Clinical Trial · NCT06039371

Supraphysiological Androgen to Enhance Treatment Activity in Metastatic Castration-Resistant Prostate Cancer, SPECTRA Study

Overview

This phase II trial studies how well giving testosterone at levels higher than normally found in the body (supraphysiological) works to enhance chemotherapy treatment, and Lutetium 177Lu-prostate specific-membrane antigen (PSMA)-617 (LuPSMA) in patients with prostate cancer that has progressed despite being previously treated with androgen therapies and has spread from where it first started (prostate) to other places in the body (metastatic castration-resistant prostate cancer). In patients that have developed progressive cancer in spite of standard hormonal treatment, administering supraphysiological testosterone may result in regression of tumors by causing deoxyribonucleic acid (DNA) damage in tumor cells that have adapted to low testosterone conditions. Carboplatin is in a class of medications known as platinum-containing compounds. Carboplatin works by killing, stopping or slowing the growth of tumor cells. Etoposide is in a class of medications known as podophyllotoxin derivatives. It blocks a certain enzyme needed for cell division and DNA repair and may kill tumor cells. Radioactive drugs, such as LuPSMA, may carry radiation directly to tumor cells and not harm normal cells. Giving supraphysiological levels of testosterone and carboplatin or etoposide or LuPSMA together may be an effective treatment for metastatic castration-resistant prostate cancer.

Sponsor

University of Washington

Phase

Phase 2

Contacts

Michael Schweizer (CONTACT)

schweize@uw.edu

206-606-6252

Michael Schweizer (PRINCIPAL_INVESTIGATOR)

ClinicalTrials.gov

NCT06039371

Drug / Compound

PSMA-617

Isotope(s):

Target(s):

PSMA

Ligand Class: Small Molecules

Chelator: DOTA

PSMA-11

Isotope(s):

Target(s):

PSMA

Ligand Class: Small Molecules

Chelator: HBED-CC

Eligibility

Inclusion

Patients must have progressed on at least one prior next-generation androgen receptor-signalling inhibitor (e.g., abiraterone, enzalutamide, etc.). There must be at least a 2-week washout period after stopping the most recent approved therapy for metastatic castration-resistant prostate cancer (mCRPC) (e.g., abiraterone, enzalutamide, Ra-223, sipuleucel-t) prior to cycle 1, day 1. If applicable, patients should be weaned off steroids at least 1 week prior to starting treatment
Documented histologically confirmed adenocarcinoma of the prostate
Patients must have a life expectancy \>= 16 weeks
Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations
Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
No prior chemotherapy for the treatment of mCRPC. Patients may have received docetaxel for the treatment of hormone-sensitive prostate cancer
At least one lesion (measurable and/or non-measurable) that can be accurately assessed at baseline by CT, positron emission tomography (PET), magnetic resonance imaging (MRI) and/or bone scan and is suitable for repeated assessment
Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L (within 30 days prior to administration of study treatment)
Must be willing to undergo metastatic biopsy and have a lesion amenable for biopsy
Prior treatment with non-chemotherapy investigational agents is permitted. There must be at least a 2-week washout period after stopping any investigational cancer agent prior to cycle 1, day 1
Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) (within 30 days prior to administration of study treatment)
Platelet count \>= 100 x 10\^9/L (within 30 days prior to administration of study treatment)
Patients must have creatinine clearance estimated using the Cockcroft-Gault equation or based on 24 hour urine test of \>= 51 mL/min (within 30 days prior to administration of study treatment)
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) / alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional upper limit of normal unless liver metastases are present in which case they must be =\< 5x ULN (within 30 days prior to administration of study treatment)
PSA must be at least 2 ng/ml and rising on two successive measurements at least two weeks apart
Patient must have evidence of castration resistant prostate cancer as evidenced by PSA progression (per Prostate Cancer Working Group 3 \[PCWG3\] criteria) and a castrate serum testosterone level (i.e., =\< 50 mg/dL)
Male patients and their partners, who are sexually active and of childbearing potential, must agree to the use of two highly effective forms of contraception in combination, throughout the period of taking study treatment and for 6 months after last dose of study drug(s) to prevent pregnancy in a partner
Hemoglobin \>= 9 g/dL with no blood transfusion in the past 28 days (within 30 days prior to administration of study treatment)
Subjects enrolling to Cohort 3 must demonstrate evidence of PSMA expression on 68Ga-PSMA-11 PET as defined in the VISION trial

Exclusion

Prior history of deep venous thrombosis or pulmonary embolism within 5 years prior to enrollment in the study and not currently on systemic anticoagulation.
Patients with known active hepatitis (i.e., hepatitis B or C) due to risk of transmitting the infection through blood or other body fluids
Patients with a known hypersensitivity to the testosterone cypionate, etoposide, carboplatin or any of the excipients of these products
Patients with symptomatic uncontrolled brain metastases. A scan to confirm the absence of brain metastases is not required. Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days
Tumor causing urinary outlet obstruction that requires catheterization for voiding. Patients that require catheterization to void secondary to benign strictures or other non-cancer causes will be permitted to enroll. Patients with percutaneous nephrostomy tubes will also be permitted to enroll
Patients with pain attributable to their prostate cancer.
Excluded due to risk of venous thromboembolism from hormone supplementation
Any psychological, familial, sociological, or geographical condition that could potentially interfere with compliance with the study protocol and follow-up schedule
Planning to receive concurrent treatment with another systemic cancer therapy, aside from a luteinizing hormone releasing hormone (LHRH) analogue
Use of corticosteroids at a dose equivalent to \> 10 mg of prednisone daily
Persistent toxicities (Common Terminology Criteria for Adverse Event (CTCAE) grade \> 2) caused by previous cancer therapy, excluding alopecia
Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery
Involvement in the planning and/or conduct of the study
Evidence of disease that, in the opinion of the investigator, would put the patient at risk from testosterone therapy (e.g. femoral metastases with concern over fracture risk, spinal metastases with concern over spinal cord compression, lymph node disease with concern for ureteral obstruction)
Use of warfarin is not permitted. Low-molecular weight heparin and direct oral anticoagulants are allowed, but their use should be discussed with the principal investigator (PI) first
Patients with NYHA (New York Heart Association) class III or IV heart failure or history of a prior myocardial infarction (MI) within 5 years of enrollment to the study.
Excluded due to increased risk of cardiovascular events with testosterone supplementation
Excluded due to concern for pain flare due to testosterone supplementation