A Randomized, Open Label, Phase II Trial of Bevacizumab Plus Weekly Paclitaxel Followed by Bevacizumab Monotherapy Maintenance Versus Weekly Paclitaxel Followed by Observation in Patients With Relapsed Ovarian Sex-cord Stromal Tumours
Overview
- Phase
- Phase 2
- Intervention
- Paclitaxel
- Conditions
- Ovarian Sex-cord Stromal Tumor
- Sponsor
- ARCAGY/ GINECO GROUP
- Enrollment
- 60
- Locations
- 24
- Primary Endpoint
- clinical benefit of combining bevacizumab treatment to weekly paclitaxel
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
Bevacizumab (called also Avastin ®) is a medicine preventing the creation of new blood vessels (a process called "angiogenesis"). This can reduce blood flow of the tumor and then decreasing the contribution of nutriments and oxygen to the cancer cells and prevent the tumor from growing.
In various types of cancers, as lung, breast, colorectal and renal cancer, addition of the bevacizumab to chemotherapy allowed to improve the disease outcome. The bevacizumab already benefits from a marketing authorization (MMA) for these various types of cancers.
The bevacizumab has also obtained MMA for the treatment of the ovarian cancer in its most frequent histological form (ovarian carcinoma). Clinical trials conducted in this indication demonstrated the importance to pursue the treatment by bevacizumab after the chemotherapy is ended.
This anti-angiogenic medicine is thought to be of a potential interest in sex cords- stromal since this tumors are very well vascularized.
The ALIENOR study aims to explore the interest and the clinical benefit of associating bevacizumab to the paclitaxel in order to treat patients suffering from recurring sex cords- stromal tumor treated beforehand by platinum chemotherapy
Investigators
Eligibility Criteria
Inclusion Criteria
- •Female aged ≥ 18 years at inclusion
- •Histologically confirmed diagnosis of ovarian Sex cord-stromal tumors including the following cell types: granulosa cell tumours (adults and juveniles types), granulosa cell-theca cell tumour, Sertoli-Leydig cell tumours, malignant steroid cell tumours, gynandroblastoma, unclassified SCST and mixed tumours
- •Documented relapse of SCST defined by progression of disease (radiologic, clinic or biological progression)
- •At least one measurable site of disease as defined by RECIST 1.1
- •Tumours within a previously irradiated field will be designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence \> 90 days following completion of radiotherapy.
- •Patients must have been pre-treated with at least 1 prior line of platinum-based chemotherapy
- •Adequate bone marrow, liver and renal functions including the following:
- •Absolute neutrophil count ≥ 1.5 G/L, platelet count ≥ 100 G/L, and hemoglobin ≥ 9 g/dL. Prior transfusion is authorized to keep haemoglobin level to ≥9g/dL
- •AST/ALT ≤ 3 x upper limit of normal (ULN) (or ≤ 5.0 ULN if liver metastasis) and total bilirubin ≤ 1.5 ULN
- •Serum creatinine ≤ 1.5 ULN or calculated creatinine clearance ≥ 50 mL/min according to Cockcroft formula (or to MDRD formula for patients older than 65 years-old).
Exclusion Criteria
- •Prior systemic therapy with bevacizumab
- •Active peripheral neuropathy ≥ grade 3 (NCI-CTCAE v4.3)
- •Prior history of other malignancies other than ovarian SCST (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix) unless the subjects has been free of the disease for at least 3 years or 5 years for breast cancer
- •No resolution of specific toxicities related to any prior anti-cancer therapy to grade ≤1, excluding alopecia, according to the NCI-CTCAE v.4.3
- •History or evidence of thrombotic or hemorrhagic disorders, including cerebro-vascular accident/stroke or transient ischemic attack or sub-arachnoids' haemorrhage within 6 months prior to first dose of study drugs
- •Uncontrolled arterial hypertension (systolic ≥ 150 mmHg or diastolic ≥ 100 mmHg) despite optimal antihypertensive therapy or clinically significant cardiovascular disease including one of the following:
- •Myocardial infarction or instable angina within 6 months prior to first dose of study drugs
- •NYHA grade ≥ II congestive heart failure
- •Serious cardiac arrhythmia requiring medication
- •Peripheral vascular disease ≥ grade 3
Arms & Interventions
A - Paclitaxel
patients will receive paclitaxel alone at the dose 80 mg/m² administered by intravenous injection at D1, D8 and D15 every 4 weeks for 6 cycles. Thereafter, patients will be followed-up with imaging exams every 12 weeks. At the time of confirmed progression, patients could receive bevacizumab 15 mg/kg every 3 weeks for 12 months following investigator's decision. In some cases, longer therapy may be allowed after discussion with the Principal Investigator/Sponsor
Intervention: Paclitaxel
B - Paclitaxel + Bevacizumab followed by Bevacizumab
patients will receive paclitaxel at the dose 80 mg/m² administered by intravenous injection at D1, D8 and D15 every 4 weeks + Bevacizumab at the dose 10 mg/kg administered by intravenous injection every 2 weeks (D1 and D15) for 6 cycles. Thereafter, patients will receive IV injection of bevacizumab 15 mg/kg every 3 weeks for up to 1 year
Intervention: Paclitaxel
B - Paclitaxel + Bevacizumab followed by Bevacizumab
patients will receive paclitaxel at the dose 80 mg/m² administered by intravenous injection at D1, D8 and D15 every 4 weeks + Bevacizumab at the dose 10 mg/kg administered by intravenous injection every 2 weeks (D1 and D15) for 6 cycles. Thereafter, patients will receive IV injection of bevacizumab 15 mg/kg every 3 weeks for up to 1 year
Intervention: Bevacizumab
Outcomes
Primary Outcomes
clinical benefit of combining bevacizumab treatment to weekly paclitaxel
Time Frame: after 6 months of treatment
To evaluate the clinical benefit of combining bevacizumab treatment to weekly paclitaxel measured by the non-progression rate after 6 months of treatment.