Rectal NeoplasmsPhase 1NCT04926324
A Safety Study Adding Niraparib and Dostarlimab to Radiation Therapy for Rectal Cancers
A Phase 1 study testing Niraparib, Dostarlimab and Short course radiation in people with Rectal Neoplasms and Rectal Neoplasm Malignant, run by University of Iowa at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rectal Neoplasms, Rectal Neoplasm Malignant
- What is being tested?
- Niraparib, Dostarlimab and Short course radiation
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Jul 2022to 24 Nov 2025
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 39Show fewer
- 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.
- Active Crohn's disease or another inflammatory bowel disease
- Any T or N stage disease that is deemed unresectable by colorectal surgery without neoadjuvant therapy
- Prior anti-PD-L1 therapy, PARPi therapy, or known germline BRCA-1/2 mutation as patients with germline BRCA-1/2 mutations have an increased risk of severe normal tissue injury to combination radiation and PARP inhibition.
- Received a live vaccine within 14 days of initiating protocol therapy.
- Received colony stimulating factors (e.g., granulocyte colony-stimulating factor, granulocyte macrophage colony stimulating factor, or recombinant erythropoietin) within 4 weeks prior to Day 1 of protocol therapy.
- Major surgery within 3 weeks prior to Day 1 of protocol therapy (participant must recover from any surgical effects).
- 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 Day 1 of protocol therapy.
- Known hypersensitivity to niraparib and dostarlimab components or excipients.
- Known grade 3 or 4 anemia, neutropenia or thrombocytopenia due to prior chemotherapy that persisted > 4 weeks and was related to the most recent treatment.
- Known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML)
- 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 and cervical cancer that has been definitively treated).
- Known history of ≥ grade 3 immune-related AE with prior immunotherapy, with the exception of non-clinically significant lab abnormalities.
- Diagnosis of immunodeficiency or has received systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to initiating protocol therapy.
- Patients with known HIV who have documented detectable viral load or patients with a documented undetectable viral load and a CD 4 count < 350 cells within 6 months of study treatment day
- Known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [qualitative] is detected).
- Active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- History of interstitial lung disease.
- Active or uncontrolled infection necessitating hospitalization or treatment delay.
- Known serious, uncontrolled medical disorder or nonmalignant systemic disease that preclude eligibility to undergo low anterior resection (LAR). Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 90 days) myocardial infarction, uncontrolled major seizure disorder, or any psychiatric disorder that prohibits obtaining informed consent
- Pregnancy. Participant must have a negative serum pregnancy test within 72 hours prior to taking study treatment if of childbearing potential and agrees use a highly effective method of contraception from screening through 180 days after the last dose of niraparib and after the last dose of dostarlimab, or is of nonchildbearing potential. Nonchildbearing potential is defined as follows (by other than medical reasons):
- ≥ 60 years of age
- Post-hysterectomy. Documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by an ultrasound.
- Actively breastfeeding. Participant must agree to not breastfeed during the study or for 8 weeks after the last dose of study treatment.
- Declines to use a highly effective method of contraception (see Section 5.2.1 for a list of acceptable birth control methods). Eligible patients must agree to highly effective methods of contraception starting with the first dose of study treatment through 180 days after the last dose of niraparib and dostarlimab.
Trial locations and contacts
1 site in 1 country.
United States1 site
Holden Comprehensive Cancer Center at the University of Iowa
Iowa City, Iowa, 52242
About this study
Official title: A Phase 1b/2 Trial of Preoperative Niraparib, Dostarlimab, and Hypofractionated Radiotherapy for the Treatment of Locally-advanced Rectal Cancers.
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.
Read the detailed description
Standard of care therapy for resectable locally advanced rectal cancer includes pelvic radiation (short or long course), chemotherapy, and (if indicated) surgery.
In this study, participants will:
- Take niraparib by mouth once daily for up to 12 weeks.
- Receive radiation therapy once daily for five days (Monday through Friday).
- Receive intravenous (IV) dostarlimab once every three weeks for up to 12 weeks.
- Provide feedback about how they feel and their quality of life. This is done through short surveys as well as discussing with the study team.
- Undergo a sigmoidoscopy (i.e. scope of the tumor) and biopsy about halfway through treatment
- Provide tumor tissue and blood samples for analysis
- Conditions
- Rectal Neoplasms, Rectal Neoplasm Malignant
- Being tested
- Niraparib, Dostarlimab, Short course radiation
- Keywords
- niraparib, dostarlimab, radiation therapy, total neoadjuvant therapy
- Medical subject headings
- Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NiraparibDrug
Also called Zejula
Niraparib is a drug FDA-approved for use in maintenance treatment of adults with advanced ovarian cancer, fallopian tube cancer, or primary peritoneal cancer.
DostarlimabDrug
Also called Jemperli
Dostarlimab, sold under the brand name Jemperli, is a monoclonal antibody medication used for the treatment of endometrial cancer.
Short course radiationRadiation
Also called IMRT, VMAT
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.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Drug: Niraparib; Drug: Dostarlimab; Radiation: Short course radiation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determination of recommended phase 2 niraparib dose
The recommended dose will be determined by incidence of dose limiting toxicities.
Measured: 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
Measured: 8
Secondary outcomes (8)
Determine overall survival (OS)
Time from treatment day 1 to death from any cause
Measured: Time (measured in days) until death from any cause, up to 20 years post-treatment.
Determine progression free survival (PFS)
Time (measured in days) to documented disease progression in imaging as described by the RECIST criteria.
Measured: From treatment day 1 to disease progression, up to 15 years post-treatment
Determine metastasis free survival
Time (measured in days) to documented disease progression outside of the pelvis or death from any cause.
Measured: From treatment day 1 to disease progression or death, up to 20 years post-treatment.
Determine local recurrence free survival
Time (measured in days) to disease progression within the pelvis or death from any cause.
Measured: From treatment day 1 to disease progression or death, up to 20 years post-treatment.
Determine ostomy free survival
Time (measured in days) to receipt of permanent ostomy or death from any cause.
Measured: From treatment day 1 up to 20 years post-treatment.
Determine objective response rate
Objective response rate, measured using the standardized RECIST criteria, is a reflection of complete tumor response and partial tumor response. The
Measured: 3 months post-radiation
Determination of the pathologic complete response
Absence of viable tumor in the primary tumor bed and all regional nodes in patients recommended to undergo surgical resection regardless of response to neoadjuvant therapy.
Measured: At surgery; up to 1 year post-treatment
Determination of the organ preservation rate
Organ perservation defined as day 1 therapy to receipt of rectal resection for any reason
Measured: From treatment day 1 up to 15 years post-treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jun 2021
- Study start7 Jul 2022
- Primary completion18 Nov 2024
- Study completion24 Nov 2025
Why it stopped: Toxicity in phase 1
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Rectal NeoplasmsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Iowa
- Sponsor type
- University, hospital or other
- Collaborators
- GlaxoSmithKline
- Responsible party
- Principal investigator, Kellie Bodeker, PhD, University of Iowa
- Investigators
- Joseph Caster, MD, PhD, Principal investigator, Thomas Jefferson University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04926324
- Sponsor's protocol ID
- 202103459
- Status last verified
- Jun 2026
- First submitted
- 8 Jun 2021
- Last updated
- 29 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual researchers should contact the research team for data sharing. A fully executed data usage agreement is required for data sharing. Data are only shared from those participants who provided consent for sharing.
Publications
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.
PubMed 32036006
Study at a glance
From the registry record, last updated by the sponsor on 29 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b/2 Trial of Preoperative Niraparib, Dostarlimab, and Hypofractionated Radiotherapy for the Treatment of Locally-advanced Rectal Cancers.
- ClinicalTrials.gov ID
- NCT04926324
- Acronym / sponsor ID
- 202103459
- Conditions
- Rectal Neoplasms, Rectal Neoplasm Malignant
- Keywords
- niraparib, dostarlimab, radiation therapy, total neoadjuvant therapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Toxicity in phase 1
- Enrolment
- 3 participants (actual)
- Lead sponsor
- University of IowaUniversity, hospital or other
- Collaborators
- GlaxoSmithKline
- Study start
- 7 Jul 2022 (actual)
- Primary completion
- 18 Nov 2024 (actual)
- Study completion
- 24 Nov 2025 (actual)
- First posted
- 15 Jun 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Standard of care therapy for resectable locally advanced rectal cancer includes pelvic radiation (short or long course), chemotherapy, and (if indicated) surgery.
In this study, participants will:
- Take niraparib by mouth once daily for up to 12 weeks.
- Receive radiation therapy once daily for five days (Monday through Friday).
- Receive intravenous (IV) dostarlimab once every three weeks for up to 12 weeks.
- Provide feedback about how they feel and their quality of life. This is done through short surveys as well as discussing with the study team.
- Undergo a sigmoidoscopy (i.e. scope of the tumor) and biopsy about halfway through treatment
- Provide tumor tissue and blood samples for analysis
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 (starting) | Experimental | Drug: Niraparib, Drug: Dostarlimab, Radiation: Short course radiationniraparib, 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 |
| Cohort 2 | Experimental | Drug: Niraparib, Drug: Dostarlimab, Radiation: Short course radiationniraparib, 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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).
Key exclusion criteria (39 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NiraparibAlso: ZejulaNiraparib is a drug FDA-approved for use in maintenance treatment of adults with advanced ovarian cancer, fallopian tube cancer, or primary peritoneal cancer. | Drug | Cohort 1 (starting), Cohort 2 |
| DostarlimabAlso: JemperliDostarlimab, sold under the brand name Jemperli, is a monoclonal antibody medication used for the treatment of endometrial cancer. | Drug | Cohort 1 (starting), Cohort 2 |
| Short course radiationAlso: IMRT, VMATParticipants 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. | Radiation | Cohort 1 (starting), Cohort 2 |
Primary outcome
Determination of recommended phase 2 niraparib dose
Time frame: From treatment day 1 for up to 16 weeks.
The recommended dose will be determined by incidence of dose limiting toxicities.
Determination of the clinical complete response rate
Time frame: 8
Clinical evaluation of the tumor by both flexible sigmoidoscopy and pelvic MRI
8 secondary outcomes
Determine overall survival (OS)
Time frame: Time (measured in days) until death from any cause, up to 20 years post-treatment.
Determine progression free survival (PFS)
Time frame: From treatment day 1 to disease progression, up to 15 years post-treatment
Determine metastasis free survival
Time frame: From treatment day 1 to disease progression or death, up to 20 years post-treatment.
Determine local recurrence free survival
Time frame: From treatment day 1 to disease progression or death, up to 20 years post-treatment.
Determine ostomy free survival
Time frame: From treatment day 1 up to 20 years post-treatment.
Determine objective response rate
Time frame: 3 months post-radiation
Determination of the pathologic complete response
Time frame: At surgery; up to 1 year post-treatment
Determination of the organ preservation rate
Time frame: From treatment day 1 up to 15 years post-treatment
Results and safety
The study was stopped early (reason given: Toxicity in phase 1). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jun 2026.
- Background: PubMed 32036006Seyedin 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.
- Individual participant dataSharing planned: Yes. Individual researchers should contact the research team for data sharing. A fully executed data usage agreement is required for data sharing. Data are only shared from those participants who provided consent for sharing.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Joseph Caster, MD, PhD principal investigator
Thomas Jefferson University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Niraparib, Dostarlimab and Short course radiation in people with Rectal Neoplasms and Rectal Neoplasm Malignant, run by University of Iowa at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 39 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 29 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Toxicity in phase 1). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Determination of recommended phase 2 niraparib dose (time frame: From treatment day 1 for up to 16 weeks.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04926324, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jun 2026.