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Metastatic Prostate CancerPhase 2ARROWNCT03939689

I-131-1095 Radioligand Plus Enzalutamide vs Enzalutamide for mCRPC That Progressed During Abiraterone (ARROW).

A Phase 2 study testing I-131-1095 and Enzalutamide in people with Metastatic Prostate Cancer and Castration-resistant Prostate Cancer, run by Progenics Pharmaceuticals, Inc. at 27 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This clinical trial was done to show whether a radioactive drug (I-131-1095) that binds to prostate-specific membrane antigen (PSMA) is useful in treating metastatic prostate cancer that is positive for PSMA. Read more about this study

Who is it for?
Ages 18 years and older, men only
What is being tested?
I-131-1095 and Enzalutamide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
120 participants
Where
27 sitesin 2 countries
Study dates
30 May 2019to 24 Sep 2024
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male ≥ 18 years of age
  • Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features at initial diagnosis
  • Castration-resistant prostate cancer, with serum testosterone ≤ 50 ng/dL at Screening
  • Radiographic evidence of metastatic disease prior to Randomization or up to 21 days prior to Screening
  • Disease progression on prior abiraterone therapy as defined by meeting at least one of the following criteria per the investigator:
  • PSA progression as defined by a minimum of two rising PSA levels at least 1 week apart
Show all 19Show fewer
  • Soft tissue disease progression defined by RECIST 1.1
  • Bone disease progression defined by two or more new lesions on bone scan
  • Planned to receive treatment with enzalutamide
  • Subjects who are ineligible or choose not to receive taxane-based chemotherapy based on personal preference or physician opinion. Examples of conditions that could make a patient ineligible or refuse to receive taxane-based chemotherapy, but would allow them to still be eligible to receive I-131-1095 include the following:
  • Poor performance status
  • Prior intolerance to cytotoxic agents
  • History of another malignancy suspected for recurrence or metastases
  • 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
  • Subjects receiving bisphosphonate therapy must have been on stable doses for at least 4 weeks prior to Randomization
  • ECOG performance status 0-2
  • If sexually active, agree to use a medically acceptable method of birth control or sexual abstinence from the time of dosing through 28 days after the last dose of I-131-1095. Female partners must use hormonal or barrier contraception unless postmenopausal or abstinent.
  • Estimated life expectancy of at least 6 months as determined by the Investigator.
  • Able and willing to provide signed informed consent and comply with protocol requirements

Who cannot join

  • Received any anti-tumor therapy within 4 weeks of Randomization, with the exception of abiraterone, GnRH therapy and non-radioactive bone-targeted agents
  • Received prior chemotherapy for castration-resistant prostate cancer
  • Superscan as evidenced on baseline bone scan
  • Treatment with Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223 within 6 months prior to Randomization
  • Prior hemi-body irradiation
  • Prior PSMA-targeted radioligand therapy
Show all 23Show fewer
  • Major surgery within 4 weeks of Randomization
  • Impaired organ function as evidenced by the following laboratory values at Screening:
  • Absolute neutrophil count < 1500 μL
  • Platelet count < 100,000/μL
  • Hemoglobin < 9.5 g/dL
  • Albumin < 3.0 g/dL (30 g/L)
  • Total bilirubin > 2 x ULN unless in instances of known or suspected Gilbert's disease
  • AST or ALT > 2.5 x ULN
  • Calculated creatinine clearance (CrCL) < 30 mL/min (Cockroft-Gault equation), or currently on renal dialysis.
  • QT interval corrected for heart rate (QTc) > 470 msec
  • Previous use of enzalutamide for more than 7 days prior to consent
  • Planned initiation of alternative therapy for prostate cancer, investigational therapy, or participation in clinical trials during the study
  • History or risk of seizure (i.e., clinically significant neurological disorder) or any other condition that contraindicates treatment with enzalutamide
  • Gastrointestinal disorder affecting absorption of oral medications
  • Known or suspected brain metastasis or active leptomeningeal disease
  • Active malignancy other than prostate cancer, with the exception of curatively treated non-melanoma skin cancer, carcinoma in situ, or non-muscle invasive bladder/urothelial cancer
  • Subjects with any medical condition or other circumstances that, in the opinion of the investigator, compromise obtaining reliable data, achieving study objectives, or completing the study.

Trial locations and contacts

27 sites in 2 countries.

27 sites in 2 countries

United States20 sites

  • University of Michigan Comprehensive Cancer Center

    Ann Arbor, Michigan, 48109

  • University of Maryland

    Baltimore, Maryland, 21201

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • University of Virginia Cancer Center

    Charlottesville, Virginia, 22908

  • The University of Chicago

    Chicago, Illinois, 60637

  • City of Hope

    Duarte, California, 91010

  • University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

  • University of Iowa

    Iowa City, Iowa, 52242

  • VA Greater Los Angeles Healthcare System

    Los Angeles, California, 90073

  • UCLA

    Los Angeles, California, 90095-7370

  • Tulane Medical School

    New Orleans, Louisiana, 70112

  • Hoag Family Cancer Institute

    Newport Beach, California, 92663

  • VA Palo Alto Healthcare System

    Palo Alto, California, 94303

  • University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • LifeSpan Cancer Institute

    Providence, Rhode Island, 09206

  • Virginia Mason Medical Center

    Seattle, Washington, 98101

  • University of Washington - Seattle Cancer Care Alliance

    Seattle, Washington, 98109

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • SUNY Upstate Medical University

    Syracuse, New York, 13210

  • Medstar Georgetown University Hospital

    Washington D.C., District of Columbia, 20007

Other trials in United States

Canada7 sites

  • Centre Hospitalier Del' Universite de Montreal

    Montreal, Quebec

  • Jewish General Hospital

    Montreal, Quebec

  • The Ottawa Hospital

    Ottawa, Ontario, K1H 8L6

  • Centre Hospitalier Universitaire de Quebec

    Québec, Quebec

  • Centre Hospitalier Universitaire de Sherbrooke

    Sherbrooke, Quebec

  • London Health Sciences Centre

    Toronto, Ontario

  • University Health Network - Princess Margaret Cancer Centre

    Toronto, Ontario

Other trials in Canada

About this study

Official title: A Multicenter, Randomized, Controlled Phase 2 Study: Efficacy and Safety of I-131-1095 Radiotherapy in Combination With Enzalutamide in mCRPC Patients Who Are 18F-DCFPyL PSMA-avid, Chemotherapy-naïve, and Progressed on Abiraterone (ARROW )

This clinical trial was done to show whether a radioactive drug (I-131-1095) that binds to prostate-specific membrane antigen (PSMA) is useful in treating metastatic prostate cancer that is positive for PSMA. The trial enrolled men whose PSMA-positive metastatic prostate cancer had progressed while they were taking abiraterone. During the trial, all of the men took enzalutamide (standard-of-care therapy) once a day. However, some of the men also had up to 4 doses (8 weeks apart) of I-131-1095 (in addition to taking enzalutamide once a day). At specified times during the trial, all of the men had blood tests (to measure levels of prostate-specific antigen [PSA]) and imaging studies (to assess tumor status). The two groups of men were then compared in several ways. The main comparison was the percentage of men in each group with at least a 50% decrease in PSA levels. Other comparisons involved the response of the tumors (as seen on imaging) and overall survival. To assess safety, the number of adverse events in both groups were also compared.

Read the detailed description

This phase 2 clinical trial (conducted in the United States and Canada) enrolled chemotherapy-naïve men whose PSMA-positive (as shown by piflufolastat F18 imaging) metastatic prostate cancer had progressed during treatment with abiraterone. The participants were stratified by risk factors at Screening and then randomized 2:1 either to receive PSMA radioligand therapy (up to four 8-week cycles of I-131-1095) plus standard treatment with enzalutamide or to receive standard treatment with enzalutamide as monotherapy. The prostate-specific antigen (PSA) levels and radiographic response or progression (RECIST v1.1 criteria for soft tissue and PCWG3 criteria for bone) were then monitored for up to 53 weeks of randomized treatment. The primary outcome measure was PSA response rate (percentage of participants with a confirmed ≥50% decrease in serum PSA). Other outcome measures included percentage of participants with partial or complete response (radiographic), duration of response, time to progression (PSA or radiographic), time to next treatment for prostate cancer, and overall survival.

Being tested
I-131-1095, Enzalutamide
Keywords
bone metastases, 18F-DCFPyL, PSMA PET, PSMA-avidity, biomarker, radioligand therapy, adjunct radiation therapy, dosimetry, SPECT/CT, docetaxel
Medical subject headings
Prostatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • I-131-1095Drug

    Also called 131 I-PSMA-1095, 131I-LNTH-1095

    Participants received up to 4 (8-week) cycles of I-131-1095: 100 mCi for the first dose. Subsequent dose(s) were reduced to 75 mCi for participants experiencing any dose-limiting toxicities. The third and fourth therapeutic doses could be reduced to 75 mCi on the basis of dosimetry assessment after administration of 10 mCi of I-131-1095 prior to the third dosing cycle. Participants also received the label dosage of enzalutamide once daily for up to 53 weeks.

  • EnzalutamideDrug

    Also called Xtandi

    Participants received the label dosage of enzalutamide once daily for up to 53 weeks.

Study groups in NCT03939689
Study groupRoleWhat they receive
EnzalutamideActive comparatorParticipants received the label dosage of enzalutamide once daily for up to 53 weeks.
Receives: Drug: Enzalutamide
I-131-1095 in combination with enzalutamideExperimentalParticipants received up to 4 (8-week) cycles of I-131-1095: 100 mCi for the first dose. Subsequent dose(s) were reduced to 75 mCi for participants experiencing any of the dose-limiting toxicities. The third and fourth therapeutic doses could be reduced to 75 mCi on the basis of dosimetry assessment after administration of 10 mCi of I-131-1095 prior to the third dosing cycle. Participants also received the label dosage of enzalutamide once daily for up to 53 weeks.
Receives: Drug: I-131-1095; Drug: Enzalutamide

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. PSA Response Rate

    The percentage of participants with a PSA response according to PCWG3 criteria. PCWG3 defines PSA response as the first occurrence of a 50 percent or more decline in PSA from baseline, confirmed by a second measurement at least 3 weeks later.

    Measured: Up to 53 weeks

Secondary outcomes (6)

  1. Objective Response Rate (ORR)

    The proportion of participants who have a partial response (PR) or complete response (CR) based on RECIST 1.1 for soft tissue or PCWG3 for bone (PCWG3-modified RECIST 1.1).

    Measured: Up to 53 weeks

  2. Radiographic Progression Free Survival (rPFS)

    Time from randomization to the first occurrence of radiographic progression based on RECIST 1.1 for soft tissue (≥20% increase in the sum of the longest diameter of the target lesions [relative to the smallest value recorded since the treatment started] or the appearance of ≥1 new lesion) or PCWG3-modified RECIST 1.1 for bone, respectively, or unequivocal clinical progression, or death on study from any cause.

    Measured: Up to 5 years.

  3. Overall Survival (OS)

    Overall Survival is defined as time from randomization to death from any cause.

    Measured: Up to 5 years

  4. PSA Progression

    Time from randomization to the date of the first PSA increase from baseline ≥ 25 percent and ≥ 2 ng/ml above nadir confirmed by a second PSA assessment defining progression ≥ 3 weeks later per PCWG3.

    Measured: Up to 53 weeks

  5. Duration of Response

    Time from the first date of complete response (CR) or partial response (PR) to the first occurrence of radiographic progression based on PCWG3-modified RECIST 1.1, or unequivocal clinical progression. Complete response was defined as disappearance of all target lesions. Partial response was defined as ≥30% decrease from baseline in the sum of the longest diameter of target lesions.

    Measured: Up to 5 years.

  6. Time to Initiation of Next Treatment for Prostate Cancer

    Time from randomization to initiation of any new treatment for prostate cancer.

    Measured: Up to 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 May 2019
  2. Study start30 May 2019
  3. Primary completion21 Sep 2023
  4. Study completion24 Sep 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
The study population includes patients with PSMA-avid mCRPC whose disease has progressed despite abiraterone therapy, and are planned for treatment with enzalutamide.
Masking
None (open label)
Enrolment
120 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03939689
Sponsor's protocol ID
1095-2301
Acronym
ARROW
Status last verified
May 2025
First submitted
3 May 2019
Last updated
14 Oct 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Afshar-Oromieh A, Haberkorn U, Zechmann C, Armor T, Mier W, Spohn F, Debus N, Holland-Letz T, Babich J, Kratochwil C. Repeated PSMA-targeting radioligand therapy of metastatic prostate cancer with 131I-MIP-1095. Eur J Nucl Med Mol Imaging. 2017 Jun;44(6):950-959. doi: 10.1007/s00259-017-3665-9. Epub 2017 Mar 9.

    PubMed 28280855

  • Zechmann CM, Afshar-Oromieh A, Armor T, Stubbs JB, Mier W, Hadaschik B, Joyal J, Kopka K, Debus J, Babich JW, Haberkorn U. Radiation dosimetry and first therapy results with a (124)I/ (131)I-labeled small molecule (MIP-1095) targeting PSMA for prostate cancer therapy. Eur J Nucl Med Mol Imaging. 2014 Jul;41(7):1280-92. doi: 10.1007/s00259-014-2713-y. Epub 2014 Feb 28.

    PubMed 24577951

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing I-131-1095 and Enzalutamide in people with Metastatic Prostate Cancer and Castration-resistant Prostate Cancer, run by Progenics Pharmaceuticals, Inc. at 27 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 27 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Oct 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

PSA Response Rate (time frame: Up to 53 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03939689, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Oct 2025.

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