The most effective strategy for managing distantly metastatic invasive carcinomas of the
cervix is not defined. Based on the success of niraparib in breast and ovarian cancer trials
and the concern for toxicities and comorbidities limiting the compliance of concurrent
cisplatin for cervical cancer, this study is a phase I/II study of women diagnosed with
distantly metastatic (Stage IV) disease to determine the maximum tolerated dose and to
evaluate the safety, tolerability and preliminary efficacy of niraparib, an orally available
small molecule PARP inhibitor when administered concurrently with definitive regional
radiotherapy for treatment of cervical cancer. Women enrolled in this study will receive 3-6
cycles of induction-style carboplatin and paclitaxel followed by definitive doses of pelvic
radiotherapy along with the oral niraparib given at the same time.
1. Participant must have histologically confirmed diagnosis of invasive squamous cell or
adenocarcinoma of the cervix, FIGO Stage IV.
2. Participant must have an Eastern Cooperative Oncology Group (ECOG) performance status
of ≤ 1.
3. Participant must be ≥ 18 years of age.
4. Participant must have adequate organ function within 28 days of registration, defined
- Absolute neutrophil count ≥ 1,500/µL
- Platelets ≥ 100,000/µL
- Hemoglobin ≥ 9 g/dL
- Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or calculated creatinine
clearance ≥ 30 mL/min using the Cockcroft-Gault equation
- Total bilirubin ≤ 1.5 x ULN (≤2.0 in patients with known Gilberts syndrome) OR
direct bilirubin ≤ 1 x ULN
- Aspartate aminotransferase and alanine aminotransferase ≤ 2.5 x ULN unless liver
metastases are present, in which case they must be ≤ 5 x ULN
5. Participant receiving corticosteroids may continue as long as their dose is stable for
least 4 weeks prior to initiating protocol therapy.
6. Participant must agree to not donate blood during the study or for 90 days after the
last dose of study treatment.
7. Female participant of childbearing potential must have a negative serum pregnancy test
within 14 days prior to registration. Pregnancy test should be repeated within 7 days
before CT simulation if more than 14 days has passed since the previous pregnancy
test. (If serum test is falsely positive, pregnancy can be excluded by appropriate
pelvic imaging.) Patient must agree to abstain from activities that could result in
pregnancy from screening through completion of 7 days of pelvic radiotherapy. Females
of non-childbearing potential is defined as follows (by other than medical reasons):
- ≥45 years of age and has not had menses for >1 year
- Post-hysterectomy, post-bilateral oophorectomy, post external beam radiation of 6
Gy to the pelvis, or post-tubal ligation. Documented hysterectomy or oophorectomy
must be confirmed with medical records of the actual procedure or confirmed by a
phyiscal exam or imaging.
8. Participant must agree to not breastfeed during the study and for 180 days after the
last dose of study treatment.
9. Participant must be able to understand the study procedures and agree to participate
in the study by providing written informed consent
10. Participant must have completed 3-6 cycles of carbo/taxol with clinical evidence of CR
(complete response) or PR (partial response) by RECIST criteria no less than 4 weeks
and no greater than 12 weeks prior to initiation of protocol therapy.
11. Participant must be eligible for chemoradiation treatment in the opinion of the
12. Participants who are HIV+ must have CD4 counts >200/dL and demonstrate documented
13. Chemotherapy-related hematological toxicities must have resolved to Grade 1 or less.
1. Participant must not be simultaneously enrolled in any interventional clinical trial.
2. Participant must not have known documented intra-uterine pregnancy.
3. Participant must not have had major surgery ≤ 3 weeks prior to initiating protocol
therapy and participant must have recovered from any surgical effects.
4. Participant must not have received investigational therapy ≤ 4 weeks, or within a time
interval less than at least 5 half-lives of the investigational agent, whichever is
shorter, prior to initiating protocol therapy.
5. Participant last treatment with platinum based chemotherapy was ≥12 weeks from
initiation of protocol therapy.
6. Participant has had radiation therapy encompassing >20% of the bone marrow within 2
weeks; or any radiation therapy within 1 week prior to Day 1 of protocol therapy.
7. Participant must not have a known hypersensitivity to niraparib components or
8. Participant must not have received colony stimulating factors (e.g. granulocyte
colony-stimulating factor, granulocyte macrophage colony stimulating factor, or
recombinant erythropoietin) within 4 weeks prior to initiating protocol therapy.
9. Participant must not have any known history of myelodysplastic syndrome (MDS) or acute
myeloid leukemia (AML).
10. Participant must not have a serious, uncontrolled medical disorder, nonmalignant
systemic disease, or active, uncontrolled infection. Examples include, but are not
limited to, uncontrolled ventricular arrhythmia, NYHA Class ¾ heart failure, recent
(within 90 days) myocardial infarction, uncontrolled major seizure disorder, or any
psychiatric disorder that prohibits obtaining informed consent. Participant must not
have had a CVA within 6 months of registration.
11. Participant must not have had diagnosis, detection, or treatment of another type of
cancer ≤ 2 years prior to initiating protocol therapy (except basal or squamous cell
carcinoma of the skin that has been definitively treated).