BOOST: Evaluation of Optimal Treatment Duration of Bevacizumab Combination With Standard Chemotherapy in Patients With Ovarian Cancer

Sponsor

AGO Study Group (Other)

Overall Status

Completed

CT.gov ID

NCT01462890

Collaborator

ARCAGY/ GINECO GROUP (Other), Nordic Society of Gynaecological Oncology - Clinical Trials Unit (Other)

927

Enrollment

131

Locations

Arms

121

Actual Duration (Months)

7.1

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether the early and continuous addition of bevacizumab for up to 30 months to the standard chemotherapy is more effective than the early and continuous addition of bevacizumab for up to 15 months.

Condition or Disease	Intervention/Treatment	Phase
Genital Diseases, Female Ovarian Diseases Ovarian Neoplasms Fallopian Tube Neoplasms Peritoneal Neoplasms	Biological: Bevacizumab Drug: Paclitaxel Drug: Carboplatin Other: specialized pathology review (Germany only)	Phase 3

Detailed Description

Determination whether the early and continuous addition of bevacizumab for up to 30 months to the standard chemotherapy is more effective than the early and continuous addition of bevacizumab for up to 15 months

Study Design

Study Type:

Interventional

Actual Enrollment :

927 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Randomized Phase III studyRandomized Phase III study

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Prospective Randomised Phase III Trial to Evaluate Optimal Treatment Duration of First-line Bevacizumab in Combination With Carboplatin and Paclitaxel in Patients With Primary Epithelial Ovarian, Fallopian Tube or Peritoneal Cancer

Actual Study Start Date :

Nov 1, 2011

Actual Primary Completion Date :

Dec 31, 2020

Actual Study Completion Date :

Dec 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Other: Control Arm Patients receive bevacizumab iv followed by paclitaxel iv and carboplatin iv on day 1. Treatment repeats every 3 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then continue to receive bevacizumab iv alone every 3 weeks for 16 cycles.	Biological: Bevacizumab 15 mg/kg, iv on day 1 every 3 weeks up to and including cycle 22 vs cycle 44 Drug: Paclitaxel 175 mg/m², iv on day 1 every 3 weeks for 6 cycles Drug: Carboplatin AUC 5, iv on day 1 every 3 weeks for 6 cycles Other: specialized pathology review (Germany only) before randomization
Experimental: Research Arm Patients receive bevacizumab iv followed by paclitaxel iv and carboplatin iv on day 1. Treatment repeats every 3 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then continue to receive bevacizumab iv alone every 3 weeks for 38 cycles.	Drug: Paclitaxel 175 mg/m², iv on day 1 every 3 weeks for 6 cycles Drug: Carboplatin AUC 5, iv on day 1 every 3 weeks for 6 cycles Other: specialized pathology review (Germany only) before randomization

Arm

Intervention/Treatment

Other: Control Arm

Patients receive bevacizumab iv followed by paclitaxel iv and carboplatin iv on day 1. Treatment repeats every 3 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then continue to receive bevacizumab iv alone every 3 weeks for 16 cycles.

Biological: Bevacizumab

15 mg/kg, iv on day 1 every 3 weeks up to and including cycle 22 vs cycle 44

Drug: Paclitaxel

175 mg/m², iv on day 1 every 3 weeks for 6 cycles

Drug: Carboplatin

AUC 5, iv on day 1 every 3 weeks for 6 cycles

Other: specialized pathology review (Germany only)

before randomization

Experimental: Research Arm

Drug: Paclitaxel

175 mg/m², iv on day 1 every 3 weeks for 6 cycles

Drug: Carboplatin

AUC 5, iv on day 1 every 3 weeks for 6 cycles

Other: specialized pathology review (Germany only)

before randomization

Outcome Measures

Primary Outcome Measures

Progression Free Survival (PFS) [every 12 weeks until progression or up to 30 months, thereafter every 6 months]

Secondary Outcome Measures

Objective response rate (ORR) [every 12 weeks until progression or up to 30 months, thereafter every 6 months]
Overall survival (OS) [every 3 weeks, 31 months after start of treatment, thereafter every 6 months]
Health related Quality of life (QoL) [baseline, then every 12 weeks until progression, 31 months after start of treatment or if applicable 4 weeks after last dose of bevacizumab (whichever occurs later)]
Safety and tolerability, i.e. type, frequency, severity and duration of adverse reactions [every 3 weeks, 31 months after start of treatment or if applicable 4 weeks after last dose of bevacizumab (whichever occurs later)]
Translational Research - Tumor Tissue Block [Assessment at end of study planned]
may be obtained at any time during therapy, preferably at cycle 1 or at a subsequent visit
Translational Research - Complementary and Alternative Treatment Questionnaires [baseline, 6 months and 12 months after start of treatment, if required at timepoint of treatment termination]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Signed written informed consent obtained prior to initiation of any study specific procedures and treatment as confirmation of the patients awareness and willingness to comply with the study requirements
Primary diagnosis is confirmed by specialized pathology review (Germany only)
Females aged ≥ 18 years
Histologically confirmed, newly diagnosed
Epithelial ovarian carcinoma
Fallopian tube carcinoma
Primary peritoneal carcinoma AND FIGO stage IIb - IV (all grades and all histological types)
Patients should have already undergone surgical debulking, by a surgeon experienced in the management of ovarian cancer, with the aim of maximal surgical cytoreduction according to the GCIG Conference Consensus Statement. There must be no planned surgical debulking prior to disease progression. Patients with stage III and IV disease in whom initial surgical debulking was not appropriate or possible will still be eligible providing
the patient has a histological diagnosis and
debulking surgery prior to disease progression is not foreseen
Patients must be able to commence cytotoxic chemotherapy within 8 weeks of cytoreductive surgery. The first dose of bevacizumab can be omitted in both arms if the investigator decides to start chemotherapy within 4 weeks of surgery.
ECOG 0-2
Life expectancy > 3 months
Adequate bone marrow function (within 14 days prior to randomization)
ANC ≥ 1.5 x 10^9/L
PLT ≥ 100 x 10^9/L
Hb ≥ 9 g/dL (can be post-transfusion)
Adequate coagulation parameters (within 14 days prior to randomization)
Patients not receiving anticoagulant medication who have an INR ≤ 1.5 and an aPTT ≤ 1.5 x ULN
The use of full-dose oral or par-enteral anticoagulants is permitted as long as the INR or aPTT is within therapeutic limits (according to institution medical standard) and the patient has been on a stable dose of anticoagulants for at least two weeks at the time of randomization.
Adequate liver function (within 14 days prior to randomization)
Serum bilirubin ≤ 1.5 x ULN
Serum transaminases ≤ 2.5 x ULN
Urine dipstick for proteinuria < 2+. If urine dipstick is ≥ 2+, 24 hour urine must demonstrate ≤ 1 g of protein in 24 hours
Adequate postoperative GFR > 40 ml/min (estimates based on the Cockroft-Gault or Jelliffe formula are sufficient)

Exclusion Criteria:

Non-epithelial origin of the ovary, the fallopian tube or the peritoneum
Borderline tumours (tumours of low malignant potential) and FIGO stage Ia - IIa tumours
Planned intraperitoneal cytotoxic chemotherapy
Prior systemic anti-cancer therapy for ovarian cancer (for example chemotherapy, monoclonal antibody therapy, tyrosine kinase inhibitor therapy or hormonal therapy)
Surgery (including open biopsy) within 4 weeks prior to anticipated first dose of bevacizumab (allowing for the fact that bevacizumab can be omitted from the first cycle of chemotherapy). It is strongly recommended that an interval of 7 days is left between the insertion of any central venous access devices (CVADs) and the onset of bevacizumab treatment.
Any planned surgery during the study treatment period plus 4 additional weeks to allow for bevacizumab clearance
Uncontrolled hypertension (sustained elevation of BP systolic > 150mmHg and/or diastolic > 100mmHg despite antihypertensive therapy)
Any previous radiotherapy to the abdomen or pelvis
Significant traumatic injury during 4 weeks preceding the potential first dose of bevacizumab
History or clinical suspicion of brain metastases or spinal cord compression. CT/MRI of the brain is mandatory (within 4 weeks prior to randomization) in case of suspected brain metastases. Spinal MRI is mandatory (within 4 weeks prior to randomization) in case of suspected spinal cord compression.
History or evidence upon neurological examination of central nervous system (CNS) disease, unless adequately treated with standard medical therapy e.g. uncontrolled seizures
Previous Cerebro-Vascular Accident (CVA), Transient Ischaemic Attack (TIA) or Sub-Arachnoid Haemorrhage (SAH) within 6 months prior to randomization
Fertile woman of childbearing potential not willing to use adequate contraception (oral contraceptives, intrauterine device or barrier method of contraception in conjunction with spermicidal jelly or surgically sterile) for the study duration and at least 6 months afterwards
Pregnant or lactating women
Treatment with other investigational agents, or participation in another clinical trial testing a drug within the past 4 weeks before start of therapy concomitantly with this trial
Malignancies other than ovarian cancer within 5 years prior to randomization, except for adequately treated
carcinoma in situ of the cervix
and/or basal cell skin cancer
and/or non-melanomatous skin cancer
carcinoma in situ of the breast
and/or early endometrial carcinoma as specified below. Patients may have received previous adjuvant chemotherapy for other malignancies e.g. breast or colorectal carcinoma if diagnosed over 5 years ago with no evidence of subsequent recurrence.
Patients with synchronous primary endometrial carcinoma, or a past history of primary endometrial carcinoma, are excluded unless ALL of the following criteria for describing the endometrial carcinoma are met
Disease stage FIGO stage ≤ IA (tumour invades less than one half of the myometrium)
Known hypersensitivity to bevacizumab and its excipients, Chinese hamster ovary cell products or other recombinant human or humanised antibodies
Non healing wound, active ulcer or bone fracture. Patients with granulating incisions healing by secondary intention with no evidence of facial dehiscence or infection are eligible but require 3 weekly wound examinations
History or evidence of thrombotic or hemorrhagic disorders within 6 months prior to randomization
Clinically significant cardiovascular disease, including
Myocardial infarction or unstable angina within 6 months of randomization
NYHA ≥ Grade 2 Congestive Heart Failure (CHF)
Poorly controlled cardiac arrhythmia despite medication (patients with rate-controlled atrial fibrillation are eligible)
Grade ≥ 3 peripheral vascular disease (i.e. symptomatic and interfering with activities of daily living requiring repair or revision)
Current or recent (within 10 days prior to randomization) chronic use of aspirin > 325 mg/day
Pre-existing sensory or motor neuropathy ≥ Grade 2
Evidence of any other disease, metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contra-indicates the use of an investigational drug or puts the patient at high risk for treatment-related complications

Contacts and Locations

Locations

	City	Country
1	Aalborg	Denmark
2	Copenhagen	Denmark
3	Herlev	Denmark
4	Kuopio	Finland
5	Oulu	Finland
6	Tampere	Finland
7	Turku	Finland
8	Angers	France
9	Besancon	France
10	Blois	France
11	Bordeaux	France
12	Caen	France
13	Cahors	France
14	Clamart	France
15	Clermont-Ferrand	France
16	Creteil	France
17	Dax	France
18	Draguignan	France
19	Grenoble	France
20	Limoges	France
21	Lyon	France
22	Mougins	France
23	Nancy	France
24	Nantes	France
25	Nice	France
26	Nimes	France
27	Orleans	France
28	Paris	France
29	Pau	France
30	Plérin	France
31	Poitiers	France
32	Quimper	France
33	Reims	France
34	Rouen	France
35	Saint-Herblain	France
36	Strasbourg	France
37	Toulouse	France
38	Vandoeuvre-Les-Nancy	France
39	Vannes	France
40	Villejuif	France
41	Aachen	Germany
42	Arnsberg	Germany
43	Aschaffenburg	Germany
44	Augsburg	Germany
45	Bad Homburg vor der Höhe	Germany
46	Berlin	Germany
47	Bochum	Germany
48	Bonn	Germany
49	Bottrop	Germany
50	Brandenburg	Germany
51	Bremen	Germany
52	Chemnitz	Germany
53	Coburg	Germany
54	Deggendorf	Germany
55	Dessau	Germany
56	Dresden	Germany
57	Düsseldorf	Germany
58	Ebersberg	Germany
59	Eggenfelden	Germany
60	Erlangen	Germany
61	Essen	Germany
62	Esslingen	Germany
63	Flensburg	Germany
64	Frankfurt/M.	Germany
65	Freiburg	Germany
66	Fürstenfeldbruck	Germany
67	Fürth	Germany
68	Georgsmarienhütte	Germany
69	Gera	Germany
70	Greifswald	Germany
71	Göttingen	Germany
72	Gütersloh	Germany
73	Halle (Saale)	Germany
74	Hamburg	Germany
75	Hanau am Main	Germany
76	Hannover	Germany
77	Heidelberg	Germany
78	Henstedt-Ulzburg	Germany
79	Hildesheim	Germany
80	Jena	Germany
81	Kaiserslautern	Germany
82	Karlsruhe	Germany
83	Kassel	Germany
84	Kiel	Germany
85	Krefeld	Germany
86	Köln	Germany
87	Lich	Germany
88	Limburg	Germany
89	Lübeck	Germany
90	Lüneburg	Germany
91	Magdeburg	Germany
92	Mainz	Germany
93	Mannheim	Germany
94	Marburg	Germany
95	Minden	Germany
96	München	Germany
97	Neumarkt	Germany
98	Neuss	Germany
99	Nordhausen	Germany
100	Offenbach	Germany
101	Offenburg	Germany
102	Oldenburg	Germany
103	Osnabrück	Germany
104	Ravensburg	Germany
105	Regensburg	Germany
106	Reutlingen	Germany
107	Rosenheim	Germany
108	Rostock	Germany
109	Rottweil	Germany
110	Saalfeld	Germany
111	Salzgitter	Germany
112	Schweinfurt	Germany
113	Schwäbisch Hall	Germany
114	Sigmaringen	Germany
115	Solingen	Germany
116	Stralsund	Germany
117	Stuttgart	Germany
118	Torgau	Germany
119	Trier	Germany
120	Tübingen	Germany
121	Ulm	Germany
122	Viersen	Germany
123	Wiesbaden	Germany
124	Witten	Germany
125	Wolfsburg	Germany
126	Worms	Germany
127	Bergen	Norway
128	Oslo	Norway
129	Trondheim	Norway
130	Falun	Sweden
131	Uppsala	Sweden