Extensive-stage Small-cell Lung Cancer, Locally Advanced Breast Cancer, Metastatic Breast Cancer, Platinum-Sensitive Fallopian Tube Carcinoma, Platinum-sensitive Ovarian Cancer, Platinum-Sensitive Peritoneal Cancer, Solid Tumor
Conditions
Keywords
PARP
Brief summary
An open-label, two-part Phase I/Ib study of RP12146 in adult patients with locally advanced or metastatic solid tumors. The first part (Part 1) is a Phase I dose-escalation, 3+3 design, open-label, MTD determination study and will enroll patients who have tumors known to harbour DNA repair deficiencies. The second part (Part 2) is a Phase Ib, dose-expansion at the MTD (or optimal dose) and will enroll patients with a confirmed deleterious HRR mutation in their tumor as identified by a central genomics testing laboratory.
Interventions
DRUGRP12146
starting dose of 100 mg QD
Sponsors
Rhizen Pharmaceuticals SA
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
. 1. Provision of full informed consent prior to any study-specific procedures. 2. Patients must be ≥18 years of age, at the time of signing informed consent. 3. Dose escalation phase, patients with histologically and/or cytologically confirmed malignant solid tumor whose disease has progressed following at least one standard therapy and who have no other acceptable standard treatment options. Tumor types will include breast, ovarian, fallopian tube, or peritoneal cancer, extensive-stage small cell lung cancer (ES-SCLC), prostate, pancreatic, colorectal gastric, biliary tract, and endometrial cancer. 4. Dose-expansion phase patients with histologically and/or cytologically confirmed malignant solid tumor (breast, ovarian, fallopian tube, or peritoneal cancer, extensive-stage small cell lung cancer (ES-SCLC), with one of the documented deleterious mutations of specified HRR genes and whose disease has progressed following at least one standard therapy. 5. Patients with at least one measurable lesion per RECIST version 1.1 at baseline that can be accurately assessed by CT-scan or MRI and is suitable for repeated assessment at follow up-visits. 6. ECOG performance status 0 to 2. 7. Use of contraception measures
Exclusion criteria
1. Patients with HER2 positive breast cancer 2. Patients receiving anticancer therapy 3. Patient who has not recovered from acute toxicities of previous therapy except treatment-related alopecia. 4. Prior treatment with a PARP inhibitor 5. Major surgery within 4 weeks of starting study treatment or any patient who has not recovered from the effects of major surgery. 6. Patient with symptomatic uncontrolled brain metastasis. 7. Pregnancy and lactation 8. Patients with uncontrolled disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum tolerated dose (MTD) of RP12146 in patients with locally advanced or metastatic solid tumors | 28 days | The MTD was defined as the highest dose level at which no more than 1 in 6 participants experienced a dose-limiting toxicity (DLT) during the first 28-day cycle of treatment |
| Number of Participants With Treatment-emergent Adverse Events as Assessed by CTCAE Criteria v5.0 | 2 years | Summary of Treatment-Emergent Adverse Events-(Causality All). Patients will be monitored for adverse events and both related and as well as non-related adverse events will be captured during the study. All adverse events (irrespective of causality) will be reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUC | Day 1 to Day 28 | Pharmacokinetics: Area Under the Concentration Curve (AUC) of RP12146 |
| Overall response rate (ORR) | 2 years | Sum of the percentages of Complete Response and Partial Response |
| Tmax | Day 1 to Day 28 | Pharmacokinetics: Time to Reach Maximum Concentration (Tmax) of RP12146 |
| Progression free survival (PFS) | 2 years | It is defined as time from the first dose of study treatment to documented disease progression |
| Clinical benefit rate (CBR) | 2 years | Sum of the percentages of Complete response, partial response and stable disease |
| Cmax | Day 1 to Day 28 | Pharmacokinetics: Maximum Concentration (Cmax) of RP12146 |
Countries
Czechia, Poland
Outcome results
None listed