NCT03795272

Rucaparib Maintenance Therapy in Advanced Cervical Cancer

A Randomized Double-blind Placebo-controlled Phase II Trial of Rucaparib Maintenance Therapy for Patients With Locally Advanced Cervical Cancer.

• Status: Withdrawn
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: Nordic Society of Gynaecological Oncology - Clinical Trials Unit · Academic / Other
• Sex: Female
• Age: 18 Years – 100 Years
• Healthy volunteers: Not accepted

Summary

To evaluate the efficacy of PARP inhibitor, rucaparib as maintenance therapy for locally advanced cervical cancer

Detailed description

The use of concomitant cisplatin-based chemo-radiation for cervical cancer has improved survival of locally advanced cervical cancer patients and has become the standard of care. A meta-analysis revealed that the addition of concurrent chemotherapy to radiation increased the 5-year overall survival rate by 6% (HR 0.81: 60 vs 66%), and 5-year disease-free survival rate by 8%, though there is still considerable need for improvement as most patients who relapse are incurable. The unmet need is particularly higher in patients that are at high risk of recurrence. The main negative prognostic factors are higher FIGO stage as well as the presence of positive lymph nodes. Current studies are evaluating role of adjuvant chemotherapy following chemo-radiation in locally advanced disease and will possibly improve survival by reducing risk of distant metastases, however at the cost of excessive toxicity. PARP inhibitors have shown considerable clinical benefit especially in platinum-sensitive relapsed ovarian cancer. Several PARP inhibitors have been evaluated in other gynaecological malignancies and three PARP inhibitors (olaparib, rucaparib \& niraparib) are approved by European Medicines Agency and Food \& Drug Administration for treatment or as maintenance therapy in ovarian cancer. Human papillomavirus causes oxidative stress that may result in DNA single-strand breaks. In cervical cancer PARP-1 expression/activity may be up-regulated in response to the ongoing oxidative stress (HPV and inflammation), and this may promote progression. This may create a vicious circle of inflammation, PARP activation, NAD+ consumption, adenosine triphosphate consumption, necrosis, and inflammation. PARPi may limit the role of PARP-1 in promoting inflammation and oxidative stress. There is theoretical plausibility that PARPi may have a role in the treatment of cervical carcinoma. This phase II randomized placebo-controlled double-blind study will evaluate the efficacy and safety of rucaparib as adjuvant treatment for patients with locally advanced cervical cancer who are responding to chemo-radiation. This investigator-initiated study will be performed within the GCIG/ENGOT collaboration

Conditions

• Cervical Cancer

Interventions

Type	Name	Description
DRUG	Rucaparib	2:1 randomization to receive rucaparib/placebo twice daily for 24 month
DRUG	Placebo	placebo

Timeline

• Start date: 2019-10-01
• Primary completion: 2019-10-10
• Completion: 2019-10-10
• First posted: 2019-01-07
• Last updated: 2019-11-01

Locations

2 sites across 1 country: Denmark