Head and Neck Cancer
Conditions
Keywords
Squamous Cell Cancer
Brief summary
Primary: Two-year progression-free (tumor does not grow or spread) survival in subjects treated with everolimus versus placebo after definitive local therapy.
Interventions
DRUGEverolimus (RAD 001)
10mg of Everolimus or Placebo taken by mouth once daily for 1 year or until progression (whichever comes first).
OTHERPlacebo
Sponsors
Novartis Pharmaceuticals
University of Chicago
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of Squamous cell carcinoma of the head and neck (stage IVa or IVb). No evidence (absence)of disease by scan. * 18 years or older. * Performance status 70% or better. * Adequate marrow, renal and liver function (will be tested by labs). \_ Able give consent.
Exclusion criteria
* Currently receiving anti-cancer treatment. * Major surgery or traumatic injury within 4 weeks. * Radiotherapy related toxicities. * Lip, nasopharynx, nasal cavity, paranasal sinus, salivary gland, skin, or thyroid primary tumors * Receiving other investigational drugs. * Receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent. * Receive immunization with attenuated live vaccines (seasonal flu shot)1 week before starting this . * Show evidence of disease (cancer). * Uncontrolled medical conditions such as: unstable angina, congestive heart failure, diabetes, severely impaired lung function. * Liver disease such as cirrhosis, severe hepatic impairment, Hepatitis B or C. * Active, uncontrolled severe infections * Other malignancies within the past 3 years except for adequately treated carcinoma of the cervix or basal or squamous cell carcinomas of the skin. * Known History of HIV positivity. * Impaired gastrointestinal function that may alter absorption of Everolimus such as ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection. * 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. ) * Male patient whose sexual partner(s) are Women of child bearing potential who are not willing to use adequate. contraception, during the study and for 8 weeks after the end of treatment * Patients who have received prior treatment with an mTOR inhibitor (sirolimus, temsirolimus, everolimus). * Patients with a known hypersensitivity to Everolimus or other rapamycin analogues (sirolimus, temsirolimus) or to its excipients. * History of noncompliance to medical regimens. * Patients unwilling to or unable to comply with the protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 2 Year Progression Free Survival Rate | 2 years | Time to disease progression or death from any cause--2 year rate |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Site of Progression: Local-regional | 4 years | Number of patients with local-regional progression |
| Site of Progression: Distant | 4 years | Number of patients with distant progression |
| Site of Progression: Unknown | 4 years | Number of patients with unknown site of progression |
| Number of Participants With Toxicity | 4 years | Adverse event rate, any type, any grade regardless of attribution |
| Akt/mTOR Pathway Activation | Baseline | mTOR positive in tumor tissue |
| Correlation of Akt/mTOR Status With Progression-free Survival | 4 years | mTOR positive in tumor tissue |
| Determine if PTEN Status is a Predictive Biomarker | 4 years | Differential effect of PTEN status on progression-free survival between the two arms |
| Second Primary Tumor | 4 years | Number of patients with second primary tumor |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Everolimus (RAD001) Subjects will receive Everolimus 10 mg daily
Everolimus (RAD 001): 10mg of Everolimus or Placebo taken by mouth once daily for 1 year or until progression (whichever comes first). | 28 |
| Placebo Subjects will receive double-blind placebo
Placebo | 24 |
| Total | 52 |
Baseline characteristics
| Characteristic | Everolimus (RAD001) | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 58.0 years | 57.7 years | 57.4 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 6 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 25 Participants | 45 Participants | 20 Participants |
| Region of Enrollment United States | 28 participants | 52 participants | 24 participants |
| Sex: Female, Male Female | 5 Participants | 9 Participants | 4 Participants |
| Sex: Female, Male Male | 23 Participants | 43 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 4 / 28 | 4 / 24 |
| other Total, other adverse events | 25 / 28 | 14 / 24 |
| serious Total, serious adverse events | 3 / 28 | 5 / 24 |
Outcome results
Primary
2 Year Progression Free Survival Rate
Time to disease progression or death from any cause--2 year rate
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Everolimus (RAD001) | 2 Year Progression Free Survival Rate | 56.1 percentage of patients |
| Placebo | 2 Year Progression Free Survival Rate | 55.9 percentage of patients |
p-value: 0.995% CI: [-0.33, 0.33]Comparison of Kaplan-Meier estimates
p-value: 0.54Log Rank
Secondary
Akt/mTOR Pathway Activation
mTOR positive in tumor tissue
Time frame: Baseline
Population: Data were not collected.
Secondary
Correlation of Akt/mTOR Status With Progression-free Survival
mTOR positive in tumor tissue
Time frame: 4 years
Population: Data were not collected.
Secondary
Determine if PTEN Status is a Predictive Biomarker
Differential effect of PTEN status on progression-free survival between the two arms
Time frame: 4 years
Population: Data were not collected.
Secondary
Number of Participants With Toxicity
Adverse event rate, any type, any grade regardless of attribution
Time frame: 4 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Everolimus (RAD001) | Number of Participants With Toxicity | 25 Participants |
| Placebo | Number of Participants With Toxicity | 16 Participants |
p-value: 0.086Fisher Exact
Secondary
Second Primary Tumor
Number of patients with second primary tumor
Time frame: 4 years
Population: Data not systematically recorded.
Secondary
Site of Progression: Distant
Number of patients with distant progression
Time frame: 4 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Everolimus (RAD001) | Site of Progression: Distant | 2 Participants |
| Placebo | Site of Progression: Distant | 2 Participants |
Secondary
Site of Progression: Local-regional
Number of patients with local-regional progression
Time frame: 4 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Everolimus (RAD001) | Site of Progression: Local-regional | 2 Participants |
| Placebo | Site of Progression: Local-regional | 5 Participants |
Secondary
Site of Progression: Unknown
Number of patients with unknown site of progression
Time frame: 4 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Everolimus (RAD001) | Site of Progression: Unknown | 1 Participants |
| Placebo | Site of Progression: Unknown | 1 Participants |