Efficacy and Safety of Bevacizumab (Avastin®) Combined to Weekly Paclitaxel Followed by Bevacizumab (Avastin®) Alone in Patients With Relapsed Ovarian Sex-cord Stromal Tumours (ALIENOR)

NCT01770301 | Completed Phase 2 DMC

• 1 other identifier: ALIENOR (GINECO-OV222)
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 24

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

Conditions

Ovarian Sex-cord Stromal Tumor

Outcome Measures

Primary Outcomes (1)

• clinical benefit of combining bevacizumab treatment to weekly paclitaxel

  To evaluate the clinical benefit of combining bevacizumab treatment to weekly paclitaxel measured by the non-progression rate after 6 months of treatment.

  after 6 months of treatment

Study Arms (2)

A - Paclitaxel

ACTIVE COMPARATOR

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

Drug: Paclitaxel

B - Paclitaxel + Bevacizumab followed by Bevacizumab

EXPERIMENTAL

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

Drug: Paclitaxel; Drug: Bevacizumab

Interventions

Paclitaxel DRUG

A - Paclitaxel; B - Paclitaxel + Bevacizumab followed by Bevacizumab

Bevacizumab DRUG

B - Paclitaxel + Bevacizumab followed by Bevacizumab

Eligibility Criteria

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

You may qualify if:

• 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).
• Adequate coagulation panel:
• PT ≤ 1.2 ULN
• aPTT ≤ 1.5 ULN
• INR ≤ 1.5 ULN
• Adequate neurologic function: only neuropathy (sensory and motor) grade ≤ 1 (CTCAE v4.3) are allowed
• ECOG Performance status of 0, 1, or 2 (Appendix 5)

You may not qualify if:

• 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
• Prior treatments:
• 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 or use of any other inhibitor of platelet aggregation
• Intake of granulocyte growth factor within 3 weeks before study entry
• 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

Sponsors & Collaborators

• ARCAGY/ GINECO GROUP: lead
• Roche Pharma AG: collaborator

Study Sites (24)

Hôpital Jean Minjoz

Besançon, 25030, France

Location

Institut Bergonié

Bordeaux, 33076, France

Location

Polyclinique Bordeaux Nord

Bordeaux, France

Location

Centre François Baclesse

Caen, 14076, France

Location

Centre Jean Perrin

Clermont-Ferrand, 63000, France

Location

Centre Georges François Leclerc

Dijon, 21079, France

Location

Centre Oscar Lambret

Lille, 59020, France

Location

Centre Léon Bérard

Lyon, 69373, France

Location

Institut Paoli Calmettes

Marseille, 13009, France

Location

ICM Val d'Aurelle

Montpellier, 34298, France

Location

ORACLE - Centre d'Oncologie de Gentilly

Nancy, 54100, France

Location

Hôpital Privé du Confluent

Nantes, 44202, France

Location

Hôpital Cochin

Paris, 75014, France

Location

Groupe Hospitalier Diaconesses - Croix Saint-Simon

Paris, 75020, France

Location

Hôpital Tenon

Paris, 75020, France

Location

Centre CARIO - HPCA

Plérin, 22190, France

Location

CHU de Poitiers - Hôpital de la Milétrie

Poitiers, 86021, France

Location

Institut Jean Godinot

Reims, 51056, France

Location

Centre Henri Becquerel

Rouen, 76038, France

Location

ICO Centre René Gauducheau

Saint-Herblain, 44800, France

Location

Hôpitaux Universitaires de Strasbourg

Strasbourg, 67200, France

Location

Institut Claudius Regaud

Toulouse, 31059, France

Location

ICL Institut de Cancérologie de Lorraine

Vandœuvre-lès-Nancy, 54511, France

Location

Gustave Roussy

Villejuif, 94805, France

Location

Related Publications (2)

• Gaitskell K, Rogozinska E, Platt S, Chen Y, Abd El Aziz M, Tattersall A, Morrison J. Angiogenesis inhibitors for the treatment of epithelial ovarian cancer. Cochrane Database Syst Rev. 2023 Apr 18;4(4):CD007930. doi: 10.1002/14651858.CD007930.pub3.

  PMID: 37185961 DERIVED

• Ray-Coquard I, Harter P, Lorusso D, Dalban C, Vergote I, Fujiwara K, Gladieff L, Luck HJ, Floquet A, Chevalier-Place A, Schnelzer A, Pignata S, Selle F, Sehouli J, Brocard F, Mangili G, Pautier P, De Giorgi U, Provansal M, Heudel PE. Effect of Weekly Paclitaxel With or Without Bevacizumab on Progression-Free Rate Among Patients With Relapsed Ovarian Sex Cord-Stromal Tumors: The ALIENOR/ENGOT-ov7 Randomized Clinical Trial. JAMA Oncol. 2020 Dec 1;6(12):1923-1930. doi: 10.1001/jamaoncol.2020.4574.

  PMID: 33030515 DERIVED

MeSH Terms

Interventions

Paclitaxel; Bevacizumab

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Isabelle RAY-COQUARD, MD, PhD

  Centre Léon Bérard, LYON, FRANCE

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 15, 2013
• First Posted: January 17, 2013
• Study Start: February 1, 2013
• Primary Completion: December 1, 2017
• Study Completion: April 1, 2021
• Last Updated: July 2, 2021

Record last verified: 2021-06

Locations

FR (24)