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

Solid Tumor Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05566574
• Other study ID #: 22-222
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: September 30, 2022
• Est. completion date: September 30, 2025

Study information

• Verified date: March 2024
• Source: Memorial Sloan Kettering Cancer Center
• Contact: Nancy Lee, MD
• Phone: 212-639-3341
• Email: leen2[@]mskcc.org
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. The study researchers will do tests to find the highest dose of RP3500 that causes few or mild side effects.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 74
• Est. completion date: September 30, 2025
• Est. primary completion date: September 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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)
• ECOG performance status 0-2
• Age =18 years
• Expected survival greater than 6 months
• 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:

1. 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

2. Total bilirubin =1.5 × ULN or <3.0 × ULN if known Gilbert's disease

3. Serum albumin =2.5 g/dL

4. 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:

1. No red blood cell or platelet transfusions or growth factors within 7 days of the first dose of RP-3500

2. Hemoglobin =9.5 g/dL

3. ANC =1700 cells/mm^3

4. 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 7 months following last dose of study drug and male patients must follow the recommendations for 4 months following last dose of study drug. Male patients must also refrain from donating sperm during their participation in the study and for 4 months following last dose of study drug

Exclusion Criteria:

• 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
• 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

Related Conditions & MeSH terms

• Metastatic Cancer
• Neoplasm Metastasis
• Solid Tumor

Intervention

Drug:
• RP-3500
RP-3500 on Days 1-5.

Radiation:
• External Beam Radiotherapy (EBRT)
Palliative radiation therapy (4Gy x 5 fractions) to a metastatic site on Days 1-5

Locations

Country	Name	City	State
United States	Memorial Sloan Kettering Basking Ridge (Limited Protocol Activites)	Basking Ridge	New Jersey
United States	Memorial Sloan Kettering Cancer Center at Suffolk-Commack (All Protocol Activities)	Commack	New York
United States	Memorial Sloan Kettering Westchester (All Protocol Activities)	Harrison	New York
United States	Memorial Sloan Kettering Monmouth (All Protocol Activities)	Middletown	New Jersey
United States	Memorial Sloan Kettering Bergen (Limited Protocol Activities)	Montvale	New Jersey
United States	Memorial Sloan Kettering Cancer Center (All Protocol Activities)	New York	New York
United States	Memorial Sloan Kettering Nassau (Limited Protocol Activities)	Uniondale	New York

Sponsors (2)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center	Repare Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	2 years
Primary	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.	2 years

External Links

•   Memorial Sloan Kettering Cancer Center