J591 in Patients With Advanced Prostate Cancer and Unfavorable Circulating Tumor Cell Counts

NCT02552394 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 1503015998
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This clinical trial is for men with advanced prostate cancer that may have spread to other parts of the body. Currently, once prostate cancer cells have spread from the prostate to other organs it is not treatable by surgery. The purpose of this study is to treat patients with an experimental antibody (i.e. that has not been FDA approved) called J591 that attaches itself to a special protein on cancer cells called PSMA to try to eliminate these cancer cells (called circulating tumor cells) from the circulation. In the initial phase of the study, 6 participants will receive the experimental J591 treatment. Routine blood tests, research blood tests, physical exam will be performed at each visit. Participants will also be asked to complete a questionnaire about how they are feeling. Participants will have a radiographic scan every 3 months to check the status of their disease. Participants who tolerate the treatment well may be re-treated at the same level every 3 months, and may continue on treatment as long as they are responding to therapy and not experiencing unacceptable side effects.

Conditions

Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• Changes in frequency of achieving a decrease in Circulating tumor count (CTC)

  Determine the effect of mAb Hu-J591 on reducing circulating tumor cells (CTCs) from \> 5/7.5 mL of whole blood to \< 5/7.5 mL of whole blood in metastatic prostate cancer (PC) with elevated baseline CTC count and to identify the least effective dose that clears CTCs.

  CTCs will be measured on Day 1, Day 8, Day 29, Day 57, and Day 85, then monthly until the date of first documented progression, or death from any cause, whichever came first assessed up to 100 months

Secondary Outcomes (3)

• Changes in prostate specific antigen (PSA) measurable disease response

  Response will be measured by performing CT scans every 3 months from baseline until the date of first documented progression, or death from any cause, whichever came first assessed up to 100 months

• Change in duration of Circulating tumor count (CTC) response

  Labs will be collected at Screening, Day 1, Day 8, Day 29, Day 57 and Day 85

• Change in disease response through the optional (but recommended) prostate specific membrane antigen (PSMA) PET/CT imaging

  Performed prior to treatment at screening and at 3 months/12 weeks or as clinically indicated

Study Arms (1)

HuJ591 Administration

EXPERIMENTAL

6 subjects will be treated at 300 mg dose. The decision about treating subjects at the lower dose will depend upon their response. If ≥4 of 6 subjects respond at the 300 mg level, then 6 more subjects will be recruited at the 200 mg level. If ≥4 of 6 subjects respond at the 200 mg level than 6 more subjects will be recruited at the next dose level of 100 mg. If ≥ 4/6 subjects respond at this level, then 6 subjects will be recruited at the last dose level of 50 mg. At any level, if the first four consecutive subjects respond, the next two subjects will be enrolled in the same dose-level cohort and further subjects will be recruited at the next dose level. Response at every dose level is defined by conversion from an unfavorable CTC count at baseline to a favorable CTC count.

Drug: huJ591

Interventions

huJ591 DRUG

HuJ591 will be administered as an intravenous infusion at a concentration of 5 mg/mL and rate of \<5 mg/minute. Pre-medications prior to J591 infusion with diphenhydramine 25 - 50 mg p.o. or IV and acetaminophen 500 - 650 mg p.o.

Also known as: J591

HuJ591 Administration

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologic/Cytologic diagnosis of prostate carcinoma
• Subject must have progressive metastatic prostate cancer as defined as at least any one of the following:
• New lesions on bone scan
• Progression of disease on CT/MRI as defined by RECIST
• PSA progression defined by an absolute value 2 ng/mL with an increase in PSA determined by two separate measurements taken at least one week apart and confirmed by a third, and if necessary, a fourth measurement. If the third measurement is not greater than the second measurement, then a fourth measurement must be taken; the fourth measurement must be greater than the second measurement for the subject to be eligible for enrollment in the study. Furthermore, the confirmatory PSA measurement (i.e., the third or, if applicable, fourth PSA measurement) must be 2 ng/mL and ≥ 25% above the previous nadir.
• Increase in circulating tumor cell (CTC) count via CellSearch methodology in the absence of responding tumor by other criteria.
• Subjects must remain on a stable hormonal therapy regimen.
• Subjects who have received traditional anti-androgen (i.e. bicalutamide, nilutamide, flutamide) therapy with a resulting PSA decline must continue anti-androgen therapy or demonstrate progression following discontinuation of anti-androgen therapy (not necessary for those who never responded to anti-androgen addition).
• Medical or surgical castration will be continued for the duration of the trial in all subjects.
• Subjects who have any measure of progression on androgen receptor signaling inhibitors (such as enzalutamide or apalutamide) or CYP17 inhibitors (such as abiraterone acetate) and wish to continue must remain on a stable regimen.
• CTCs ≥ 5 per 7.5ml of whole blood performed by CellSearch system within 1 month of enrollment (may be performed as part of screening).
• Subjects capable of fathering children must agree to use an effective method of contraception for the duration of the trial.

You may not qualify if:

• Prior cytotoxic chemotherapy and/or radiation therapy within 4 weeks of treatment
• Bilirubin (total) \> 1.5x ULN; subjects with known Gilbert's syndrome are eligible if direct bilirubin is within normal limits
• Serum Creatinine \> 3x ULN
• Absolute Neutrophil Count \<1000/µL
• Hemoglobin \<8 g/dL
• Platelet Count \<50,000/µL
• ECOG Performance Status \>2
• Life expectancy \< 6 months
• Any serious illness(es) involving the cardiac, respiratory, CNS, renal, hepatic or hematological organ systems which in the investigator's opinion might preclude completion of this study or interfere with determination of causality of any adverse effects experienced in this study
• Prior investigational therapy (medications or devices) within 4 weeks of treatment. Furthermore, other investigational anti-cancer therapy is not permitted during the treatment phase.

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead

Study Sites (1)

Weill Cornell Medical College

New York, New York, 10021, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

J591 monoclonal antibody

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Study Officials

• Scott Tagawa, MD

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 3, 2015
• First Posted: September 17, 2015
• Study Start: July 1, 2015
• Primary Completion: November 14, 2019
• Study Completion: January 3, 2021
• Last Updated: April 6, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)