AGO-OVAR 2.29 Atezolizumab in combination with Bevacizumab and chemotherapy versus Bevacizumab and chemotherapy in recurrent ovarian cancer – a randomized phase III study
Zusammenfassung der Studie
The study investigates the effect and safety of adding Atezolizumab to Bevacizumab and standard chemotherapy (Paclitaxel or Pegylated Liposomal Doxorubicin (PLD)) in women with recurrent ovarian cancer. The aim of this study is to determine whether the combination of Atezolizumab with Bevacizumab shrinks the tumor while preventing tumor cells from invading other parts of the body. Approximately 550 patients are expected to participate in this international study. Patients will be randomly assigned (known as randomization) to 2 treatment groups: chemotherapy plus Bevacizumab and Atezolizumab or chemotherapy plus Bevacizumab and placebo. Treatment assignment is done randomly by a computer, meaning that neither the patient nor the investigator can determine the treatment group. Atezolizumab is a new drug administered to people with various tumor diseases. It is approved by health authorities in Switzerland for the treatment of certain forms of lung cancer, bladder cancer, and breast cancer. Bevacizumab is also approved by health authorities in Switzerland for the treatment of various advanced cancers.
(BASEC)
Untersuchte Intervention
• In the study, the medications are administered at specific time intervals, called cycles; one cycle lasts 4 weeks.
• Atezolizumab or placebo and Bevacizumab are administered every two weeks in conjunction with a non-platinum-based standard chemotherapy: Paclitaxel (administered weekly) or PLD (administered every four weeks). During the first four weeks, hospital visits occur weekly (a total of four visits). After that, visits depend on the standard chemotherapy regimen of the respective patient. All medications are given intravenously (i.v.), meaning through access directly into the vein.
• Before, during, and after the study, the health status of the patients is regularly monitored.
• During chemotherapy, the effect on the tumor is checked by radiological control every 9 weeks in the first year, then every 12 weeks.
• Study participants will be followed up after the end of the study treatment depending on the course of the disease.
• The duration of participation (number of cycles) depends on the tolerability of the therapy and the progression of the disease. However, the maximum duration of study treatment is 24 months.
• The study will last approximately 5 years in total.
(BASEC)
Untersuchte Krankheit(en)
recurrent ovarian cancer
(BASEC)
Women with advanced or recurrent ovarian, fallopian tube, or primary peritoneal cancer (peritoneal cancer) may participate and have had their first or second recurrence (relapse) within 6 months after platinum-based chemotherapy. Patients with a third recurrence may also participate if the platinum-based chemotherapy was given more than 6 months ago. The diagnosis must be confirmed by a tissue/tumor sample. Additionally, participants must be at least 18 years old. (BASEC)
Ausschlusskriterien
No patients may participate in this clinical trial if they have participated simultaneously or within 28 days prior to the start of this study in another clinical trial or another clinical research project, or have received another unapproved investigational drug or radiotherapeutic intervention. Patients with another serious illness or if a major surgery is planned in the near future are also not eligible for participation. Pregnant or breastfeeding women may not participate in this clinical trial. (BASEC)
Studienstandort
Basel, Chur, Luzern, St Gallen, Andere
(BASEC)
Baden, Frauenfeld
(BASEC)
Sponsor
AGO Research GmbH SAKK
(BASEC)
Kontakt für weitere Auskünfte zur Studie
Allgemeine Auskünfte
Kliniken Essen-Mitte, Germany
(ICTRP)
Wissenschaftliche Auskünfte
Kliniken Essen-Mitte, Germany
(ICTRP)
Name der bewilligenden Ethikkommission (bei multizentrischen Studien nur die Leitkommission)
Ethikkommission Nordwest- und Zentralschweiz EKNZ
(BASEC)
Datum der Bewilligung durch die Ethikkommission
15.01.2021
(BASEC)
ICTRP Studien-ID
NCT03353831 (ICTRP)
Offizieller Titel (Genehmigt von der Ethikkommission)
AGO-OVAR 2.29 / ENGOT-ov34 Atezolizumab in combination with Bevacizumab and Chemotherapy versus Bevacizumab and Chemotherapy in recurrent ovarian cancer – a randomized Phase III trial - An ENGOT Trial (BASEC)
Wissenschaftlicher Titel
Atezolizumab in Combination With Bevacizumab and Chemotherapy Versus Bevacizumab and Chemotherapy in Recurrent Ovarian Cancer - a Randomized Phase III Trial (ICTRP)
Öffentlicher Titel
Atezolizumab With Bevacizumab and Chemotherapy vs Bevacizumab and Chemotherapy in Early Relapse Ovarian Cancer (ICTRP)
Untersuchte Krankheit(en)
Recurrent Ovarian Carcinoma (ICTRP)
Untersuchte Intervention
Drug: BevacizumabDrug: AtezolizumabDrug: ChemotherapyDrug: Placebos (ICTRP)
Studientyp
Interventional (ICTRP)
Studiendesign
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Care Provider, Investigator). (ICTRP)
Ein-/Ausschlusskriterien
Inclusion Criteria:
1. Patients with histologically diagnosed ovarian, fallopian tube, or primary
peritoneal cancer
2. Relapsed disease
3. Patients with up to three prior therapies. In patients with 1 or 2 prior treatment
lines, the treatment free interval after platinum has to be less than 6 months in
addition patients with three prior lines of chemotherapy who are not considered for
platinum-containing chemotherapy lines are also eligible
4. Measurable disease, evaluable disease in combination with GCIG CA-125 criteria, or
histologically proven relapse/progression
5. Mandatory de novo tumor biopsy (not older than 3 months) sent to central laboratory
as formalin-fixed, paraffin-embedded (FFPE) sample for determination of PDL1 status
prior to randomization for stratification.
6. Availability of a representative archival FFPE tumor sample (preferable from primary
diagnosis)
7. Patient has not progressed on the chosen/planned chemotherapy (PLD or Paclitaxel) in
any prior line
8. Patients previously treated with bevacizumab are eligible, with the exclusion of
those patients that has suspended bevacizumab for more than 2 subsequent cycles or
permanently discontinued bevacizumab during their previous treatment due to
toxicity.
9. Females aged = 18 years at signing at time of signing informed consent form
10. Signed written informed consent and ability to comply with the study protocol, in
the investigator's judgement
11. Adequate hematological, renal and hepatic function within 28 days prior to first
administration of study treatment:
- Hemoglobin = 9.0 g/dL
- Absolute neutrophil count (ANC) = 1.5 x 10xE^9/L
- Platelet count = 100 x 10xE^9/L
- Total bilirubin = 1.5 x institutional upper limit of normal (ULN)
- Aspartate aminotransferase /Serum Glutamic Oxaloacetic Transaminase (ASAT/SGOT)
and Alanine aminotransferase /Serum Glutamic Pyruvate Transaminase (ALAT/SGPT)
= 2.5 x ULN, unless liver metastases are present, in case of liver metastases
values must be = 5 x ULN
- Serum creatinine = 1.5 x institutional ULN
- Patient not receiving anticoagulant medication who has an International
Normalized Ratio (INR) = 1.5 and an Activated ProThrombin Time (aPTT) = 1.5 x
ULN. The use of full-dose oral or parenteral anticoagulants is permitted as
long as the INR or aPTT is within therapeutic limits (according to site medical
standard). If the patient is on oral anticoagulants, dose has to be stable for
at least two weeks at the time of randomization
- Urine dipstick for proteinuria < 2+. If urine dipstick is = 2+, 24-hours urine
must demonstrate = 1 g of protein in 24 hours.
12. Patients must have adequately controlled blood pressure (BP), with a systolic BP of
= 140 mmHg and diastolic BP of = 90 mmHg for eligibility. Patients must have a BP of
= 140/90 mmHg taken in the clinic setting by a medical professional within 2 weeks
prior to starting study.
13. Estimated life expectancy of at least 3 months
14. ECOG performance status 0 - 1
15. Negative urine or serum pregnancy test within 7 days of study treatment in women of
childbearing potential (WOCBP), confirmed prior to treatment on day 1
16. For women of childbearing potential: agreement to remain abstinent (refrain from
heterosexual intercourse) or use a contraceptive method with a failure rate of < 1%
per year during the treatment period and for at least 5 months after administration
of the last dose of atezolizumab/placebo and 6 months after the last dose of
bevacizumab, paclitaxel, or PLD, whichever is later.
17. For countries where this will apply to: a patient will be eligible for randomization
in this study only, if either affiliated to, or a beneficiary of a social security
category.
18. Willingness and ability to comply with scheduled visits, treatment plans, laboratory
tests, and other study procedures, that include the completion of patient-reported
outcomes questionnaires.
Exclusion Criteria:
1. Non-epithelial tumor origin of the ovary, the fallopian tube or the peritoneum (i.e.
germ cell tumors)
2. Ovarian tumors of low malignant potential (e.g. borderline tumors)
3. Malignancies other than ovarian cancer within 5 years prior to randomisation, with
the exception of those with a negligible risk of metastasis or death (e.g., 5-year
OS rate > 90%) and treated with expected curative outcome (such as adequately
treated carcinoma in situ of the cervix, non melanoma skin carcinoma, ductal
carcinoma in situ, or Stage I uterine cancer)
4. More than three prior systemic anticancer regimens maintenance therapies (e.g. with
bevacizumab, olaparib or niraparib) are not calculated as separate line.
5. Prior systemic anticancer therapy within 28 days before randomization (except
bevacizumab: 20 days).
6. Prior radiotherapy to the pelvis or the abdomen.
7. Administration of other simultaneous chemotherapy drugs, any other anticancer
therapy or anti-neoplastic hormonal therapy, or simultaneous radiotherapy during the
trial treatment period (hormonal replacement thera-py is permitted).
8. Prior treatment with anti-CD137 or immune checkpoint blockade therapies, anti-PD1,
or anti-PD-L1 therapeutic antibodies or anti-CTLA 4
9. Prior randomization in AGO-OVAR 2.29.
10. Treatment with systemic immunostimulatory agents (in-cluding but not limited to
interferon-alpha (IFN-a) and interleukin-2 (IL-2) within 4 weeks or five half-lives
of the drug (whichever is longer) prior to cycle 1, day 1.
11. Treatment with systemic corticosteroids or other systemic immunosuppressive
medications (including but not limited to prednisone, dexamethasone,
cyclophos-phamide, azathioprine, methotrexate, thalidomide, and antitumor necrosis
factor [TNF] agents) within 2 weeks prior to cycle 1, day 1, or anticipated
requirement for systemic immunosuppressive medications during the trial.
The use of inhaled corticosteroids for chronic obstruc-tive pulmonary disease,
mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic
hypotension, and low-dose supplemental corticosteroids for adrenocortical
insufficiency are allowed.
12. Patients with a history of allergic reaction to IV contrast requiring steroid
pre-treatment should have screening and subsequent tumor assessments performed using
magnetic resonance imaging (MRI).
13. Administration of a live, attenuated vaccine within 4 weeks prior to cycle 1, day 1
or anticipation that such a live attenuated vaccine will be required during the
study or within 5 months after the last dose of atezolizumab/placebo. Influenza
vaccination should be given during influenza season only. Patients must not receive
live, attenuated influenza vaccination
14. Major surgery within 4 weeks of starting study treatment or patient who has not
completely recovered from the effects of any major surgery. Core biopsy or other
minor surgical procedure within 7 days prior to day 1, cycle 1 is permitted.
15. Previous allogeneic bo (ICTRP)
nicht verfügbar
Primäre und sekundäre Endpunkte
Overall Survival (OS);Progression-free survival (ICTRP)
patient reported outcomes (QLQ and PRO-CTCAE);Objective Response Rate (ORR);Duration of Response (DOR);Efficacy regarding PD-L1 status (ICTRP)
Registrierungsdatum
14.11.2017 (ICTRP)
Einschluss des ersten Teilnehmers
nicht verfügbar
Sekundäre Sponsoren
Hoffmann-La Roche (ICTRP)
Weitere Kontakte
Philipp Harter, MD, PhD, Kliniken Essen-Mitte, Germany (ICTRP)
Sekundäre IDs
AGO-OVAR 2.29 (ICTRP)
Angaben zur Verfügbarkeit von individuellen Teilnehmerdaten
nicht verfügbar
Weitere Informationen zur Studie
https://clinicaltrials.gov/ct2/show/NCT03353831 (ICTRP)
Ergebnisse der Studie
Zusammenfassung der Ergebnisse
nicht verfügbar
Link zu den Ergebnissen im Primärregister
nicht verfügbar