Cabazitaxel - PF Induction Chemotherapy

• Status: Completed
• Trial end date: 2015-01-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Krzysztof Misiukiewicz
• Collaborators: Icahn School of Medicine at Mount Sinai; Sanofi
• Treatments: Cisplatin; Fluorouracil

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; bilirubinand/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.