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

Phase 2

Active, not recruiting

• Conditions: Advanced Solid Tumors; mCRPC; Prostatic Neoplasms; Genital Neoplasms, Male; Neoplasms by Site; CRPC; Metastatic Castrate-resistant Prostate Cancer; PT-112; Urogenital Neoplasms
• Interventions: Drug: PT-112 Injection

• Registration Number: NCT02266745
• Lead Sponsor: Promontory Therapeutics Inc.

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 Timeline

• Study Start: 2014-07
• Study First Submitted: 2014-10-13
• Study First Submitted QC: 2014-10-13
• Study First Posted: 2014-10-17
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-03
• Last Update Posted: 2024-04-05
• Primary Completion: 2024-08-01
• Study Completion: 2025-04-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Male
• Target Recruitment: 109

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

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

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR) in patients with RECIST-measurable disease, evaluated using PCWG3-modified RECIST criteria	up to 24 months	Cohort D only
Disease Control Rate by disease manifestation, evaluated using PCWG3-modified RECIST criteria	up to 24 months	Cohort D only
Median duration of response (DOR) as defined by PCWG3-modified RECIST criteria	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)	up to 24 months	Cohort D only
Time to PSA progression by PCWG3 criteria	up to 24 months	Cohort D only
Median overall survival (OS)	up to 24 months	Cohort D only
Change in disease related pain based on ACS Daily Pain Diary assessment	up to 24 months	Cohort D only
Percentage of patients achieving PSA50 as defined by PCWG3 criteria	up to 24 months	Cohort D only
Median radiographic progression free survival (rPFS) by PCWG3 criteria	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)	up to 24 months	Cohort D only

Trial Locations

Locations (25)

Bordeaux; 🇫🇷 Bordeaux, France

Indianapolis; 🇺🇸 Indianapolis, Indiana, United States

Boston; 🇺🇸 Boston, Massachusetts, United States

Minneapolis; 🇺🇸 Minneapolis, Minnesota, United States

Nice; 🇫🇷 Nice, France

New York; 🇺🇸 New York, New York, United States

Paris; 🇫🇷 Paris, France

University of Texas MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Arizona; 🇺🇸 Phoenix, Arizona, United States

Rochester; 🇺🇸 Rochester, Minnesota, United States

Omaha; 🇺🇸 Omaha, Nebraska, United States

Colorado; 🇺🇸 Aurora, Colorado, United States

Duarte; 🇺🇸 Duarte, California, United States

Tucson; 🇺🇸 Tucson, Arizona, United States

Jacksonville; 🇺🇸 Jacksonville, Florida, United States

Orlando; 🇺🇸 Orlando, Florida, United States

Brooklyn; 🇺🇸 Brooklyn, New York, United States

Durham; 🇺🇸 Durham, North Carolina, United States

Rennes; 🇫🇷 Rennes, France

Seattle; 🇺🇸 Seattle, Washington, United States

Besançon; 🇫🇷 Besançon, France

Caen; 🇫🇷 Caen, France

Clermont-Ferrand; 🇫🇷 Clermont-Ferrand, France

Marseille; 🇫🇷 Marseille, France

Albuquerque; 🇺🇸 Albuquerque, New Mexico, United States