Clinical Trials /

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

NCT03644342

Description:

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.

Related Conditions:
  • Cervical Adenocarcinoma
  • Cervical Squamous Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of Niraparib With Radiotherapy for Treatment of Metastatic Invasive Carcinoma of the Cervix
  • Official Title: Phase I/II Study of Niraparib With Radiotherapy for Treatment of Metastatic Invasive Carcinoma of the Cervix

Clinical Trial IDs

  • ORG STUDY ID: H-40404
  • NCT ID: NCT03644342

Conditions

  • Metastatic Carcinoma of the Cervix

Interventions

DrugSynonymsArms
NirapaibZejulaNiraparib Arm

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Niraparib ArmExperimentalFor the purposes of this study, two dose levels of Niraparib (100 mg and 200 mg) will be evaluated concomitant with the concurrent administration of pelvic radiotherapy.
  • Nirapaib

Eligibility Criteria

        Inclusion Criteria:

          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
             as follows:

               -  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
             treating investigator.

         12. Participants who are HIV+ must have CD4 counts >200/dL and demonstrate documented
             HAART compliance

         13. Chemotherapy-related hematological toxicities must have resolved to Grade 1 or less.

        Exclusion Criteria:

          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
             excipients.

          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).
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum tolerated dose of niraparib
Time Frame:12 months after end of treatment
Safety Issue:
Description:Maximum tolerated dose (MTD) of niraparib when administered concurrently with whole pelvic radiotherapy.

Secondary Outcome Measures

Measure:acute toxicity profile of niraparib
Time Frame:12 months after end of treatment
Safety Issue:
Description: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.
Measure:Change in the quality of life measured using FACT-Cx questionnaire
Time Frame:12 months after end of treatment
Safety Issue:
Description: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
Measure:tumor response
Time Frame:End of treatment (8 weeks) and every 3 months during follow-up phase for up to 5 years
Safety Issue:
Description:tumor response outside the radiation field using RECIST 1.1 for women receiving niraparib concurrently with whole pelvic radiotherapy.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Michelle S Ludwig

Trial Keywords

  • cervical cancer
  • Niraparib
  • radiotherapy
  • carcinoma of the cervix

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