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A Phase I Study of Oral Administration of mTOR Inhibitor Everolimus (RAD001) in Association With Cisplatin and Radiotherapy for the Treatment of Locally Advanced Cervix Cancer

Phase 1
18 Years
Open (Enrolling)
Locally Advanced Cervical Cancer

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Trial Information

A Phase I Study of Oral Administration of mTOR Inhibitor Everolimus (RAD001) in Association With Cisplatin and Radiotherapy for the Treatment of Locally Advanced Cervix Cancer

Inclusion Criteria:

1. ECOG performance of 0, 1 or 2.

2. Evidence of measurable disease of unidimensional form.

3. Epidermoid carcinoma confirmed by histological examination of cervix, stages IIB to
IIIB (according to clinical and radiological evaluation), without previous treatment.
Absence of positive paraaortic lymph nodes at PET (Positron Emission Tomography).

4. Adequate function of organ, according to following criteria:

1. Serum levels of aspartate aminotransferase (ASAT/AAT/AST) and alanine
aminotransferase (ALT) ≤2.5 x ULN (Upper Limit of Normal)

2. Total serum bilirubin ≤1.5 ULN

3. Absolute neutrophils counting ≥1.500/mm3

4. Platelet counting ≥100.000/mm3

5. Hemoglobin ≥10.0 g/dL

6. Serum calcium ≤12.0 mg/dL

7. Serum creatinine ≤1.5 x ULN and estimate creatinine clearance (Cockroft-Gault)
≥60 mL/min

8. Prothrombin time ≤1.5 x ULN Obs.: The serum levels of potassium, magnesium,
sodium and calcium outside normality range should be corrected before the
administration of the first dose of investigational product.

5. Patients with at least one measurable lesion in the baseline period, according to
criteria RECIST, version 1.1.

6. Adequate lipid profile: total cholesterol <300 mg/dL and triglycerides <200 mg/dL.

7. Willingness to follow the treatment plan, scheduled visits, laboratory and
radiological examinations, as well as other procedures.

8. Signed and dated informed consent form, indicating that the patient (or his/her
representative) has received information about all relevant study aspects, before
his/her inclusion.

Women with possibility to become pregnant should present a negative serum examination for
pregnancy, done within the period of 7 days before the administration of study treatment;
and should be willing to use a contraceptive method along the entire study, and for 3
months after the last administration of investigational drug.

Exclusion Criteria:

1. Major surgery <4 weeks before study treatment starting.

2. Any malignant neoplasia in the last 5 years, except for adequately treated melanoma
skin cancer.

3. Metastases in the initial diagnostic evaluation [thorax and abdomen computerized
tomography (with contrast), pelvis magnetic resonance and PET scanning].

4. Occurrence of some of the following events, during the period of 12 months previously
to study medication administration: unstable angina pectoris, symptomatic congestive
heart failure (II, III, IV of NYHA), myocardium infarction, severe uncontrolled
cardiac arrhythmia, cerebrovascular accident.

5. Positive serology for HIV infection.

6. Patients with positive examinations for hepatitis B (HBsAg, anti-HBs without previous
vaccination against HBV and anti-HBc) and hepatitis C (HCV RNA detectable by PCR).

7. Any psychologic, familial, social or geographic problem that could embarrass the
adhesion to protocol and study scheme.

8. Patients using other agents under investigation or receiving investigational
medications ≤4 weeks before the study treatment starting.

9. Patients presenting some severe and/or uncontrolled medical problem, or other
disturbances that could affect their participation in the study, such as, for

- Unstable angina pectoris, symptomatic congestive heart failure (II, III, IV of
NYHA), myocardial infarction ≤12 months before the first administration of study
medication, severe uncontrolled cardiac arrhythmia, cerebrovascular accident ≤12
months before the starting of study medication administration;

- Severely compromised pulmonary function defined by spirometry with 50% of
anticipated normal value or decompensated pulmonary disease.

- Uncontrolled diabetes satisfactorily defined by a fast glycemia result >2.0 x

- Any active or uncontrolled disease/infection (acute or chronic) compromising the
patient evaluation capability or impeding him/her to complete the study.

- Hepatic disease with cirrhosis, decompensated hepatic disease, active chronic
hepatitis, or persistent chronic hepatitis.

- Compromising of gastrointestinal (GI) function, or GI disease that could
significantly alter the everolimus absorption.

10. Patients unwilling or unable to accomplish the protocol requirements.

11. Hypersensitivity to everolimus or any of its excipients, or to other rapamycins (for
instance: sirolimus, temsirolimus).

12. Patients receiving systemic immunosuppressive agents chronically. Inhaling or topic
corticosteroids are acceptable. The patients should be receiving stable chronic (not
increased within the last month) doses of corticosteroids, with the maximal dose
corresponding to 20 mg de prednisone or 10 mg of dexamethasone per day.

Pregnant (that is, having positive examination for beta human chorionic gonadotropin) or
lactating women.

Other protocol-defined inclusion/exclusion criteria may apply

Type of Study:


Study Design:

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

The toxicity criteria will be evaluated according to National Cancer Institute - Common Toxicity Criteria for Adverse Events (NCI-CTCAE), version 3.0.

Outcome Time Frame:

12 month

Safety Issue:


Principal Investigator

Novartis Pharmaceuticals

Investigator Role:

Study Director

Investigator Affiliation:

Novartis Pharmaceuticals


Brazil: National Health Surveillance Agency

Study ID:




Start Date:

December 2011

Completion Date:

March 2013

Related Keywords:

  • Locally Advanced Cervical Cancer
  • Cervical cancer,
  • radiotherapy,
  • chemotherapy,
  • rad001,
  • everolimus
  • Uterine Cervical Neoplasms