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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01217177
First received: October 6, 2010
Last updated: April 17, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Locally Advanced Cervical Cancer
Drug: everolimus
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • The toxicity criteria will be evaluated according to National Cancer Institute - Common Toxicity Criteria for Adverse Events (NCI-CTCAE), version 3.0. [ Time Frame: 12 month ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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) [ Time Frame: 12 month ] [ Designated as safety issue: No ]

Estimated Enrollment: 9
Study Start Date: December 2011
Estimated Study Completion Date: April 2014
Estimated Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 2.5 mg everolimus + radiotherapy + cisplatin
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
Other Name: RAD001
Experimental: 5.0 mg everolimus + radiotherapy + cisplatin
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
Other Name: RAD001
Experimental: 10 mg everolimus + radiotherapy + cisplatin
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
Other Name: RAD001

  Eligibility

Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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 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.
  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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01217177

Contacts
Contact: Novartis Pharmaceuticals +41613241111
Contact: Novartis Pharmaceuticals

Locations
Brazil
Novartis Investigative Site Recruiting
Rio de Janeiro, RJ, Brazil, 20230-130
Novartis Investigative Site Recruiting
Rio de Janeiro, Brazil
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01217177     History of Changes
Other Study ID Numbers: CRAD001C24128
Study First Received: October 6, 2010
Last Updated: April 17, 2014
Health Authority: Brazil: National Health Surveillance Agency
Brazil: ANVISA (Angência Nacional Vigilãncia Sanitária)

Keywords provided by Novartis:
Cervical cancer,
radiotherapy,
chemotherapy,
rad001,
everolimus

Additional relevant MeSH terms:
Uterine Cervical Neoplasms
Genital Diseases, Female
Genital Neoplasms, Female
Neoplasms
Neoplasms by Site
Urogenital Neoplasms
Uterine Cervical Diseases
Uterine Diseases
Uterine Neoplasms
Cisplatin
Everolimus
Sirolimus
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antineoplastic Agents
Immunologic Factors
Immunosuppressive Agents
Pharmacologic Actions
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014