A Safety Study Adding Niraparib and Dostarlimab to Radiation Therapy for Rectal Cancers

NCT04926324 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: 202103459
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

This clinical trial is designed to determine the maximum tolerated dose of niraparib when combined with dostarlimab and hypofractionated radiation for locally advanced rectal cancer. Once this is determined, this dose will be tested to identify what impact it has on the tumor as well as patient reported outcome measures.

Conditions

Rectal Neoplasms; Rectal Neoplasm Malignant

Keywords

niraparib; dostarlimab; radiation therapy; total neoadjuvant therapy

Outcome Measures

Primary Outcomes (2)

• Determination of recommended phase 2 niraparib dose

  The recommended dose will be determined by incidence of dose limiting toxicities.

  From treatment day 1 for up to 16 weeks.

• Determination of the clinical complete response rate

  Clinical evaluation of the tumor by both flexible sigmoidoscopy and pelvic MRI

  8

Secondary Outcomes (8)

• Determine overall survival (OS)

  Time (measured in days) until death from any cause, up to 20 years post-treatment.

• Determine progression free survival (PFS)

  From treatment day 1 to disease progression, up to 15 years post-treatment

• Determine metastasis free survival

  From treatment day 1 to disease progression or death, up to 20 years post-treatment.

• Determine local recurrence free survival

  From treatment day 1 to disease progression or death, up to 20 years post-treatment.

• Determine ostomy free survival

  From treatment day 1 up to 20 years post-treatment.

Study Arms (2)

Cohort 1 (starting)

EXPERIMENTAL

niraparib, 100 mg orally once daily for up to 12 weeks dostarlimab, 500 mg infused (IV) once every 3 weeks for up to 12 weeks radiation therapy, 5 Gray (Gy) per day for 5 consecutive days

Drug: Niraparib; Drug: Dostarlimab; Radiation: Short course radiation

Cohort 2

EXPERIMENTAL

niraparib, 200 mg orally once daily for up to 12 weeks dostarlimab, 500 mg infused (IV) once every 3 weeks for up to 12 weeks radiation therapy, 5 Gray (Gy) per day for 5 consecutive days

Drug: Niraparib; Drug: Dostarlimab; Radiation: Short course radiation

Interventions

Niraparib DRUG

Niraparib is a drug FDA-approved for use in maintenance treatment of adults with advanced ovarian cancer, fallopian tube cancer, or primary peritoneal cancer.

Also known as: Zejula

Cohort 1 (starting); Cohort 2

Dostarlimab DRUG

Dostarlimab, sold under the brand name Jemperli, is a monoclonal antibody medication used for the treatment of endometrial cancer.

Also known as: Jemperli

Cohort 1 (starting); Cohort 2

Short course radiation RADIATION

Participants will be treated with intensity modulated radiation therapy (IMRT) or volumetric modulated arc therapy (VMAT) to minimize mean dose to femoral, pelvic, and lumbar bone marrow. The entire mesorectum will be treated to a total dose of 25 Gy.

Also known as: IMRT, VMAT

Cohort 1 (starting); Cohort 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability to understand and willingness to provide independent informed consent; legally authorized representative consent and/or power-of-attorney is not allowed.
• Age at least 18 years at the time of study drug administration
• Resectable locally advanced rectal cancer (i.e., T3 to T4 or T1-T4 with N1-2 M0).
• Recommended to receive total neoadjuvant therapy consisting of preoperative radiation therapy followed by systemic FOLFOX chemotherapy
• Adequate performance status (ECOG of 0 or 1; or KPS of \>70).
• Agree to adhere to lifestyle considerations throughout study duration
• Agree to not donate blood during the study or for 90 days after the last dose of study treatment.

You may not qualify if:

• Absolute neutrophil count \< 1,500 cells /µL
• Platelets \< 100,000 cells/µL
• Hemoglobin \<9 g/dL
• Serum creatinine \> 1.5 x upper limit of normal (ULN) or calculated creatinine clearance 60mL/min using the Cockcroft-Gault equation
• Total bilirubin \> 1.5 x ULN (\>2.0 x ULN in patients with known Gilberts syndrome) or direct bilirubin \> 1 x ULN
• Aspartate aminotransferase and alanine aminotransferase \> 2.5 x ULN
• International normalized ratio (INR) or prothrombin time (PT) \>1.5× ULN unless patient is receiving anticoagulant therapy as long as PT or partial thromboplastin (PTT) is within therapeutic range of intended use of anticoagulants.
• Activated partial thromboplastin time (aPTT) \>1.5× ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
• Uncontrolled arterial hypertension, i.e. systolic BP \> 140 mmHg, diastolic BP \> 90 mmHg.
• Platelet transfusion ≤ 4 weeks prior to initiating protocol therapy.
• Presence of any M1 metastatic lesions.
• Prior pelvic radiotherapy
• Indication for total neoadjuvant therapy or alternative radiation regimen
• Recommended to receive a chemotherapy regimen other than FOLFOX chemotherapy. CapeOX (oral xeloda plus oxaliplatin) is an acceptable alternative as it contains the core fluoropyrimidine + oxaliplatin backbone.
• Indication for alternative radiation dose or fractionation regimen.

Sponsors & Collaborators

• University of Iowa: lead
• GlaxoSmithKline: collaborator

Study Sites (1)

Holden Comprehensive Cancer Center at the University of Iowa

Iowa City, Iowa, 52242, United States

Location

Related Publications (1)

• Seyedin SN, Hasibuzzaman MM, Pham V, Petronek MS, Callaghan C, Kalen AL, Mapuskar KA, Mott SL, Spitz DR, Allen BG, Caster JM. Combination Therapy with Radiation and PARP Inhibition Enhances Responsiveness to Anti-PD-1 Therapy in Colorectal Tumor Models. Int J Radiat Oncol Biol Phys. 2020 Sep 1;108(1):81-92. doi: 10.1016/j.ijrobp.2020.01.030. Epub 2020 Feb 6.

  PMID: 32036006 BACKGROUND

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

niraparib; dostarlimab

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Kellie Bodeker, Ph.D.

  University of Iowa

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Director of Theranostics Research

Study Record Dates

• First Submitted: June 8, 2021
• First Posted: June 15, 2021
• Study Start: July 7, 2022
• Primary Completion: November 18, 2024
• Study Completion: December 26, 2024
• Last Updated: June 29, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Study protocol and informed consent will be shared after primary completion. Statistical analysis plan will be shared with results reporting.
• Access Criteria: An IRB-stamped signed usage agreement will be required in addition to a data sharing agreement between the academic centers.

Locations

US (1)