Study in Locally Advanced Squamous Cell Carcinoma of Head and Neck

Phase 2

Terminated

Conditions: Head and Neck Cancer

Interventions: Drug: Placebo
Drug: Everolimus

Registration Number: NCT01133678

Lead Sponsor: University of Chicago

Brief Summary: Primary

Compare response rates (relative change in tumor size) to induction chemotherapy consisting of cisplatin/paclitaxel/cetuximab +/- everolimus.

Secondary:

Determine the maximum administered dose (MAD), maximum tolerated dose (MTD), dose limiting toxicity (DLT), and safety of everolimus with cisplatin/paclitaxel/cetuximab induction chemotherapy (phase I portion)

Detailed Description: Results reported here are for the randomized, phase II portion of the trial.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 50

Inclusion Criteria

Treatment naïve stage III (hypopharynx, or nasopharynx primary) or stage IVa/IVb (all sites) histologically proven SCCHN with no definitive evidence of metastatic disease
Patients with unknown primary site of tumor and histologically proven squamous cell carcinoma of a cervical lymph node felt to arise from a site in the head and neck are eligible
Patients must have at least one measurable site of disease according to RECIST criteria
Age ≥ 18 years
Karnofsky performance status > 70%
Adequate bone marrow function as shown by: ANC ≥ 1.5 x 109/L, Platelets ≥ 100 x 109/L, Hb >9 g/dL
Adequate liver function as shown by:
Serum bilirubin ≤ 1.5 x ULN
ALT and AST ≤ 2.5x ULN
INR and PTT ≤1.5. (Anticoagulation is allowed if target INR ≤ 1.5 on a stable dose of warfarin or on a stable dose of LMW heparin for >2 weeks at time of randomization.)
Adequate renal function: serum creatinine ≤ 1.5 x ULN
Fasting serum cholesterol ≤300 mg/dL OR ≤7.75 mmol/L AND fasting triglycerides ≤ 2.5 x ULN. NOTE: In case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication.
Signed informed consent

Exclusion Criteria

Patients currently receiving anticancer therapies or who have received anticancer therapies within 4 weeks of the start of study drug (including chemotherapy, radiation therapy, antibody based therapy, etc.)
Patients, who have had a major surgery [defined as requiring general anesthesia but not including tonsillectomy, neck dissection, or panendoscopy (triple endoscopy or examination under general anesthesia)], or significant traumatic injury within 4 weeks of start of study drug; patients who have not recovered from the side effects of any major surgery; or patients that may require major surgery during the course of the study
Prior treatment with any investigational drug within the preceding 4 weeks
Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent. Topical or inhaled corticosteroids are allowed.
Patients should not receive immunization with attenuated live vaccines within one week of study entry or during study period
Unequivocal demonstration of metastatic disease (i.e. M1 disease).
Other malignancies within the past 3 years except for adequately treated carcinoma of the cervix or basal or squamous cell carcinomas of the skin.
Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
Symptomatic congestive heart failure of New York heart Association Class III or IV
Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease
Severely impaired lung function as defined as spirometry and DLCO that is 50% of the normal predicted value and/or 02 saturation that is 88% or less at rest on room air
Uncontrolled diabetes as defined by fasting serum glucose >1.5 x ULN
Active (acute or chronic) or uncontrolled severe infections
Liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis
A known history of HIV seropositivity
Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of everolimus (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection)
Nota bene: subjects that require administration of everolimus through a feeding tube are allowed to participate
Patients with an active, bleeding diathesis
Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods. If barrier contraceptives are being used, these must be continued throughout the trial by both sexes. Hormonal contraceptives are not acceptable as a sole method of contraception. (Women of childbearing potential must have a negative urine or serum pregnancy test within 7 days prior to administration of everolimus)
Patients who have received prior treatment with an mTOR inhibitor for SCCHN (sirolimus, temsirolimus, everolimus).
Patients with a known hypersensitivity to everolimus (everolimus) or other rapamycins (sirolimus, temsirolimus) or to its excipients
Patients with a know hypersensitivity to cetuximab, cremaphor, paclitaxel, carboplatin, 5FU, hydroxyurea, or any compounds of similar chemical or biologic composition
History of noncompliance to medical regimens
Patients unwilling to or unable to comply with the protocol
Baseline neurologic deficit (> grade II neuropathy)
Prior severe infusion reaction (grade 4) to a monoclonal antibody

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo 5 mg PO Daily for 2 21-day cycles
Everolimus	Everolimus	Everolimus 5 mg PO Daily for 2 21-day cycles

Primary Outcome Measures

Name	Time	Method
Tumor Responses	Baseline and 2 months	Change in tumor size (sum of longest diameters of target lesions) after two cycles of induction therapy, expressed as log of ratio of post-treatment to baseline measure.

Secondary Outcome Measures

Name	Time	Method

Trial Locations

Locations (2): The University of Chicago Medical Center
🇺🇸
Chicago, Illinois, United States
NorthShore University Health System
🇺🇸
Evanston, Illinois, United States