Biomarker Analysis of Castration-resistant Prostate Cancer Undergoing Bipolar Androgen Therapy

NCT04424654 | Completed Phase 2

• 1 other identifier: HSL-1820
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 2

Brief Summary

This is an open label phase II, single-arm, biomarker multi-institutional pilot study. Men with progressive metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen deprivation therapy (ADT) and at least one prior second generation AR-targeted therapy (either abiraterone or enzalutamide) will be enrolled in this study. All patients will receive treatment with testosterone cypionate 400 mg, intramuscular, every 28 days for a maximum of 3 cycles or limiting toxicity, if it occurs before the end of the scheduled therapy. After 3 cycles of BAT (12 weeks), patients may continue receiving this therapy off study at the discretion of the treating physician, if clinical/radiographic benefit. During the study period, patients will have plasma collected for cell-free tumor DNA analysis and CTC ARV7 status and also will perform 68Gallium-PSMA PET at baseline and then every 6 weeks.

Conditions

Prostate Cancer

Keywords

Castration-resistant prostate cancer; Bipolar androgen therapy; PSMA-PET

Outcome Measures

Primary Outcomes (1)

• Ga68-PSMA uptake and response to Bipolar Androgen Therapy (BAT)

  To evaluate the correlation between baseline Galium68-PSMA/PET maximal standard uptake value (SUVmax) and response to bipolar androgen therapy based on Prostate Cancer Working Group 3 (PCWG3).

  12 weeks

Secondary Outcomes (8)

• PSMA SUV kinetics during BAT

  12 weeks

• ARV7 status and response to BAT

  12 weeks

• AR mutational status and response to BAT

  12 weeks

• ARV7 status kinetics during BAT

  12 weeks

• cfDNA kinetics during BAT

  12 weeks

Study Arms (1)

Bipolar Androgen Therapy (BAT)

EXPERIMENTAL

Testosterone cypionate 400 mg IM every 28 days for 3 cycles

Drug: Testosterone cypionate

Interventions

Testosterone cypionate DRUG

Testosterone cypionate 400 mg IM

Also known as: Testosterone

Bipolar Androgen Therapy (BAT)

Eligibility Criteria

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

You may qualify if:

• Willing and able to provide signed informed consent.
• Males aged 18 years of age and above.
• Histological or cytologic proof of adenocarcinoma of the prostate.
• Known castration-resistant disease, defined according to PCWG3 criteria as: castrate serum testosterone level ≤ 50 ng/dL (≤ 1.7 nmol/L). Subjects who have failed initial hormonal therapy, either by orchiectomy or by using a GnRH agonist in combination with an anti-androgen, must first progress through anti-androgen withdrawal prior to being eligible. The minimum timeframe to document failure of anti-androgen withdrawal will be 4 weeks.
• Disease progression: serum PSA progression defined as 2 consecutive increases in PSA over a previous reference value within 6 months, each measurement at least 1 week apart, or documented bone lesions by the appearance of ≥ 2 new lesions by bone scintigraphy or dimensionally measurable soft tissue metastatic lesion assessed by CT or MRI.
• Absolute PSA ≥ 1.0 ng/mL at screening.
• Prior treatment with abiraterone, enzalutamide, apalutamide, darolutamide, bicalutamide, and/or ketoconazole is allowed. There is no limit on the maximum number or types of prior hormonal therapies received.
• Must be maintained on a GnRH analogue or have undergone orchiectomy.
• Radiographic evidence of metastatic disease by CT scan and/or bone scan, performed within the prior 6 months
• Karnofsky Performance Status (KPS): ≥ 80% within 14 days before start of study treatment (ECOG \< 2)
• Asymptomatic or minimally symptomatic mCRPC according to Brief Pain Inventory - Short Form (BPI-SF) performed during screening: asymptomatic is defined as BPI-SF item #3 score of 0 to 1; minimally symptomatic is defined as BPI-SF item #3 score of 2 to 4.
• Archived tumor tissue obtained prior to enrollment from a metastatic tumor lesion or from a primary tumor lesion (formalin fixed paraffin-embedded \[FFPE\] block or unstained tumor tissue sections). Tumor sample may be from core biopsy, punch biopsy, excisional biopsy, or surgical specimen).
• Participants must have adequate organ and bone marrow function measured within 28 days prior to administration of study treatment as defined below:
• Hemoglobin ≥ 9.0 g/dL with no blood transfusion in the past 28 days
• Absolute neutrophil count (ANC) ≥ 1.0 x 109/L

You may not qualify if:

• External-beam radiotherapy within the last 4 weeks prior to start of study treatment.
• Prior oral anti-androgen (e.g. bicalutamide, nilutamide, enzalutamide, apalutamide, darolutamide), or androgen synthesis inhibitor (e.g. abiraterone, orteronel) within the past 4 weeks is not permitted. 5-alpha reductase inhibitor therapies are not allowed as well.
• Prior treatment with chemotherapy for the treatment of metastatic hormone- sensitive prostate cancer is allowed if the last dose of chemotherapy was ≥ 6 months prior to enrollment. In addition, one prior chemotherapy agent for mCRPC will be allowed after a minimum wash-out period of 4 weeks prior to enrollment.
• Patients who have received prior treatment with bipolar androgen therapy (e.g. testosterone, BAT).
• Pain due to metastatic prostate cancer requiring opioid therapy.
• Patients with an intact prostate AND urinary obstructive symptoms are excluded (which includes patients with urinary symptoms from benign prostatic hyperplasia (BPH).
• Patients receiving anticoagulation therapy are not eligible for study.
• Patients with prior history of an arteriovenous thromboembolic event that occurred within the last 12 months are excluded.
• Participation in another clinical study with an investigational product during the last 4 weeks.
• Evidence of disease in sites or extent that, in the opinion of the investigator, would put the patient at risk from therapy with testosterone (e.g. femoral metastases with concern over fracture risk, severe and extensive spinal metastases with concern over spinal cord compression, extensive liver metastases).
• Concurrent use of other anticancer agents or treatments, with the following exceptions:
• Ongoing treatment with LHRH agonists or antagonists, denosumab or bisphosphonate (e.g. zoledronic acid) is allowed. Ongoing treatment should be kept at a stable schedule; however, if medically required, a change of dose, compound, or both is allowed.
• Any treatment modalities involving major surgery within 4 weeks prior to the start of study treatment.
• Symptomatic nodal disease, i.e. scrotal, penile or leg edema (CTCAE ≥ Grade 3).
• Patients are excluded if they have active, known brain metastases or leptomeningeal metastases.

Sponsors & Collaborators

• Hospital Sirio-Libanes: lead
• Hospital Moinhos de Vento: collaborator

Study Sites (2)

Hospital Moinhos de Vento

Porto Alegre, Rio Grande do Sul, 90035-000, Brazil

Location

Hospital Sirio-Libanes

São Paulo, 01308050, Brazil

Location

Related Publications (1)

• Gongora ABL, Marshall CH, Velho PI, Lopes CDH, Marin JF, Camargo AA, Bastos DA, Antonarakis ES. Extreme Responses to a Combination of DNA-Damaging Therapy and Immunotherapy in CDK12-Altered Metastatic Castration-Resistant Prostate Cancer: A Potential Therapeutic Vulnerability. Clin Genitourin Cancer. 2022 Apr;20(2):183-188. doi: 10.1016/j.clgc.2021.11.015. Epub 2021 Dec 24. No abstract available.

  PMID: 35027313 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

testosterone 17 beta-cypionate; Testosterone

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Androstenols; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Testosterone Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 3, 2020
• First Posted: June 11, 2020
• Study Start: September 22, 2020
• Primary Completion: May 1, 2022
• Study Completion: July 1, 2022
• Last Updated: August 3, 2022

Record last verified: 2021-04

Locations

BR (2)