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

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

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Neoplasms; Advanced Solid Tumors; mCRPC; Metastatic Castrate-resistant Prostate Cancer; CRPC; PT-112
• Intervention / Treatment: Drug: PT-112 Injection

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
• Enrollment (Estimated): 109
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Besançon, France
    • Besançon
  • Bordeaux, France
    • BORDEAUX
  • Caen, France
    • CAEN
  • Clermont-Ferrand, France
    • Clermont-Ferrand
  • Marseille, France
    • Marseille
  • Nice, France
    • NICE
  • Paris, France
    • Paris
  • Rennes, France
    • RENNES
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Arizona
    • Tucson, Arizona, United States, 85719
      • Tucson
  • California
    • Duarte, California, United States, 91010
      • Duarte
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Colorado
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Jacksonville
    • Orlando, Florida, United States, 32806
      • Orlando
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indianapolis
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Boston
  • Minnesota
    • Minneapolis, Minnesota, United States, 55426
      • Minneapolis
    • Rochester, Minnesota, United States, 55905
      • Rochester
  • Nebraska
    • Omaha, Nebraska, United States, 68130
      • Omaha
  • New Mexico
    • Albuquerque, New Mexico, United States, 87190
      • Albuquerque
  • New York
    • Brooklyn, New York, United States, 11215
      • Brooklyn
    • New York, New York, United States, 10065
      • New York
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Durham
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas MD Anderson Cancer Center
  • Washington
    • Seattle, Washington, United States, 19024
      • Seattle

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 2: PT-112 injection; Arm 2: PT-112 Injection, administered by intravenous infusion, biweekly 250 mg/m2	Drug: PT-112 Injection; Other Names: PT-112
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	Drug: PT-112 Injection; Other Names: PT-112
Experimental: Arm 1: PT-112 injection; Arm 1: PT-112 Injection, administered by intravenous infusion, biweekly 360 mg/m2	Drug: PT-112 Injection; Other Names: PT-112

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Initial design: Comparison of two dose levels, administered on Days 1 and 15 of each 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	28-day cycle
Modified design: Define the recommended dose and schedule for PT-112 for pivotal studies	Define the recommended dose and schedule for PT-112 for pivotal studies. Cohort D only	28-day cycle

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Promontory Therapeutics Inc.
• Investigators: Principal Investigator: Daniel D. Karp, MD, M.D. Anderson Cancer Center

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start: July 1, 2014
• Primary Completion (Estimated): August 1, 2024
• Study Completion (Estimated): April 1, 2025

Study Registration Dates

• First Submitted: October 13, 2014
• First Submitted That Met QC Criteria: October 13, 2014
• First Posted (Estimated): October 17, 2014

Study Record Updates

• Last Update Posted (Actual): April 5, 2024
• Last Update Submitted That Met QC Criteria: April 3, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: PT-112
• Additional Relevant MeSH Terms: Prostatic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Neoplasms; Prostatic Neoplasms; Neoplasms by Site; Urogenital Neoplasms; Genital Neoplasms, Male
• Other Study ID Numbers: PT-112-101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes