Study in Locally Advanced Squamous Cell Carcinoma of Head and Neck

NCT01133678 | Terminated Phase 2 Results

• 1 other identifier: 10-069-B
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 2

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)

Conditions

Head and Neck Cancer

Keywords

Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Tumor Responses

  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.

  Baseline and 2 months

Study Arms (2)

Everolimus

EXPERIMENTAL

Everolimus 5 mg PO Daily for 2 21-day cycles

Drug: Everolimus

Placebo

EXPERIMENTAL

Placebo 5 mg PO Daily for 2 21-day cycles

Drug: Placebo

Interventions

Everolimus DRUG

Phase II Portion (2 21-day cycles of induction therapy) Cisplatin (75 mg/m2 day 1) Paclitaxel (175 mg/m2, day 1) Cetuximab(400 mg/m2 loading dose day 1 then 250mg/m2 weekly ) Everolimus 5 mg PO daily. Following induction patients received \[paclitaxel (100 mg/m2 IV weekly), 5-FU (600 mg/m2 IV day 1-5), hydroxyurea 500 mg BID PO (day 1-5), and hyperfractionated twice daily radiotherapy (150 cGy per fraction) day 1-5 of a 14 day cycle which is repeated to deliver the prescribed radiotherapy dose.

Also known as: Cisplatin, Paclitaxel, Cetuximab, Everolimus

Everolimus

Placebo DRUG

Phase II Portion (2 21-day cycles of induction therapy) Cisplatin (75 mg/m2 day 1) Paclitaxel(175 mg/m2, day 1) Cetuximab(400 mg/m2 loading dose day 1 then 250mg/m2 weekly ) Placebo PO daily. Following induction patients received \[paclitaxel (100 mg/m2 IV weekly), 5-FU (600 mg/m2 IV day 1-5), hydroxyurea 500 mg BID PO (day 1-5), and hyperfractionated twice daily radiotherapy (150 cGy per fraction) day 1-5 of a 14 day cycle which is repeated to deliver the prescribed radiotherapy dose.

Also known as: Cisplatin, Paclitaxel, Cetuximab, Placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 89 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Chicago: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (2)

The University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

NorthShore University Health System

Evanston, Illinois, 60201, United States

Location

Related Publications (1)

• 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.

  PMID: 26884588 DERIVED

Related Links

• The University of Chicago Comprehensive Cancer Center Web Page

MeSH Terms

Conditions

Head and Neck Neoplasms; Carcinoma, Squamous Cell

Interventions

Everolimus; Cisplatin; Paclitaxel; Cetuximab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Squamous Cell

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Everett Vokes, MD
• Organization: University of Chicago

evokes@medicine.bsd.uchicago.edu

(773) 702-6227

Study Officials

• Everett Vokes, M.D.

  The University of Chicago Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 27, 2010
• First Posted: May 31, 2010
• Study Start: May 4, 2010
• Primary Completion: January 1, 2015
• Study Completion: January 1, 2015
• Last Updated: May 8, 2020
• Results First Posted: May 8, 2020

Record last verified: 2020-04

Locations

US (2)