Clinical Trial
Open access until Mar. 1, 2025

Disease: Castration-Resistant Prostate Cancer, CRPC, and Salivary Gland Cancer, SGC, (NCT04249947)

Disease info:

Prostate cancer is cancer that occurs in the prostate. The prostate is a small walnut-shaped gland in males that produces the seminal fluid that nourishes and transports sperm. Prostate cancer is one of the most common types of cancer. Many prostate cancers grow slowly and are confined to the prostate gland, where they may not cause serious harm. However, while some types of prostate cancer grow slowly and may need minimal or even no treatment, other types are aggressive and can spread quickly.

Prostate cancer may cause no signs or symptoms in its early stages. Advanced prostate cancer may lead to various symptoms, including:

  • Trouble urinating
  • Decreased force in the stream of urine
  • Blood in the urine
  • Blood in the semen
  • Bone pain
  • Losing weight without trying
  • Erectile dysfunction

Researchers have found several factors that might affect a man’s risk of developing prostate cancer. These include: age, race, ethnicity, family history, geography and genetic factors. Several heritable mutations have been linked to hereditary prostate cancer, including mutations in the following genes:

  • BRCA1 and BRCA2: These tumour suppressor genes normally help to repair errors in genomic DNA (or cause the cell to die if the error cannot be fixed). Inherited mutations in these genes more commonly cause breast and ovarian cancer in women, but changes in these genes (especially BRCA2) may also account for a small number of prostate cancers.
  • CHEK2ATMPALB2, and RAD51D: Mutations in these DNA repair genes might also be responsible for some hereditary prostate cancers.
  • DNA mismatch repair genes (such as MSH2MSH6MLH1, and PMS2): These genes normally help fix mismatches in genomic DNA that may occur during cell division. Men with inherited mutations in one of these genes have a condition known as Lynch syndrome (also known as hereditary non-polyposis colorectal cancer, or HNPCC), and are at increased risk of colorectal, prostate, and some other cancers.
  • RNASEL (formerly HPC1): The normal function of this tumour suppressor gene is to help cells die when something goes wrong inside them. Inherited mutations in this gene might allow abnormal cells to live for longer than they should, which can lead to an increased risk of prostate cancer.
  • HOXB13: This gene is important in the development of the prostate gland. Mutations in this gene have been linked to early-onset prostate cancer that runs in some families. Fortunately, this mutation is rare.

Other inherited gene mutations may account for some hereditary prostate cancers, and research is being done to find these genes.

Advanced prostate cancer has been known under a number of names over the years, including hormone-resistant prostate cancer (HRPC) and androgen-insensitive prostate cancer (AIPC). Most recently, the terms CRPC or castration-recurrent prostate cancer were introduced with the realisation that intracrine/paracrine androgen production is significant in the resistant of prostate cancer cells to testosterone suppression therapy. 

CRPC occurs when prostate cancer progresses under therapy-induced castration conditions. Several mechanisms have been proposed to explain this acquired resistance, many of which are driven by the androgen receptor (AR). Recent findings, however, sub-classified CRPC by downregulation/absence of AR in certain subtypes that consequently do not respond to anti-androgen therapies.

Prostate cancer that is detected early — when it's still confined to the prostate gland — is associated with the best chances for successful treatment.

Salivary gland cancer occurs when benign or malignant tumours grow in one of the several different salivary glands within and near the mouth. Salivary gland cancers are rare, making up just 6% to 8% of all head and neck cancers in the United States. 

Frequency:
An estimated 313,780 new cases of prostate cancer will be diagnosed in the United States for 2025. Salivary gland cancers are rare. There are about 2,000 to 2,500 cases in the US each year.
Official title:
A Phase 1 Dose Escalation and Expanded Cohort Study of P-PSMA-101 in Subjects With Metastatic Castration-Resistant Prostate Cancer (mCRPC) and Advanced Salivary Gland Cancers (SGC)
Who:
Partners:
Locations:

United States, California 

City of Hope Comprehensive Cancer Center, Duarte, California, United States, 91010

University of California San Diego, San Diego, California, United States, 92093

University of California San Francisco, San Francisco, California, United States, 94143

 

United States, Colorado 

Sarah Cannon Research Institute at HealthONE, Denver, Colorado, United States, 80218


United States, Louisiana 

Tulane University Hospital and Clinic, New Orleans, Louisiana, United States, 70112

 

United States, Maryland 

University of Maryland, Baltimore, Baltimore, Maryland, United States, 21201

 

United States, Massachusetts 

Dana-Farber Cancer Institute, Boston, Massachusetts, United States, 02215

Massachusetts General Hospital, Boston, Massachusetts, United States, 02215

 

United States, New York 

Memorial Sloan Kettering Cancer Center, New York, New York, United States, 10065

 

United States, Tennessee 

Tennessee Oncology, Nashville, Tennessee, United States, 37203

Study start:
Feb. 28, 2020
Enrollment:
40 participants
Gene editing method:
PiggyBac transposon gene insertion platform
Type of edit:
Gene insertion
Gene:
PSMA-targeted Centyrin CAR, iCasp9-based safety switch, and DHFR
Delivery method:
PiggyBac DNA delivery system - Ex-vivo
Indicator
IND Enabling Pre-clinical
Phase I Safety
Phase II Safety and Dosing
Phase III Safety and Efficacy

Status: Terminated

Description

This is an open label, multi-center Phase 1 study that will follow a 3 + 3 design of dose-escalating cohorts of single and multiple doses of P-PSMA-101 to determine a Recommended Phase 2 Dose (RP2D). Additional participants will be treated with P-PSMA-101 at the determined RP2D.

Following consent, enrolled participants will undergo a leukapheresis procedure to obtain peripheral blood mononuclear cells (PBMCs) which will be sent to a manufacturing site to produce P-PSMA-101 CAR-T cells. The cells will then be returned to the investigational site and administered after a lymphodepleting chemotherapy regimen. Rimiducid may be administered as indicated.

Last updated: Feb. 26, 2025
close
Search CRISPR Medicine