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

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ClinicalTrials.gov Identifier: NCT03644342
Recruitment Status : Recruiting
First Posted : August 23, 2018
Last Update Posted : April 26, 2021
Sponsor:
Collaborator:
Tesaro, Inc.
Information provided by (Responsible Party):
Michelle S Ludwig, Baylor College of Medicine

Tracking Information
First Submitted Date  ICMJE June 4, 2018
First Posted Date  ICMJE August 23, 2018
Last Update Posted Date April 26, 2021
Actual Study Start Date  ICMJE July 15, 2019
Estimated Primary Completion Date March 1, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 21, 2018)
  • Maximum tolerated dose of niraparib [ Time Frame: 12 months after end of treatment ]
    Maximum tolerated dose (MTD) of niraparib when administered concurrently with whole pelvic radiotherapy.
  • Difference in local progression-free survival [ Time Frame: 12 months after end of treatment ]
    Difference in local progression-free survival for patients who have received 1 or more doses of niraparib with pelvic radiation as part of their treatment for a metastatic cervical cancer.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 21, 2018)
  • acute toxicity profile of niraparib [ Time Frame: 12 months after end of treatment ]
    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.
  • Change in the quality of life measured using FACT-Cx questionnaire [ Time Frame: 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
  • tumor response [ Time Frame: End of treatment (8 weeks) and every 3 months during follow-up phase for up to 5 years ]
    tumor response outside the radiation field using RECIST 1.1 for women receiving niraparib concurrently with whole pelvic radiotherapy.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Niraparib With Radiotherapy for Treatment of Metastatic Invasive Carcinoma of the Cervix
Official Title  ICMJE Phase I/II Study of Niraparib With Radiotherapy for Treatment of Metastatic Invasive Carcinoma of the Cervix
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Metastatic Carcinoma of the Cervix
Intervention  ICMJE Drug: Nirapaib
(see treatment regimen and method of treatment assignment)
Other Name: Zejula
Study Arms  ICMJE Experimental: Niraparib Arm
For 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.
Intervention: Drug: Nirapaib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 22, 2021)
24
Original Estimated Enrollment  ICMJE
 (submitted: August 21, 2018)
20
Estimated Study Completion Date  ICMJE March 2, 2026
Estimated Primary Completion Date March 1, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Participant must have histologically confirmed diagnosis of invasive squamous cell or adenocarcinoma of the cervix, FIGO Stage IIIC2 or IV (see Appendix 5 of the currently approved protocol).
  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 physical 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 platinum based chemotherapy (acceptable regimens in Appendix 7) 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. If bevacizumab used, 6 weeks must elapse between administration of bevacizumab and start of radiation 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.
  14. Participant must have had a CT (chest/abdomen/pelvis) or PET-CT, within 56 days of registration

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. Participant that has received prior treatment with a PARP inhibitor is excluded from this study.
  5. Participant last treatment with platinum based chemotherapy was ≥12 weeks from initiation of protocol therapy.
  6. Participant must not receive any additional chemotherapy while on study.
  7. 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.
  8. Participant must not have a known hypersensitivity to niraparib components or excipients.
  9. 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.
  10. Participant must not have any known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).
  11. 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 III/IV 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.
  12. 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).
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Michelle S Ludwig, MD, MPH, PhD 713-566-3757 Michelle.Ludwig@bcm.edu
Contact: Matthew L Anderson, MD, PhD 813-974-1806 mlander5@health.usf.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03644342
Other Study ID Numbers  ICMJE H-40404
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Michelle S Ludwig, Baylor College of Medicine
Study Sponsor  ICMJE Michelle S Ludwig
Collaborators  ICMJE Tesaro, Inc.
Investigators  ICMJE
Principal Investigator: Michelle S Ludwig, MD, MPH, PhD Baylor College of Medicine
PRS Account Baylor College of Medicine
Verification Date April 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP