Phase I Low Dose WART in Combination With Weekly Paclitaxel for Platinum Resistant Ovarian Cancer
Status:
Unknown status
Trial end date:
2018-08-01
Target enrollment:
Participant gender:
Summary
Background: Epithelial Ovarian Cancer is the most lethal amongst the gynecologic malignancies
and is the fifth leading cause of cancer death in women in the United States.1 Despite
initial high response rates, 50% to 75% of women who present with advanced disease suffer
relapse and require re treatment2.The optimal treatment for platinum resistant ovarian cancer
remains hotly debated. Combination chemotherapy is not favored due to its increased toxicity
and lack of convincing benefit when compared to single agent chemotherapy.3,4 Recently, the
addition of bevacizumab to single agent chemotherapy in the AURELIA study improved
progression free survival (PFS) from 3.4 months to 6.7 months. Response rates were also
improved from 11.8% versus 27.3% (p= 0 .001).9 Aim: To determine the maximal tolerated dose
(MTD) of weekly paclitaxel in combination with LDWART. The recommended phase II dose (RP2D)
will be based on the MTD in this Phase I study. Method: This study is designed as a
prospective, single arm phase I study with 3+3 with dose de-escalation and cohort expansion.
All patients will receive weekly paclitaxel at a pre specified dose of 80 mg/m2, 70 mg/m2,
60mg/m2 or 50 mg/m2 via intravenous infusion according to institution specific standard
practices. Cycles of chemotherapy will be administered weekly without interruption on Days
1,8,15,22,29,36 for a total of 6 weekly cycles in combination with LDWART(Fig.1). LDWART will
be given at 60 cGy fractions, twice daily for two days, with a minimum of 4 hours inter
fraction interval, starting on day 1 of each cycle of weekly paclitaxel for 6 weeks.(Fig.1).
Importance of proposed research: The combination of a LDWART with weekly paclitaxel may
improve the efficacy of the current standard weekly paclitaxel in platinum resistant ovarian
cancer patients. Potential benefits and risks: The combination may improve treatment
response. Adding LDWART may increase treatment risks, but these will be monitored closely.