Clinical trial NCT01379339: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: 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
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
Collaborators: name: Sanofi
name: Icahn School of Medicine at Mount Sinai
First posted: 2011-06-23
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Maximum Tolerated Dose (MTD)
timeFrame: at 1 week
measure: Maximum Tolerated Dose (MTD)
timeFrame: at 4 weeks
measure: Maximum Tolerated Dose (MTD)
timeFrame: at 7 weeks
measure: Maximum Tolerated Dose (MTD)
timeFrame: at 9 weeks
measure: Dose-limiting toxicity (DLT)
timeFrame: at 1 week
measure: Dose-limiting toxicity (DLT)
timeFrame: at 4 weeks
measure: Dose-limiting toxicity (DLT)
timeFrame: at 7 weeks
measure: Dose-limiting toxicity (DLT)
timeFrame: at 9 weeks
Secondary outcomes:
measure: Toxicity Profile
timeFrame: at 9 weeks
measure: Overall Response Rate
timeFrame: at 9 weeks
measure: Progression Free Survival/Overall Survival
timeFrame: for 3 years
Other outcomes:
Locations:
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Krzysztof Misiukiewicz, M.D.
role: PRINCIPAL_INVESTIGATOR
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