A Study of mTOR Inhibitor Everolimus (RAD001) in Association With Cisplatin and Radiotherapy for Locally Advanced Cervix Cancer

NCT01217177 | Completed Phase 1

• 1 other identifier: CRAD001C24128
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 2

Brief Summary

The cervix cancer is the second malignant neoplasia more common between women. The combined treatment involving chemotherapy and radiotherapy was defined as the standard. This study will evaluate the safety, toxicity and maximal tolerated dose (MTD) of everolimus in association with cisplatin and pelvic radiotherapy, in patients with squamous cells carcinoma of uterine cervix, in stages IIB and IIIB.

Conditions

Locally Advanced Cervical Cancer

Keywords

Cervical cancer,; radiotherapy,; chemotherapy,; rad001,; everolimus

Outcome Measures

Primary Outcomes (1)

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

  12 month

Secondary Outcomes (1)

• The objective response rate will be evaluated according to clinical/gynecological examination and inconformity with the RECIST criteria (Response Evaluation Criteria in Solid Tumors, version 1.1)

  12 month

Study Arms (3)

2.5 mg everolimus + radiotherapy + cisplatin

EXPERIMENTAL

patients treated with daily doses of everolimus (2.5mg) in association with radiotherapy and cisplatin (40 mg/m2 of body surface per week, 5 cycles during radiotherapy)

Drug: everolimus

5.0 mg everolimus + radiotherapy + cisplatin

EXPERIMENTAL

patients treated with daily doses of everolimus (5.0mg) in association with radiotherapy and cisplatin (40 mg/m2 of body surface per week, 5 cycles during radiotherapy)

Drug: everolimus

10 mg everolimus + radiotherapy + cisplatin

EXPERIMENTAL

patients treated with daily doses of everolimus (10mg) in association with radiotherapy and cisplatin (40 mg/m2 of body surface per week, 5 cycles during radiotherapy)

Drug: everolimus

Interventions

everolimus DRUG

Also known as: RAD001

10 mg everolimus + radiotherapy + cisplatin; 2.5 mg everolimus + radiotherapy + cisplatin; 5.0 mg everolimus + radiotherapy + cisplatin

Eligibility Criteria

• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• ECOG performance of 0, 1 or 2.
• Evidence of measurable disease of unidimensional form.
• 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).
• Adequate function of organ, according to following criteria:
• Serum levels of aspartate aminotransferase (ASAT/AAT/AST) and alanine aminotransferase (ALT) ≤2.5 x ULN (Upper Limit of Normal)
• Total serum bilirubin ≤1.5 ULN
• Absolute neutrophils counting ≥1.500/mm3
• Platelet counting ≥100.000/mm3
• Hemoglobin ≥10.0 g/dL
• Serum calcium ≤12.0 mg/dL
• Serum creatinine ≤1.5 x ULN and estimate creatinine clearance (Cockroft-Gault) ≥60 mL/min
• 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.
• Patients with at least one measurable lesion in the baseline period, according to criteria RECIST, version 1.1.
• Adequate lipid profile: total cholesterol \<300 mg/dL and triglycerides \<200 mg/dL.
• Willingness to follow the treatment plan, scheduled visits, laboratory and radiological examinations, as well as other procedures.

You may not qualify if:

• Major surgery \<4 weeks before study treatment starting.
• Any malignant neoplasia in the last 5 years, except for adequately treated melanoma skin cancer.
• Metastases in the initial diagnostic evaluation \[thorax and abdomen computerized tomography (with contrast), pelvis magnetic resonance and PET scanning\].
• 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.
• Positive serology for HIV infection.
• 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).
• Any psychologic, familial, social or geographic problem that could embarrass the adhesion to protocol and study scheme.
• Patients using other agents under investigation or receiving investigational medications ≤4 weeks before the study treatment starting.
• Patients presenting some severe and/or uncontrolled medical problem, or other disturbances that could affect their participation in the study, such as, for instance:
• 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 ULN;
• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (2)

Novartis Investigative Site

Rio de Janeiro, Rio de Janeiro, 20230-130, Brazil

Location

Novartis Investigative Site

Rio de Janeiro, Brazil

Location

MeSH Terms

Conditions

Uterine Cervical Neoplasms

Interventions

Everolimus

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 6, 2010
• First Posted: October 8, 2010
• Study Start: December 1, 2011
• Primary Completion: April 1, 2014
• Study Completion: April 1, 2014
• Last Updated: April 3, 2015

Record last verified: 2015-04

Locations

BR (2)