What is the mechanism of action of this treatment?

Prostate cancer treatments often target specific mechanisms to inhibit cancer growth and spread. Targeted radiotherapy, such as I-131-1095, binds to prostate-specific membrane antigen (PSMA) on cancer cells, delivering radiation directly to the tumor and minimizing damage to surrounding tissues. Androgen deprivation therapy (ADT) reduces levels of male hormones that fuel prostate cancer growth, while immunotherapy stimulates the immune system to attack cancer cells. These treatments are crucial as they offer more precise and effective options, potentially improving outcomes and reducing side effects for prostate cancer patients.

What side effects are associated with this type of intervention?

Common treatments for prostate cancer, particularly targeted radiotherapies like lutetium Lu 177 vipivotide tetraxetan and androgen receptor-targeted therapies such as enzalutamide, have several known side effects. Lutetium Lu 177 vipivotide tetraxetan is associated with myelosuppression, nephrotoxicity, and salivary gland toxicity (including pain, swelling, and dry mouth). Enzalutamide commonly causes fatigue, anorexia, and nausea. These treatments aim to target PSMA-expressing cancer cells, similar to I-131-1095 radiotherapy, and share a profile of side effects that includes both systemic and localized toxicities.

What prior FDA approvals exist?

The FDA has approved several treatments for prostate cancer that target PSMA-expressing cells. One notable approval is for lutetium Lu 177 vipivotide tetraxetan, a radioligand therapy that binds to PSMA on prostate cancer cells and delivers targeted radiation. This treatment has shown significant improvements in progression-free survival and overall survival in patients with metastatic castration-resistant prostate cancer (mCRPC). Additionally, radium-223 dichloride (Ra-223) is another radiopharmaceutical approved for mCRPC, which targets bone metastases by mimicking calcium and delivering alpha radiation to bone lesions. These therapies represent a growing class of targeted radiotherapies aimed at improving outcomes for prostate cancer patients.

What other types of research exist?

Promising novel alternatives to I-131-1095 radiotherapy for prostate cancer patients include: 1) [177Lu]-PSMA-617 radionuclide treatment, which has shown high response rates and low toxicity in mCRPC patients. 2) Combination therapies such as Ra-223 with enzalutamide or abiraterone, which have shown potential in improving survival and reducing fracture risk when combined with osteoclast inhibitors. 3) Pembrolizumab for patients with dMMR or high TMB tumors, offering a targeted immunotherapy option. These alternatives are supported by clinical trial data and ongoing research.

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Antiandrogen

I-131-1095 + Enzalutamide for Prostate Cancer (ARROW Trial)

Phase 2

Waitlist Available

Research Sponsored by Progenics Pharmaceuticals, Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Subjects receiving bisphosphonate therapy must have been on stable doses for at least 4 weeks prior to Randomization

Other serious medical conditions such as symptomatic peripheral neuropathy CTCAE Grade 2 or higher; or clinically significant cardiovascular disease per the Investigator or treating physician

Must not have

Received prior chemotherapy for castration-resistant prostate cancer

Gastrointestinal disorder affecting absorption of oral medications

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline to week 53 (concomitant medications); from week 54 up to 5 years (anti-cancer therapies only)

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new combination treatment for men with advanced prostate cancer that has spread and is resistant to standard hormone therapy. The treatment combines a radioactive drug with another drug that blocks male hormones. The goal is to see if this combination works better than the hormone-blocking drug alone.

Who is the study for?

Men over 18 with advanced prostate cancer that's resistant to hormone therapy and has spread, but haven't had chemotherapy. They must have worsening disease despite previous treatment with abiraterone, be ineligible or refuse taxane-based chemo, and agree to use birth control. Excluded are those who've taken enzalutamide before or have certain health issues like poor organ function or a history of seizures.

What is being tested?

This phase 2 trial tests if I-131-1095 radiotherapy plus enzalutamide is better than enzalutamide alone for men whose prostate cancer worsens after abiraterone treatment. Participants' tumors must show PSMA presence on scans. The study randomly assigns patients in a 2:1 ratio to either the combination therapy or just enzalutamide.

What are the potential side effects?

Possible side effects include typical reactions from radiation such as nausea, fatigue, and blood count changes; and from enzalutamide like hot flashes, fatigue again, muscle weakness, and potentially seizures in predisposed individuals.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have been on a steady dose of bisphosphonate therapy for at least 4 weeks.

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I do not have severe nerve damage or major heart problems.

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My bone scan shows two or more new lesions indicating my disease is progressing.

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I am scheduled to start treatment with enzalutamide.

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My cancer has worsened despite taking abiraterone.

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I have a history of cancer that might have returned or spread.

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I can take care of myself and am up and about more than half of the day.

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My prostate cancer was confirmed without specific aggressive features.

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My prostate cancer is not responding to hormone therapy, and my testosterone levels are low.

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I have difficulty performing daily activities.

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I am a man aged 18 or older.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have had chemotherapy for prostate cancer that did not respond to hormone therapy.

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I have a stomach or intestine condition that affects how I absorb pills.

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I have not had major surgery in the last 4 weeks.

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I haven't had treatments with specific radioactive drugs in the last 6 months.

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My kidney function is very low or I am on dialysis.

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My recent lab tests show my organs are not working properly.

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I have brain metastasis or active leptomeningeal disease.

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I have a condition that makes it unsafe for me to take enzalutamide.

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I have used enzalutamide for more than a week before agreeing to this study.

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I have had PSMA-targeted therapy before.

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I have had radiation treatment on half of my body.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ baseline to week 53 (concomitant medications); from week 54 up to 5 years (anti-cancer therapies only)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline to week 53 (concomitant medications); from week 54 up to 5 years (anti-cancer therapies only)

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline to week 53 (concomitant medications); from week 54 up to 5 years (anti-cancer therapies only) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

PSA Response Rate

Secondary study objectives

Adverse Events Resulting In Discontinuation Of Study Drug (Safety Outcome Measure)

Changes From Baseline In Overall Electrocardiogram (ECG) Assessment At Follow-up (Safety Outcome Measure)

Changes In Blood Pressure (Safety Outcome Measure)

+13 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: I-131-1095 in combination with enzalutamideExperimental Treatment2 Interventions

Group II: EnzalutamideActive Control1 Intervention

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Enzalutamide

2014

Completed Phase 4

~3820

0 / 22Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Prostate cancer treatments often target specific mechanisms to inhibit cancer growth and spread. Targeted radiotherapy, such as I-131-1095, binds to prostate-specific membrane antigen (PSMA) on cancer cells, delivering radiation directly to the tumor and minimizing damage to surrounding tissues. Androgen deprivation therapy (ADT) reduces levels of male hormones that fuel prostate cancer growth, while immunotherapy stimulates the immune system to attack cancer cells. These treatments are crucial as they offer more precise and effective options, potentially improving outcomes and reducing side effects for prostate cancer patients.

177Lu-EB-PSMA Radioligand Therapy with Escalating Doses in Patients with Metastatic Castration-Resistant Prostate Cancer.[177Lu]-PSMA-617 radionuclide treatment in patients with metastatic castration-resistant prostate cancer (LuPSMA trial): a single-centre, single-arm, phase 2 study.Standard of Care Versus Metastases-directed Therapy for PET-detected Nodal Oligorecurrent Prostate Cancer Following Multimodality Treatment: A Multi-institutional Case-control Study.