A Phase I/II Trial of VB-111 and Paclitaxel for Recurrent Platinum-Resistant Müllerian Cancer

A Phase I/II Trial of Multiple Dose VB-111 and Weekly Paclitaxel for the Treatment of Recurrent Platinum-Resistant Müllerian Cancer

This is a prospective, open label, dose escalating, Phase I/II study, measuring mainly the safety and tolerability of the combination of intravenous administration of VB-111 and paclitaxel in patients with platinum resistant ovarian cancer.

Inclusion Criteria:

• Patients aged > 18
• Histologically confirmed epithelial ovarian, peritoneal, or fallopian tube cancer, and uterine papillary serous carcinomas (UPSC), and gynecologic malignant mixed müllerian tumors (MMMTs).
• Must have had prior platinum or platinum based therapy.
• Eastern Cooperative Oncology Group (ECOG) status 0-1.
• Platinum resistant or refractory disease within 6 months of completing or while receiving a platinum and taxane containing regimen
• Measurable disease
• Adequate bone marrow and hematological function.
• Must have recovered from acute toxicity from prior treatment
• Prior treatment with an anti-angiogenic agent is not an exclusion criterion.
• No prior GI perforation, or GI obstruction or involvement of the bowel on imaging
• Known hypersensitivity to Cremophor EL. However, participants are eligible if they have had a prior paclitaxel reaction, but subsequently tolerated the drug at rechallenge.
• No patients receiving other investigational therapy for the past 30 days before dosing.

Exclusion Criteria:

• More than 3 prior lines of chemotherapy for recurrent cancer.
• History of other active malignancy, other than superficial basal cell and superficial squamous cell, or carcinoma in situ of the cervix within last 2 years.
• Life expectancy of less than 3 months
• CTC Grade 1 or greater neuropathy (motor or sensory) from comorbidity other than prior taxane exposure, such as diabetes.
• Inadequately controlled hypertension or prior history of hypertensive crisis or hypertensive encephalopathy.
• New York Heart Association (NYHA) Grade II or greater congestive heart failure.
• History of myocardial infarction or unstable angina within 6 months prior to study Day 1.
• History of stroke or transient ischemic attack within 6 months prior to Day 1.
• Known CNS disease, except for treated brain metastasis
• Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Day 1.
• History of hemoptysis (1/2 teaspoon of bright red blood per episode) within 1 month prior to Day 1.
• Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation).