Overview

This trial is active, not recruiting.

Condition head and neck cancer
Treatments everolimus escalating dose, everolimus or placebo
Phase phase 2
Targets mTOR, FKBP-12
Sponsor University of Chicago
Collaborator Novartis Pharmaceuticals
Start date May 2010
End date December 2016
Trial size 80 participants
Trial identifier NCT01133678, 10-069-B

Summary

Primary

Compare response rates 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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator)
Primary purpose treatment
Arm
(Experimental)
Find the highest safe dose of Everolimus when combined with induction chemotherapy.
everolimus escalating dose
Phase I Portion (2 21-day cycles) Cisplatin (100mg/m2 day 1) Paclitaxel(175mg/m2, day 1) Cetuximab(400 mg/m2 loading dose day 1 then 250mg/m2 weekly ) Everolimus escalating dose
(Experimental)
Subject will receive Everolimus or Placebo (dose determined in Phase 1 portion)
everolimus or placebo
Phase II Portion (2 28-day cycles) Cisplatin (100mg/m2 day 1) Paclitaxel(175mg/m2, day 1) Cetuximab(400 mg/m2 loading dose day 1 then 250mg/m2 weekly ) Everolimus dose determined in phase I

Primary Outcomes

Measure
Tumor Responses
time frame: 2 years

Eligibility Criteria

Male or female participants from 18 years up to 89 years old.

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

Additional Information

Official title Selection of Chemoradiotherapy Based on Response to Induction Chemotherapy - a Phase II Study in Locally Advanced Squamous Cell Carcinoma of Head and Neck
Principal investigator Everett Vokes, M.D.
Trial information was received from ClinicalTrials.gov and was last updated in March 2016.
Information provided to ClinicalTrials.gov by University of Chicago.