Immunotherapy, bevacizumab and ASA in recurrent ovarian cancer

Phase 1

• Conditions: Ovarian neoplasms; MedDRA version: 20.0Level: LLTClassification code 10051938Term: Ovarian adenocarcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: PTClassification code 10066697Term: Ovarian cancer recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: PTClassification code 10033128Term: Ovarian cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2015-004601-17-NL
• 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: 2017-06-30
• Last Update Posted: 4 April 2022

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: 96

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.
? Platinum-resistant cancer is defined as disease that responded to platinum-based chemotherapy but with documented recurrence between 28 days and six months of completing this therapy
? 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 is allowed under following conditions:
? No prior treatment with Hyperthermic intraperitoneal chemotherapy (HIPEC)
? 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
? Patients with = 2 previous treatment lines must have been previously exposed to bevacizumab or other targeted agents against VEGF or VEGF receptor
? No current, recent (within 4 weeks of randomization), or planned participation in an experimental drug study
? 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 the following laboratory results obtained within 14 days prior to randomization:
? WBC counts > 2.5 x 10^9/L and < 15.0 x 10^9/L and ANC = 1.5 x 10^9/L cells/µL (without granulocyte colony-stimulating factor support within 2 weeks prior to randomization), Lymphocyte count ? 0.5 x 10^9/L , Platelet count = 100 x 10^9/L (without requiring transfusion within 1 week prior to randomization), Hemoglobin > 9.0 g/dL (Patients may be transfused to meet the hemoglobin criterion)
? AST, ALT, and alkaline phosphatase = 2.5 x ULN, with the following exceptions:
? Patients with documented liver metastases: AST and ALT = 5 x ULN
? Patients with documented liver or bone metastases: alkaline phosphatase = 5 x ULN
? Serum total bilirubin = 1.5 x ULN
? Patients with suspicion of Gilbert disease who have serum bilirubin level = 3 x ULN may be enrolled.
? Adequate synthetic liver function with PT or INR and aPTT = 1.5 x ULN and serum albumin > 25 g/l
? Creatinine clearance estimation: = 40 ml/min/1.73m2 on the basis of the Chronic Kidney Disease Epidemiology Collaboration formula
? Estimated glomerular filtration rate = 141 x min(SCr/k,1)a x max(SCr/k,1) - 1.209 x 0.993 Age x 1.018 [if female] x [1.159 if Black] where SCr is serum creatinine (mg/dL), k 0.7 for female and 0.9 for males, a is - 0.329 for females and -0.411 for males, min indicates the mi

Exclusion Criteria

? 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
? Patients who are receiving bisphosphonate therapy or denosumab specifically to prevent skeletal events and who do not have a history of clinically significant hypercalcemia are eligible.
? Symptomatic brain or leptomeningeal disease; any brain metastases must be stable for at least 6 months
? 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.
? Significant vascular disease including stroke, transient ischemic attack, aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis within 6 months prior to randomization.
? Use of acetylsalicylic acid, NSAIDs or other COX-2 inhibitors that cannot be stopped at baseline and for the whole duration of the study. Occasional use (i.e. no more than 5 times/doses per (calendar) month) is allowed.
? Hypersensitivity to the active ingredient acetylsalicylic acid or any of the excipients, hypersensitivity to Chinese hamster ovary (CHO) cell products or other recombinant human or humanised antibodies or fusion proteins.
? Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation) and current or recent (within 10 days 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
? Prophylactic anticoagulation for the patency of venous access devices is allowed, provided the activity of the agent results in PT or an INR < 1.5 x ULN and aPTT is within normal limits within 1 week prior to randomization.
? Prophylactic or therapeutic use of low molecular-weight heparin (e.g., enoxaparin) is allowed.
? Obvious signs of, or risks for gastrointestinal fistula formation or perforation, such as
? History of bowel obstruction, including sub- occlusive disease, related to the underlying disease and history of abdominal fistula, tracheoesophageal fistula, gastrointestinal perforation or intra-abdominal abscess.
? Clinical symptoms of recent bowel obstruction or paralytic ileus, but excluding postoperative (within 4 weeks after abdominal surgery), or evidence of recto-sigmoid involvement by pelvic examination or bowel involvement on CT scan
? 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 = 2+ or > 1.0 g of protein in a 24-hour urine collection (All patients with = 2+ protein on dipstick urinalysis at baseline must undergo

Study & Design

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