Immunotherapy, bevacizumab and ASA in recurrent ovarian cancer

Phase 1

• Conditions: MedDRA version: 19.1Level: LLTClassification code 10051938Term: Ovarian adenocarcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Ovarian neoplasms; MedDRA version: 20.0Level: PTClassification code 10066697Term: Ovarian cancer recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]; MedDRA version: 20.0Level: PTClassification code 10033128Term: Ovarian cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

• Registration Number: EUCTR2015-004601-17-FR
• Lead Sponsor: European Organisation For Research and Treatment of Cancer (EORTC)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-05-04
• Last Update Posted: 19 April 2022

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: 160

Inclusion Criteria

?Recurrent, histologically proven, platinum-resistant, epithelial ovarian cancer, fallopian tube and primary peritoneal cancer in advanced or metastatic stage. Histological diagnosis by image guided biopsy, laparoscopy or laparotomy. Tumors diagnosed on cytology only and borderline tumors (i.e. low malignant potential) are excluded
?At least one lesion accessible to biopsy without putting patient at risk
?Prior systemic (chemotherapy, hormonal therapy, biologic agents, and/or vaccines) or radiation treatment:
*Systemic anti-tumoral treatment: wash-out period of 21 days prior to the first study treatment
*Any number of platinum-based chemotherapy lines are allowed but a maximum of 2 previous non-platinum containing lines
*Prior treatment with bevacizumab or other targeted agents against VEGF or VEGF receptor is allowed, but at least 18 weeks must have elapsed since their last administration
*Eligible patients with = 2 previous treatment lines must have been previously exposed to bevacizumab or other targeted agents against VEGF or VEGF receptor
*Recovery from any toxic effects of prior therapy to = Grade 1 per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v4.0) except fatigue or alopecia.
*Radiation therapy: recovery period of 14 days prior to the first study treatment; exception: single fraction radiotherapy with the indication of pain control and no prior radiation to the pelvis
?Age =18 years
?WHO PS: 0-2 for patients having received no more than two previous lines of therapy. WHO PS: 0-1 for patients having received >2 previous lines of therapy
?Life expectancy of = 12 weeks
?Adequate hematologic and end organ function, defined by laboratory results (see protocol at section 3.1 for details) obtained within 14 days prior to randomization
?Patients with past/resolved HBV infection (defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen [anti-HBc] antibody test) are eligible. HBV DNA must be obtained in patients with positive hepatitis B core antibody prior to randomization
?Patients positive for HCV antibody are eligible only if PCR is negative for HCV RNA
?Women of childbearing potential (WOCP: defined as a sexually mature woman who 1) has not undergone a hysterectomy or bilateral oophorectomy or 2) has not been naturally post-menopausal (amenorrhoea following cancer therapy does not rule out childbearing potential) for at least 12 consecutive months (i.e. has had menses at any time in the preceding 12 consecutive months)) must:
Have a negative serum pregnancy test within 7 days prior to randomization.
Agree to remain sexually abstinent, have a partner who is sterile (i.e., vasectomy), or use two medically effective methods of contraception during dosing and through 90 days after last study treatment. An effective method is the combination of the following (a+b): a. Hormonal method eg, birth control pills; b. Placement of an intrauterine device (IUD) or intrauterine system (fUS), barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/ gel/film/ cream/vaginal suppository. This requirement should be followed from screening through 24 weeks after last study treatment.
During treatment: Patient should agree to urine pregnancy test to be performed before each treatment;
Agree to discontinue treatment in case of pregnancy or positive pregnancy test.
?Before patient registrat

Exclusion Criteria

?current, recent (within 4 weeks of randomization), or planned
participation in an experimental drug study
?uncontrolled hypercalcemia [>1.5 mmol/L (4.8 mg/dL) ionized calcium, or Total Ca>3 mmol/L (12 mg/dL) or corrected serum calcium >ULN] or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab
?symptomatic brain or leptomeningeal disease; any brain metastases not stable for at least 6 months
?presence of uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
?significant cardiovascular disease, such as:
*inadequately controlled hypertension (defined as systolic blood pressure>150 mm Hg and/or diastolic blood pressure>100 mm Hg despite intensive medical management) or prior history of hypertensive crisis or hypertensive encephalopathy. Anti-hypertensive therapy is allowed.
*New York Heart Association Class II or greater congestive heart failure and history of myocardial infarction or unstable angina within 6 months prior to randomization (Appendix D)
*significant vascular disease including stroke, transient ischemic attack, aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis within 6 months prior to randomization
?evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation) and current or recent (within 10days prior to randomization) use of dipyridamole, ticlopidine, clopidogrel, cilostazol, prasugrel, or ticagrelor; or use of full dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic (as opposed to prophylactic) purpose
?obvious signs of, or risks for gastrointestinal fistula formation or perforation, such as:
*History of abdominal or tracheoesophageal fistula or gastrointestinal perforation within 6 months prior to randomization
*clinical signs or symptoms of gastrointestinal obstruction or requirement for routine parenteral hydration, parenteral nutrition, or tube feeding
?serious, non-healing or dehiscing wound, active ulcer, or untreated bone fracture. Surgery (including open but not core biopsy) within 4 weeks prior to randomization, or anticipation of the need for major surgery during study treatment
?proteinuria, as demonstrated by urine dipstick >1+ or > 1.0 g of protein in a 24-hour urine collection (All patients with > or = 2+ protein on dipstick urinalysis at baseline must undergo a 24 hour urine collection for protein and will remain eligible if < 1.0 g of protein detected) within 2 weeks of randomization
?history of inflammatory bowel disease or any autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, type I diabetes mellitus, vasculitis, or glomerulonephritis
?history of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan
?positivity for infections:
*signs or symptoms of infection or therapeutic use of antibiotics (exceptprophylactic antibiotics) within 2 weeks prior to randomization and severe infections within 4 weeks prior to randomization, including but not limited to hospitalizatio

Study & Design

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

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective of the study is to evaluate the efficacy and safety of 5 different treatments involving atezolizumab, bevacizumab and/or acetylsalicylic acid in advanced recurrent platinum-resistant ovarian, fallopian tube or primary peritoneal cancer patients in order to select the optimal treatments for further development in phase III.<br><br>;Secondary Objective: The secondary objectives of the study are to:<br>?assess the biological activity and immunological effects of each treatment in the tumor microenvironment and in the peripheral blood <br>?assess the effect of treatment on disease control and overall survival;Primary end point(s): The primary endpoint is progression-free survival rate at 6 months (PFS-6) according to RECIST v1.1 as assessed by the local investigator. Safety is assessed according to CTCAE v4.0.;Timepoint(s) of evaluation of this end point: at 6 months