Rucaparib Maintenance Therapy in Advanced Cervical Cancer (MaRuC)
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|ClinicalTrials.gov Identifier: NCT03795272|
Recruitment Status : Not yet recruiting
First Posted : January 7, 2019
Last Update Posted : September 6, 2019
|Condition or disease||Intervention/treatment||Phase|
|Cervical Cancer||Drug: Rucaparib Drug: Placebo||Phase 2|
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
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||162 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||This is a multicentre, phase 2, double-blind, placebo-controlled trial of maintenance rucaparib to obtain evidence of clinical benefit of rucaparib in locally advanced cervical cancer.|
|Masking:||Triple (Participant, Care Provider, Investigator)|
|Masking Description:||double-blinded placebo-controlled|
|Official Title:||A Randomized Double-blind Placebo-controlled Phase II Trial of Rucaparib Maintenance Therapy for Patients With Locally Advanced Cervical Cancer.|
|Estimated Study Start Date :||November 1, 2019|
|Estimated Primary Completion Date :||November 1, 2022|
|Estimated Study Completion Date :||November 1, 2024|
Patients will be treated with active oral drug, Rucaparib twice daily for 24 months
2:1 randomization to receive rucaparib/placebo twice daily for 24 month
Other Name: active maintenance
Placebo Comparator: Placebo
Patients will be treated with oral placebo twice daily for 24 months
Other Name: matched placebo maintenance
- Progression-Free Survival in months [ Time Frame: 42 months ]the time from randomization until the date of the first objective radiological disease progression according to investigator assessment of RECIST v1.1 or death by any cause, whichever occurs first.
- Progression Free Survival in Sub-Population in months [ Time Frame: 42 months ]the time from randomization until the date of the first objective radiological disease progression according to investigator assessment of RECIST v1.1 or death by any cause, whichever occurs first for the predefined study subgroups.
- Patient Reported Outcomes [ Time Frame: 42 months ]Quality of Life Questionnaire
- Overall Survival in months [ Time Frame: 60 months ]the time from randomization until the date of death by any cause
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03795272
|Contact: Mansoor R Mirza, MDfirstname.lastname@example.org|
|Copenhagen, Sjaelland, Denmark, 2100|
|Rigshospitalet||Not yet recruiting|
|København Ø, Sjaelland, Denmark, 2100|
|Contact: Kirsten Pors, RN +45353311 email@example.com|
|Contact: MANSOOR RAZA MIRZA, MD +4535459624 firstname.lastname@example.org|