Treatment of Castration Resistant Prostate Cancer Using Multi-Targeted Recombinant Ad5 PSA/MUC1/Brachyury Based Immunotherapy Vaccines

NCT03481816 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 18007318-C-0073
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Metastatic castration resistant prostate cancer (mCRPC) keeps growing even when the amount of testosterone in the body is reduced to very low levels. mCRPC is incurable. Researchers want to develop vaccines to teach the immune system to target and kill cancer cells. They want to test three of these vaccines (ETBX-071, ETBX-061, and ETBX-051) against mCRPC. Objective: To test the safety of combination ETBX-071, ETBX-061, and ETBX-051 and to study their effects on the immune system. Eligibility: People ages 18 and older with mCRPC that has not responded to standard therapies Design: Participants will be screened with: Medical history Physical exam Blood, urine, and heart tests Computed tomography (CT) or magnetic resonance imaging (MRI) scans Bone scan Participants will get the vaccines as shots under the skin every 3 weeks for 3 doses. They may then have the shots every 8 weeks for up to 1 year. Participants will keep a diary to record any symptoms from the vaccines. Participants will have blood tests each time they get the vaccines. They will also have scans and other tests to measure the effect the vaccines have on their tumors. Participants will have a visit within 28 days after their last treatment. This includes a physical exam and blood and urine tests. Participants will then be contacted by phone every 3 months for the first year, every 6 months for the next 2 years, and every 12 months for another 2 years. Participants will be asked to join a long-term follow up study.

Conditions

Prostatic Neoplasms; Prostatic Cancer

Keywords

mCRPC; Therapeutic Cancer Vaccines; ETBX-071; ETBX-061; ETBX-051

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Dose-Limiting Toxicities

  A dose-limiting toxicity is defined as occurring within 28 days after the first vaccine administration and meeting on of these criteria: Any Grade 3 or greater toxicity or any Grade 2 or higher autoimmune reaction as defined by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0; or generalized erythroderma or macular or papular rash.

  4 weeks after receiving the first vaccine dose

• Recommended Phase 2 Dose

  RP2D is the maximum tolerated dose declared after ≤1 of 6 participants experience a dose-limiting toxicity within the first 4 weeks.

  Within the first 4 weeks after drug is administered.

Secondary Outcomes (8)

• Percentage of Participants With an Objective Response

  Objective response at any time point during treatment on study up to 1 year

• Percentage of Participants With a Disease Control Rate (DCR) Lasting for at Least 6 Months

  6 months post treatment

• Duration of Response

  Time from recorded partial response until development of progressive disease. This was accessed every 3 weeks for the first 3 doses and then every 8 weeks up to 1 year (Arm 2)

• Progression-free Survival (PFS)

  This was accessed every 3 weeks for the first 3 doses, then every 8 weeks up to 1 year (Arm 2).

• Overall Survival (OS)

  Every 3 weeks for the first 3 doses, then every 8 weeks up to 1 year then every 3 months for 12 months and then approximately every 6 months every 6 months for 24 months and then every 12 months thereafter for another 24 months.

Study Arms (2)

Arm 1/Dose De-Escalation

EXPERIMENTAL

Subjects enrolled to dose de-escalation cohorts.

Biological: ETBX-071; adenoviral PSA vaccine; Biological: ETBX-061; adenoviral MUC1 vaccine; Biological: ETBX-051; adenoviral brachyury vaccine

Arm 2/Dose expansion

EXPERIMENTAL

Subjects enrolled at the maximum tolerated dose (MTD) after the MTD is established.

Biological: ETBX-071; adenoviral PSA vaccine; Biological: ETBX-061; adenoviral MUC1 vaccine; Biological: ETBX-051; adenoviral brachyury vaccine

Interventions

ETBX-071; adenoviral PSA vaccine BIOLOGICAL

5 x 10 to the eleventh power VP (standard dose), 1 x 10 to the eleventh power VP (DL-1), or 5 x 10 to the tenth power VP (DL-2) subcutaneous injection every 3 weeks for 3 immunizations.

Arm 1/Dose De-Escalation; Arm 2/Dose expansion

ETBX-061; adenoviral MUC1 vaccine BIOLOGICAL

5 x 10 to the eleventh power VP (standard dose), 1 x 10 to the eleventh power VP (DL-1), or 5 x 10 to the tenth power VP (DL-2) subcutaneous injection every 3 weeks for 3 immunizations.

Arm 1/Dose De-Escalation; Arm 2/Dose expansion

ETBX-051; adenoviral brachyury vaccine BIOLOGICAL

5 x 10 to the eleventh power VP (standard dose), 1 x 10 to the eleventh power VP (DL-1), or 5 x 10 to the tenth power VP (DL-2) subcutaneous injection every 3 weeks for 3 immunizations.

Arm 1/Dose De-Escalation; Arm 2/Dose expansion

Eligibility Criteria

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

You may qualify if:

• Age more than or equal to 18 years (male).
• Ability to understand and provide signed informed consent that fulfills Institutional Review Board (IRB)s guidelines.
• Cytologically or histologically confirmed prostate cancer for which no curative standard approved therapy is available by either the Laboratory of Pathology at the National Institutes of Health (NIH) Clinical Center or Walter Reed National Military Medical Center at Bethesda prior to starting this study. If no pathologic specimen is available, patients may enroll with a pathologists report showing a histological diagnosis of prostate cancer and a clinical course consistent with the disease.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• Subjects who have received prior prostate specific antigen (PSA), mucin1 (MUC1), and/or brachyury-targeted immunotherapy (e.g. vaccine) are eligible for this trial if this treatment was discontinued at least 3 months prior to enrollment.
• Resolution of all toxic side effects of prior chemotherapy, radiotherapy, or surgical procedures to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade less than or equal to1.
• Adequate hematologic function at screening, as follows:
• Absolute neutrophil count (ANC) greater than or equal to x 10 to the ninth power/L
• Hemoglobin more than or equa to 9 g/dL
• Platelets more than or equal to 75,000/microliter.
• Prothrombin (PT)-international normalized ratio (INR) \< 1.5.
• Partial thromboplastin time (PTT) \< 1.5 x upper limit of normal (ULN).
• Adequate renal and hepatic function at screening, as follows:
• Serum creatine less than or equal to 1.5x upper limit of normal (ULN) OR creatinine clearance (CrCl) more than or equal to 40mL/min (if using the Cockcroft-Gault formula below):
• Female CrCl = \[(140 - age in years) x weight in kg x 0.85\] / \[72 x serum creatinine in mg/dL\]

You may not qualify if:

• Treatment with an investigational drug study within 28 days of before starting on study treatment.
• Subjects with concurrent cytotoxic chemotherapy or radiation therapy. There must be at least 28 days between any other prior chemotherapy (or radiotherapy) and study treatment. Prior antibody therapy must be discontinued 8 weeks prior to start of study treatment. Prior hormonal therapy can be discontinued 24 hours prior to start of study treatment.
• Any prior PSA, MUC1, and/or brachyury-targeted immunotherapy (e.g., vaccine) must have been discontinued at least 12 weeks before initiation of study treatment. Subjects must have recovered from all acute toxicities from prior treatment prior to screening for this study.
• Prior treatment with Adenovirus-Based vectors immunotherapy
• Known active brain or central nervous system metastasis, or seizures requiring anticonvulsant treatment, cerebrovascular accident, or transient ischemic attack (\< 6 months prior to enrollment).
• Subjects with a history of autoimmune disease (active or past), such as but not restricted to inflammatory bowel disease, systemic lupus erythematosus, ankylosing spondylitis, scleroderma, or multiple sclerosis. Autoimmune-related thyroid disease, type I diabetes and vitiligo are permitted if the condition is well controlled.
• Subjects with serious intercurrent chronic or acute illness, such as cardiac or pulmonary disease, hepatic disease, or other illness considered by the Investigator as high risk for investigational drug treatment.
• Subjects with a history of heart disease, such as congestive heart failure (class II, III, or IV defined by the New York Heart Association functional classification), history of unstable or poorly controlled angina, or history (\< 1 year prior to enrollment) of ventricular arrhythmia.
• Subjects with a medical or psychological impediment that would impair the ability of the subject to receive therapy per protocol or impact ability to comply with the protocol or protocol-required visits and procedures.
• Presence of a known active acute or chronic infection, including human immunodeficiency virus (HIV, as determined by enzyme-linked immunosorbent assay \[ELISA\] and confirmed by western blot) and hepatitis B and hepatitis C virus (HBV/HCV, as determined by Hepatitis B surface antigen (HBsAg) and hepatitis C serology).
• Subjects on systemic intravenous or oral steroid therapy (or other immunosuppressive, such as azathioprine or cyclosporin A) are excluded on the basis of potential immune suppression. Subjects must have had at least 6 weeks of discontinuation of any steroid therapy (except that used as premedication for chemotherapy or contrast-enhanced studies) prior to enrollment. Physiologic (replacement) doses of steroids as well as nasal, topical or inhaled steroids are allowed.
• Subjects with known allergy or hypersensitivity to any component of the investigational product will be excluded.
• Subjects with acute or chronic skin disorders that will interfere with injection into the skin of the extremities or subsequent assessment of potential skin reactions will be excluded.
• Subjects vaccinated with a live (attenuated) vaccine (e.g., FluMist) or a killed (inactivated)/subunit vaccine (e.g., PNEUMOVAX, Fluzone) within 28 days or 14 days, respectively, of the first planned dose of ETBX vaccine.
• Patients with second malignancy within 3 years of enrollment; Patients curatively treated non-melanoma skin cancers or carcinoma in situ of the bladder, are not excluded.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (1)

• Bilusic M, McMahon S, Madan RA, Karzai F, Tsai YT, Donahue RN, Palena C, Jochems C, Marte JL, Floudas C, Strauss J, Redman J, Abdul Sater H, Rabizadeh S, Soon-Shiong P, Schlom J, Gulley JL. Phase I study of a multitargeted recombinant Ad5 PSA/MUC-1/brachyury-based immunotherapy vaccine in patients with metastatic castration-resistant prostate cancer (mCRPC). J Immunother Cancer. 2021 Mar;9(3):e002374. doi: 10.1136/jitc-2021-002374.

  PMID: 33762322 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Prostatic Neoplasms

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Dr. Marijo Bilusic
• Organization: National Cancer Institute

marijo.bilusic@nih.gov

240-760-6064

Study Officials

• Marijo Bilusic, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 28, 2018
• First Posted: March 29, 2018
• Study Start: July 24, 2018
• Primary Completion: January 15, 2020
• Study Completion: March 9, 2021
• Last Updated: May 19, 2021
• Results First Posted: December 22, 2020

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)