A phase 1 trial to study how safe and tolerable RP-6306 is, alone or in Combination with RP-3500 or Debio 0123, when administered in patients with certain types of cancer
- Conditions
- Advanced solid tumors with CCNE1 amplification or deleteriousmutations in FBXW7 or other proprietary geneMedDRA version: 21.0Level: LLTClassification code: 10049280Term: Solid tumour Class: 10029104Therapeutic area: Diseases [C] - Neoplasms [C04]
- Registration Number
- CTIS2023-510063-35-00
- Lead Sponsor
- Repare Therapeutics USA Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 364
Written informed consent and assent, according to local guidelines, signed and dated by the participating patient or legal guardian prior to the performance of any study-specific procedures, sampling, or analyses., Ability to comply with the protocol and study procedures detailed in the Schedule of Assessments., Ability to swallow and retain tablets and capsules whole and intact., Acceptable organ function at Screening, as evidenced by the following laboratory data: a. For Module 1: Creatinine clearance =60 mL/min calculated using the Cockcroft-Gault equation. For Module 2 and 3: Creatinine clearance =45 mL/min calculated using the Cockcroft-Gault equation or measured by 24-hour urine collection. Module 4: Creatinine clearance =60 mL/min calculated using the Cockcroft-Gault equation or measured by 24-hour urine collection. b. Total bilirubin =1.5 × ULN or <3.0 × ULN if known Gilbert's disease c. Serum albumin =2.5 g/dL d. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =3.0 × ULN or = 5.0 × ULN in the case of presence of liver metastases, Acceptable hematologic function at Screening: a. No red blood cell (RBC) or platelet transfusions or growth factors within 7 days of the first dose of RP-6306 (For Module 1). For Module 2, 3 and 4: No red blood cell (RBC) or platelet transfusions or growth factors within 14 days of the first dose of the study drug b. Hemoglobin =9.0 g/dL, except if anemia is due to potentially reversible and manageable etiology (e.g., bleeding from tumor lesion), after discussion with and approval by the Medical Monitor c. ANC =1500 cells/mm3 d. Platelet count =100,000 cells/mm3, Negative pregnancy test (serum) for women of childbearing potential at Screening and prior to the first dose of study drug.., Male patients with female partners of childbearing potential must follow a contraception method (oral contraceptives allowed) during their participation in the study for 6 months following last dose of 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., Resolution of all toxicities of prior therapy or surgical procedures to baseline or Grade 1 (except for neuropathy, hypothyroidism requiring medication, and alopecia, which must have resolved to Grade =2)., Any prior radiation must have been completed at least 7 days prior to the start of study drugs, and patients must have recovered from any acute adverse effects prior to the start of study treatment., Life expectancy =12 weeks after the start of the treatment according to the investigator's judgment., Additional Inclusion Criteria for Module 1c and module 3: Ability to consume a high-fat meal and fast for 12 hours. Module 1c will only be open to patients =18 years-of-age., Male or female and =12 years-of-age at the time of signature of the informed consent form (ICF). Patients 12 to 17 years-of-age will be enrolled only after at least 4 patients =18 years-of-age have completed 1 cycle of therapy., Lansky performance status =50 for patients =16 years of age, or ECOG score of 0, 1, or 2 (module 1) and for Module 2,3 and 4 ECOG 0 or 1., All patients must have locally advanced or metastatic resistant or refractory solid tumors. Patients <18 years-of-age will be eligible only if standard or available curative therapy does not exist. Patients =18 years-of-age are eligible if, in the opinion of the investigator, the patient is not a candidate for, or woul
Chemotherapy or small molecule antineoplastic agent given within 21 days or <5 half-lives, whichever is shorter, prior to first dose of study drug. For drugs for which 5 half-lives is =21 days, a minimum of 10 days between termination of the prior treatment and administration of study drug treatment is required. For patients with breast or prostate cancer, continuation of long-term luteinizing hormone-releasing hormone (LHRH), gonadotrophin releasing hormone (GnRH), or previously prescribed Receptor Activator of Nuclear Factor kB Ligand (RANKL) inhibitor are allowed if these medications were prescribed for at least 3 months before trial entry. Bisphosphonates are allowed if prescribed at least 28 days prior to enrollment., Patients who are pregnant or breastfeeding., Module 1: Known sensitivity to any of the ingredients of RP-6306. Module 2 and 3: Known hypersensitivity to any of the ingredients of RP-6306 or RP-3500. Module 4: Known hypersensitivity to any of the ingredients of RP-6306 or Debio 0123., Patient who are unable to swallow ablets and capsules whole and intact., Life-threatening illness, medical condition, active uncontrolled infection, or organ system dysfunction (such as ascites requiring drainage within 4 weeks prior to enrollment, coagulopathy, or encephalopathy), or other reasons which, in the investigator's opinion, could compromise the participating patient's safety, or interfere with or compromise the integrity of the study outcomes., Major surgery (excluding placement of vascular access) within 4 weeks prior to first dose of study drug, Additional exclusion criteria for Module 2 and 3: Prior therapy with an ATR, DNA-PK, PKMYT1, or WEE1 inhibitor., Uncontrolled hypertension (systolic blood pressure [BP] =160 mmHg; diastolic BP =100 mmHg) despite adequate treatment prior to first dose of Study drug ., Additional exclusion criteria for Module 4: Prior therapy with a PKMYT1 or WEE1 inhibitor., Additional exclusion criteria for Module 4: Presence of other known second malignancy with the exception of any cancer that has been in complete remission for = 2 years or completely resected squamous and basal cell carcinomas of the skin., Additional exclusion criteria for Module 4: Clinically significant gastrointestinal abnormality that would affect the absorption of drugs, such as malabsorption syndrome, major resection of the small bowel, total gastrectomy, or inflammatory bowel disease., 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 AIDSrelated outcomes could be considered eligible. Eligibility criteria for HIV positive patients should be evaluated and discussed with the sponsor's medical monitor and will be based on current and past CD4 and T-cell counts, history (if any) of AIDS defining conditions (e.g., opportunistic infections), and status of HIV treatment, Additional exclusion criteria for Module 4: Mean resting QT interval corrected for heart rate (QTc) interval using the Fridericia formula (QTcF) >450 msec (as calculated per institutional standards) obtained from 3 ECGs =1 minute apart at study entry., Additional exclusion criteria for Module 4: Patients who are receiving a drug or herbal product that is a m
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method