Phase II Study of RAD001 Head and Neck Cancer

NCT01051791 | Terminated Phase 2 Results DMC

• 1 other identifier: 08-032
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

To carry out exploratory studies to determine if activity of this regimen correlates with tumor and patient associated markers of the EGF-R/mTOR pathway These markers may correlate with activity of this regimen and provide exploratory insights in to the mechanism of this treatment approach. Expression of the pathway components including EGF-R and phosphorylated EGF-R (p-EGF-R), ERK and p-ERK, Akt and p-Akt(T308 and S473), p70s6k and p-p70s6k, S6 and p-S6, HIF-1-alpha, p27 and 4E-BP1 will be assessed. Mutation and FISH analysis for EGF-R expression will also be performed on tumor samples. Biopsies will be obtained at the following times: pre-treatment, and after 4 weeks (one cycle) of treatment. If available, original diagnostic tissue may be submitted in place of the pre-treatment biopsy.

Conditions

Squamous Cell Carcinoma of the Head and Neck

Keywords

RAD001; Everolimus

Outcome Measures

Primary Outcomes (1)

• Clinical Benefit Rate (CBR)

  The number of patients with recurrent/refractory SCCHN (head and neck squamous cell carcinoma) treated with single-agent everolimus that, experience a Complete Response (CR) + number of patients that experience a Partial Response (PR ) + number of patients that experience Stable Disease (SD) / total evaluable patients.

  Up to 60 months

Secondary Outcomes (3)

• Progression Free Survival (PFS)

  Up to 60 months

• Overall Survival (OS)

  Up to 60 months

• Objective Response Rate (ORR)

  Up to 60 months

Study Arms (1)

Everolimus 10 mg daily

EXPERIMENTAL

The study of the efficacy of everolimus will proceed in two stages after the method of Simon1. In the first stage 15 patients will be accrued and treated. If 9 or fewer patients show clinical benefit the study will be terminated. If 10 or more patients show clinical benefit the study will proceed to the second stage, accruing an additional 26 patients. If the second stage is complete and a total of 29 or more patients show clinical benefit among the 41 patients treated, the treatment CBR for will be considered high enough to warrant further study. Conversely, if the evaluation of everolimus concludes at the first stage, or if 28 or fewer patients experience a clinical benefit after completing the second stage, the therapy will not be considered for further study. 1

Drug: Everolimus 10mg daily

Interventions

Everolimus 10mg daily DRUG

RAD001 is a pill that will be taken orally (by mouth), at a dose of 10 mg, once a day for 28 days.

Also known as: Everolimus

Everolimus 10 mg daily

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically documented squamous cell CA of the head and neck
• Metastatic and/or recurrent head and neck cancer (not eligible for curative intent surgical or radiation therapy)
• Patients must have at least one measurable site of disease according to RECIST criteria that has not been previously irradiated. If the patient has had previous radiation to the marker lesion(s), there must be evidence of progression since the radiation
• Performance status 0-2
• Age ≥18 years
• Non-pregnant
• Prior treatment:
• Prior treatment for recurrent or metastatic disease required (at least one): up to but no more than 2 regimens (chemotherapy and/or biologic) allowed.
• Prior induction and concomitant chemoradiotherapy with a curative intent (with or without biologic agents) is allowed
• No other serious medical or psychiatric disease
• Required Lab Values:
• Granulocytes ≥ 1,500/µl Platelets ≥ 100,000/µl Bilirubin ≤ 1.5 x ULN INR ≥ 1.3 (or \< 3 if on anticoagulation) AST or ALT ≤ 2.5 x ULN (\< 5 x ULN in patients with liver metastases) Creatinine ≤ ULN or Creatinine Clearance \>= 60 mL/min, if creatinine above 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.
• Patients with accessible tumor tissue must agree to a pre-treatment biopsy at screening. If available, original diagnostic tissue may be submitted in place of the pre-treatment biopsy.
• 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 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 (defined as requiring general anesthesia) 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, except corticosteroids with a daily dosage equivalent to prednisone ≤ 20 mg. However, patients receiving corticosteroids must have been on a stable dosage regimen for a minimum of 4 weeks prior to the first treatment with RAD001. 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
• Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases
• 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. PFTs as clinically indicated.
• 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

• Julie E. Bauman, MD, MPH: lead
• Novartis: collaborator

Study Sites (1)

Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

Everolimus

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Barbara Stadterman, Regulatory Supervisor
• Organization: University of Pittsburgh Cancer Institute

stadtermanbm@upmc.edu

412-647-5554

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 18, 2010
• First Posted: January 20, 2010
• Study Start: January 1, 2010
• Primary Completion: April 26, 2011
• Study Completion: August 5, 2016
• Last Updated: December 19, 2017
• Results First Posted: December 19, 2017

Record last verified: 2017-11

Locations

US (1)