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A Phase I/IIB Study of Combination Weekly Carboplatin, Cetuximab and Dose Escalation of RAD001 in Recurrent Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN)

Phase 1/Phase 2
18 Years
Open (Enrolling)
Head and Neck Neoplasms, Cancer of the Head and Neck

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Trial Information

A Phase I/IIB Study of Combination Weekly Carboplatin, Cetuximab and Dose Escalation of RAD001 in Recurrent Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN)

Inclusion Criteria:

- 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

- Histologically or cytologically proven squamous cell carcinoma of the head and neck

- Patients with recurrent, refractory or metastatic squamous cell carcinoma of oral
cavity, oropharynx and larynx, hypophayrnx or paranasal sinus, and unknown primary
SCCHN who failed to respond to, or relapsed from prior chemoradiotherapy for
definitive treatment of disease.

- Evaluable locoregional and/or metastatic disease according to RECIST criteria (see
Section 6) that is not appropriate for treatment by primary surgical resection or

- Patients may not have had prior chemotherapy for recurrent or metastatic disease.

- Patients must not be candidates for curative therapy.

- Age ≥ 18 years

- ECOG performance status of 0-2 (Appendix A)

- Life expectancy of ≥ 4 months.

- Adequate bone marrow, liver and renal function as assessed by the following:

- Hemoglobin ≥ 9.0/dl

- Absolute-neutrophil count (ANC ) ≥ 1500/mm3

- Platelet count ≥ 100,000/mm3

- Total bilirubin ≤ 1.5 x ULN

- ALT and AST ≤ 2.5 x ULN (≤ 5 x ULN for patients with liver involvement)

- INR ≤ 1.5 or a PT and PTT within normal limits (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)

- 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.

- Women of childbearing potential must have a negative pregnancy test within 7 days
prior to first receiving investigational product. Sexually active women of
childbearing potential (WOCBP) must use an effective method of birth control during
the course of the study, in a manner such that risk of failure is minimized. Prior to
study enrollment, WOCBP must be advised of the importance of avoiding pregnancy
during trial participation and the potential risk factors for an unintentional
pregnancy. In addition, men enrolled on this study should understand the risks to
any sexual partner of childbearing potential and should practice an effective method
of birth control. All WOCBP should be instructed to contact the Investigator
immediately if they suspect they might be pregnant (e.g., missed or late menstrual
period) at any time during study participation.

- Signed informed consent prior to beginning protocol specific procedures. Voluntary
written informed consent before performance of any study-related procedure not part
of normal medical care, with the understanding that consent may be withdrawn by the
subject at any time without prejudice to future medical care. Patients or their legal
representatives must be able to read, understand and provide informed consent to
participate in the trial

Exclusion Criteria:

- History of prior malignancy within the past 5 years except for curatively treated
basal cell carcinoma and squamous cell carcinoma of the skin, CIN or localized
prostate cancer with a current PSA < 1.0 mg/dL on 2 successive evaluations at least 3
months apart, with the most recent evaluation within 4 weeks of study entry

- Uncontrolled brain or leptomeningeal metastases, including patients who continue to
require glucocorticoids for brain or leptomeningeal metastases. Patients with
neurological symptoms must undergo a CT scan/MRI of the brain to exclude brain

- 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.)

- Prior treatment with any investigational drug within the preceding 4 weeks

- Any unresolved toxicity (except alopecia) greater than NCI-CTCAE v3.0 grade 2 from
prior systemic anticancer therapy.

- Patients who have received prior treatment with an mTOR inhibitor (sirolimus,
temsirolimus, everolimus).

- Patients with a known hypersensitivity to RAD001 (everolimus) or other rapamycins
(sirolimus, temsirolimus) or to its excipients, or to cetuximab

- Prior therapy with Cetuximab will be allowed provided it was part of definitive
therapy and not part of treatment for recurrent or metastatic disease.

- Prior severe infusion reaction to a monoclonal antibody.

- 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

- 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

- 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

- 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

- Abnormal LFTs as follows: total bilirubin (TB) > 1.5x IULN, alanine aminotransferase
(ALT) > 1.25x IULN, and/or alkaline phosphatase > 2.5 x IULN (except when LFTs
attributed to metastatic SCCHN, in which case, TB, ALT and alkaline phosphatase must
be ≤ NCI-CTCAE, v3.0 grade 1).

- Absolute neutrophil count < 1000/mm3 or platelets < 100,000/mm3.

- A known history of HIV seropositivity

- Impairment of gastrointestinal function or gastrointestinal disease that may
significantly alter the absorption of RAD001 (e.g., 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. 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.
(WOCBP must have a negative urine or serum pregnancy test within 7 days prior to
administration of RAD001)

- History of noncompliance to medical regimens

- Patients unwilling to or unable to comply with the protocol

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To measure the safety and clinical effectiveness of the combination of carboplatin, cetuximab and RAD001 in patients with advanced (recurrent or metastatic) head and neck cancer.

Outcome Time Frame:

Within the first 21 days of therapy

Safety Issue:


Principal Investigator

Nabil F Saba, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Emory University Winship Cancer Institute


United States: Food and Drug Administration

Study ID:




Start Date:

January 2011

Completion Date:

November 2014

Related Keywords:

  • Head and Neck Neoplasms
  • Cancer of the Head and Neck
  • Head and Neck Cancer
  • Recurrent Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN)
  • Neoplasms
  • Carcinoma, Squamous Cell
  • Head and Neck Neoplasms



Emory University Winship Cancer Institute Atlanta, Georgia  30322