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Study in Locally Advanced Squamous Cell Carcinoma of Head and Neck

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by University of Chicago
Sponsor:
Collaborator:
Novartis Pharmaceuticals
Information provided by (Responsible Party):
University of Chicago
ClinicalTrials.gov Identifier:
NCT01133678
First received: May 27, 2010
Last updated: October 14, 2014
Last verified: October 2014
  Purpose

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.


Condition Intervention Phase
Head and Neck Cancer
Drug: Everolimus escalating dose
Drug: Everolimus or Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by University of Chicago:

Primary Outcome Measures:
  • Tumor Responses [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    To assess the rates of the tumor


Estimated Enrollment: 80
Study Start Date: May 2010
Estimated Study Completion Date: May 2016
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Everolimus escalating dose
Find the highest safe dose of Everolimus when combined with induction chemotherapy.
Drug: 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: Everolimus or Placebo
Subject will receive Everolimus or Placebo (dose determined in Phase 1 portion)
Drug: 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

  Eligibility

Ages Eligible for Study:   18 Years to 89 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01133678

Locations
United States, Illinois
The University of Chicago Medical Center Recruiting
Chicago, Illinois, United States, 60637
Contact: Ezra E Cohen, M.D.    773-702-4137      
NorthShore University Health System Not yet recruiting
Evanston, Illinois, United States, 60201
Contact: Michele Britto, RN    847-570-2109      
Principal Investigator: Bruce Brockstein, MD         
Sponsors and Collaborators
University of Chicago
Novartis Pharmaceuticals
Investigators
Principal Investigator: Ezra E. Cohen, M.D. The University of Chicago Medical Center
  More Information

Additional Information:
No publications provided

Responsible Party: University of Chicago
ClinicalTrials.gov Identifier: NCT01133678     History of Changes
Other Study ID Numbers: 10-069-B
Study First Received: May 27, 2010
Last Updated: October 14, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Chicago:
Squamous Cell Carcinoma

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Neoplasms, Squamous Cell
Everolimus
Sirolimus
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antineoplastic Agents
Immunologic Factors
Immunosuppressive Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014