Study in Locally Advanced Squamous Cell Carcinoma of Head and Neck

Study Description

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Brief 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.

Condition or disease	Intervention/treatment	Phase
Head and Neck Cancer	Drug: Everolimus escalating dose; Drug: Everolimus or Placebo	Phase 2

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	80 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Triple (Participant, Care Provider, 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
Actual Study Start Date :	May 4, 2010
Estimated Primary Completion Date :	August 2018
Estimated Study Completion Date :	October 2018

Arms and Interventions

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Arm	Intervention/treatment
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

Outcome Measures

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Primary Outcome Measures :

1. Tumor Responses [ Time Frame: 2 years ]
   To assess the rates of the tumor

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 89 Years (Adult, Senior)
Sexes Eligible for Study:	All
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

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Locations

United States, Illinois
The University of Chicago Medical Center
Chicago, Illinois, United States, 60637
NorthShore University Health System
Evanston, Illinois, United States, 60201

Sponsors and Collaborators

University of Chicago

Novartis Pharmaceuticals

Investigators

Principal Investigator:	Everett Vokes, M.D.	The University of Chicago Medical Center

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:

The University of Chicago Comprehensive Cancer Center Web Page 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Villaflor VM, Melotek JM, Karrison TG, Brisson RJ, Blair EA, Portugal L, De Souza JA, Ginat DT, Stenson KM, Langerman A, Kocherginsky M, Spiotto MT, Hannigan N, Seiwert TY, Cohen EE, Vokes EE, Haraf DJ. Response-adapted volume de-escalation (RAVD) in locally advanced head and neck cancer. Ann Oncol. 2016 May;27(5):908-13. doi: 10.1093/annonc/mdw051. Epub 2016 Feb 15.

Responsible Party:	University of Chicago
ClinicalTrials.gov Identifier:	NCT01133678 History of Changes
Other Study ID Numbers:	10-069-B
First Posted:	May 31, 2010
Last Update Posted:	October 11, 2017
Last Verified:	October 2017

Keywords provided by University of Chicago:

Squamous Cell Carcinoma

Additional relevant MeSH terms:

Carcinoma; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Neoplasms by Site; Everolimus	Sirolimus; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Anti-Bacterial Agents; Anti-Infective Agents; Antibiotics, Antineoplastic; Antifungal Agents