Carboplatin-Paclitaxel compared to Carboplatin-Paclitaxel-Bevacizumab in advanced (stage III-IV) or recurrent endometrial cancer.

• Conditions: endometrial cancer; MedDRA version: 14.1Level: LLTClassification code 10014770Term: Endometrioid adenocarcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Female diseases of the urinary and reproductive systems and pregancy complications [C13]

• Registration Number: EUCTR2011-003301-16-IT
• Lead Sponsor: POLICLINICO UNIVERSITARIO AGOSTINO GEMELLI

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-12-20
• Last Update Posted: 16 October 2012

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Female
• Target Recruitment: 108

Inclusion Criteria

1. =18 years of age. 2. ECOG Performance Status of 0–2. 3. Life expectancy of at least 12 weeks. 4. Patients must have advanced stage III or IV, or recurrent histologically-confirmed endometrial cancer. 5. Endometrial cancer will include all carcinomas, including endometrioid carcinoma, papillary serous carcinoma, clear cell carcinoma. 6. No previous chemotherapy lines (previous radiotherapy is allowed). 7 Measurable and not measurable disease. 8 Adequate renal and hepatic function, defined as: • Total serum bilirubin = institutional ULN unless patient has Gilbert’s syndrome in which case direct bilirubin must be < ULN for the institution. • AST and/or ALT = 2.5 x ULN for the institution. (or = 5 x ULN if liver metastases are present) • Alkaline phosphatase < 1.5 x ULN for the institution (if > 1.5 x ULN, then alkaline phosphatase liver fraction must be < 1.5 ULN). • Serum creatinine = 1.5 x ULN for the institution (or calculated creatinine clearance = 50 mL/min/1.73 m2) 9 Adequate bone marrow function, defined as: • Total leukocytes ³ 3.0 x 109/L. • ANC ³ 1.5 x 109/L. • Platelet count ³ 100 x 109/L. Able to understand and give written informed consent. 10 Females of childbearing potential must have a negative serum pregnancy test within 7 days prior to study enrollment.
one previous chemoterapy lines is allowed if platinum free interval is more than six mounths (previous radiotherapy is allowed)
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 80
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 28

Exclusion Criteria

1. Previous cytotoxic chemotherapy. 2. Women who are pregnant or lactating. 3. Presence of brain or other central nervous system metastases. 4. Anticancer treatment (Hormonal therapy, radiotherapy) within 4 weeks prior to randomization. 5. Ongoing toxicity associated with prior anticancer therapy. 6. Inadequate recovery from any prior surgical procedure or having undergone any major surgical procedure within 4 weeks prior to randomization. Patients who have recovered from placement of a central venous access port within 2 weeks of Cycle 1 Day 1 will be considered eligible. 7. Another primary malignancy within the past five years (except for non-melanoma skin cancer and cervical carcinoma in situ). 8. Current or recent (within 10 days prior to the first study drug dose) chronic daily treatment with aspirin (>325 mg/day). 9. Current or recent (within 10 days prior to the first study drug dose) use of full-dose oral or parenteral anticoagulant or thrombolytic agent for therapeutic purposes. 10. Inadequate coagulation parameters:activated partial thromboplastin time (APTT) >1.5 xULN or INR >1.5. 11. Known HIV infection. 12. Known hepatitis B or C infection. 13. Concurrent treatment with immunosuppressive or investigational agents. 14. History or evidence of thrombotic or hemorrhagic disorders; including cerebrovascular accident (CVA) / stroke or transient ischemic attack (TIA) or subarachnoid haemorrhage within _6 months prior to the first study treatment). 15. Uncontrolled hypertension (sustained systolic >150 mm Hg and/or diastolic >100 mm Hg despite antihypertensive therapy) or clinically significant (i.e. active) cardiovascular disease, including. 16. Myocardial infarction or unstable angina within _6 months prior to the first study treatment. 17. New York Heart Association (NYHA) grade II or greater congestive heart failure (CHF). 18. Serious cardiac arrhythmia requiring medication (with the exception of atrial fibrillation or paroxysmal supraventricular tachycardia). 19. Peripheral vascular disease _grade 3 (i.e.symptomatic and interfering with activities of daily living requiring repair or revision). 20. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to the first study treatment. 21. Non-healing wound, ulcer or bone fracture. Patients with granulating incisions healing by secondary intention with no evidence of facial dehiscence or infection are eligible but require three weekly wound examinations. 22. Serious active infection requiring i.v. antibiotics at enrolment. 23. Significant traumatic injury during the 4 weeks preceding the first dose of bevacizumab. 24. Known hypersensitivity to any of the study drugs or excipients (including cremophor and hamster Ovary cell products). 25. Evidence of any other medical conditions (such as psychiatric illness, peptic ulcer, etc.), physical examination or laboratory findings that may interfere with the planned treatment, affect patient compliance or place the patient at high risk from treatment related complications.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: • To compare progression-free survival (PFS) of patients with advanced or recurrent chemonaive endometrial cancer when treated with Carboplatin-Paclitaxel vs Carboplatin-Paclitaxel-Bevacizumab.;Secondary Objective: • To compare the overall survival (OS) of patients receiving Carboplatin-Paclitaxel vs Carboplatin-Paclitaxel Bevacizumab • To compare the best response rate of patients receiving Carboplatin-Paclitaxel vs Carboplatin-Paclitaxel-Bevacizumab • To assess the safety and tolerability of Carboplatin-Paclitaxel-Bevacizumab in this population • To assess changes in Quality of Life parameters in patients treated with Carboplatin-Paclitaxel compared to those treated with Carboplatin-Paclitaxel-Bevacizumab;Primary end point(s): • Progression-free survival, defined as the time from the date of randomization to the date of documented progressive disease, recurrence or death (whichever occurs first);Timepoint(s) of evaluation of this end point: 19 months

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): • Overall survival defined as the time from the date of randomization to the date of death • Best target lesion response, defined as best change in sum of the target lesions from baseline to disease progression. • Duration of response • Safety and tolerability Changes Quality of Life parameters as measured using EORTC QLQ-30 & EORTC-QLQ-EN-24;Timepoint(s) of evaluation of this end point: 36 MONTHS