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.

Study Overview

• Status: Completed
• Conditions: Platinum Resistant Ovarian Cancer
• Intervention / Treatment: Drug: Paclitaxel

• Study Type: Interventional
• Enrollment (Anticipated): 38
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: VB-111	Drug: Paclitaxel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Define toxicities	Define toxicities of a limited number of doses of combination VB-111 and weekly paclitaxel spanning anticipated effective doses.	2 years

Collaborators and Investigators

• Sponsor: Vascular Biogenics Ltd. operating as VBL Therapeutics

Publications and helpful links

General Publications

• Arend RC, Beer HM, Cohen YC, Berlin S, Birrer MJ, Campos SM, Rachmilewitz Minei T, Harats D, Wall JA, Foxall ME, Penson RT. Ofranergene obadenovec (VB-111) in platinum-resistant ovarian cancer; favorable response rates in a phase I/II study are associated with an immunotherapeutic effect. Gynecol Oncol. 2020 Jun;157(3):578-584. doi: 10.1016/j.ygyno.2020.02.034. Epub 2020 Apr 5.

Study record dates

Study Major Dates

• Study Start: November 1, 2012
• Primary Completion (Actual): May 3, 2017
• Study Completion (Actual): May 3, 2017

Study Registration Dates

• First Submitted: October 18, 2012
• First Submitted That Met QC Criteria: October 18, 2012
• First Posted (Estimate): October 23, 2012

Study Record Updates

• Last Update Posted (Actual): April 24, 2020
• Last Update Submitted That Met QC Criteria: April 23, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel
• Other Study ID Numbers: VB-111-157; 11-418 (Other Identifier: DF/HCC)