Apalutamide + Targeted Radiation for Prostate Cancer

Recruiting at 309 trial locations

Age: 18+

Sex: Male

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: ECOG-ACRIN Cancer Research Group

Must be taking: Androgen deprivation

Disqualifiers: Seizures, Inflammatory bowel disease, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This phase III trial tests two questions by two separate comparisons of therapies. The first question is whether enhanced therapy (apalutamide in combination with abiraterone + prednisone) added to standard of care (prostate radiation therapy and short term androgen deprivation) is more effective compared to standard of care alone in patients with prostate cancer who experience biochemical recurrence (a rise in the blood level of prostate specific antigen \[PSA\] after surgical removal of the prostate cancer). A second question tests treatment in patients with biochemical recurrence who show prostate cancer spreading outside the pelvis (metastasis) by positron emission tomography (PET) imaging. In these patients, the benefit of adding metastasis-directed radiation to enhanced therapy (apalutamide in combination with abiraterone + prednisone) is tested. Diagnostic procedures, such as PET, may help doctors look for cancer that has spread to the pelvis. Androgens are hormones that may cause the growth of prostate cancer cells. Apalutamide may help fight prostate cancer by blocking the use of androgens by the tumor cells. Metastasis-directed targeted radiation therapy uses high energy rays to kill tumor cells and shrink tumors that have spread. This trial may help doctors determine if using PET results to deliver more tailored treatment (i.e., adding apalutamide, with or without targeted radiation therapy, to standard of care treatment) works better than standard of care treatment alone in patients with biochemical recurrence of prostate cancer.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, it mentions that a short course of low-dose anti-androgen like bicalutamide is allowed before starting the study treatment. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug Apalutamide in treating prostate cancer?

Apalutamide has been shown to improve survival and delay disease progression in patients with metastatic castration-sensitive prostate cancer when added to standard hormone therapy, according to a large international study. It is also being studied in combination with radiation therapy to potentially enhance treatment outcomes for prostate cancer. ^{1 2 3 4 5}

Is the combination of Apalutamide and targeted radiation therapy safe for humans?

Apalutamide, used for prostate cancer, is generally well tolerated, with fatigue and skin reactions being common side effects. It has been studied in combination with other therapies, showing a safety profile similar to placebo in some trials. ^{1 2 3 6 7}

How is the drug Apalutamide unique in treating prostate cancer?

Apalutamide is unique because it is an oral drug that specifically targets androgen receptors, which are proteins that help prostate cancer cells grow. It is used in combination with targeted radiation to improve outcomes in prostate cancer patients, offering a novel approach compared to traditional treatments that may not combine these specific therapies. ^{1 2 3 4 6}

Research Team

Neha Vapiwala

Principal Investigator

ECOG-ACRIN Cancer Research Group

Eligibility Criteria

Men with prostate cancer that has returned after surgery, evidenced by rising PSA levels. They must be suitable for standard radiation and hormone therapy, have no spread of cancer outside the pelvis as confirmed by imaging, and meet specific health criteria like adequate blood counts and liver function.

Inclusion Criteria

Hemoglobin (Hgb) >= 9.0 g/dL

I have not started hormone therapy for cancer return before my first PET scan.

Patient must not be enrolled in another therapeutic clinical trial

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Baseline Assessment

Patients undergo SOC PET/CT or PET/MR scan at baseline to determine PET status

1 week

1 visit (in-person)

Treatment

Patients receive standard of care external beam radiation therapy (EBRT) and androgen deprivation therapy (ADT) with or without apalutamide, and possibly metastasis-directed radiation therapy based on PET results

6 months

Multiple visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

Up to 10 years

Every 3 months for 2 years, every 6 months for years 3-5, then annually for years 6-10

Treatment Details

Interventions

• Apalutamide (Antiandrogen)
• Targeted Radiation Therapy (Radiation)

Trial Overview The trial is testing if adding apalutamide (a drug blocking male hormones used by tumor cells) to standard care improves outcomes in patients whose prostate cancer has returned post-surgery. It also examines whether targeted radiation based on PET scan results offers additional benefits.

Participant Groups

Group I: Arm D (EBRT, STAD, apalutamide, RT) Experimental Treatment 18 Interventions

STEP 0: Patients undergo SOC PET/CT or PET/MR scan at baseline. Patients randomized to Arms C or D and receiving fluciclovine F18 IV undergo a repeat PET2 at time of PSA progression or clinical concerns for progression or 12 months after completion of enhanced systemic therapy, whichever occurs first. Patients in Arm C or D using another tracer for PET1 do not undergo PET2. STEP 1: Patients who are PET positive for extra pelvic metastases undergo SOC EBRT and receive goserelin acetate SC, leuprolide acetate IM, triptorelin IM, relugolix PO, or degarelix SC as in Arm A and apalutamide PO QD as in Arm B. Patients also undergo SBRT or 3D CRT, IMRT (including VMAT), and IMPT over 3-10 fractions in the absence of disease progression or unacceptable toxicity.

Group II: Arm C (EBRT, STAD, apalutamide) Experimental Treatment 13 Interventions

STEP 0: Patients undergo SOC PET/CT or PET/MR scan at baseline. Patients randomized to Arms C or D and receiving fluciclovine F18 IV undergo a repeat PET2 at time of PSA progression or clinical concerns for progression or 12 months after completion of enhanced systemic therapy, whichever occurs first. Patients in Arm C or D using another tracer for PET1 do not undergo PET2. STEP 1: Patients who are PET positive for extra pelvic metastases undergo SOC EBRT and receive goserelin acetate SC, leuprolide acetate IM, triptorelin IM, relugolix PO, or degarelix SC as in Arm A. Patients also receive apalutamide PO QD as in Arm B.

Group III: Arm B (EBRT, STAD, apalutamide) Experimental Treatment 13 Interventions

STEP 0: Patients undergo SOC PET/CT or PET/MR scan at baseline. Patients randomized to Arms C or D and receiving fluciclovine F18 IV undergo a repeat PET2 at time of PSA progression or clinical concerns for progression or 12 months after completion of enhanced systemic therapy, whichever occurs first. Patients in Arm C or D using another tracer for PET1 do not undergo PET2. STEP 1: Patients who are PET negative for extra pelvic metastases undergo SOC EBRT and receive goserelin acetate SC, leuprolide acetate IM, triptorelin IM, relugolix PO, or degarelix SC as in Arm A. Patients also receive apalutamide PO QD for 6 months in the absence of disease progression or unacceptable toxicity.

Group IV: Arm A (EBRT, short-term androgen deprivation therapy [STAD]) Active Control 12 Interventions

STEP 0: Patients undergo SOC PET/CT or PET/MR scan at baseline. Patients randomized to Arms C or D and receiving fluciclovine F18 IV undergo a repeat PET2 at time of PSA progression or clinical concerns for progression or 12 months after completion of enhanced systemic therapy, whichever occurs first. Patients in Arm C or D using another tracer for PET1 do not undergo PET2. STEP 1: Patients who are PET negative for extera pelvic metastases undergo SOC EBRT for 6 months. Patients also receive goserelin acetate SC, leuprolide acetate IM, triptorelin IM, relugolix PO, or degarelix SC for 6 months starting up to 3 months prior to EBRT but no later than 7 days after start of EBRT. All treatment continues for 6 months in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

ECOG-ACRIN Cancer Research Group

Lead Sponsor

Trials

122

Recruited

160,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a phase III study (TITAN) involving men with metastatic castration-sensitive prostate cancer, adding apalutamide to androgen deprivation therapy significantly improved median radiographic progression-free survival and overall survival.

Apalutamide was found to maintain health-related quality of life and had a safety profile similar to that of placebo when combined with androgen deprivation therapy, expanding treatment options for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apalutamide: A Review in Metastatic Castration-Sensitive Prostate Cancer. Hoy, SM.[2021]

The SAVE trial is a Phase II study involving 202 men with advanced prostate cancer, comparing the effects of apalutamide combined with salvage radiotherapy against androgen-deprivation therapy plus salvage radiotherapy.

The primary goal is to evaluate sexual function after nine months of treatment, while also assessing quality of life, safety, and short-term efficacy of apalutamide, highlighting its potential benefits in managing prostate cancer post-surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II open-label study investigating apalutamide in patients with biochemical progression after radical prostatectomy. Dirix, P., Strijbos, M., den Mooter, TV., et al.[2021]

Apalutamide is an oral androgen receptor inhibitor that effectively blocks androgen effects, and it received its first global approval in February 2018 for treating non-metastatic castration-resistant prostate cancer (nmCRPC).

Currently, apalutamide is being tested in phase III trials for various prostate cancer stages, including metastatic castration-resistant prostate cancer and high-risk localized prostate cancer, indicating its potential for broader applications in prostate cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apalutamide: First Global Approval. Al-Salama, ZT.[2019]

In a study involving 57 patients with metastatic castration-resistant prostate cancer (mCRPC), the combination of apalutamide with abiraterone acetate and prednisone was well tolerated and demonstrated significant antitumor activity, particularly in patients who had not previously been treated with androgen receptor inhibitors.

While apalutamide reduced the systemic exposure to prednisone by 61%, no significant adverse events related to mineralocorticoid excess were observed, indicating a favorable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, Safety, and Antitumor Effect of Apalutamide with Abiraterone Acetate plus Prednisone in Metastatic Castration-Resistant Prostate Cancer: Phase Ib Study. Posadas, EM., Chi, KN., de Wit, R., et al.[2021]

Apalutamide demonstrated stronger radio-sensitizing effects compared to bicalutamide in both hormone-sensitive and hormone-resistant prostate cancer cell lines, suggesting it may enhance the effectiveness of radiotherapy.

In vivo studies showed that combining apalutamide with radiotherapy resulted in significantly greater tumor necrosis in mouse models, indicating a potential for improved treatment outcomes in prostate cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apalutamide radio-sensitisation of prostate cancer. Kakouratos, C., Kalamida, D., Lamprou, I., et al.[2023]

In the SPARTAN trial, apalutamide significantly improved metastasis-free survival in men with non-metastatic castration-resistant prostate cancer (nmCRPC) receiving androgen-deprivation therapy, demonstrating its efficacy as a treatment option.

Apalutamide was generally well tolerated, with fatigue being the most common side effect, indicating a favorable safety profile while maintaining health-related quality of life for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apalutamide: A Review in Non-Metastatic Castration-Resistant Prostate Cancer. Al-Salama, ZT.[2020]

Apalutamide, an oral medication for non-metastatic castration-resistant prostate cancer, can cause a range of skin reactions, including a rare lichenoid reaction, as demonstrated in a case study of a patient after 4 months of treatment.

This case highlights the importance of a multidisciplinary approach in identifying and managing drug-related adverse events, which can improve diagnosis and treatment strategies for patients experiencing side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apalutamide-induced lichenoid reaction in a patient with non-metastatic castrate-resistant prostate cancer. Cremante, M., Puglisi, S., Gandini, A., et al.[2023]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Apalutamide: A Review in Metastatic Castration-Sensitive Prostate Cancer. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Phase II open-label study investigating apalutamide in patients with biochemical progression after radical prostatectomy. [2021]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Apalutamide: First Global Approval. [2019]

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

Pharmacokinetics, Safety, and Antitumor Effect of Apalutamide with Abiraterone Acetate plus Prednisone in Metastatic Castration-Resistant Prostate Cancer: Phase Ib Study. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Apalutamide radio-sensitisation of prostate cancer. [2023]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Apalutamide: A Review in Non-Metastatic Castration-Resistant Prostate Cancer. [2020]

7. England pubmed.ncbi.nlm.nih.gov

Apalutamide-induced lichenoid reaction in a patient with non-metastatic castrate-resistant prostate cancer. [2023]