Clinical trial NCT02266745: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Advanced Solid Tumors
CRPC
mCRPC
Metastatic Castrate-resistant Prostate Cancer
PT-112
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Keywords: PT-112
Lead sponsor: Promontory Therapeutics Inc.
Sponsor class: INDUSTRY
First posted: 2014-10-17
Enrollment: 109
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: Subjects enrolled in Cohort D Part 2 will be randomized.
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Initial design: Comparison of two dose levels, administered on Days 1 and 15 of each 28-day cycle:
timeFrame: 28-day cycle
measure: Modified design: Define the recommended dose and schedule for PT-112 for pivotal studies
timeFrame: 28-day cycle
Secondary outcomes:
measure: Disease Control Rate by disease manifestation, evaluated using PCWG3-modified RECIST criteria
timeFrame: up to 24 months
measure: Objective Response Rate (ORR) in patients with RECIST-measurable disease, evaluated using PCWG3-modified RECIST criteria
timeFrame: up to 24 months
measure: Median duration of response (DOR) as defined by PCWG3-modified RECIST criteria
timeFrame: up to 24 months
measure: Percentage of patients achieving PSA50 as defined by PCWG3 criteria
timeFrame: up to 24 months
measure: Percentage of patients who are CTC nonzero at baseline and with 0 CTCs/mL in one or more post-baseline samples (i.e., CTC0)
timeFrame: up to 24 months
measure: Percentage of patients who have ≥ 3 CTCs at baseline and ≤ 3 CTCs in one or more post-baseline samples (i.e., CTC conversion)
timeFrame: up to 24 months
measure: Median radiographic progression free survival (rPFS) by PCWG3 criteria
timeFrame: up to 24 months
measure: Median overall survival (OS)
timeFrame: up to 24 months
measure: Time to PSA progression by PCWG3 criteria
timeFrame: up to 24 months
measure: Change in disease related pain based on ACS Daily Pain Diary assessment
timeFrame: up to 24 months
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Arizona
state: Arizona
city: Tucson
country: United States
facility: Tucson
state: Arizona
city: Duarte
country: United States
facility: Duarte
state: California
city: Aurora
country: United States
facility: Colorado
state: Colorado
city: Jacksonville
country: United States
facility: Jacksonville
state: Florida
city: Orlando
country: United States
facility: Orlando
state: Florida
city: Indianapolis
country: United States
facility: Indianapolis
state: Indiana
city: Boston
country: United States
facility: Boston
state: Massachusetts
city: Minneapolis
country: United States
facility: Minneapolis
state: Minnesota
city: Rochester
country: United States
facility: Rochester
state: Minnesota
city: Omaha
country: United States
facility: Omaha
state: Nebraska
city: Albuquerque
country: United States
facility: Albuquerque
state: New Mexico
city: Brooklyn
country: United States
facility: Brooklyn
state: New York
city: New York
country: United States
facility: New York
state: New York
city: Durham
country: United States
facility: Durham
state: North Carolina
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: Seattle
state: Washington
city: Besançon
country: France
facility: Besançon
city: Bordeaux
country: France
facility: Bordeaux
city: Caen
country: France
facility: Caen
city: Clermont-Ferrand
country: France
facility: Clermont-Ferrand
city: Marseille
country: France
facility: Marseille
city: Nice
country: France
facility: Nice
city: Paris
country: France
facility: Paris
city: Rennes
country: France
facility: Rennes
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Daniel D. Karp, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.