M, Symer DE, Shah KV, Sidransky D. Evidence for a causal association between human papillomavirus and a subset of head and neck cancers. J Natl Cancer Inst. 2000 May 3;92(9):709-20. doi: 10.1093/jnci/92.9.709.
Results Reference
background
PubMed Identifier
17079134
Citation
Martinez I, Wang J, Hobson KF, Ferris RL, Khan SA. Identification of differentially expressed genes in HPV-positive and HPV-negative oropharyngeal squamous cell carcinomas. Eur J Cancer. 2007 Jan;43(2):415-32. doi: 10.1016/j.ejca.2006.09.001. Epub 2006 Oct 31.
Results Reference
background
PubMed Identifier
19917838
Citation
Cullen KJ, Schumaker L, Nikitakis N, Goloubeva O, Tan M, Sarlis NJ, Haddad RI, Posner MR. beta-Tubulin-II expression strongly predicts outcome in patients receiving induction chemotherapy for locally advanced squamous carcinoma of the head and neck: a companion analysis of the TAX 324 trial. J Clin Oncol. 2009 Dec 20;27(36):6222-8. doi: 10.1200/JCO.2009.23.0953. Epub 2009 Nov 16.
Results Reference
background
PubMed Identifier
10632346
Citation
Shiga H, Heath EI, Rasmussen AA, Trock B, Johnston PG, Forastiere AA, Langmacher M, Baylor A, Lee M, Cullen KJ. Prognostic value of p53, glutathione S-transferase pi, and thymidylate synthase for neoadjuvant cisplatin-based chemotherapy in head and neck cancer. Clin Cancer Res. 1999 Dec;5(12):4097-104.
Results Reference
background
PubMed Identifier
10191625
Citation
Nishimura T, Shiga H, Wakisaka N, Furukawa M. [Glutathione and cisplatin resistance in head and neck cancer]. Nihon Jibiinkoka Gakkai Kaiho. 1999 Feb;102(2):236-42. doi: 10.3950/jibiinkoka.102.236. Japanese.
Results Reference
background
PubMed Identifier
14678959
Citation
Cullen KJ, Newkirk KA, Schumaker LM, Aldosari N, Rone JD, Haddad BR. Glutathione S-transferase pi amplification is associated with cisplatin resistance in head and neck squamous cell carcinoma cell lines and primary tumors. Cancer Res. 2003 Dec 1;63(23):8097-102.
Results Reference
background
PubMed Identifier
11756581
Citation
Forastiere A, Koch W, Trotti A, Sidransky D. Head and neck cancer. N Engl J Med. 2001 Dec 27;345(26):1890-900. doi: 10.1056/NEJMra001375. No abstract available. Erratum In: N Engl J Med 2002 Mar 7;346(10):788.
Results Reference
background
PubMed Identifier
10637254
Citation
Temam S, Flahault A, Perie S, Monceaux G, Coulet F, Callard P, Bernaudin JF, St Guily JL, Fouret P. p53 gene status as a predictor of tumor response to induction chemotherapy of patients with locoregionally advanced squamous cell carcinomas of the head and neck. J Clin Oncol. 2000 Jan;18(2):385-94. doi: 10.1200/JCO.2000.18.2.385.
Results Reference
background
PubMed Identifier
10735894
Citation
Cabelguenne A, Blons H, de Waziers I, Carnot F, Houllier AM, Soussi T, Brasnu D, Beaune P, Laccourreye O, Laurent-Puig P. p53 alterations predict tumor response to neoadjuvant chemotherapy in head and neck squamous cell carcinoma: a prospective series. J Clin Oncol. 2000 Apr;18(7):1465-73. doi: 10.1200/JCO.2000.18.7.1465.
Results Reference
background
PubMed Identifier
20048189
Citation
Perrone F, Bossi P, Cortelazzi B, Locati L, Quattrone P, Pierotti MA, Pilotti S, Licitra L. TP53 mutations and pathologic complete response to neoadjuvant cisplatin and fluorouracil chemotherapy in resected oral cavity squamous cell carcinoma. J Clin Oncol. 2010 Feb 10;28(5):761-6. doi: 10.1200/JCO.2009.22.4170. Epub 2010 Jan 4.
Results Reference
background
PubMed Identifier
11325447
Citation
Alsner J, Sorensen SB, Overgaard J. TP53 mutation is related to poor prognosis after radiotherapy, but not surgery, in squamous cell carcinoma of the head and neck. Radiother Oncol. 2001 May;59(2):179-85. doi: 10.1016/s0167-8140(01)00301-2.
Results Reference
background
PubMed Identifier
9921989
Citation
Pena JC, Thompson CB, Recant W, Vokes EE, Rudin CM. Bcl-xL and Bcl-2 expression in squamous cell carcinoma of the head and neck. Cancer. 1999 Jan 1;85(1):164-70. doi: 10.1002/(sici)1097-0142(19990101)85:13.0.co;2-q.
Results Reference
background
PubMed Identifier
20697079
Citation
Rischin D, Young RJ, Fisher R, Fox SB, Le QT, Peters LJ, Solomon B, Choi J, O'Sullivan B, Kenny LM, McArthur GA. Prognostic significance of p16INK4A and human papillomavirus in patients with oropharyngeal cancer treated on TROG 02.02 phase III trial. J Clin Oncol. 2010 Sep 20;28(27):4142-8. doi: 10.1200/JCO.2010.29.2904. Epub 2010 Aug 9.
Results Reference
background
PubMed Identifier
20530316
Citation
Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tan PF, Westra WH, Chung CH, Jordan RC, Lu C, Kim H, Axelrod R, Silverman CC, Redmond KP, Gillison ML. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010 Jul 1;363(1):24-35. doi: 10.1056/NEJMoa0912217. Epub 2010 Jun 7.
Results Reference
background
PubMed Identifier
20032123
Citation
Paccagnella A, Ghi MG, Loreggian L, Buffoli A, Koussis H, Mione CA, Bonetti A, Campostrini F, Gardani G, Ardizzoia A, Dondi D, Guaraldi M, Cavallo R, Tomio L, Gava A; Gruppo di Studio Tumori della Testa e del Collo XRP 6976 F/2501 Study. Concomitant chemoradiotherapy versus induction docetaxel, cisplatin and 5 fluorouracil (TPF) followed by concomitant chemoradiotherapy in locally advanced head and neck cancer: a phase II randomized study. Ann Oncol. 2010 Jul;21(7):1515-1522. doi: 10.1093/annonc/mdp573. Epub 2009 Dec 23.
Results Reference
background
PubMed Identifier
18436520
Citation
Pivot X, Koralewski P, Hidalgo JL, Chan A, Goncalves A, Schwartsmann G, Assadourian S, Lotz JP. A multicenter phase II study of XRP6258 administered as a 1-h i.v. infusion every 3 weeks in taxane-resistant metastatic breast cancer patients. Ann Oncol. 2008 Sep;19(9):1547-52. doi: 10.1093/annonc/mdn171. Epub 2008 Apr 23.
Results Reference
background
PubMed Identifier
16504868
Citation
El-Mofty SK, Patil S. Human papillomavirus (HPV)-related oropharyngeal nonkeratinizing squamous cell carcinoma: characterization of a distinct phenotype. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006 Mar;101(3):339-45. doi: 10.1016/j.tripleo.2005.08.001.
Results Reference
background

Learn more about this trial

Cabazitaxel - PF Induction Chemotherapy

We'll reach out to this number within 24 hrs