A Study Evaluating the Safety, Pharmacokinetics, and Clinical Effects of Intravenously Administered PT-112 Injection in Subjects With Advanced Solid Tumors and Subsequent Dose Expansion Cohorts

• ClinicalTrials.gov Identifier: NCT02266745
• Recruitment Status: Active, not recruiting
• First Posted: October 17, 2014
• Last Update Posted: April 5, 2024
• Sponsor: Promontory Therapeutics Inc.
• Information provided by (Responsible Party): Promontory Therapeutics Inc.

Tracking Information

• First Submitted Date: October 13, 2014
• First Posted Date: October 17, 2014
• Last Update Posted Date: April 5, 2024
• Study Start Date: July 2014
• Estimated Primary Completion Date: August 1, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 10, 2023)

• Initial design: Comparison of two dose levels, administered on Days 1 and 15 of each 28-day cycle: [ Time Frame: 28-day cycle ]
  [ ] Define the recommended dose level for PT-112 for pivotal studies based on the risk/benefit ratio across Arms 1, 2 and 3. Cohort D only
• Modified design: Define the recommended dose and schedule for PT-112 for pivotal studies [ Time Frame: 28-day cycle ]
  Define the recommended dose and schedule for PT-112 for pivotal studies. Cohort D only

Original Primary Outcome Measures (submitted: October 13, 2014)

• Determine the safety and tolerability, Dose Limiting Toxicity(ies) (DLT), Maximum Tolerated Dose (MTD), and recommended Phase 2 dose(s) (RP2D) [ Time Frame: 28-day cycle ]
  The primary endpoint is to determine the safety profile and MTD of PT-112 Injection. Assessments will include drug exposure; characterization of DLTs; characterization of the type, incidence, severity, seriousness, and relationship to treatment of adverse events (AEs), and effects on vital signs and laboratory parameters.
• Assess the pharmacokinetic (PK) profile [ Time Frame: First 28-day cycle ]
  PK (pharmacokinetic) parameters, including but not limited to area under the curve (AUC), maximum plasma concentration (Cmax), trough plasma concentration (Cmin), time to maximum plasma concentration (Tmax), and plasma half-life (T1/2) will be determined.

Current Secondary Outcome Measures (submitted: November 14, 2022)

• Disease Control Rate by disease manifestation, evaluated using PCWG3-modified RECIST criteria [ Time Frame: up to 24 months ]
  Cohort D only
• Objective Response Rate (ORR) in patients with RECIST-measurable disease, evaluated using PCWG3-modified RECIST criteria [ Time Frame: up to 24 months ]
  Cohort D only
• Median duration of response (DOR) as defined by PCWG3-modified RECIST criteria [ Time Frame: up to 24 months ]
  Cohort D only
• Percentage of patients achieving PSA50 as defined by PCWG3 criteria [ Time Frame: up to 24 months ]
  Cohort D only
• Percentage of patients who are CTC nonzero at baseline and with 0 CTCs/mL in one or more post-baseline samples (i.e., CTC0) [ Time Frame: up to 24 months ]
  Cohort D only
• Percentage of patients who have ≥ 3 CTCs at baseline and ≤ 3 CTCs in one or more post-baseline samples (i.e., CTC conversion) [ Time Frame: up to 24 months ]
  Cohort D only
• Median radiographic progression free survival (rPFS) by PCWG3 criteria [ Time Frame: up to 24 months ]
  Cohort D only
• Median overall survival (OS) [ Time Frame: up to 24 months ]
  Cohort D only
• Time to PSA progression by PCWG3 criteria [ Time Frame: up to 24 months ]
  Cohort D only
• Change in disease related pain based on ACS Daily Pain Diary assessment [ Time Frame: up to 24 months ]
  Cohort D only

Original Secondary Outcome Measures (submitted: October 13, 2014)

Document any observed anti-tumor effects [ Time Frame: Day 1, Day 56 and every 56 days subsequently ]

Subjects will be assessed for clinical activity of PT-112 Injection every 2 cycles by appropriate physical examination or computed tomography imaging techniques, using RECIST v1.1; and, where appropriate, informative tumor markers every cycle.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study Evaluating the Safety, Pharmacokinetics, and Clinical Effects of Intravenously Administered PT-112 Injection in Subjects With Advanced Solid Tumors and Subsequent Dose Expansion Cohorts
• Official Title: A Phase 1, Open-Label, Dose-Escalation Study Evaluating the Safety, Pharmacokinetics, and Clinical Effects of Intravenously Administered PT-112 Injection in Subjects With Advanced Solid Tumors and Subsequent Dose Expansion Cohorts

Brief Summary

This is a Phase 1/2, open-label, multi-center, non-randomized, dose-escalation study to be conducted in two parts: the Dose Escalation Phase and the Dose Expansion Phase. The Dose Escalation Phase will determine the Maximum Tolerated Dose (MTD) and recommended Phase 2 dose(s) (RP2D) of PT-112 Injection and evaluate its safety and tolerability, and PK (pharmacokinetics).

The Dose Escalation Phase is complete and no longer enrolling.

The Dose Expansion Phase has two cohorts: one cohort for the study of PT-112 in patients with thymoma and thymic carcinoma (Cohort A), and one cohort for the study of PT-112 in metastatic castrate-resistant prostate cancer (mCRPC) (Cohort D).

Detailed Description

This is a Phase 1/2, open-label, multi-center, non-randomized, dose-escalation study to be conducted in two parts: the Dose Escalation Phase, and the Dose Expansion Phase

The Dose Escalation Phase and the Dose Expansion Thymoma Cohort are complete and no longer enrolling.

The Dose Expansion Phase of the study of PT-112 in metastatic castrate-resistant prostate cancer (mCRPC) is open and enrolling.

• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: Randomized
Intervention Model: Single Group Assignment
Intervention Model Description:

Subjects enrolled in Cohort D Part 2 will be randomized.

Masking: None (Open Label)
Primary Purpose: Treatment

Condition

• Advanced Solid Tumors
• CRPC
• mCRPC
• Metastatic Castrate-resistant Prostate Cancer
• PT-112
• Prostatic Neoplasms
• Genital Neoplasms, Male
• Urogenital Neoplasms
• Neoplasms by Site

Intervention

Drug: PT-112 Injection

Other Name: PT-112

Study Arms

• Experimental: Arm 1: PT-112 injection
  Arm 1: PT-112 Injection, administered by intravenous infusion, biweekly 360 mg/m2
  Intervention: Drug: PT-112 Injection
• Experimental: Arm 2: PT-112 injection
  Arm 2: PT-112 Injection, administered by intravenous infusion, biweekly 250 mg/m2
  Intervention: Drug: PT-112 Injection
• Experimental: Arm 3: PT-112 injection
  Arm 3: PT-112 Injection, administered by intravenous infusion, 360 mg/m2 for two doses, 250 mg/m2 for subsequent doses
  Intervention: Drug: PT-112 Injection

• Publications *: Karp DD, Camidge DR, Infante JR, Ames TD, Price MR, Jimeno J, Bryce AH. Phase I study of PT-112, a novel pyrophosphate-platinum immunogenic cell death inducer, in advanced solid tumours. EClinicalMedicine. 2022 May 27;49:101430. doi: 10.1016/j.eclinm.2022.101430. eCollection 2022 Jul.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: April 3, 2024): 109
• Original Estimated Enrollment (submitted: October 13, 2014): 80
• Estimated Study Completion Date: April 1, 2025
• Estimated Primary Completion Date: August 1, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

• Male >/= 18 years of age
• Histologically or cytologically confirmed adenocarcinoma of the prostate.
• Document current evidence of metastatic castration-resistant prostate cancer (mCRPC), where metastatic status is defined as having documented metastatic lesion(s) on either bone scan or CT/MRI scan.
• Patients who have received at least three prior intended life-prolonging therapies for metastatic disease.
• Eastern Collaborative Oncology Group (ECOG) Performance Status of 0-1.
• Progressive disease, either measurable on physical examination or imaging by Response Evaluation Criteria in Solid Tumors (RECIST v1.1) or PCWG3 or by informative tumor marker(s).
• Adequate organ function based on laboratory values.
• If there is a known history of brain metastases, either treated or untreated, the disease must be stable.

Key Exclusion Criteria:

• Any cytotoxic chemotherapy within 21 days prior to initiation of study drug.
• Any immunomodulatory drug therapy, anti-neoplastic hormonal therapy, immunosuppressive therapy, corticosteroids, or growth factor treatment within 14 days prior to initiation of study drug.
• Bone marrow reserve which is not adequate for participation in this trial.
• Radiotherapy within 14 days prior to baseline.
• Fraction of radiotherapy to >25 % of active bone marrow.
• Major surgery within 28 days prior to initiation of study drug.

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France, United States

Administrative Information

• NCT Number: NCT02266745
• Other Study ID Numbers: PT-112-101
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Promontory Therapeutics Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Promontory Therapeutics Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Daniel D. Karp, MD; M.D. Anderson Cancer Center

• PRS Account: Promontory Therapeutics Inc.
• Verification Date: April 2024