Niraparib Plus Radiotherapy Explored in Metastatic Cervical Cancer

Michelle S. Ludwig, MD, MPH, PhD, an assistant professor of radiation Oncology at Baylor College of Medicine

Michelle S. Ludwig, MD, MPH, PhD

Investigators are exploring concurrent PARP inhibition and definitive regional radiotherapy in patients with metastatic invasive cervical cancer in an ongoing phase I/II study (NCT03644342).^1,2

In the open-label trial, which launched on July 15, 2019, and is currently recruiting patients, women will receive 3 to 6 cycles of induction chemotherapy with carboplatin and paclitaxel followed by niraparib (Zejula) and definitive pelvic radiotherapy. The primary objective of the trial is to determine the maximum-tolerated dose of niraparib when given concurrently with radiotherapy and to evaluate the safety, tolerability, and early efficacy of the regimen.

There is currently no standard-of-care treatment for patients with metastatic cervical cancer, said lead study author, Michelle S. Ludwig, MD, MPH, PhD, an assistant professor of radiation Oncology at Baylor College of Medicine, in an interview with OncLive, and the toxicities of concurrent cisplatin and radiation can be prohibitive for patients.

“Platinum-based chemotherapy is considered the gold standard for concurrent chemosensitization; however, the addition of cisplatin-based chemotherapy increases the incidence of acute hematological and gastrointestinal toxicities that not infrequently preclude completion of standard-of-care chemoradiation,” said Ludwig.

To be eligible for enrollment on the trial, patients ≥18 years of age must have stage IV cervical cancer, an ECOG performance status of ≤1, adequate organ function, and have achieved a complete or partial response (PR) to 3 to 6 cycles of carboplatin and paclitaxel within 4 to 12 weeks of starting study treatment.

“The fundamental hypothesis of this proposal is that niraparib can be effectively used to sensitize invasive cervical cancers to radiotherapy,” said Ludwig.

Investigators hope to accrue 20 patients to the trial. Patients will receive niraparib at a daily dose of 100 mg and 200 mg with concurrent radiotherapy for a duration of 8 weeks. Upon completion, patients’ tumors will be measured for response every 3 months for up to 5 years.

The maximum-tolerated dose of niraparib and local progression-free survival among patients who received ≥1 dose of niraparib with pelvic radiation will serve as the coprimary endpoints of the trial. Secondary endpoints will include the acute toxicity profile of niraparib, quality of life as assessed by the Functional Assessment of Cancer Therapy-Cervix questionnaire, and tumor response.

The study, which has completed enrollment at Baylor College of Medicine and is currently recruiting to the Smith Clinic at Harris Health System, has an estimated completion date of March 2, 2026.

“Cervical cancer is a disease more common in medically underserved patients who have less access to screening and vaccination, and less access to clinical trials. The newest cancer treatments are often only available to patients of higher socioeconomic status,” said Ludwig. “We are excited to bring access to clinical trials to improve the care of the medically underserved patients in Harris County, as we have one of the highest volume centers in the country for this patient population of advanced cervical cancer.”

Niraparib, an oral targeted therapy, has demonstrated benefit in breast and ovarian cancers and is indicated for use as maintenance therapy in adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete response or PR to platinum-based chemotherapy. In October 2019, niraparib was also approved for use in patients with advanced ovarian, fallopian tube, or primary peritoneal cancer who have been treated with ≥3 prior chemotherapy regimens, and whose cancer is associated with homologous recombination deficiency—positive status.

References

1. Baylor recruiting participants for cervical cancer clinical trial [news release]: Houston, TX. Baylor College of Medicine. Published January 29, 2020. https://bit.ly/38HyjEw. Accessed February 11, 2020.
2. Study of Niraparib With Radiotherapy for Treatment of Metastatic Invasive Carcinoma of the Cervix (NIVIX). https://clinicaltrials.gov/ct2/show/results/NCT03644342?view=results. Updated August 23, 2018. Updated December 5, 2019. Accessed February 11, 2020.