Apalutamide + Hormone and Radiation Therapies for Prostate Cancer

(INNOVATE Trial)

Recruiting at 372 trial locations

Age: 18+

Sex: Male

Trial Phase: Phase 3

Sponsor: NRG Oncology

Must be taking: GnRH agonist/antagonist

Must not be taking: 5-alpha reductase inhibitors

Disqualifiers: Metastatic disease, Seizure history, Cardiac disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 11

Duration: 24 months

586 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether adding apalutamide (Erleada) to standard hormone and radiation treatments can better control prostate cancer that has spread to nearby lymph nodes after surgery. Apalutamide blocks male hormones that help cancer grow. The researchers aim to determine if this combination can prevent the cancer from spreading longer than the usual treatment. Men who have undergone prostate surgery and have cancer spread to pelvic lymph nodes might be suitable candidates, especially if they have detectable PSA levels post-surgery. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial requires you to stop or substitute any medications that lower the seizure threshold at least 30 days before joining. If you're using a 5-alpha reductase inhibitor, you must stop it before randomization. Other medications are not specifically mentioned, so it's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that apalutamide is generally safe for patients. Most people in studies tolerated apalutamide well, with serious side effects being rare. For instance, in the SPARTAN and TITAN studies, only a small number of patients (0.2%) experienced serious issues like a stroke. In the real-world ARON-3 study, apalutamide remained safe and effective. Apalutamide is already approved for treating other types of prostate cancer, which supports its safety. Always consult your doctor to understand how these findings apply to you. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for prostate cancer?

Researchers are excited about apalutamide for prostate cancer because it offers a novel approach by directly targeting androgen receptors, which play a key role in the growth of prostate cancer cells. Unlike standard treatments that primarily involve hormone therapy and radiation, apalutamide acts as an androgen receptor inhibitor, potentially improving outcomes by more effectively blocking the signals that fuel cancer growth. This could enhance the effectiveness of existing therapies and offer hope for better management of prostate cancer with fewer side effects.

What evidence suggests that adding apalutamide to hormone and radiation therapies might be an effective treatment for prostate cancer?

Research has shown that adding apalutamide to standard hormone therapy and radiation can benefit prostate cancer patients. In this trial, participants in Arm II will receive apalutamide along with hormone and radiation therapies. Studies have demonstrated that patients taking apalutamide with hormone therapy had a 65.1% survival rate after 48 months, compared to 51.8% for those taking a placebo. Another study found that apalutamide reduced the risk of death by 23% in patients with metastatic prostate cancer. Apalutamide works by preventing male hormones from attaching to cancer cells, which helps stop or slow the cancer's growth. These findings suggest that apalutamide can significantly extend the time patients live without their cancer spreading. ^{2 5 6 7 8}

Who Is on the Research Team?

Ronald C Chen

Principal Investigator

NRG Oncology

Are You a Good Fit for This Trial?

Men with prostate cancer who've had surgery and have lymph node involvement but no distant metastasis. They must have a detectable PSA level post-surgery, good organ function, and be on or willing to start hormone therapy. Excluded are those currently on certain medications, with recent seizures or severe cardiovascular events, uncontrolled infections or hypertension, inability to swallow pills, inflammatory bowel disease, prior chemotherapy for prostate cancer, or overlapping radiation treatment.

Inclusion Criteria

Hemoglobin >= 9.0 g/dL, independent of transfusion and/or growth factors (within 90 days prior to registration)

Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (Note: In subjects with Gilbert's syndrome, if total bilirubin is > 1.5 x ULN, measure direct and indirect bilirubin and if direct bilirubin is =< 1.5 x ULN, subject is eligible) (within 90 days prior to registration)

Platelet count >= 100,000 x 10^9/uL independent of transfusion and/or growth factors (within 90 days prior to registration)

Exclusion Criteria

I am currently using a 5-alpha reductase inhibitor but can stop if needed.

History of any of the following: Seizure or known condition that may pre-dispose to seizure (e.g. prior stroke within 1 year prior to registration, brain arteriovenous malformation, Schwannoma, meningioma, or other benign central nervous system [CNS] or meningeal disease which may require treatment with surgery or radiation therapy), Severe or unstable angina, myocardial infarction, arterial or venous thromboembolic events (e.g., pulmonary embolism, cerebrovascular accident including transient ischemic attacks), or clinically significant ventricular arrhythmias within 12 months prior to registration, New York Heart Association functional classification III/IV (Note: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association functional classification.), History of any condition that in the opinion of the investigator, would preclude participation in this study

Current evidence of any of the following: Known gastrointestinal disorder affecting absorption of oral medications, Active uncontrolled infection, Presence of uncontrolled hypertension (persistent systolic blood pressure [BP] >= 160 mmHg or diastolic BP >= 100 mmHg). Subjects with a history of hypertension are allowed, provided that BP is controlled to within these limits by anti-hypertensive treatment, Any chronic medical condition requiring a higher dose of corticosteroid than 10 mg prednisone/prednisolone once daily, Baseline moderate and severe hepatic impairment (Child-Pugh Class B & C), Inability to swallow oral pills, Any current condition that in the opinion of the investigator, would preclude participation in this study, Patients must not plan to participate in any other therapeutic clinical trials while receiving treatment on this study, Patients with inflammatory bowel disease

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive standard of care hormone therapy and radiation therapy, with or without apalutamide, for up to 24 months

24 months

5 visits per week for radiation therapy over 5-8 weeks, plus regular follow-ups

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

Every 6 months

Long-term follow-up

Annual monitoring for metastasis-free survival and other outcomes

Up to 7.5 years

Annually

What Are the Treatments Tested in This Trial?

Interventions

• Apalutamide

Trial Overview The trial is testing if adding Apalutamide to usual hormone therapy plus radiation after surgery can better prevent the spread of prostate cancer compared to standard treatment alone. It's a phase III study where patients receive high energy x-rays and drugs that block male hormones which may fuel cancer growth.

How Is the Trial Designed?

Group I: Arm II (hormone therapy, radiation therapy, apalutamide) Experimental Treatment 10 Interventions

Patients undergo standard of care hormone therapy and radiation therapy as in Arm I. Patients also receive apalutamide PO QD on days 1-90 of each cycle. Cycles repeat every 90 days for 8 cycles in the absence of disease progression or unacceptable toxicity. Patients in both arms may undergo CT, MRI, bone scan, and PET as clinically indicated throughout the study. Patients may also undergo blood sample collection throughout the study.

Group II: Arm I (hormone therapy, radiation therapy) Active Control 9 Interventions

Patients receive standard of care hormone therapy per physician discretion for 24 months. Patients also undergo standard of care pelvis and prostate bed radiation therapy 5 days per week over 5-6 or 7-8 weeks beginning within 90 days of randomization in the absence of disease progression or unacceptable toxicity. Patients in both arms may undergo CT, MRI, bone scan, and PET as clinically indicated throughout the study. Patients may also undergo blood sample collection throughout the study.

Who Is Running the Clinical Trial?

NRG Oncology

Lead Sponsor

Trials

242

Recruited

105,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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 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]

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, 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]

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]

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]

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]

Citations

1. jnj.com jnj.com/media-center/press-releases/erleada-apalutamide-demonstrates-statistically-significant-and-clinically-meaningful-improvement-in-overall-survival-compared-to-enzalutamide-in-patients-with-metastatic-castration-sensitive-prostate-cancer

ERLEADA® (apalutamide) demonstrates statistically ... Largest head-to-head real-world study in mCSPC demonstrated that ERLEADA® reduced risk of death by 23 percent at 24 months compared to ...

2. erleadahcp.com erleadahcp.com/efficacy/

Efficacy | ERLEADA® (apalutamide) HCP Median follow-up time was 44.0 months. 1. The survival rate at 48 months was 65.1% for ERLEADA ® + ADT patients vs 51.8% for placebo + ADT patients.

3. nature.com nature.com/articles/s41391-024-00929-6

Survival outcomes of apalutamide as a starting treatment Starting treatment with APA + ADT was associated with a significantly reduced risk of death compared with ENZ + ADT (aHR, 95%CI) (0.66, 0.51– ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39893578/

Real-world clinical usage and efficacy of apalutamide in ... The secondary outcomes were the efficacy of apalutamide: PSA response (50% or 90% decline), progression-free survival, and skin-adverse events ( ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2588931124002530

Apalutamide in Metastatic Castration-sensitive Prostate ... Our results show that apalutamide is a safe and effective drug in the real-world setting as well as in clinical trials.

6. erleadahcp.com erleadahcp.com/patient-reported-outcomes/

PATIENT-REPORTED OUTCOMES FOR HRQoL 1-6 Across the SPARTAN and TITAN studies, 3 patients (0.2%) treated with ERLEADA® and 2 patients (0.2%) treated with placebo died from a cerebrovascular event.

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39613567/

Results from the Multicenter Real-world ARON-3 Study Our results show that apalutamide is a safe and effective drug in the real-world setting as well as in clinical trials.

8. nejm.org nejm.org/doi/full/10.1056/NEJMoa1903307

Apalutamide for Metastatic, Castration-Sensitive Prostate ... In our trial, initial therapy with apalutamide in patients with metastatic, castration-sensitive prostate cancer led to improved clinical outcomes. The intent ...