High-Dose Testosterone + Chemotherapy for Prostate Cancer

Overseen by Michael Schweizer

Age: 18+

Sex: Male

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: University of Washington

Must not be taking: Warfarin, Corticosteroids

Disqualifiers: Other malignancy, Brain metastases, Uncontrolled hypertension, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial tests if high levels of a hormone combined with cancer treatment can help treat prostate cancer that has spread and is not responding to usual treatments. The hormone may damage cancer cell DNA, and the treatment helps kill or slow the cancer cells.

Will I have to stop taking my current medications?

The trial requires a 2-week period without taking your most recent prostate cancer therapy before starting the study. If you're on steroids, you should stop them at least 1 week before starting treatment. Discuss any other medications with the study team to ensure they don't interfere with the trial.

What data supports the effectiveness of the drug combination of high-dose testosterone and chemotherapy for prostate cancer?

A pilot trial showed that combining androgen treatment with chemotherapy (Carboplatin) led to a complete or partial response in 73.3% of patients with metastatic prostate cancer, with a median progression-free survival of 31 months. This suggests that the combination can be effective in managing advanced prostate cancer. ^{1 2 3 4 5}

Is high-dose testosterone combined with chemotherapy safe for prostate cancer treatment?

Research on high-dose testosterone therapy, known as bipolar androgen therapy, has been conducted in men with castration-resistant prostate cancer, showing that it can be administered safely. However, specific safety data for the combination of high-dose testosterone with chemotherapy is not directly available from the provided studies. ^{6 7 8 9 10}

What makes the High-Dose Testosterone + Chemotherapy treatment for prostate cancer unique?

This treatment is unique because it combines high doses of testosterone with chemotherapy, which is a novel approach for prostate cancer. Unlike traditional hormone therapies that lower testosterone, this method uses high testosterone levels to potentially inhibit cancer growth, especially in castration-resistant prostate cancer, by causing DNA damage in cancer cells. ^{1 3 5 6 11}

Research Team

Michael Schweizer

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Eligibility Criteria

Men over 18 with advanced prostate cancer resistant to hormone therapy and no prior chemo for this condition. They must have rising PSA levels, adequate organ function, ECOG status of 2 or less, life expectancy of at least 16 weeks, and agree to use two forms of contraception. Cannot join if they've had major surgery recently, uncontrolled medical issues, other cancers (with exceptions), known allergies to trial drugs or certain infections.

Inclusion Criteria

You have a life expectancy of at least 16 weeks.

You must agree to the terms of any study prior to participating.

I haven't had chemotherapy for metastatic castration-resistant prostate cancer, but may have had docetaxel for hormone-sensitive cancer.

Exclusion Criteria

I am taking more than 10 mg of prednisone or its equivalent daily.

I do not have any serious uncontrolled health conditions.

My cancer's location puts me at risk if I receive testosterone therapy.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive supraphysiological testosterone and chemotherapy (carboplatin or etoposide) in 28-day cycles

16 weeks

1 visit per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 3 years

Every 6 months

Treatment Details

Interventions

• Carboplatin (Chemotherapy)
• Etoposide (Chemotherapy)
• Testosterone Cypionate (Hormone Therapy)

Trial Overview The SPECTRA study is testing whether high doses of testosterone combined with chemotherapy drugs Carboplatin or Etoposide can help treat metastatic castration-resistant prostate cancer by damaging the DNA in tumor cells that thrive in low testosterone environments.

Participant Groups

Group I: Cohort Ic (testosterone cypionate, carboplatin) Experimental Treatment 8 Interventions

Patients 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.

Group II: Cohort IIc (testosterone cypionate, etoposide) Experimental Treatment 8 Interventions

Patients 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.

Group III: Cohort IIa (testosterone cypionate, etoposide) Active Control 8 Interventions

Patients 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.

Group IV: Cohort IIb (testosterone cypionate, etoposide) Active Control 8 Interventions

Patients 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.

Group V: Cohort Ia (testosterone cypionate, carboplatin) Active Control 8 Interventions

Patients 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.

Group VI: Cohort Ib (testosterone cypionate, carboplatin) Active Control 8 Interventions

Patients 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.

Carboplatin is already approved in Canada for the following indications:

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

University of Washington

Lead Sponsor

Trials

1,858

Recruited

2,023,000+

Dr. Timothy H. Dellit

University of Washington

Chief Executive Officer since 2023

MD from University of Washington

Dr. Anneliese Schleyer

University of Washington

Chief Medical Officer since 2023

MD, MHA

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

Findings from Research

In a study of 28 hormone-resistant prostate cancer patients, combined treatment with Testosterone and 32P led to distinct improvements in 26 patients, with a mean remission duration of 3 months and a mean survival rate of 7 months.

The treatment appeared to stimulate the uptake of 32P in the bone matrix surrounding the tumors rather than directly in the tumor cells, suggesting a unique mechanism of action for the androgen in enhancing the effectiveness of the isotope.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment with 32P of carcinoma of the prostate (author's transl)]. Vangelista, R., Fiorentino, M., Pizzi, G., et al.[2022]

In a study involving 39 patients with localized prostate cancer, neoadjuvant treatment with degarelix alone resulted in significantly higher levels of intratumoral dihydrotestosterone (DHT) compared to combinations of degarelix with bicalutamide or LHRH agonist with bicalutamide, suggesting a unique mechanism of action for degarelix.

Patients receiving degarelix had lower serum follicle-stimulating hormone (FSH) levels after 12 weeks compared to those on LHRH agonist, indicating potential advantages in hormonal regulation during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase II, Randomized, Open-Label Study of Neoadjuvant Degarelix versus LHRH Agonist in Prostate Cancer Patients Prior to Radical Prostatectomy. Sayyid, RK., Evans, A., Hersey, K., et al.[2017]

The pilot study involving 12 patients with locally advanced prostate cancer demonstrated that the immunotherapy D17DT was well tolerated and led to significant reductions in serum testosterone and PSA levels in some patients.

Four patients achieved castrate levels of testosterone that were maintained for up to 9 months, suggesting that immunizing against GnRH could be an effective alternative to traditional hormonal therapies, especially in those with higher anti-GnRH antibody titres.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-GnRH antibodies can induce castrate levels of testosterone in patients with advanced prostate cancer. Simms, MS., Scholfield, DP., Jacobs, E., et al.[2018]

The ARTFORM study is a randomized controlled trial designed to assess the effectiveness of testosterone replacement therapy in improving quality of life for male patients with advanced cancer and low testosterone levels.

The primary outcome will be measured through health-related quality of life questionnaires at week 12, providing insights into how androgen replacement may alleviate cancer-related symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Androgen replacement therapy for cancer-related symptoms in male advanced cancer patients: study protocol for a randomised prospective trial (ARTFORM study). Izumi, K., Shigehara, K., Nohara, T., et al.[2018]

In a pilot trial involving 15 patients with untreated metastatic prostate cancer, a combination of maximal androgen blockade and intermittent cytotoxic therapy led to significant responses, with 20% achieving a complete response and 53.3% a partial response, alongside a median progression-free survival of 31 months.

While the treatment showed promising efficacy, it was associated with severe side effects, including high rates of thrombocytopenia (87%) and leukopenia (80%), necessitating dose adjustments in most treatment cycles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot trial of chemohormonal therapy for metastatic prostate carcinoma. Dawson, NA., Wilding, G., Weiss, RB., et al.[2019]

Androgen ablation is effective for treating metastatic prostate cancer, but patients eventually develop castration-resistant prostate cancer (CRPC), which still expresses androgen receptors (AR).

A new clinical trial is testing 'bipolar androgen therapy' using intramuscular testosterone injections to achieve supraphysiologic levels, aiming to inhibit CRPC growth by preventing cancer cells from adapting to hormonal changes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bipolar androgen therapy: the rationale for rapid cycling of supraphysiologic androgen/ablation in men with castration resistant prostate cancer. Denmeade, SR., Isaacs, JT.[2021]

Leuprolide effectively suppresses testicular androgen production in human males with prostatic cancer, mimicking the effects of surgical castration.

The treatment leads to a decrease in pituitary hormones LH and FSH, which in turn reduces testosterone and dihydrotestosterone levels, demonstrating its potential as a non-surgical alternative for managing prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of synthetic agonist analogue of gonadotropin-releasing hormone (leuprolide) on testicular androgen production in patients with carcinoma of prostate. Santen, RJ., Warner, B.[2013]

In a study of 16 patients with hormone refractory prostate cancer, a moderate dose of diethylstilbestrol diphosphate (250 mg/day) significantly reduced PSA levels from an average of 528 ng/ml to 154 ng/ml, indicating effective treatment.

The treatment also provided pain relief for many patients, with four experiencing complete pain disappearance, and it was associated with minimal toxicity, as no serious side effects were reported, including cardiovascular issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Moderate dose diethylstilbestrol diphosphate therapy in hormone refractory prostate cancer. Takezawa, Y., Nakata, S., Kobayashi, M., et al.[2019]

Teverelix DP, a gonadotropin-releasing hormone antagonist, effectively suppresses testosterone levels to below the castration threshold in patients with advanced prostate cancer, with two specific subcutaneous regimens achieving a mean duration of castration of approximately 55 to 69 days.

The treatment is safe and well-tolerated, with the most common side effect being mild injection site reactions, and no severe adverse events reported, indicating a favorable safety profile for this new therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, Pharmacokinetic and Pharmacodynamic Evaluation of Teverelix for the Treatment of Hormone-Sensitive Advanced Prostate Cancer: Phase 2 Loading-Dose-Finding Studies. MacLean, CM., Ulys, A., Jankevičius, F., et al.[2023]

Pretreatment with either diethylstilbestrol diphosphate (DES-P) or chlormadinone acetate (CMA) for two weeks before administering leuprolide acetate effectively prevented disease flare in prostate cancer patients, as indicated by stable PSA levels.

Patients who received DES-P or CMA showed no significant increase in testosterone levels after leuprolide administration, unlike those who did not receive pretreatment, highlighting the efficacy of these agents in managing hormone levels during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibition of disease flare with diethylstilbestrol diphosphate and chlormadinone acetate administration for two weeks prior to slow-releasing leuprolide acetate in prostatic cancer patients. Ohuchi, H., Noguchi, K., Kinoshita, Y., et al.[2014]

In a novel approach, four heavily pretreated Japanese patients with castration-resistant prostate cancer showed clinical responses to high doses of testosterone, challenging traditional androgen deprivation therapy.

One of the patients treated was on hemodialysis, indicating that this treatment may be applicable even in complex medical situations, suggesting a potential new avenue for therapy in difficult cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical response in metastatic castration-resistant prostate cancer (mCRPC) cases treated with supra-physiological doses of testosterone: Bipolar androgen therapy. Hoshi, S., Bilim, V., Hoshi, K., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

[Treatment with 32P of carcinoma of the prostate (author's transl)]. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

A Phase II, Randomized, Open-Label Study of Neoadjuvant Degarelix versus LHRH Agonist in Prostate Cancer Patients Prior to Radical Prostatectomy. [2017]

3. England pubmed.ncbi.nlm.nih.gov

Anti-GnRH antibodies can induce castrate levels of testosterone in patients with advanced prostate cancer. [2018]

4. Japan pubmed.ncbi.nlm.nih.gov

Androgen replacement therapy for cancer-related symptoms in male advanced cancer patients: study protocol for a randomised prospective trial (ARTFORM study). [2018]

5. United States pubmed.ncbi.nlm.nih.gov

A pilot trial of chemohormonal therapy for metastatic prostate carcinoma. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

Bipolar androgen therapy: the rationale for rapid cycling of supraphysiologic androgen/ablation in men with castration resistant prostate cancer. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Evaluation of synthetic agonist analogue of gonadotropin-releasing hormone (leuprolide) on testicular androgen production in patients with carcinoma of prostate. [2013]

8. England pubmed.ncbi.nlm.nih.gov

Moderate dose diethylstilbestrol diphosphate therapy in hormone refractory prostate cancer. [2019]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Safety, Pharmacokinetic and Pharmacodynamic Evaluation of Teverelix for the Treatment of Hormone-Sensitive Advanced Prostate Cancer: Phase 2 Loading-Dose-Finding Studies. [2023]

10. Japan pubmed.ncbi.nlm.nih.gov

Inhibition of disease flare with diethylstilbestrol diphosphate and chlormadinone acetate administration for two weeks prior to slow-releasing leuprolide acetate in prostatic cancer patients. [2014]

11. England pubmed.ncbi.nlm.nih.gov

Clinical response in metastatic castration-resistant prostate cancer (mCRPC) cases treated with supra-physiological doses of testosterone: Bipolar androgen therapy. [2023]