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Niraparib + Dostarlimab + Radiation for Rectal Cancer (TOPAZ Trial)

Phase 1 & 2

Waitlist Available

Led By Joseph M. Caster, M.D., Ph.D.

Research Sponsored by Joseph Caster, Ph.D., M.D.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Resectable locally advanced rectal cancer (i.e., T3 to T4 or T1-T4 with N1-2 M0)

Age at least 18 years at the time of study drug administration

Must not have

Received a live vaccine within 14 days of initiating protocol therapy

Prior pelvic radiotherapy

Timeline

Screening 3 weeks

Treatment Varies

Follow Up at surgery; up to 1 year post-treatment

Awards & highlights

No Placebo-Only Group

Summary

This trial is designed to find the best dose of niraparib to combine with dostarlimab and hypofractionated radiation for locally advanced rectal cancer, and to see what effect this has on the tumor and patient reported outcome measures.

Who is the study for?

Adults at least 18 years old with resectable locally advanced rectal cancer (T3 to T4 or N1-2 M0) who can consent, have an adequate performance status, and are recommended for preoperative radiation therapy. Participants must not donate blood during the study and agree to lifestyle considerations. Exclusions include certain blood count levels, liver function abnormalities, uncontrolled hypertension, recent major surgery or vaccines, other cancer treatments within specific timeframes, known hypersensitivities or severe reactions to similar drugs.

What is being tested?

The trial is testing the highest dose of niraparib that's safe when given with dostarlimab and short course radiation in patients with rectal cancer. It aims to find out how this combination affects both tumor response and patient-reported outcomes.

What are the potential side effects?

Potential side effects may include fatigue, nausea, low blood cell counts leading to increased infection risk or bleeding problems; heartburn; changes in liver function tests; allergic reactions; high blood pressure; and possibly others as it's a safety study.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My rectal cancer is advanced but can be surgically removed.

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I am 18 years old or older.

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I am mostly active and can carry out daily activities.

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I am advised to undergo radiation therapy before surgery.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have not received a live vaccine in the last 14 days.

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I have had radiation therapy to my pelvic area before.

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I have not had a platelet transfusion in the last 4 weeks.

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I haven't needed systemic treatment for an autoimmune disease in the last 2 years.

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I have active Crohn's disease or another type of inflammatory bowel disease.

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My colorectal cancer cannot be surgically removed without prior treatment.

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I have a history of lung scarring or fibrosis.

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I do not have any serious health issues that would prevent me from having a specific type of surgery.

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I have not had major surgery in the last 3 weeks.

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My cancer has spread to distant parts of my body.

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I am recommended to have intensive therapy before surgery.

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I do not have any serious infections that required hospital stay or delayed treatment.

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I haven't had treatment for another cancer type, except skin or treated cervical cancer, in the last 2 years.

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My kidney function is within the normal range.

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I have a history of MDS or AML.

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I have had anti-PD-L1 or PARPi therapy, or I have a BRCA-1/2 gene mutation.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ at surgery; up to 1 year post-treatment

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~at surgery; up to 1 year post-treatment

This trial's timeline: 3 weeks for screening, Varies for treatment, and at surgery; up to 1 year post-treatment for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Determination of recommended phase 2 niraparib dose

Determination of the clinical complete response rate

Secondary study objectives

Determination of the organ preservation rate

Determination of the pathologic complete response

Determine local recurrence free survival

+5 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: Cohort 2Experimental Treatment3 Interventions

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

Group II: Cohort 1 (starting)Experimental Treatment3 Interventions

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

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Niraparib

2018

Completed Phase 4

~2400

Dostarlimab

2020

Completed Phase 3

~1760