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Solid TumorPhase 1/2NCT05566574

A Study of RP-3500 in Combination With Standard Radiation Therapy in People With Solid Tumor Cancer

A Phase 1/2 study testing RP-3500 and External Beam Radiotherapy (EBRT) in people with Solid Tumor and Metastatic Cancer, run by Memorial Sloan Kettering Cancer Center at 7 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

The purpose of this study is to test the safety of the study drug, RP-3500 when given in combination with palliative external beam radiotherapy (EBRT) to people who have metastatic solid tumor cancer with a mutation of the ATM gene. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Solid Tumor, Metastatic Cancer
What is being tested?
RP-3500 and External Beam Radiotherapy (EBRT)
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
49 participants
Where
7 sitesUnited States
Study dates
30 Sep 2022to 30 Sep 2026
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

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

  • Histologically confirmed malignancy with at least one metastatic lesion amenable to radiotherapy. Bone, visceral, and soft tissue are eligible.
  • Mutation in ATM (deleterious or VUS; somatic or germline; monoallelic or biallelic)
  • Note: Homozygous Deletion in the ATM gene will also be allowed
  • ECOG performance status 0-2 or KPS equivalent
  • Age ≥18 years
  • Expected survival greater than 6 months
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  • Participant or Legally Authorized Representative (LAR) able to provide written informed consent
  • Patients of reproductive potential must agree to practice an effective contraceptive method
  • Ability to swallow capsules and retain oral medications
  • Acceptable organ function at Screening, as evidenced by the following laboratory data:
  • Serum creatinine ≤1.5 × upper limit of normal (ULN) or calculated creatinine clearance ≥60 mL/min using the Cockcroft-Gault equation or by 24-hour urine collection
  • Total bilirubin ≤1.5 × ULN or <3.0 × ULN if known Gilbert's disease
  • Serum albumin ≥2.5 g/dL
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN unless liver metastases are present and thought to be a reason for AST/ALT elevation, in which case they must be ≤5 × ULN
  • Acceptable hematologic function at Screening:
  • No red blood cell or platelet transfusions or growth factors within 7 days of the first dose of RP-3500
  • Hemoglobin ≥9.5 g/dL
  • ANC ≥1700 cells/mm^3
  • Platelet count ≥130,000 cells/mm^3
  • Resolution of all toxicities of prior therapy or surgical procedures to baseline or Grade 1 (except for neuropathy, hypothyroidism requiring medication and alopecia can be resolved to Grade ≤2)
  • Negative pregnancy test (serum or urine) for women of childbearing potential (WOCBP) at Screening and prior to first study drug. Non-WOCBP is defined as 1) adequate time of amenorrhea for > 12 months plus adequate FSH level or 2) surgically or anatomically infertile
  • Male patients with female partners of childbearing potential and WOCBP must follow a contraception method (oral contraceptives allowed) at least as conservative as Clinical Trial Facilitation Group (CTFG) recommendations during their participation in the study. WOCBP must follow the recommendations until 6 months following last dose of study drug and male patients must follow the recommendations for 6 months following last dose of study drug. Male patients must also refrain from donating sperm during their participation in the study and for 6 months following last dose of study drug

Who cannot join

  • Previous radiotherapy to the intended treatment site
  • Prior therapy with an ATR or DNA-dependent protein kinase (DNA-PK) inhibitor
  • Serious medical co-morbidities precluding radiotherapy
  • Pregnant or breast-feeding women
  • No other concurrent systemic therapy during the entire duration of protocol treatment. Patients can have other systemic treatments up until the start of protocol treatment. Patients can also have other systemic treatments after the completion of protocol treatments
  • Known hypersensitivity to any of the ingredients of RP-3500
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  • Uncontrolled hypertension (systolic blood pressure [BP] ≥160 mmHg; diastolic BP ≥100 mmHg) despite adequate treatment prior to first dose of RP-3500
  • Patients with active, uncontrolled bacterial, fungal, or viral infection, including hepatitis B virus (HBV), hepatitis C virus (HCV), known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness. In equivocal cases, patients whose viral load is negative, may be eligible. HIV seropositive patients who are healthy and low risk for AIDS related outcomes could be considered eligible. Eligibility criteria for HIV positive patients should be evaluated and discussed, and will be based on current and past CD4 and T-cell counts, history (if any) of AIDS-defining conditions (eg, opportunistic infections), and status of HIV treatment
  • Moderate or severe hepatic impairment (ie, Child-Pugh class B or C)
  • History or presence of an abnormal ECG that is clinically significant in the investigator's opinion, including complete left bundle branch block, second- or third-degree heart block, or recent history of myocardial infarction that in the opinion of the investigator will pose an increased risk of rhythm abnormalities
  • History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias such as structural heart disease (eg, severe left ventricular systolic dysfunction, left ventricular hypertrophy), coronary heart disease (symptomatic or with ischemia demonstrated by diagnostic testing), clinically significant electrolyte abnormalities (eg, hypokalemia, hypomagnesemia, hypocalcemia), or family history of sudden unexplained death or long QT syndrome
  • Current treatment with medications that are well-known to prolong the QT interval
  • Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol and/or follow-up procedures outlined in the protocol
  • Patients who are receiving strong CYP3A inhibitors or inducers, P-gp inhibitors and/or BCRP inhibitors
  • Patients with germline homozygous ATM mutations

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

United States7 sites

  • Memorial Sloan Kettering Basking Ridge (Limited Protocol Activites)

    Basking Ridge, New Jersey, 07920

  • Memorial Sloan Kettering Cancer Center at Suffolk-Commack (All Protocol Activities)

    Commack, New York, 11725

  • Memorial Sloan Kettering Westchester (All Protocol Activities)

    Harrison, New York, 10604

  • Memorial Sloan Kettering Monmouth (All Protocol Activities)

    Middletown, New Jersey, 07748

  • Memorial Sloan Kettering Bergen (Limited Protocol Activities)

    Montvale, New Jersey, 07645

  • Memorial Sloan Kettering Cancer Center (All Protocol Activities)

    New York, New York, 10065

  • Memorial Sloan Kettering Nassau (Limited Protocol Activities)

    Uniondale, New York, 11553

Other trials in United States

About this study

Official title: RP-3500 (ATRi) + External Beam Radiotherapy (EBRT) for the Palliative Treatment of Metastatic Disease

The purpose of this study is to test the safety of the study drug, RP-3500 when given in combination with palliative external beam radiotherapy (EBRT) to people who have metastatic solid tumor cancer with a mutation of the ATM gene. The study researchers will do tests to find the highest dose of RP3500 that causes few or mild side effects.

Being tested
RP-3500, External Beam Radiotherapy (EBRT)
Keywords
Palliative treatment, RP-3500 (ATRi), External Beam Radiotherapy (EBRT), 22-222
Medical subject headings
Neoplasm Metastasis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RP-3500Drug

    RP-3500 on Days 1-5.

  • External Beam Radiotherapy (EBRT)Radiation

    Palliative radiation therapy (4Gy x 5 fractions) to a metastatic site on Days 1-5

Study groups in NCT05566574
Study groupRoleWhat they receive
RP-3500 in Combination With Standard Radiation TherapyExperimentalPatients with metastatic cancers with identified mutations in ATM will be enrolled. All patients will receive a standard palliative RT (4Gy x 5 fractions) on Days 1-5 in combination with RP-3500 on Days 1-5. In the first phase of the study, a 3+3 study design will be used to identify a safe dose of RP-3500 (starting at 80 mg QD) in combination with palliative RT.
Receives: Drug: RP-3500; Radiation: External Beam Radiotherapy (EBRT)
Pilot subcohortExperimentalThe primary objective is to assess 6 month local control rate of patients of new metastatic lesions with pathogenic ATM who haves received prior RP-3500 and palliative RT.
Receives: Drug: RP-3500; Radiation: External Beam Radiotherapy (EBRT)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Phase I - Safety and Tolerability of RP-3500 in combination with radiation therapy

    by assessing the grade and frequency of adverse events and serious adverse events. A dose limiting toxicity (DLT) will be graded according to NCI CTCAE v5.0.

    Measured: 2 years

  2. Phase II - Assess 6 month local control rate of patients with pathogenic ATM who received RP-3500 and palliative RT

    Imaging per discretion of treating physician, and may include PET, CT and MRI imaging.

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Oct 2022
  2. Study start30 Sep 2022
  3. Primary completion30 Sep 2026 (estimated)
  4. Study completion30 Sep 2026 (estimated)

Resources

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Parallel groups
Model description
Single arm, phase I/II trial to assess safety and tolerability of RP-3500 and palliative RT.
Masking
None (open label)
Enrolment
49 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05566574
Sponsor's protocol ID
22-222
Status last verified
Dec 2025
First submitted
30 Sep 2022
Last updated
17 Dec 2025
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing RP-3500 and External Beam Radiotherapy (EBRT) in people with Solid Tumor and Metastatic Cancer, run by Memorial Sloan Kettering Cancer Center at 7 sites 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 22 inclusion and 15 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: under way, not looking for participants, as of the sponsor's last update on 17 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

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?

Phase I - Safety and Tolerability of RP-3500 in combination with radiation therapy (time frame: 2 years). 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 NCT05566574.

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 17 Dec 2025.

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