A Study of First Line Treatment With Avastin (Bevacizumab) in Combination With Carboplatin and Weekly Paclitaxel in Patients With Ovarian Cancer

A Single-arm Phase II Clinical Study Investigating the Addition of Bevacizumab to Carboplatin and Weekly Paclitaxel as First-line Treatment in Patients With Epithelial Ovarian Cancer

This single arm study evaluated the efficacy and safety of first-line chemotherapy with carboplatin and dose-dense weekly paclitaxel plus bevacizumab (Avastin) in participants with epithelial ovarian, fallopian tube, or primary peritoneal cancer. Participants received 6-8 3-week cycles of treatment with bevacizumab 7.5 mg/kg intravenously (iv) on Day 1 of each cycle, paclitaxel 80 mg/m^2 iv on days 1, 8, and 15 of each cycle, and carboplatin iv to an area under the curve (AUC) of 6 on day 1 of each cycle. Following combination chemotherapy, bevacizumab could be continued to be given as a monotherapy.

Study Overview

• Status: Completed
• Conditions: Ovarian Cancer
• Intervention / Treatment: Drug: Bevacizumab; Drug: Paclitaxel; Drug: Carboplatin

• Study Type: Interventional
• Enrollment (Actual): 190
• Phase: Phase 2

Contacts and Locations

Study Locations

• Brazil
  • SP
    • Jau, SP, Brazil, 17210-080
      • Hospital Amaral Carvalho
    • Sao Paulo, SP, Brazil, 05403-000
      • Hospital das Clinicas - FMUSP, Oncologia
• France
  • Avignon, France, 84902
    • Centre Hospitalier Henri Duffaut; Hematologie
  • Bordeaux, France, 33077
    • Polyclinique Bordeaux Nord Aquitaine; Chimiotherapie Radiotherapie
  • Bordeaux, France, 33000
    • Clinique Tivoli; Sce Radiotherapie
  • Brive La Gaillarde, France, 19312
    • Ch De Brive La Gaillarde; Radiotherapie Oncologie
  • Clamart, France, 92141
    • Hopital Antoine Beclere; Service de Medecine Interne
  • Dijon, France, 21079
    • Centre Georges Francois Leclerc; Oncologie 3
  • GAP, France, 05000
    • Chi Alpes Du Sud Site De Gap; Med Interne Et Polyvalente
  • Grenoble, France, 38000
    • Institut Daniel Hollard
  • Marseille, France, 13285
    • Hôpital Saint Joseph; Oncologie Medicale
  • Metz Tessy, France, 74370
    • CHRA;Hematologie
  • Nice, France, 06189
    • Centre Antoine Lacassagne; Hopital De Jour A2
  • Paris, France, 75970
    • HOPITAL TENON; Cancerologie Medicale
  • Paris, France, 75674
    • GH Paris Saint Joseph; Hopital De Jour Oncologie
  • Poitiers, France, 86021
    • Hopital De La Miletrie; Hematologie Et Oncologie Medicale
  • St Priest En Jarez, France, 42271
    • Institut de Cancerologie de La Loire; Radiotherapie
  • Strasbourg, France, 67065
    • Centre Paul Strauss; Oncologie Medicale
  • Toulouse, France, 31059
    • Institut Claudius Regaud; Departement Oncologie Medicale
  • Vandoeuvre Les Nancy, France, 54511
    • Centre Alexis Vautrin; Oncologie Medicale
• Italy
  • Campania
    • Napoli, Campania, Italy, 80131
      • IRCCS Istituto Nazionale Tumori Fondazione Pascale; Oncologia Medica B
  • Emilia-Romagna
    • Modena, Emilia-Romagna, Italy, 41100
      • A.O. Universitaria Policlinico Di Modena; Oncologia
  • Lazio
    • Roma, Lazio, Italy, 00168
      • Universita' Cattolica Del Sacro Cuore; Reparto Ginecologia Oncologica
  • Molise
    • Campobasso, Molise, Italy, 86100
      • Universita' Cattolica Del Sacro Cuore; Reparto Ginecologia Oncologica
• Netherlands
  • Alkmaar, Netherlands, 1815 JD
    • Medisch Centrum Alkmaar
  • Amsterdam, Netherlands, 1105 AZ
    • Academisch Medisch Centrum; Inwendige Geneeskunde
  • Enschede, Netherlands, 7511 JX
    • Medisch Spectrum Twente Enschede; Internal Medicine
  • Groningen, Netherlands, 9713 GZ
    • Academ Ziekenhuis Groningen; Medical Oncology
  • Leidschendam, Netherlands, 2262 BA
    • Mc Haaglanden, Locatie Antoniushove; Interne Geneeskunde
  • Tilburg, Netherlands, 5022 GC
    • Sint Elizabeth Ziekenhuis; Inwendige Geneeskunde
  • Zwolle, Netherlands, 8025 AB
    • Isala Klinieken, Locatie Sophia; Inwendige Geneeskunde
• Norway
  • Oslo, Norway, 0379
    • The Norvegian Radium Hospital Montebello; Dept of Oncology
  • Trondheim, Norway, 7006
    • St. Olavs Hospital; Kvinneklinikken
• Russian Federation
  • Krasnodar, Russian Federation, 350040
    • Regional Clinical Oncology Dispensary
  • Moscow, Russian Federation, 143423
    • City Clinical Oncology Hospital
  • Moscow, Russian Federation, 115478
    • Russian Oncology Research Center n.a. N.N. Blokhin Dpt of Clinical Pharmacology and Chemotherapy
  • Moscow, Russian Federation, 107005
    • Oncology Hospital; Chemotherapy Dept.
  • Obninsk, Kaluzhskaya Region, Russian Federation, 249034
    • Medical Radiological Scientific Center; Department of Radiotherapy of Gynaecological Disease
  • Saint-Petersburg, Russian Federation, 197022
    • St. Petersburg Oncology & Gynecology; City Clinical Oncology Dispensary
  • Stavropol, Russian Federation, 355045
    • SBI of Healthcare of Stavropol region Stavropol Regional Clinical Oncology Dispensary
• Spain
  • Barcelona, Spain, 08035
    • Hospital Univ Vall d'Hebron; Servicio de Oncologia
  • Barcelona, Spain, 08041
    • Hospital de la Santa Creu i Sant Pau; Servicio de Oncologia
  • Madrid, Spain, 28040
    • Hospital Universitario Clínico San Carlos; Servicio de Oncologia
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañon; Servicio de Oncologia
  • Madrid, Spain, 28033
    • Centro Oncologico MD Anderson Internacional; Servicio de Oncologia
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz; Servicio de Oncologia
  • Malaga, Spain, 29010
    • Hospital Clinico Universitario Virgen de la Victoria; Servicio de Oncologia
  • Valencia, Spain, 46009
    • Instituto Valenciano Oncologia; Oncologia Medica
  • Valencia, Spain, 46010
    • Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia
• Sweden
  • Gothenburg, Sweden, SE-41 343
    • Sahlgrenska Universitetssjukhuset; Onkology
  • Linköping, Sweden, 58185
    • Uni Hospital Linkoeping; Dept. of Oncology
  • Umea, Sweden, 90185
    • Norrlands Uni Hospital; Onkologi Avd.
  • Uppsala, Sweden, 75185
    • Akademiska sjukhuset, Onkologkliniken
  • Örebro, Sweden, 70185
    • Örebro University Hospital; Department of Gynecologic Oncology
• United Kingdom
  • London, United Kingdom, SW3 6JJ
    • Royal Marsden Hospital; Dept of Med-Onc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria

• Female patients, ≥ 18 years of age.
• Epithelial ovarian, fallopian tube, or primary peritoneal cancer.
• Initial surgery, but no chemotherapy or radiotherapy.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.

Exclusion Criteria

• Non-epithelial tumors.
• Ovarian tumors with low malignant potential.
• Previous systemic anti-cancer therapy for ovarian cancer.
• History or evidence of synchronous primary endometrial cancer.
• Current or recent daily treatment with aspirin (> 325mg/day) or with full dose anticoagulant or thrombolytic agents for therapeutic purposes.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Bevacizumab + paclitaxel + carboplatin; Participants received 6-8 (at the investigator's discretion) 3-week cycles of bevacizumab 7.5 mg/kg intravenously (iv) on Day 1 of each cycle, paclitaxel 80 mg/m^2 iv on Days 1, 8, and 15 of each cycle, and carboplatin iv to an area under the curve of 6 on Day 1 of each cycle. The initial dose of carboplatin was calculated according to the Calvert formula (mg = [glomerular filtration rate + 25] x 6). Following the combination treatments, participants received up to 17 3-week cycles of bevacizumab 7.5 mg/g iv alone.

Drug: Bevacizumab; Bevacizumab was supplied as a sterile solution for infusion.; Other Names: Avastin; Drug: Paclitaxel; Paclitaxel was supplied locally in commercial batches.; Other Names: Taxol; Drug: Carboplatin; Carboplatin was supplied locally in commercial batches.; Other Names: Paraplatin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival	Progression-free survival was defined as the time from the first administration of any study treatment to the first disease progression using Response Evaluation Criteria In Solid Tumors (RECIST) or death from any cause, whichever occurred first.	Baseline to the data cut-off date of 19 Jul 2012 for analysis of the primary Outcome Measure (follow-up time up to 3 years, 1 month)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With an Objective Response	An objective response was defined as either a complete response (CR) or a partial response (PR). Using the Response Evaluation Criteria in Solid Tumors (RECIST), a CR was defined as the disappearance of all target lesions and all non-target lesions, normalization of tumor marker level, and no new lesions and a PR was defined as the disappearance of all target lesions and persistence of ≥ 1 non-target lesions and/or the maintenance of tumor marker level above the normal limits, or, at least a 30% decrease in the sum of the longest diameter of target lesions, and no new lesions or unequivocal progression of existing non-target lesions. Only participants with measurable disease were included in the analysis according to RECIST only. Only participants with a Baseline ovarian cancer mucin CA-125 level ≥ 2 times the upper limit of normal who had a ≥ 50% reduction of CA-125 from Baseline were included in the analysis according to CA-125 level.	Baseline to the data cut-off date of 19 Jul 2012 for analysis of the primary Outcome Measure (follow-up time up to 3 years, 1 month)
Duration of Response	Duration of response was defined as the interval between the date of the first documented response by RECIST to the date of first disease progression or death, whichever occurred earlier. Disease progression was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of 1 or more new lesions or the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions. Only participants with measurable disease were included in the analysis according to RECIST only. Only participants with a Baseline ovarian cancer mucin CA-125 level ≥ 2 times the upper limit of normal who had a ≥ 50% reduction of CA-125 from Baseline were included in the analysis according to CA-125 level.	Baseline to the data cut-off date of 19 Jul 2012 for analysis of the primary Outcome Measure (follow-up time up to 3 years, 1 month)
Overall Survival at 1 Year and 2 Years	Reported are the percentage of participants that were alive at 1 year and 2 years after enrolling in the study.	Baseline to Year 2
Biological Progression-free Interval	Biological progression-free interval is defined as the interval from the date of the first administration of any study treatment to the date of the first documented serial elevation of the ovarian cancer mucin CA-125. More precisely, this is defined as the first documented increase in CA-125 levels as follows: (1) CA-125 greater than or equal to 2 times the upper level of normal (ULN) on 2 occasions at least 1 week apart (for patients with CA-125 within normal range pre-treatment) or (2) CA-125 greater than or equal to 2 times the ULN on 2 occasions at least 1 week apart (for patients with elevated CA-125 pre-treatment and initial normalisation of CA-125 on-treatment) or (3) CA-125 greater than or equal to 2 times the nadir value, which is the lowest observed CA-125 value per patient on 2 occasions at least 1 week apart (for patients with elevated CA-125 pre-treatment which never normalised).	Baseline to the data cut-off date of 19 Jul 2012 for analysis of the primary Outcome Measure (follow-up time up to 3 years, 1 month)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

General Publications

• Gonzalez-Martin A, Gladieff L, Tholander B, Stroyakovsky D, Gore M, Scambia G, Kovalenko N, Oaknin A, Ronco JP, Freudensprung U, Pignata S; OCTAVIA Investigators. Efficacy and safety results from OCTAVIA, a single-arm phase II study evaluating front-line bevacizumab, carboplatin and weekly paclitaxel for ovarian cancer. Eur J Cancer. 2013 Dec;49(18):3831-8. doi: 10.1016/j.ejca.2013.08.002. Epub 2013 Sep 2.

Study record dates

Study Major Dates

• Study Start (Actual): June 25, 2009
• Primary Completion (Actual): July 31, 2012
• Study Completion (Actual): July 1, 2013

Study Registration Dates

• First Submitted: July 6, 2009
• First Submitted That Met QC Criteria: July 10, 2009
• First Posted (Estimate): July 13, 2009

Study Record Updates

• Last Update Posted (Actual): November 6, 2017
• Last Update Submitted That Met QC Criteria: October 5, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Carboplatin; Paclitaxel; Bevacizumab
• Other Study ID Numbers: MO22225; 2008-008336-85 (EudraCT Number)