NCT02545010

Phase I Low Dose WART in Combination With Weekly Paclitaxel for Platinum Resistant Ovarian Cancer

Phase I Study of Low Dose Whole Abdominal Radiation Therapy (LDWART) in Combination With Weekly Paclitaxel for Platinum Resistant Ovarian Cancer With Predominant Non-visceral Abdominal Disease

• Status: Unknown
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 24 (estimated)
• Sponsor: National University Hospital, Singapore · Academic / Other
• Sex: Female
• Age: 21 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Ovarian Cancer

Interventions

Type	Name	Description
DRUG	Paclitaxel	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. Post treatment assessments will be conducted starting Day 43. Patients will then continue chemotherapy off trial protocol with weekly paclitaxel without concurrent LDWART starting Day 50 till disease progression, intolerable toxicity, patient refusal or deemed inappropriate to continue treatment by treating physician.
RADIATION	LDWART (Low Dose Whole Abdominal Radiation Therapy)	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. LDWART will not be administered if doses of weekly paclitaxel are withheld for any reason since it functions as a "chemosensitizer". LDWART will be administered together weekly paclitaxel immediately at point of recovery from toxicity and patient is deemed to be able to continue with treatment by investigator.

Timeline

• Start date: 2015-09-01
• Primary completion: 2017-08-01
• Completion: 2018-08-01
• First posted: 2015-09-09
• Last updated: 2016-06-22

Locations

1 site across 1 country: Singapore