Safety, Pharmacokinetics and Anti-tumor Activity of RP12146, in Patients With Solid Tumors

Solid Tumor Clinical Trial

Official title:

A Multi-center, Open-label, Phase I/Ib Study to Assess the Safety, Pharmacokinetics and Anti-tumor Activity of RP12146, a Poly (ADP-ribose) Polymerase (PARP) Inhibitor, in Patients With Locally Advanced or Metastatic Solid Tumors

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05002868
• Other study ID #: RP12146-2101
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: October 5, 2021
• Est. completion date: April 30, 2024

Study information

• Verified date: May 2023
• Source: Rhizen Pharmaceuticals SA
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 23
• Est. completion date: April 30, 2024
• Est. primary completion date: April 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Neoplasms
• Extensive-stage Small-cell Lung Cancer
• Hypersensitivity
• Locally Advanced Breast Cancer
• Metastatic Breast Cancer
• Platinum-Sensitive Fallopian Tube Carcinoma
• Platinum-sensitive Ovarian Cancer
• Small Cell Lung Carcinoma
• Solid Tumor

Intervention

Drug:
• RP12146
starting dose of 100 mg QD

Locations

Country	Name	City	State
Czechia	Multiscan s.r.o.	Horovice
Czechia	FN Olomouc, Oncology clinic,	Olomouc
Poland	Klinika Onkologii ICZMP	Lódz
Poland	Pratia Poznan Medical Center	Poznan
Poland	Clinical Trials Site Nasz Lekarz	Torun
Poland	Maria Sklodowska-Curie Memorial National Oncology Institute	Warszawa

Sponsors (1)

Lead Sponsor	Collaborator
Rhizen Pharmaceuticals SA

Countries where clinical trial is conducted

Czechia,  Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose (MTD) of RP12146 in patients with locally advanced or metastatic solid tumors	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	28 days
Primary	Number of Participants With Treatment-emergent Adverse Events as Assessed by CTCAE Criteria v5.0	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.	2 years
Secondary	Tmax	Pharmacokinetics: Time to Reach Maximum Concentration (Tmax) of RP12146	Day 1 to Day 28
Secondary	Cmax	Pharmacokinetics: Maximum Concentration (Cmax) of RP12146	Day 1 to Day 28
Secondary	AUC	Pharmacokinetics: Area Under the Concentration Curve (AUC) of RP12146	Day 1 to Day 28
Secondary	Overall response rate (ORR)	Sum of the percentages of Complete Response and Partial Response	2 years
Secondary	Clinical benefit rate (CBR)	Sum of the percentages of Complete response, partial response and stable disease	2 years
Secondary	Progression free survival (PFS)	It is defined as time from the first dose of study treatment to documented disease progression	2 years