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Phase I Study of Cabazitaxel - Platinum Fluorouracil Induction Chemotherapy in Patients With Locally Advanced Squamous Cell Carcinoma of the Head and Neck


Phase 1
18 Years
N/A
Open (Enrolling)
Both
Squamous Cell Carcinoma of the Head and Neck

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Trial Information

Phase I Study of Cabazitaxel - Platinum Fluorouracil Induction Chemotherapy in Patients With Locally Advanced Squamous Cell Carcinoma of the Head and Neck


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.


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 Neutrophilc Count (ANC) >/= 1.5 x 10^9/L, Platelets >/= 100 x 10^9/L;
bilirubin and/or Alanine Aminotransferase (ALT) documented liver metastases; serum creatinine
- 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.

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Factorial Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum Tolerated Dose (MTD)

Outcome 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.

Outcome Time Frame:

at 3 weeks

Safety Issue:

Yes

Principal Investigator

Krzysztof Misiukiewicz, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Mount Sinai School of Medicine

Authority:

United States: Institutional Review Board

Study ID:

11-0646(0001)(01)

NCT ID:

NCT01379339

Start Date:

April 2011

Completion Date:

April 2014

Related Keywords:

  • Squamous Cell Carcinoma of the Head and Neck
  • Cabazitaxel
  • Cabazitaxel and Cisplatin
  • Phase I
  • PF Induction Chemotherapy
  • Squamous Cell Carcinoma
  • Head and Neck
  • Sanofi-Aventis Oncology
  • Locally Advanced
  • Carcinoma
  • Carcinoma, Squamous Cell
  • Head and Neck Neoplasms

Name

Location

Mount Sinai School of MedicineNew York, New York  10029