Clinical trial NCT03575819: A Phase 1 Study of FOR46 in Patients With Metastatic Castration-Resistant Prostate Cancer (mCRPC)
Official title: A Phase 1 Study of FOR46 Administered Every 21 Days in Patients With Metastatic Castration-Resistant Prostate Cancer (mCRPC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Prostate Cancer Metastatic
Keywords: castration-resistant
androgen-signaling blockade progression
Lead sponsor: Fortis Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2018-07-03
Enrollment: 56
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Following completion of the dose escalation phase of the study and determination of a recommended phase 2 dose, patients will be enrolled into a dose expansion cohort.
Primary purpose: TREATMENT

Brief summary: This study will test the safety and efficacy of FOR46 given every 21 days to patients with metastatic castration-resistant prostate cancer.

The name of the study drug involved in this study is: FOR46 for Injection (FOR46)

Detailed description: This study is designed to evaluate the safety, tolerability and antitumor activity of FOR46 in patients with metastatic castration-resistant prostate cancer. This study will be conducted in two parts:

Dose escalation:

This part will evaluate increasing doses of FOR46 to identify the maximum tolerated dose (MTD). The first patient enrolled on the study will receive the lowest dose of FOR46. Once this dose is shown to be safe, a second patient will be enrolled at the next higher dose. Patients will continue to be enrolled into either single or multiple patient groups receiving increasing doses until the MTD is reached.

Dose expansion:

This part of the study will further evaluate the safety, tolerability and antitumor activity of FOR46 at a dose shown to be safe in the dose escalation part of the study. Patients will be enrolled into 1 of 2 groups, based on histology.

Eligibility criteria: Inclusion Criteria:

* Male ≥ 18 years of age
* Has histologically confirmed prostate cancer that is metastatic and has progressed as defined by PCWG3 criteria during or after treatment with at least 1 ASI (eg, abiraterone, enzalutamide, apalutamide), or another second-generation anti-androgen or cytochrome P450 (CYP)17A1 inhibitor, with the most recent ASI administered in the castration-resistant setting
* Has serum testosterone levels \< 50 ng/dL during screening. Patients without a history of bilateral orchiectomy are required to remain on luteinizing hormone-releasing hormone (LHRH) analog during the course of protocol therapy
* ECOG performance status of 0 or 1
* Adequate hematologic, renal and hepatic function
* Males with female partners of childbearing potential must agree to use 2 effective methods of contraception
* Patients must provide signed informed consent
* Patients enrolled into the dose expansion phase must have prostate carcinoma without histologic evidence of small-cell/neuroendocrine carcinoma features on prior biopsy or must have unequivocal histologic evidence of small-cell/neuroendocrine prostate carcinoma (pure or mixed). Patients with treatment-emergent small-cell neuroendocrine cancer (pure or mixed) may have received no more than on prior chemotherapy regimen for mCRPC
* Patients enrolled into the dose expansion phase must be willing to undergo a metastatic tumor biopsy or has tissue available from a prior post-castration resistant tumor biopsy

Exclusion Criteria:

* Persistent clinically significant toxicities from previous anticancer therapy
* Has NCI CTCAE Grade ≥ 2 peripheral neuropathy from any etiology or has a genetic disorder that is associated with peripheral neuropathy even without current neuropathic manifestations
* Prior treatment with cytotoxic chemotherapy for mCRPC (chemotherapy in the hormone-sensitive setting is allowed if \> 6 months before study entry)
* Has received external-beam radiation or systemic anticancer therapy within 14 days before first dose of FOR46
* Has received treatment with an investigational drug within 28 days before first dose of FOR46
* Has had a major surgical procedure within 28 days before administration of FOR46 dose
* Clinically significant cardiovascular disease
* Uncontrolled, clinically significant pulmonary disease
* Has a history of brain or leptomeningeal metastases.
* Uncontrolled intercurrent illness
* Has a known positive status for HIV or either active/chronic hepatitis B/C
* Requires medications that are strong inhibitors or strong inducers of CYP3A4
* \[Dose escalation only\] Has a history of episodic atrial fibrillation or flutter (patients with chronic atrial fibrillation are not excluded)

Primary outcomes:
measure: Occurrence of toxicity
timeFrame: Through 1 month following last dose
measure: Occurrence of dose-limiting toxicities
timeFrame: Through 1 month following last dose
measure: Disease response/composite response
timeFrame: 12 months
Secondary outcomes:
measure: Characterize FOR46 plasma concentration
timeFrame: Through 1 month following last dose
measure: Characterize the FOR46 area under the curve
timeFrame: Through 1 month following last dose
measure: Characterize FOR46 elimination
timeFrame: Through 1 month following last dose
measure: Antidrug Antibodies
timeFrame: Through 1 month following last dose
measure: Median radiographic progression-free survival
timeFrame: 12 months
Other outcomes:
measure: Exploratory Endpoint: Tumor expression of CD46
timeFrame: Through 1 month following last dose
Locations:
city: Los Angeles
country: United States
facility: UCLA Institute of Urologic Oncology
state: California
city: San Francisco
country: United States
facility: UCSF Helen Diller Family Comprehensive Cancer Center
state: California
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Portland
country: United States
facility: OHSU Knight Cancer Institute
state: Oregon
Study officials:
affiliation: Fortis Therapeutics, Inc.
name: Andrew Dorr, MD
role: STUDY_DIRECTOR
References: