Trial Outcomes & Findings for Study of Niraparib With Radiotherapy for Treatment of Metastatic Invasive Carcinoma of the Cervix (NCT NCT03644342)

Last Updated: 2024-09-03

Results Overview

Maximum tolerated dose (MTD) of niraparib when administered concurrently with whole pelvic radiotherapy. The initial treatment dose is 100 mg, and for every 3 patients the dose is escalated and de-escalated, and additional patients are treated by the study design. Participants continue to be enrolled and assigned to treatment doses according to these rules until 17 efficacy evaluable participants are enrolled to any single dose level.

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

4 participants

Primary outcome timeframe

7 weeks during concurrent radiation therapy and niraparib administration

Results posted on

2024-09-03

Participant Flow

The study was open to accrual in July 2019 and closed in September 2023 due to slow accrual and an expected change in standard care.

This study uses the Basian Optimal interval (BOIN)design. The initial treatment dose is 100 mg, and then for every 3 patients the dose is escalated if the observed toxicity rate at the current dose is low, de-escalated if the observed toxicity rate is high, and additional patients are treated if the observed toxicity rate is between indeterminate.

Participant milestones

Participant milestones
Measure	Niraparib Arm - 100 mg For the purposes of this study, two dose levels of Niraparib (100 mg will be evaluated concomitant with the concurrent administration of pelvic radiotherapy. Nirapaib: (see treatment regimen and method of treatment assignment)	Niraparib Arm - 200 mg For the purposes of this study, two dose levels of Niraparib (200 mg) will be evaluated concomitant with the concurrent administration of pelvic radiotherapy. Nirapaib: (see treatment regimen and method of treatment assignment)
Overall Study STARTED	3	1
Overall Study COMPLETED	1	0
Overall Study NOT COMPLETED	2	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Niraparib Arm - 100 mg For the purposes of this study, two dose levels of Niraparib (100 mg will be evaluated concomitant with the concurrent administration of pelvic radiotherapy. Nirapaib: (see treatment regimen and method of treatment assignment)	Niraparib Arm - 200 mg For the purposes of this study, two dose levels of Niraparib (200 mg) will be evaluated concomitant with the concurrent administration of pelvic radiotherapy. Nirapaib: (see treatment regimen and method of treatment assignment)
Overall Study Adverse Event	2	0
Overall Study Protocol Violation	0	1

Baseline Characteristics

Study of Niraparib With Radiotherapy for Treatment of Metastatic Invasive Carcinoma of the Cervix

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Niraparib Arm - 100 mg n=3 Participants For the purposes of this study, two dose levels of Niraparib (100 mg will be evaluated concomitant with the concurrent administration of pelvic radiotherapy. Nirapaib: (see treatment regimen and method of treatment assignment)	Niraparib Arm - 200 mg n=1 Participants For the purposes of this study, two dose levels of Niraparib (200 mg) will be evaluated concomitant with the concurrent administration of pelvic radiotherapy. Nirapaib: (see treatment regimen and method of treatment assignment)	Total n=4 Participants Total of all reporting groups
Age, Continuous	61 years n=99 Participants	40 years n=107 Participants	52 years n=206 Participants
Sex: Female, Male Female	3 Participants n=99 Participants	1 Participants n=107 Participants	4 Participants n=206 Participants
Sex: Female, Male Male	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Asian	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Black or African American	1 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants
Race (NIH/OMB) White	0 Participants n=99 Participants	1 Participants n=107 Participants	1 Participants n=206 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=99 Participants	0 Participants n=107 Participants	2 Participants n=206 Participants

PRIMARY outcome

Timeframe: 7 weeks during concurrent radiation therapy and niraparib administration

Population: The study enrolled 4 patients on dose level 1(100mg). One patient was dosed incorrectly on dose leve 2 (200mg) and was taken off-study and not evaluable. There were 3 patients evaluable for this study.

Outcome measures

Outcome measures
Measure	Niraparib Arm - 100 mg n=3 Participants For the purposes of this study, two dose levels of Niraparib (100 mg will be evaluated concomitant with the concurrent administration of pelvic radiotherapy. Nirapaib: (see treatment regimen and method of treatment assignment)
Number of Participants With Dose-limiting Toxicities Niraparib Experienced DLT's and discontinued niraparib therapy	2 participants
Number of Participants With Dose-limiting Toxicities Niraparib Tolerated niraparib at the prescribed 100mg dose without significant toxicity	1 participants

PRIMARY outcome

Timeframe: Up to 12 months from the time of treatment initiation to progression

Local progression-free survival for patients who have received 1 or more doses of niraparib with pelvic radiation as part of their treatment for metastatic cervical cancer.

Outcome measures

Outcome measures
Measure	Niraparib Arm - 100 mg n=3 Participants For the purposes of this study, two dose levels of Niraparib (100 mg will be evaluated concomitant with the concurrent administration of pelvic radiotherapy. Nirapaib: (see treatment regimen and method of treatment assignment)
Local Progression-free Survival	NA months No patients had progression. Therefore, the median survival does not exist.

SECONDARY outcome

Timeframe: 12 months after end of treatment, up to 1 year

acute toxicity profile of niraparib administered concurrently with whole pelvic radiotherapy according to the CTCAE version 4 as well as the grade of each toxicity. only serious adverse events will be reported here.

Outcome measures

Outcome measures
Measure	Niraparib Arm - 100 mg n=3 Participants For the purposes of this study, two dose levels of Niraparib (100 mg will be evaluated concomitant with the concurrent administration of pelvic radiotherapy. Nirapaib: (see treatment regimen and method of treatment assignment)
Acute Toxicity Profile of Niraparib	0 participants

SECONDARY outcome

Timeframe: 12 months after end of treatment

Functional Assessment of Cancer Therapy-Cervix (FACT Cx). It measures health related quality of life for people with cervical cancer in 4 domains: physical well being, social/family well being, emotional well being, and functional well being. All questions are a 0-4 scale. The total score is then calculated as the sum of the un-weighted subscale scores (0-27). For all FACIT scales and symptom indices, the higher the score the better the QOL

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: at 28 days after completing radiation therapy (XRT completion) and at every 3 months up to 12 months

Number of tumor responses outside the radiation field using RECIST 1.1 for women receiving niraparib concurrently with whole pelvic radiotherapy. Response and progression will be evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee (Version 1.1). Changes in only the largest unidimensional measurement (diameter) of index tumor lesions are used to assess response by RECIST criteria

Outcome measures

Outcome measures
Measure	Niraparib Arm - 100 mg n=3 Participants For the purposes of this study, two dose levels of Niraparib (100 mg will be evaluated concomitant with the concurrent administration of pelvic radiotherapy. Nirapaib: (see treatment regimen and method of treatment assignment)
Tumor Response	0 tumors

Adverse Events

Niraparib Arm - 100 mg

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Niraparib Arm - 200 mg

Serious events: 1 serious events

Other events: 1 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Niraparib Arm - 100 mg n=3 participants at risk For the purposes of this study, two dose levels of Niraparib (100 mg will be evaluated concomitant with the concurrent administration of pelvic radiotherapy. Nirapaib: (see treatment regimen and method of treatment assignment)	Niraparib Arm - 200 mg n=1 participants at risk For the purposes of this study, two dose levels of Niraparib (200 mg) will be evaluated concomitant with the concurrent administration of pelvic radiotherapy. Nirapaib: (see treatment regimen and method of treatment assignment)
Infections and infestations Urinary tract infection	0.00% 0/3 • From the start of the treatment to 12 months after the end of treatment, up to 2 years.	100.0% 1/1 • Number of events 1 • From the start of the treatment to 12 months after the end of treatment, up to 2 years.
Injury, poisoning and procedural complications Injury, poisoning and procedural complications - Other, specify	0.00% 0/3 • From the start of the treatment to 12 months after the end of treatment, up to 2 years.	100.0% 1/1 • Number of events 1 • From the start of the treatment to 12 months after the end of treatment, up to 2 years.

Other adverse events

Additional Information

Michelle S. Ludwig, MD, MPH, PhD

Baylor College of Medicine

Phone: 713-566-3662

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Niraparib Arm - 100 mg n=3 participants at risk For the purposes of this study, two dose levels of Niraparib (100 mg will be evaluated concomitant with the concurrent administration of pelvic radiotherapy. Nirapaib: (see treatment regimen and method of treatment assignment)	Niraparib Arm - 200 mg n=1 participants at risk For the purposes of this study, two dose levels of Niraparib (200 mg) will be evaluated concomitant with the concurrent administration of pelvic radiotherapy. Nirapaib: (see treatment regimen and method of treatment assignment)
Blood and lymphatic system disorders Anemia	66.7% 2/3 • Number of events 4 • From the start of the treatment to 12 months after the end of treatment, up to 2 years.	0.00% 0/1 • From the start of the treatment to 12 months after the end of treatment, up to 2 years.
Blood and lymphatic system disorders Blood and lymphatic system disorders - Other, specify	0.00% 0/3 • From the start of the treatment to 12 months after the end of treatment, up to 2 years.	100.0% 1/1 • Number of events 2 • From the start of the treatment to 12 months after the end of treatment, up to 2 years.
Gastrointestinal disorders Constipation	33.3% 1/3 • Number of events 3 • From the start of the treatment to 12 months after the end of treatment, up to 2 years.	0.00% 0/1 • From the start of the treatment to 12 months after the end of treatment, up to 2 years.
Gastrointestinal disorders Diarrhea	66.7% 2/3 • Number of events 2 • From the start of the treatment to 12 months after the end of treatment, up to 2 years.	100.0% 1/1 • Number of events 1 • From the start of the treatment to 12 months after the end of treatment, up to 2 years.
Gastrointestinal disorders Dysphagia	0.00% 0/3 • From the start of the treatment to 12 months after the end of treatment, up to 2 years.	100.0% 1/1 • Number of events 1 • From the start of the treatment to 12 months after the end of treatment, up to 2 years.
Gastrointestinal disorders Nausea	100.0% 3/3 • Number of events 6 • From the start of the treatment to 12 months after the end of treatment, up to 2 years.	100.0% 1/1 • Number of events 2 • From the start of the treatment to 12 months after the end of treatment, up to 2 years.
Gastrointestinal disorders Stomach pain	33.3% 1/3 • Number of events 1 • From the start of the treatment to 12 months after the end of treatment, up to 2 years.	0.00% 0/1 • From the start of the treatment to 12 months after the end of treatment, up to 2 years.
Gastrointestinal disorders Vomiting	66.7% 2/3 • Number of events 2 • From the start of the treatment to 12 months after the end of treatment, up to 2 years.	100.0% 1/1 • Number of events 2 • From the start of the treatment to 12 months after the end of treatment, up to 2 years.
Investigations Alkaline phosphatase increased	66.7% 2/3 • Number of events 3 • From the start of the treatment to 12 months after the end of treatment, up to 2 years.	100.0% 1/1 • Number of events 1 • From the start of the treatment to 12 months after the end of treatment, up to 2 years.
Investigations Investigations - Other, specify	0.00% 0/3 • From the start of the treatment to 12 months after the end of treatment, up to 2 years.	100.0% 1/1 • Number of events 2 • From the start of the treatment to 12 months after the end of treatment, up to 2 years.
Investigations Lymphocyte count decreased	100.0% 3/3 • Number of events 15 • From the start of the treatment to 12 months after the end of treatment, up to 2 years.	100.0% 1/1 • Number of events 5 • From the start of the treatment to 12 months after the end of treatment, up to 2 years.
Investigations Neutrophil count decreased	66.7% 2/3 • Number of events 5 • From the start of the treatment to 12 months after the end of treatment, up to 2 years.	0.00% 0/1 • From the start of the treatment to 12 months after the end of treatment, up to 2 years.
Investigations Platelet count decreased	100.0% 3/3 • Number of events 11 • From the start of the treatment to 12 months after the end of treatment, up to 2 years.	0.00% 0/1 • From the start of the treatment to 12 months after the end of treatment, up to 2 years.
Investigations Weight gain	33.3% 1/3 • Number of events 1 • From the start of the treatment to 12 months after the end of treatment, up to 2 years.	0.00% 0/1 • From the start of the treatment to 12 months after the end of treatment, up to 2 years.
Investigations Weight loss	66.7% 2/3 • Number of events 2 • From the start of the treatment to 12 months after the end of treatment, up to 2 years.	100.0% 1/1 • Number of events 1 • From the start of the treatment to 12 months after the end of treatment, up to 2 years.
Investigations White blood cell decreased	100.0% 3/3 • Number of events 4 • From the start of the treatment to 12 months after the end of treatment, up to 2 years.	100.0% 1/1 • Number of events 1 • From the start of the treatment to 12 months after the end of treatment, up to 2 years.
Metabolism and nutrition disorders Anorexia	66.7% 2/3 • Number of events 2 • From the start of the treatment to 12 months after the end of treatment, up to 2 years.	0.00% 0/1 • From the start of the treatment to 12 months after the end of treatment, up to 2 years.
Metabolism and nutrition disorders Hyperglycemia	33.3% 1/3 • Number of events 1 • From the start of the treatment to 12 months after the end of treatment, up to 2 years.	100.0% 1/1 • Number of events 1 • From the start of the treatment to 12 months after the end of treatment, up to 2 years.
Metabolism and nutrition disorders Hypoalbuminemia	66.7% 2/3 • Number of events 5 • From the start of the treatment to 12 months after the end of treatment, up to 2 years.	100.0% 1/1 • Number of events 1 • From the start of the treatment to 12 months after the end of treatment, up to 2 years.
Metabolism and nutrition disorders Hypocalcemia	33.3% 1/3 • Number of events 1 • From the start of the treatment to 12 months after the end of treatment, up to 2 years.	0.00% 0/1 • From the start of the treatment to 12 months after the end of treatment, up to 2 years.
Metabolism and nutrition disorders Hypokalemia	0.00% 0/3 • From the start of the treatment to 12 months after the end of treatment, up to 2 years.	100.0% 1/1 • Number of events 1 • From the start of the treatment to 12 months after the end of treatment, up to 2 years.
Metabolism and nutrition disorders Hypomagnesemia	33.3% 1/3 • Number of events 2 • From the start of the treatment to 12 months after the end of treatment, up to 2 years.	0.00% 0/1 • From the start of the treatment to 12 months after the end of treatment, up to 2 years.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	33.3% 1/3 • Number of events 3 • From the start of the treatment to 12 months after the end of treatment, up to 2 years.	0.00% 0/1 • From the start of the treatment to 12 months after the end of treatment, up to 2 years.
Nervous system disorders Paresthesia	33.3% 1/3 • Number of events 1 • From the start of the treatment to 12 months after the end of treatment, up to 2 years.	0.00% 0/1 • From the start of the treatment to 12 months after the end of treatment, up to 2 years.
Nervous system disorders Presyncope	33.3% 1/3 • Number of events 1 • From the start of the treatment to 12 months after the end of treatment, up to 2 years.	0.00% 0/1 • From the start of the treatment to 12 months after the end of treatment, up to 2 years.
Renal and urinary disorders Urinary incontinence	33.3% 1/3 • Number of events 1 • From the start of the treatment to 12 months after the end of treatment, up to 2 years.	0.00% 0/1 • From the start of the treatment to 12 months after the end of treatment, up to 2 years.
Reproductive system and breast disorders Vaginal discharge	100.0% 3/3 • Number of events 4 • From the start of the treatment to 12 months after the end of treatment, up to 2 years.	0.00% 0/1 • From the start of the treatment to 12 months after the end of treatment, up to 2 years.
Reproductive system and breast disorders Vaginal dryness	33.3% 1/3 • Number of events 2 • From the start of the treatment to 12 months after the end of treatment, up to 2 years.	0.00% 0/1 • From the start of the treatment to 12 months after the end of treatment, up to 2 years.
Reproductive system and breast disorders Vaginal fistula	33.3% 1/3 • Number of events 1 • From the start of the treatment to 12 months after the end of treatment, up to 2 years.	0.00% 0/1 • From the start of the treatment to 12 months after the end of treatment, up to 2 years.
Skin and subcutaneous tissue disorders Pruritus	33.3% 1/3 • Number of events 1 • From the start of the treatment to 12 months after the end of treatment, up to 2 years.	0.00% 0/1 • From the start of the treatment to 12 months after the end of treatment, up to 2 years.
Skin and subcutaneous tissue disorders Rash maculo-papular	66.7% 2/3 • Number of events 3 • From the start of the treatment to 12 months after the end of treatment, up to 2 years.	0.00% 0/1 • From the start of the treatment to 12 months after the end of treatment, up to 2 years.
Vascular disorders Hypertension	100.0% 3/3 • Number of events 5 • From the start of the treatment to 12 months after the end of treatment, up to 2 years.	0.00% 0/1 • From the start of the treatment to 12 months after the end of treatment, up to 2 years.
Vascular disorders Lymphedema	33.3% 1/3 • Number of events 1 • From the start of the treatment to 12 months after the end of treatment, up to 2 years.	0.00% 0/1 • From the start of the treatment to 12 months after the end of treatment, up to 2 years.