A Study to Determine the Safety of BTP-114 for Treatment in Patients With Advanced Solid Tumors With BRCA Mutations

January 11, 2019 updated by: Placon Therapeutics

Escalation Study of BTP-114 in Patients With Advanced Solid Tumors and BRCA or DNA Repair Mutation

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

95

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Florida
      • Sarasota, Florida, United States, 34232
        • Placon Therapeutics Clinical Trial Site
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Placon Therapeutics Clinical Trial Site
      • Boston, Massachusetts, United States, 02215
        • Placon Therapeutics Clinical Trial Site
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Placon Therapeutics Clinical Trial Site
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • Placon Therapeutics Clinical Trial Site
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Placon Therapeutics Clinical Trial Site
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Placon Therapeutics Clinical Trial Site
    • Texas
      • Houston, Texas, United States, 77030
        • Placon Therapeutics Clinical Trial Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

INCLUSION:

All Patients

  1. Male or female aged ≥18 years.
  2. ECOG PS score of 0-1.
  3. Adequate organ function.
  4. Ability to understand and willingness to sign informed consent form prior to initiation of study procedures.
  5. 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.

  6. 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:

  7. Locally advanced solid tumor other than a primary central nervous system (CNS) tumor for which the patient has received ≤3 prior lines

  8. 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:

  1. History of leptomeningeal disease or spinal cord compression.
  2. Underwent major surgery within 4 weeks before first treatment.
  3. Received cancer-directed therapy 14 days (6 weeks for mitomycin C and nitrosoureas) before start of treatment.
  4. Grade 2 or greater peripheral neuropathy at start of treatment.
  5. If female, pregnant or breast-feeding.
  6. Known human immunodeficiency virus (HIV) infection or hepatitis B or C infection
  7. Any primary brain tumor (e.g., astrocytoma, glioblastoma).
  8. Hypersensitivity or history of anaphylactic reaction to any platinum-containing agents.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: BTP-114
Intravenous (IV) treatment n 21-day cycles
Drug: BTP-114

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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.
From the date of the first dose up to approximately 52 weeks.
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.
From the date of the first dose up to approximately 52 weeks.
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.
From the date of first dose up to approximately 52 weeks.
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.
From the date of the first dose to documented disease progression assessed up to approximately 52 weeks.
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.
From the date of the first dose to documented disease progression assessed up to approximately 52 weeks.
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.
Assessed up to approximately 52 weeks.
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.
Assessed up to approximately 52 weeks.

Other Outcome Measures

Outcome Measure
Time Frame
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.
From the date of the first dose to documented disease progression assessed up to approximately 52 weeks.
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.
From the date of the first dose to documented disease progression assessed up to approximately 52 weeks.
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.
Assessed up to approximately 52 weeks.
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.
Assessed up to approximately 52 weeks.
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.
Time points on Day 1, Day 3 or Day 4, Day 15 of Cycle 1 and Day 1 of subsequent cycles.
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.
Time points on Day 1, Day 3 or Day 4, Day 15 of Cycle 1 and Day 1 of subsequent cycles.
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
Time points on Day 1, Day 3 or Day 4, Day 15 of Cycle 1 and Day 1 of subsequent cycles

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Placon Therapeutics

Investigators

  • Principal Investigator: Erika P Hamilton, MD, Tennessee Oncology, PLLC

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2016

Primary Completion (Anticipated)

April 1, 2020

Study Completion (Anticipated)

August 1, 2020

Study Registration Dates

First Submitted

October 5, 2016

First Submitted That Met QC Criteria

October 28, 2016

First Posted (Estimate)

October 31, 2016

Study Record Updates

Last Update Posted (Actual)

January 14, 2019

Last Update Submitted That Met QC Criteria

January 11, 2019

Last Verified

January 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BTP-114-001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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