Apalutamide + Hormone and Radiation Therapies for Prostate Cancer

(INNOVATE Trial)

Recruiting at 334 trial locations

Age: 18+

Sex: Male

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

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

Pivotal Trial (Near Approval)

Prior Safety Data

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This phase III trial studies whether adding apalutamide to the usual treatment improves outcome in patients with lymph node positive prostate cancer after surgery. Radiation therapy uses high energy x-ray to kill tumor cells and shrink tumors. Androgens, or male sex hormones, can cause the growth of prostate cancer cells. Drugs, such as apalutamide, may help stop or reduce the growth of prostate cancer cell growth by blocking the attachment of androgen to its receptors on cancer cells, a mechanism similar to stopping the entrance of a key into its lock. Adding apalutamide to the usual hormone therapy and radiation therapy after surgery may stabilize prostate cancer and prevent it from spreading and extend time without disease spreading compared to the usual approach.

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.

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

Research shows that Apalutamide, when added to hormone therapy, significantly improves survival and delays disease progression in men with certain types of prostate cancer, such as metastatic castration-sensitive and non-metastatic castration-resistant prostate cancer. It also maintains quality of life and is generally well tolerated. ^{1 2 3 4 5}

Is Apalutamide safe for humans?

Apalutamide, also known as Erleada, is generally well tolerated in humans, with fatigue and skin reactions being some of the most common side effects reported in studies. It has been approved for use in various types of prostate cancer, indicating a recognized safety profile. ^{2 3 4 5 6}

How does the drug apalutamide differ from other prostate cancer treatments?

Apalutamide is unique because it is an oral drug that directly blocks the androgen receptor, which is crucial in prostate cancer growth, and it is used in combination with hormone and radiation therapies to enhance treatment effectiveness. This combination aims to improve outcomes in patients with prostate cancer by potentially increasing the effectiveness of radiation therapy, which is a novel approach compared to traditional treatments. ^{1 2 3 4 7}

Research Team

Ronald C Chen

Principal Investigator

NRG Oncology

Eligibility Criteria

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

Trial Timeline

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

Treatment Details

Interventions

• Apalutamide (Antiandrogen)

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.

Participant Groups

Group I: Arm II (hormone therapy, radiation therapy, apalutamide) Experimental Treatment 5 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. Cycles repeat every 90 days for 8 cycles in the absence of disease progression or unacceptable toxicity.

Group II: Arm I (hormone therapy, radiation therapy) Active Control 4 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.

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+

Findings from Research

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]

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 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]

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, 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]

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]

References

1. 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]

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

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

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

Apalutamide: First Global Approval. [2019]

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

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

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

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

6. England pubmed.ncbi.nlm.nih.gov

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

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

Apalutamide radio-sensitisation of prostate cancer. [2023]