A Phase 1/2 Study of RAD001 in Combination w/ Cetuximab and Cisplatin as First-line Therapy in Recurrent & Metastatic Squamous Cell Cancer of the Head & Neck
1. Patients must have histologically or cytologically confirmed diagnosis of squamous
cell carcinoma of the head and neck, with recurrent or metastatic disease.
2. Patients must have measurable disease, defined as at least one lesion that can be
accurately measured in at least one dimension (longest diameter to be recorded) as
>20 mm with conventional techniques or as >10 mm with spiral CT scan. See Section 11
for the evaluation of measurable disease.
3. Patients must have had no prior monoclonal antibodies or small molecule
tyrosine-kinase inhibitors for the treatment of recurrent or metastatic SCCHN. In
addition, no prior chemotherapy for the treatment of recurrent or metastatic SCCHN is
4. If the patient has had previous radiation to the marker lesion(s), there must be
evidence of progression since the radiation. Patients must be greater than or equal
to 12 weeks from completion of prior curative intent therapy including surgery,
radiation, or systemic anticancer therapy. If palliative radiation therapy is given
for recurrent or metastatic disease, patients must be greater than or equal to four
weeks from treatment.
5. No concurrent malignancy except curatively treated basal or squamous cell carcinoma
of the skin or carcinoma in situ of the cervix. Patients with prior history of
malignancies must be disease free for greater than or equal to two years.
6. Age >18 years.
7. Life expectancy of greater than 4.5 months.
8. ECOG performance status <2 (Karnofsky >60%; see Appendix A).
9. Patients must have normal organ and marrow function as defined below:
- leukocytes >3,000/mcL
- absolute neutrophil count >1,500/mcL
- platelets >100,000/mcL
- total bilirubin less than or equal to 1.5 X institutional upper limit of normal
or within normal institutional limits. or
- AST(SGOT)/ALT(SGPT) <3.0 X institutional upper limit of normal - creatinine
within normal institutional limits OR
- creatinine clearance >60 mL/min/1.73 m2 for patients with creatinine levels
above institutional normal 3.1.8
10. As the investigational agent RAD001 requires enteral administration, patients must be
able to receive adequate enteral nutrition by mouth or through a G-tube device.
11. The effects of RAD001 on the developing human fetus at the recommended therapeutic
dose are unknown. For this reason and because agents used in this trial are known to
be teratogenic, women of child-bearing potential and men must agree to use adequate
contraception (hormonal or barrier method of birth control; abstinence) prior to
study entry and for the duration of study participation. Should a woman become
pregnant or suspect she is pregnant while participating in this study, she should
inform her treating physician immediately.
12. Ability to understand and the willingness to sign a written informed consent
1. Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
nitrosoureas or mitomycin C) prior to entering the study or those who have not
recovered from adverse events due to agents administered more than 4 weeks earlier.
2. Patients may not be receiving any other investigational agents.
3. Patients with known brain metastases should be excluded from this clinical trial
because of their poor prognosis and because they often develop progressive neurologic
dysfunction that would confound the evaluation of neurologic and other adverse
4. History of allergic reactions attributed to compounds of similar chemical or biologic
composition to RAD001 or other agents used in the study.
5. Patients receiving any medications or substances that are inhibitors or inducers of
the isoenzyme CYP3A are ineligible. Lists including medications and substances known
or with the potential to interact with the CYP3A isoenzymes are provided in the
6. Patients receiving chronic treatment with systemic steroids or other
immunosuppressive agents are ineligible.
7. Patients with a known hypersensitivity to RAD001 (everolimus) or other rapamycin
(sirolimus, temsirolimus) or its excipients.
8. Impairment of gastrointestinal function or gastrointestinal disease that may
significantly alter the absorption of RAD001 (e.g. ulcerative disease; uncontrolled
nausea, vomiting, or diarrhea; malabsorption syndrome or small bowel resection).
9. Patients with active bleeding diathesis or patients on oral anti-vitamin K agent
(excluding low dose warfarin).
10. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, severely impaired lung function or psychiatric illness/social situations
that would limit compliance with study requirements Severely impaired lung function
is defined as spirometry and DLCO that is 50% of the normal predicted value and /or
O2 saturation that is 88% or less on room air.
11. Pregnant women are excluded from this study because RAD001 is a mTOR inhibitor with
the potential for teratogenic or abortifacient effects. Because there is an unknown
but potential risk for adverse events in nursing infants secondary to treatment of
the mother with RAD001, breastfeeding should be discontinued. These potential risks
may also apply to other agents used in this study.
12. HIV-positive patients on combination antiretroviral therapy are ineligible because of
the potential for pharmacokinetic interactions with RAD001. In addition, these
patients are at increased risk of lethal infections when treated with
marrow-suppressive therapy. Appropriate studies will be undertaken in patients
receiving combination antiretroviral therapy when indicated.