Clinical trial NCT05002868: Safety, Pharmacokinetics and Anti-tumor Activity of RP12146, in Patients With Solid Tumors
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumor
Extensive-stage Small-cell Lung Cancer
Locally Advanced Breast Cancer
Metastatic Breast Cancer
Platinum-sensitive Ovarian Cancer
Platinum-Sensitive Fallopian Tube Carcinoma
Platinum-Sensitive Peritoneal Cancer
Keywords: PARP
Lead sponsor: Rhizen Pharmaceuticals SA
Sponsor class: INDUSTRY
First posted: 2021-08-12
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Maximum tolerated dose (MTD) of RP12146 in patients with locally advanced or metastatic solid tumors
timeFrame: 28 days
measure: Number of Participants With Treatment-emergent Adverse Events as Assessed by CTCAE Criteria v5.0
timeFrame: 2 years
Secondary outcomes:
measure: Tmax
timeFrame: Day 1 to Day 28
measure: Cmax
timeFrame: Day 1 to Day 28
measure: AUC
timeFrame: Day 1 to Day 28
measure: Overall response rate (ORR)
timeFrame: 2 years
measure: Clinical benefit rate (CBR)
timeFrame: 2 years
measure: Progression free survival (PFS)
timeFrame: 2 years
Other outcomes:
Locations:
city: Hořovice
country: Czechia
facility: Multiscan s.r.o.
city: Kraków
country: Poland
facility: SP ZOZ University Hospital in Krakow Oncology Clinic, 50 Kopernika Street
city: Poznań
country: Poland
facility: Pratia Poznań Medical Center
city: Toruń
country: Poland
facility: Clinical Trials Site Nasz Lekarz
city: Warszawa
country: Poland
facility: Maria Skłodowska-Curie Memorial National Oncology Institute
city: Łódź
country: Poland
facility: Klinika Onkologii ICZMP
Study officials:
References: