Supraphysiological Androgen to Enhance Treatment Activity in Metastatic Castration-Resistant Prostate Cancer, SPECTRA Study
SPECTRA: Supraphysiological Androgen to Enhance Treatment Activity
4 other identifiers
interventional
69
1 country
1
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started May 2024
Typical duration for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 21, 2023
CompletedFirst Posted
Study publicly available on registry
September 15, 2023
CompletedStudy Start
First participant enrolled
May 21, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 31, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 31, 2027
January 14, 2026
January 1, 2026
2.9 years
August 21, 2023
January 12, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Greater than or equal to 50% decline in prostate-specific antigen from baseline (PSA50) response rate
Will assess \>= 50% decline in PSA following treatment with combination bipolar androgen therapy (BAT) and genotoxic chemotherapy (at least 12 weeks of total therapy). Will be calculated as the percentage with 95% confidence interval (CI) of the total number of subjects that achieved a PSA50 response.
From baseline up to 3 years
Secondary Outcomes (6)
Radiographic response
Up to 3 years
Radiographic progression-free survival (PFS)
The start of treatment until disease progression (per modified RECIST criteria or PCWG3 criteria for bone lesions), clinical progression (as determined by the treating physician), or death, whichever occurs first, assessed up to 3 years
PSA PFS
Time from the start of treatment until PSA progression (as defined by PCWG3 criteria), assessed up to 3 years
Overall survival
The start of treatment until death from any cause, assessed up to 3 years
Patient-reported outcome measure (PROMS) questionnaires
Up to 3 years
- +1 more secondary outcomes
Study Arms (9)
Cohort Ia (testosterone cypionate, carboplatin)
ACTIVE COMPARATORPatients continue to receive ADT per standard of care and receive testosterone cypionate IM on day 1 of cycle 1. Patients then receive testosterone cypionate IM and carboplatin IV on day 1 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. All patients undergo a biopsy, blood sample collection, bone scan and CT scan throughout the study.
Cohort Ib (testosterone cypionate, carboplatin)
ACTIVE COMPARATORPatients continue to receive ADT per standard of care and receive carboplatin IV on day 1 of cycle 1. Patients then receive testosterone cypionate IM and carboplatin IV on day 1 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. All patients undergo a biopsy, blood sample collection, bone scan and CT scan throughout the study.
Cohort Ic (testosterone cypionate, carboplatin)
EXPERIMENTALPatients continue to receive ADT per standard of care and receive testosterone cypionate IM and carboplatin IV on day 1 of cycle 1. Patients then receive testosterone cypionate IM and carboplatin IV on day 1 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. All patients undergo a biopsy, blood sample collection, bone scan and CT scan throughout the study.
Cohort IIa (testosterone cypionate, etoposide)
ACTIVE COMPARATORPatients continue to receive ADT per standard of care and receive testosterone cypionate IM on day 1 of cycle 1. Patients then receive testosterone cypionate IM on day 1 and etoposide PO QD on days 1-14 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. All patients undergo a biopsy, blood sample collection, bone scan and CT scan throughout the study.
Cohort IIb (testosterone cypionate, etoposide)
ACTIVE COMPARATORPatients continue to receive ADT per standard of care and receive etoposide PO QD on days 1-14 of cycle 1. Patients then receive testosterone cypionate IM on day 1 and etoposide PO QD on days 1-14 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. All patients undergo a biopsy, blood sample collection, bone scan and CT scan throughout the study.
Cohort IIc (testosterone cypionate, etoposide)
EXPERIMENTALPatients continue to receive ADT per standard of care and receive testosterone cypionate IM on day 1 and etoposide PO QD on days 1-14 of cycle 1. Patients then receive testosterone cypionate IM on day 1 and etoposide PO QD on days 1-14 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. All patients undergo a biopsy, blood sample collection, bone scan and CT scan throughout the study.
Cohort IIIa (ADT, testosterone cypionate, LuPSMA)
EXPERIMENTALPatients continue to receive ADT per standard of care and receive testosterone cypionate IM on day 1 of cycles 1-6. Patients receive LuPSMA IV on day 1 of cycles 2-6. Cycles repeat every 6 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive testosterone cypionate IM on day 1 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. All patients undergo a biopsy on study and blood sample collection on study, and bone scans, DEXA and CT scans throughout the trial. Patients may also undergo an optional second biopsy at the end of study treatment. Patients also undergo 68Ga-PSMA PET at screening and SPECT/CT throughout the study.
Cohort IIIb (ADT, testosterone cypionate, LuPSMA)
EXPERIMENTALPatients continue to receive ADT per standard of care and LuPSMA IV on day 1 of cycles 1-6. Patients also receive testosterone cypionate IM on day 1 of cycles 2-6 . Cycles repeat every 6 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients receive testosterone cypionate IM on day 1 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo 68Ga-PSMA PET at screening and SPECT/CT throughout the study. All patients undergo a biopsy on study and blood sample collection on study, and bone scans, DEXA and CT scans throughout the trial. Patients may also undergo an optional second biopsy at the end of study treatment.
Cohort IIIc (ADT, testosterone cypionate, LuPSMA)
EXPERIMENTALPatients continue to receive ADT per standard of care and receive testosterone cypionate IM on day 1 and LuPSMA IV on day 1 of cycles 1-6. Cycles repeat every 6 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive testosterone cypionate IM on day 1 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo 68Ga-PSMA PET at screening and SPECT/CT throughout the study. All patients undergo a biopsy on study and blood sample collection on study, and bone scans, DEXA and CT scans throughout the trial. Patients may also undergo an optional second biopsy at the end of study treatment.
Interventions
Undergo a biopsy
Undergo blood sample collection
Undergo bone scan
Given IV
Given PO
Undergo CT
Ancillary studies
Ancillary studies
Given IM
Given LuPSMA IV
Undergo DEXA
Given gallium 68Ga-PSMA-617
Undergo 68Ga-PSMA PET
Undergo SPECT/CT
Eligibility Criteria
You may qualify if:
- Must be willing to provide informed consent prior to any study specific procedures
- Age \>= 18 years
- Documented histologically confirmed adenocarcinoma of the prostate
- 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)
- PSA must be at least 2 ng/ml and rising on two successive measurements at least two weeks apart
- 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
- Subjects enrolling to Cohort 3 must demonstrate evidence of PSMA expression on 68Ga-PSMA-11 PET as defined in the VISION trial
- No prior chemotherapy for the treatment of mCRPC. Patients may have received docetaxel for the treatment of hormone-sensitive prostate cancer
- 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
- Hemoglobin \>= 9 g/dL with no blood transfusion in the past 28 days (within 30 days prior to administration of study treatment)
- Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L (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)
- Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) (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)
- 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)
- +6 more criteria
You may not qualify if:
- Involvement in the planning and/or conduct of the study
- Other malignancy unless curatively treated with no evidence of disease for \>= 2 years except: adequately treated non-melanoma skin cancer, non-muscle invasive bladder cancer
- Persistent toxicities (Common Terminology Criteria for Adverse Event (CTCAE) grade \> 2) caused by previous cancer therapy, excluding alopecia
- 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
- Use of corticosteroids at a dose equivalent to \> 10 mg of prednisone daily
- Planning to receive concurrent treatment with another systemic cancer therapy, aside from a luteinizing hormone releasing hormone (LHRH) analogue
- 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
- Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery
- Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, uncontrolled major seizure disorder, uncontrolled hypertension (blood pressure \[BP\] \>= 165/100), history of prior stroke, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease or any psychiatric disorder that prohibits obtaining informed consent
- Patients with a known hypersensitivity to the testosterone cypionate, etoposide, carboplatin or any of the excipients of these products
- Patients with known active hepatitis (i.e., hepatitis B or C) due to risk of transmitting the infection through blood or other body fluids
- Evidence of serious and/or unstable pre-existing medical, psychiatric or other condition (including laboratory abnormalities) that could interfere with patient safety or provision of informed consent to participate in this study
- Any psychological, familial, sociological, or geographical condition that could potentially interfere with compliance with the study protocol and follow-up schedule
- 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)
- Patients with pain attributable to their prostate cancer.
- +6 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University of Washingtonlead
- National Cancer Institute (NCI)collaborator
Study Sites (1)
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, 98109, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Michael Schweizer
Fred Hutch/University of Washington Cancer Consortium
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 21, 2023
First Posted
September 15, 2023
Study Start
May 21, 2024
Primary Completion (Estimated)
March 31, 2027
Study Completion (Estimated)
December 31, 2027
Last Updated
January 14, 2026
Record last verified: 2026-01
Data Sharing
- IPD Sharing
- Will not share