Back to resultsA Study to Determine the Safety of BTP-114 for Treatment in Patients With Advanced Solid Tumors With BRCA Mutations
Primary Purpose
Pancreatic Neoplasms, Ovarian Neoplasms, Breast Neoplasms
Status
Unknown status
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
BTP-114
Sponsored by
About this trial
This is an interventional treatment trial for Pancreatic Neoplasms focused on measuring BRCA, BRCA1, BRCA2, Pancreatic cancer, Ovarian cancer, Castrate resistant prostate cancer, Triple negative breast cancer, Breast cancer, DNA repair mutation-positive solid tumors
Eligibility Criteria
INCLUSION:
All Patients
- Male or female aged ≥18 years.
- ECOG PS score of 0-1.
- Adequate organ function.
- Ability to understand and willingness to sign informed consent form prior to initiation of study procedures.
- Measurable disease per RECIST, OR for patients with a primary diagnosis of castration resistant prostate cancer, progressive disease (PD) by prostate surface antigen (PSA) or imaging in the setting of medical or surgical castration.
Documented BRCA mutation, with the following exceptions: a) Patient is intended to be enrolled in a Single-patient Cohort; b) Patient has an advanced DNA repair mutation-positive solid tumor and is intended to be enrolled in Expansion Cohort 5.
Patients in the Dose-escalation Phase:
- Locally advanced solid tumor other than a primary central nervous system (CNS) tumor for which the patient has received ≤3 prior lines
Confirmed solid tumor in one of the following categories:
- BRCA mutation-positive pancreatic cancer for which the patient received up to 1 prior line of cytotoxic chemotherapy in the advanced disease setting.
- Advanced BRCA mutation-positive castration-resistant prostate cancer (CRPC) for which the patient received up to 2 prior lines of cytotoxic chemotherapy in the advanced disease setting.
- Advanced BRCA mutation-positive ovarian cancer for which the patient received up to 3 prior lines of cytotoxic chemotherapy in the advanced disease setting.
- Advanced BRCA mutation-positive triple-negative breast cancer (TNBC) for which the patient received up to 3 prior lines of cytotoxic chemotherapy in the advanced disease setting.
- Advanced DNA repair mutation-positive solid tumors, including, but not limited to BRCA and non-BRCA DNA mutations, who have received up to 3 prior lines of cytotoxic chemotherapy in the advanced disease setting. DNA-repair mutations may include, but are not limited to ATM, CHEK2, PALB2, and RAD51D. Abnormal homologous repair deficiency (HRD) tests will also be allowed.
Note that in both dose escalation and dose expansion portions of the study, prior targeted therapy including prior poly ADP ribose polymerase (PARP) inhibitor therapy, prior immunotherapy, or prior hormonal therapy is permissible. Patients with castration resistant prostate cancer may have received unlimited prior hormonal therapies.
EXCLUSION:
- History of leptomeningeal disease or spinal cord compression.
- Underwent major surgery within 4 weeks before first treatment.
- Received cancer-directed therapy 14 days (6 weeks for mitomycin C and nitrosoureas) before start of treatment.
- Grade 2 or greater peripheral neuropathy at start of treatment.
- If female, pregnant or breast-feeding.
- Known human immunodeficiency virus (HIV) infection or hepatitis B or C infection
- Any primary brain tumor (e.g., astrocytoma, glioblastoma).
- Hypersensitivity or history of anaphylactic reaction to any platinum-containing agents.
Sites / Locations
- Placon Therapeutics Clinical Trial Site
- Placon Therapeutics Clinical Trial Site
- Placon Therapeutics Clinical Trial Site
- Placon Therapeutics Clinical Trial Site
- Placon Therapeutics Clinical Trial Site
- Placon Therapeutics Clinical Trial Site
- Placon Therapeutics Clinical Trial Site
- Placon Therapeutics Clinical Trial Site
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
BTP-114
Arm Description
Intravenous (IV) treatment n 21-day cycles
Outcomes
Primary Outcome Measures
Part 1 - Maximum tolerated dose (MTD) of BTP-114 determined during the dose escalation phase of study based on number of patients experiencing a dose-limiting toxicity.
Part 1 - Recommended Phase 2 Dose (RP2D) of BTP-114 based on the MTD, review of adverse event data and review of AUC, Tmax and t1/2 obtained from PK data during the dose escalation phase of the study.
Part 1 - Number of patients experiencing treatment-related adverse events as assessed by CTCAE v4.3 during the study.
Part 2 - Proportion of patients with an objective response (ORR) using the Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1 or the Prostate Cancer Clinical Trials Working Group 2 (PCWG2) criteria.
Part 2 - Proportion of patients whose disease is controlled (DCR) using RECIST, Version 1.1 or PCWG2 criteria.
Part 2 - Duration of response (DOR) measured from the date of first CR or PR until the first date of progressive disease or death from any cause.
Part 2 - Progression-free survival (PFS) measured as the time from the date of initiation of BTP-114 treatment to the documented disease progression (PD) or death from any cause.
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02950064
Brief Title
A Study to Determine the Safety of BTP-114 for Treatment in Patients With Advanced Solid Tumors With BRCA Mutations
Official Title
Escalation Study of BTP-114 in Patients With Advanced Solid Tumors and BRCA or DNA Repair Mutation
Study Type
Interventional
2. Study Status
Record Verification Date
January 2019
Overall Recruitment Status
Unknown status
Study Start Date
September 2016 (undefined)
Primary Completion Date
April 2020 (Anticipated)
Study Completion Date
August 2020 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Placon Therapeutics
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a phase 1, Open-label, multicenter Dose Escalation study of BTP-114, a novel platinum product, in patients with advanced solid tumors and BRCA or other DNA repair mutation. This clinical study is comprised of 2 sequential parts: Part 1 (Dose Escalation) and Part 2 (Expansion). The purpose of this study is to evaluate the safety, pharmacokinetics and the anti-cancer activity of BTP-114.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pancreatic Neoplasms, Ovarian Neoplasms, Breast Neoplasms, Prostatic Neoplasms
Keywords
BRCA, BRCA1, BRCA2, Pancreatic cancer, Ovarian cancer, Castrate resistant prostate cancer, Triple negative breast cancer, Breast cancer, DNA repair mutation-positive solid tumors
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
95 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
BTP-114
Arm Type
Experimental
Arm Description
Intravenous (IV) treatment n 21-day cycles
Intervention Type
Drug
Intervention Name(s)
BTP-114
Intervention Description
Part 1 (Escalation) IV treatment of BTP-114 in 21-day cycles. Doses will be increased in sequential cohorts until the maximum tolerated dose is determined which will lead to the recommended phase 2 dose
Part 2 (Expansion) 5 cohorts of patients will be treated at the RP2D of IV BTP-114 in 21-day cycles for the tumor types pancreatic cancer, castration-resistant prostate cancer, ovarian cancer, triple-negative breast cancer and deoxyribonucleic acid (DNA) repair mutation-positive advanced solid tumors.
Primary Outcome Measure Information:
Title
Part 1 - Maximum tolerated dose (MTD) of BTP-114 determined during the dose escalation phase of study based on number of patients experiencing a dose-limiting toxicity.
Time Frame
From the date of the first dose up to approximately 52 weeks.
Title
Part 1 - Recommended Phase 2 Dose (RP2D) of BTP-114 based on the MTD, review of adverse event data and review of AUC, Tmax and t1/2 obtained from PK data during the dose escalation phase of the study.
Time Frame
From the date of the first dose up to approximately 52 weeks.
Title
Part 1 - Number of patients experiencing treatment-related adverse events as assessed by CTCAE v4.3 during the study.
Time Frame
From the date of first dose up to approximately 52 weeks.
Title
Part 2 - Proportion of patients with an objective response (ORR) using the Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1 or the Prostate Cancer Clinical Trials Working Group 2 (PCWG2) criteria.
Time Frame
From the date of the first dose to documented disease progression assessed up to approximately 52 weeks.
Title
Part 2 - Proportion of patients whose disease is controlled (DCR) using RECIST, Version 1.1 or PCWG2 criteria.
Time Frame
From the date of the first dose to documented disease progression assessed up to approximately 52 weeks.
Title
Part 2 - Duration of response (DOR) measured from the date of first CR or PR until the first date of progressive disease or death from any cause.
Time Frame
Assessed up to approximately 52 weeks.
Title
Part 2 - Progression-free survival (PFS) measured as the time from the date of initiation of BTP-114 treatment to the documented disease progression (PD) or death from any cause.
Time Frame
Assessed up to approximately 52 weeks.
Other Pre-specified Outcome Measures:
Title
Part 1 - Proportion of patients with an objective response (ORR) using the Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1 or the Prostate Cancer Clinical Trials Working Group 2 (PCWG2) criteria.
Time Frame
From the date of the first dose to documented disease progression assessed up to approximately 52 weeks.
Title
Part 1 - Proportion of patients whose disease is controlled (DCR) using RECIST, Version 1.1 or PCWG2 criteria.
Time Frame
From the date of the first dose to documented disease progression assessed up to approximately 52 weeks.
Title
Part 1 - Duration of response (DOR) measured from the date of first CR or PR until the first date of progressive disease or death from any cause.
Time Frame
Assessed up to approximately 52 weeks.
Title
Part 1 - Progression-free survival (PFS) measured as the time from the date of initiation of BTP-114 treatment to the documented disease progression (PD) or death from any cause.
Time Frame
Assessed up to approximately 52 weeks.
Title
Part 1 - Plasma Pharmacokinetics (PK) estimates of platinum concentration, Area under plasma Concentration (AUC) 0 to t.
Time Frame
Time points on Day 1, Day 3 or Day 4, Day 15 of Cycle 1 and Day 1 of subsequent cycles.
Title
Part 1 - Plasma Pharmacokinetics (PK) estimates of platinum concentration, time of Maximum concentration (Tmax).
Time Frame
Time points on Day 1, Day 3 or Day 4, Day 15 of Cycle 1 and Day 1 of subsequent cycles.
Title
Part 1 - Plasma Pharmacokinetics (PK) estimates of platinum concentration Half-life (T1/2).
Time Frame
Time points on Day 1, Day 3 or Day 4, Day 15 of Cycle 1 and Day 1 of subsequent cycles
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
INCLUSION:
All Patients
Male or female aged ≥18 years.
ECOG PS score of 0-1.
Adequate organ function.
Ability to understand and willingness to sign informed consent form prior to initiation of study procedures.
Measurable disease per RECIST, OR for patients with a primary diagnosis of castration resistant prostate cancer, progressive disease (PD) by prostate surface antigen (PSA) or imaging in the setting of medical or surgical castration.
Documented BRCA mutation, with the following exceptions: a) Patient is intended to be enrolled in a Single-patient Cohort; b) Patient has an advanced DNA repair mutation-positive solid tumor and is intended to be enrolled in Expansion Cohort 5.
Patients in the Dose-escalation Phase:
Locally advanced solid tumor other than a primary central nervous system (CNS) tumor for which the patient has received ≤3 prior lines
Confirmed solid tumor in one of the following categories:
BRCA mutation-positive pancreatic cancer for which the patient received up to 1 prior line of cytotoxic chemotherapy in the advanced disease setting.
Advanced BRCA mutation-positive castration-resistant prostate cancer (CRPC) for which the patient received up to 2 prior lines of cytotoxic chemotherapy in the advanced disease setting.
Advanced BRCA mutation-positive ovarian cancer for which the patient received up to 3 prior lines of cytotoxic chemotherapy in the advanced disease setting.
Advanced BRCA mutation-positive triple-negative breast cancer (TNBC) for which the patient received up to 3 prior lines of cytotoxic chemotherapy in the advanced disease setting.
Advanced DNA repair mutation-positive solid tumors, including, but not limited to BRCA and non-BRCA DNA mutations, who have received up to 3 prior lines of cytotoxic chemotherapy in the advanced disease setting. DNA-repair mutations may include, but are not limited to ATM, CHEK2, PALB2, and RAD51D. Abnormal homologous repair deficiency (HRD) tests will also be allowed.
Note that in both dose escalation and dose expansion portions of the study, prior targeted therapy including prior poly ADP ribose polymerase (PARP) inhibitor therapy, prior immunotherapy, or prior hormonal therapy is permissible. Patients with castration resistant prostate cancer may have received unlimited prior hormonal therapies.
EXCLUSION:
History of leptomeningeal disease or spinal cord compression.
Underwent major surgery within 4 weeks before first treatment.
Received cancer-directed therapy 14 days (6 weeks for mitomycin C and nitrosoureas) before start of treatment.
Grade 2 or greater peripheral neuropathy at start of treatment.
If female, pregnant or breast-feeding.
Known human immunodeficiency virus (HIV) infection or hepatitis B or C infection
Any primary brain tumor (e.g., astrocytoma, glioblastoma).
Hypersensitivity or history of anaphylactic reaction to any platinum-containing agents.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Erika P Hamilton, MD
Organizational Affiliation
Tennessee Oncology, PLLC
Official's Role
Principal Investigator
Facility Information:
Facility Name
Placon Therapeutics Clinical Trial Site
City
Sarasota
State/Province
Florida
ZIP/Postal Code
34232
Country
United States
Facility Name
Placon Therapeutics Clinical Trial Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Placon Therapeutics Clinical Trial Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Placon Therapeutics Clinical Trial Site
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Placon Therapeutics Clinical Trial Site
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Placon Therapeutics Clinical Trial Site
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Facility Name
Placon Therapeutics Clinical Trial Site
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
Placon Therapeutics Clinical Trial Site
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Undecided
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A Study to Determine the Safety of BTP-114 for Treatment in Patients With Advanced Solid Tumors With BRCA Mutations
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