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Phase I Everolimus Dose Finding Study for the Treatment of Stage IV or Recurrent, Non-resectable, Cervical Cancer With Standard Whole Pelvic Radiation Therapy in Combination With Weekly Cisplatin and Daily Everolimus

Phase 1
18 Years
Not Enrolling
Cervical Cancer

Thank you

Trial Information

Phase I Everolimus Dose Finding Study for the Treatment of Stage IV or Recurrent, Non-resectable, Cervical Cancer With Standard Whole Pelvic Radiation Therapy in Combination With Weekly Cisplatin and Daily Everolimus

This Phase 1, single-site, dose-escalation study is being conducted to determine the MTD of
RAD001 as part of a specified combination regimen. The combination regimen will be standard
field whole pelvic RT in combination with cisplatin at 40mg/m2 weekly with RAD001 at dose
escalation daily starting at 5 mg qod, then 5 mg qd, then 10 mg qd during the period of
whole pelvic radiation therapy.

Inclusion Criteria:

- Patients must have at least one measurable site of disease according to Response
Evaluation Criteria in Solid Tumors criteria that has not been previously irradiated.

- Female patient aged ≥18 years.

- Patient has life expectancy of at least 12 weeks at study start.

- Patient has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at
study start.

- Patient has diagnosis of stage IV or recurrent, non-resectable, cervical cancer at
study start.

- Patient has received no prior chemotherapy.

- Patient has adequate hematologic function:

- Absolute neutrophil count [ANC] ≥1500/μL

- Platelets ≥100,000/μL

- Hemoglobin > 9g/dL

- Patient has adequate renal function:

- Serum creatinine ≤ 2.0 mg/dL

- Calculated creatinine clearance ≥ 50 mL/min

- Patient has adequate hepatic function:

- Serum bilirubin ≤1.5 x ULN

- ALT and AST ≤2.5 × ULN (≤ 5 x ULN in patients with liver metastases)

- INR <1.5 (or < 3 on anticoagulants)

- Patient has fasting serum cholesterol ≤300 mg/dL OR ≤7.75 mmol/L AND fasting
triglycerides ≤ 2.5 x ULN.

- Patient is able to provide signed informed consent.

Exclusion Criteria:

- Patient has neuroendocrine or small cell carcinoma of the cervix.

- Patient has previously used any biologic therapy with VEGF, VEGFR, or ErbB1/ErbB2

- Patient is currently receiving anticancer therapies or has received anticancer
therapies within 4 weeks of the start of study drug (including chemotherapy,
radiation therapy, antibody based therapy, etc.).

- Patient has had a major surgery or significant traumatic injury within 4 weeks of
start of study drug; patient has not recovered from the side effects of any major
surgery (defined as requiring general anesthesia) or patient might require major
surgery during the course of the study.

- Patient has had prior treatment with any investigational drug within the preceding 4
weeks before study start.

- Patient is 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 should also avoid close contact
with people who have received live vaccines during treatment with everolimus.
Examples of live vaccines are: intranasal influenza, measles, mumps, rubella, oral
polio, BCG, yellow fever, and TY21a typhoid vaccines.

- Patient has known brain or leptomeningeal metastases.

- Patient has had other malignancies within the past 3 years except for adequately
treated squamous cell carcinomas of the skin.

- Patients has 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 defined as spirometry and diffusing capacity
(DLCO) that is 50% of the normal predicted value and/or O2 saturation that is
88% or less at rest on room air.

- Uncontrolled diabetes as defined by fasting serum glucose >1.5 × ULN.

- Active (acute or chronic) or uncontrolled severe infections.

- Liver disease such as cirrhosis, chronic active hepatitis or chronic persistent

- Patient has a known history of human immunodeficiency virus seropositivity.

- Patient has 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

- Patient has an active, bleeding diathesis.

- Female patient who is pregnant or breast feeding, or an adult of reproductive
potential who is not using effective birth control methods. If barrier contraceptives
are being used, these must be continued throughout the trial and for up to 8 weeks
after ending treatment by both sexes. Hormonal contraceptives are not acceptable as a
sole method of contraception. (Women of childbearing potential must have a negative
urine or serum pregnancy test within 7 days prior to administration of RAD001.)

- Patient has received prior treatment with an mTOR inhibitor (sirolimus, temsirolimus,

- Patient has a known hypersensitivity to RAD001 (everolimus) or other rapamycins
(sirolimus, temsirolimus) or to its excipients.

- Patient has history of noncompliance to medical regimens.

- Patient is unwilling to or unable to comply with the protocol.

Type of Study:


Study Design:

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

Outcome Measure:

To determine the maximum tolerated dose for RAD001 as adjunct therapy to standard upfront treatment of advanced stage cervical cancer in combination with weekly cisplatin and whole pelvic external beam radiation

Outcome Time Frame:

every 7 days

Safety Issue:


Principal Investigator

Todd D Tillmanns, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

The West Clinic


United States: Institutional Review Board

Study ID:




Start Date:

December 2009

Completion Date:

December 2010

Related Keywords:

  • Cervical Cancer
  • Stage IV or Recurrent Cervical cancer
  • Uterine Cervical Neoplasms