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Safety, Pharmacokinetics and Anti-tumor Activity of RP12146, a PARP Inhibitor, in Patients With Locally Advanced or Metastatic Solid Tumors

Primary Purpose

Solid Tumor, Extensive-stage Small-cell Lung Cancer, Locally Advanced Breast Cancer

Status
Active
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
RP12146
Sponsored by
Rhizen Pharmaceuticals SA
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Solid Tumor focused on measuring PARP

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Multiscan s.r.o.
  • FN Olomouc, Oncology clinic,
  • Pratia Poznań Medical Center
  • Clinical Trials Site Nasz Lekarz
  • Maria Skłodowska-Curie Memorial National Oncology Institute
  • Klinika Onkologii ICZMP

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

RP12146

Arm Description

RP12146 will be administered orally daily (QD or BID)

Outcomes

Primary Outcome Measures

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
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.

Secondary Outcome Measures

Tmax
Pharmacokinetics: Time to Reach Maximum Concentration (Tmax) of RP12146
Cmax
Pharmacokinetics: Maximum Concentration (Cmax) of RP12146
AUC
Pharmacokinetics: Area Under the Concentration Curve (AUC) of RP12146
Overall response rate (ORR)
Sum of the percentages of Complete Response and Partial Response
Clinical benefit rate (CBR)
Sum of the percentages of Complete response, partial response and stable disease
Progression free survival (PFS)
It is defined as time from the first dose of study treatment to documented disease progression

Full Information

First Posted
August 5, 2021
Last Updated
May 30, 2023
Sponsor
Rhizen Pharmaceuticals SA
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1. Study Identification

Unique Protocol Identification Number
NCT05002868
Brief Title
Safety, Pharmacokinetics and Anti-tumor Activity of RP12146, a PARP Inhibitor, in Patients With Locally Advanced or Metastatic 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

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
October 5, 2021 (Actual)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
February 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Rhizen Pharmaceuticals SA

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
23 (Actual)

8. Arms, Groups, and Interventions

Arm Title
RP12146
Arm Type
Experimental
Arm Description
RP12146 will be administered orally daily (QD or BID)
Intervention Type
Drug
Intervention Name(s)
RP12146
Intervention Description
starting dose of 100 mg QD
Primary Outcome Measure Information:
Title
Maximum tolerated dose (MTD) of RP12146 in patients with locally advanced or metastatic solid tumors
Description
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
Time Frame
28 days
Title
Number of Participants With Treatment-emergent Adverse Events as Assessed by CTCAE Criteria v5.0
Description
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.
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Tmax
Description
Pharmacokinetics: Time to Reach Maximum Concentration (Tmax) of RP12146
Time Frame
Day 1 to Day 28
Title
Cmax
Description
Pharmacokinetics: Maximum Concentration (Cmax) of RP12146
Time Frame
Day 1 to Day 28
Title
AUC
Description
Pharmacokinetics: Area Under the Concentration Curve (AUC) of RP12146
Time Frame
Day 1 to Day 28
Title
Overall response rate (ORR)
Description
Sum of the percentages of Complete Response and Partial Response
Time Frame
2 years
Title
Clinical benefit rate (CBR)
Description
Sum of the percentages of Complete response, partial response and stable disease
Time Frame
2 years
Title
Progression free survival (PFS)
Description
It is defined as time from the first dose of study treatment to documented disease progression
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria. Provision of full informed consent prior to any study-specific procedures. Patients must be ≥18 years of age, at the time of signing informed consent. 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. 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. 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. ECOG performance status 0 to 2. Use of contraception measures Exclusion Criteria: Patients with HER2 positive breast cancer Patients receiving anticancer therapy Patient who has not recovered from acute toxicities of previous therapy except treatment-related alopecia. Prior treatment with a PARP inhibitor Major surgery within 4 weeks of starting study treatment or any patient who has not recovered from the effects of major surgery. Patient with symptomatic uncontrolled brain metastasis. Pregnancy and lactation Patients with uncontrolled disease
Facility Information:
Facility Name
Multiscan s.r.o.
City
Hořovice
ZIP/Postal Code
268 31
Country
Czechia
Facility Name
FN Olomouc, Oncology clinic,
City
Olomouc
ZIP/Postal Code
779 00
Country
Czechia
Facility Name
Pratia Poznań Medical Center
City
Poznań
Country
Poland
Facility Name
Clinical Trials Site Nasz Lekarz
City
Toruń
Country
Poland
Facility Name
Maria Skłodowska-Curie Memorial National Oncology Institute
City
Warszawa
Country
Poland
Facility Name
Klinika Onkologii ICZMP
City
Łódź
ZIP/Postal Code
93-338
Country
Poland

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Safety, Pharmacokinetics and Anti-tumor Activity of RP12146, a PARP Inhibitor, in Patients With Locally Advanced or Metastatic Solid Tumors

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