Evaluation of treatment combination Atezolizumab/Bevacizumab +/- Chemotherapy in patients with recurrent ovarian cancer

Phase 1

• Conditions: Efficacy of atezolizumab in combination with non-platinum based chemotherapy and bevacizumab versus the combination of a non-platinum based chemotherapy and bevacizumab in recurrent ovarian cancer; MedDRA version: 21.0 Level: PT Classification code 10016182 Term: Fallopian tube cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1 Level: PT Classification code 10057529 Term: Ovarian cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1 Level: PT Classification code 10066697 Term: Ovarian cancer recurrent System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2017-000202-37-ES
• Lead Sponsor: AGO Research GmbH

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-10-21
• Last Update Posted: 1 February 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Not specified
• Target Recruitment: 664

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.Patient agrees and is able to provide a recent tumor biopsy (not older than 3 months) or agrees and has a tumor lesion amenable for taking a new tumor biopsy.
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. A washout period of at least 20 days after last bevacizumab treatment must be adhered.
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 admin-istration of study treatment:
Hemoglobin = 9.0 g/dl
-Absolute neutrophil count (ANC) = 1.5 x 10E9/L
-Platelet count = 100 x 10E9/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 Transam-inase (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 ran-domization
-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 treatmen

Exclusion Criteria

1.Non-epithelial tumor origin of the ovary, the fallopian tube or the peritoneum
2.Ovarian tumors of low malignant potential
3.Malignancies other than ovarian cancer within 5 years prior to randomisation.
4.More than three prior systemic anticancer regimens; maintenance therapies are not calculated as separate line.
5.Prior systemic anticancer therapy within 28 days before randomization.
6.Prior radiotherapy to the pelvis or the abdomen.
7.Administration of other simultaneous chemotherapy drugs, any other anticancer ther-apy or anti-neoplastic hormonal therapy, or simultaneous radiotherapy during the trial treatment period.
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 (including but not limited to inter-feron-alpha and interleukin-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 medi-cations within 2 weeks prior to Cycle 1, Day 1, or anticipated requirement for systemic immu-nosuppressive medications during the trial
12.the use of inhaled corticosteroids for chronic obstructive pulmonary disease, mineral-ocorticoids.
13.Prophylactic antiemetic corticosteroids shall be avoided if possible in patients treated with pegylated liposomal doxorubicin regimen.
14.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)
15.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.
16.Major surgery within 4 weeks of starting study treatment or patient who has not com-pletely recovered from the effects of any major surgery.
17.Previous allogeneic bone marrow transplant or previous solid organ transplantation
18.Current treatment with anti-viral therapy for HBV.
19.History of idiopathic pulmonary fibrosis, organizing pneumonia, or evidence of active pneumonitis on screening chest CT scan.
20.Previous Cerebro-Vascular Accident, Transient Ischemic Attack or Sub-Arachnoids Hemorrhage within 6 months prior to randomization
21.History or evidence of thrombotic or hemorrhagic disorders within 6 months prior to randomization
22.History or clinical suspicion of brain metastases or spinal cord compression.
23.History of autoimmune disease.
24.Any prior history of hypertensive crisis (CTCAE grade 4) or hypertensive encephalopathy
25.Immunocompromised patients, e.g., patients who are known to be serologically posi-tive for human immunodeficiency virus (HIV). Patients with active hepatitis B or hepatitis C
26.Persistent toxicities (= CTCAE grade 2) with the exception of alopecia, caused by previous cancer treatment.

Study & Design

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