Evaluation of efficacy and safety of bevacizumab (Avastin®) combined to weekly paclitaxel followed by bevacizumab (Avastin®) alone versus weekly paclitaxel followed by observation in patients with relapsed ovarian sex-cord stromal tumours

Phase 1

• Conditions: Patients with an histologically confirmed diagnosis of ovarian sex-cord stromal tumor in relapse after a platinum-based chemotherapy.; MedDRA version: 20.0Level: PTClassification code 10033128Term: Ovarian cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2012-002841-39-DE
• Lead Sponsor: ARCAGY GINECO

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2013-06-28
• Study Completion: 2021-04-28
• Last Update Posted: 27 November 2023

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: 60

Inclusion Criteria

I1.Female aged >= 18 years at inclusion
I2.Histologically confirmed diagnosis of ovarian SCST including the following cell types: granulosa cell tumors (adults and juveniles types), granulosa cell theca cell tumor, Sertoli-Leydig cell tumors, malignant steroïd cell tumors, gynandroblastoma, unclassified SCST and mixed tumors
I3.Documented relapse of SCST defined by progression of disease (radiologic, clinic or biological progression)
I4.At least one measurable site of disease as defined by RECIST 1.1
-Tumors 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.
I5.Patients must have been pre-treated with at least 1 prior line of platinum based chemotherapy
I6.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).
I7.Adequate coagulation panel:
•PT = 1.2 ULN
•aPTT = 1.5 ULN
•INR = 1.5 ULN
I8.Adequate neurologic function: only neuropathy (sensory and motor) grade = 1 (CTCAE v4.0) are allowed
I9.ECOG Performance status of 0, 1, or 2
I10.Life expectancy = 4 months
I11.Satisfactory cardiac function defined as no history of cardiac insufficiency.
I12.Ability to understand and sign informed consent and willingness to comply with the study procedures before study entry
I13.Women of childbearing potential* are required to have a negative serum pregnancy test within 7 days prior to study treatment initiation (i.e. Cycle 1 Day 1)
*: Female patients who meet at least one of the following criteria are defined as women of non-childbearing potential:
•= 50 years old and naturally amenorrheic for = 1 year
•Permanent premature ovarian failure confirmed by a specialist gynaecologist
•Previous bilateral salpingo- oopherectomy or hysterectomyoophrectomy
•XY genotype, Turner’s syndrome, or uterine agenesis
•Female patient who do not meet at least of the above criteria are defined as women of childbearing potential
I14.Willingness to use adequate contraceptive method during the whole study period and for up to 6 months after the last treatment intake
I15.Covered by a medical insurance (in country where applicable)

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 60
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

E1.Prior systemic therapy with bevacizumab
E2.Active peripheral neuropathy = grade 2 (NCI-CTCAE v4.0)
E3.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
E4.No resolution of specific toxicities related to any prior anti-cancer therapy to grade =1, excluding alopecia, according to the NCI-CTCAE v.4.0
E5.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.
E6.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
E7.History of bowel obstruction, including sub-occlusive syndrome and history of abdominal fistula, gastro-intestinal perforation or intra-abdominal abscess during the year prior to inclusion
E8.Prior treatments:
•Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study inclusion
•Current or recent treatment with another investigational drug within 30 days of first study treatment dosing or within 6 weeks in case of prior nitrozo-urea and or mitomycin C treatment. In case of hormonotherapy , patients will be eligible if hormonotherapy is discontinued within at least 1 week before treatment initiation
•Current or recent (within 10 days prior to randomization) chronic use of aspirin
•> 325 mg/day for use of any other inhibitor of platelet aggregation
•Chronic treatment (i.e. > 15 days) with non steroids anti-inflammatory agents unless a washout period of 15 days was observed before the inclusion.
• Intake of granulocyte growth factor within 3 weeks before study entry
E9. Treatment during the study:
• Debulking surgery prior to disease progression is not foreseen
• Concurrent radiotherapy during the study treatment
E10.Presence of hematuria and proteinuria = 2+ (urine dipstick). Patients with = 2+ proteinuria on dipstick at screening should undergo a 24-hour urine collection and will be eligible only if 24-h proteinuria = 1 g
E11.Untreated evolutive brain metastases
E12.Active bacteria or fungal infection (grade =2, CTC AE V4.0)
E13.Known HIV1, HIV2 or chronic hepatitis B or C infection
E14.Hypersensitivity to Chinese hamster ovary (CHO) cell products or other recombinant human or humanized antibodies
E15.Any contraindications to paclitaxel treatment: for example severe hypersensitivity reactions to paclitaxel, macrogolglycerol ricinoleate (polyoxyl castor oil) or to any of the excipients (Ethanol Citric acid) (refer to Taxol® SPC for further details)

Study & Design

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