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Metastatic Castrate Resistant Prostate CancerPhase 1NCT03737370

Fractionated Docetaxel and Radium 223 in Metastatic Castration-Resistant Prostate Cancer

A Phase 1 study testing Docetaxel and Radium 223 in people with Metastatic Castrate Resistant Prostate Cancer, run by Tufts Medical Center at 4 sites in United States.

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

The objective of this study is to determine the maximum safe dose of Ra-223 in combination with fractionated (split doses) docetaxel when given to subjects and to determine the best administering dose. The study will look at side effects that may happen while taking the combination treatment. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Docetaxel and Radium 223
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
43 participants
Where
4 sitesUnited States
Study dates
30 Jan 2018to 30 Sep 2025
Phase
Phase 1
Are there results?
None posted in the registry

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
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically or cytologically confirmed adenocarcinoma of the prostate
  • Documented metastatic castration resistant disease with PSA progression, radiographic progression, or both, despite medical or surgical castration
  • Two or more bone metastases detected on skeletal scintigraphy
  • Eligible for docetaxel chemotherapy
  • ECOG Performance Status 0-2
  • Adequate organ function:
Show all 17Show fewer
  • Hemoglobin > 10 g/dL
  • Absolute Neutrophil Count ≥ 1,500 K/mL
  • Platelet count ≥ 150,000 x 10^9/L
  • Total bilirubin ≤ 1.5x upper limit of normal range, excluding Gilbert syndrome
  • Serum AST ≤ 1.5 x upper limit of normal range
  • Serum ALT ≤ 1.5 x upper limit of normal range
  • Estimated glomerular filtration rate (GFR) > 30mL/min
  • Ongoing castration (androgen deprivation therapy or prior orchiectomy)
  • Male subjects with female sexual partners of childbearing potential must agree to use at least one highly effective methods of birth control.
  • Ability to understand and willingness to sign an informed consent form prior to initiation of any study procedures.
  • Age ≥ 18 years

Who cannot join

  • Prior radionuclide therapy for CRPC
  • Prior docetaxel for CRPC. (Permitted if given for castration sensitive disease > 6 months prior).
  • Antiandrogen therapy within 4 weeks of enrollment. However, patients with primary failure of secondary anti-androgen therapy OR symptomatic progression, objective progression and/or biochemical evidence of rising PSA less than 4 weeks after discontinuation of anti-androgen therapy will not have anti-androgen withdrawal responses and will not be excluded.
  • Preexisting peripheral neuropathy grade 2 or higher.
  • Other serious medical condition as judged by the investigator.
  • Active second malignancy that requires therapy.
Show all 14Show fewer
  • Known brain or leptomeningeal metastases
  • Concurrent enrollment in any other investigational anticancer therapy
  • Treatment with any myelosuppressive agent within 30 days of enrollment
  • Presence of bulky visceral metastases, defined as any of the following:
  • ≥ 4 lung lesions (at least 1cm each in size in the longest diameter) or pulmonary lymphangitic metastasis
  • Liver metastases with sum of lesion diameters totaling ≥ 5cm
  • Evidence of neuroendocrine or small cell differentiation on prior biopsy
  • History of severe hypersensitivity reactions to docetaxel or to drugs formulated with polysorbate 80

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • Lahey Hospital & Medical Center

    Boston, Massachusetts, 01805

  • Tufts Medical Center

    Boston, Massachusetts, 02111

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • Henry Ford Health System

    Detroit, Michigan, 48202

Other trials in United States

About this study

Official title: A Phase I Trial of Fractionated Docetaxel and Radium 223 in Metastatic Castration-Resistant Prostate Cancer (CRPC)

The objective of this study is to determine the maximum safe dose of Ra-223 in combination with fractionated (split doses) docetaxel when given to subjects and to determine the best administering dose. The study will look at side effects that may happen while taking the combination treatment. A total of approximately 18 subjects will take part in the dose escalation part of the study and an additional 25 subjects will participate in the expansion cohort. This study will be conducted across four centers in the United States.

Read the detailed description

The primary objective of this study is to assess the safety and toxicity of a fractionated docetaxel schedule in combination with standard Ra-223.

Secondary Objectives include: assessment of progression-free survival, time to treatment failure, overall survival, ability of subjects to complete 6 cycles of the combination therapy, assessment of Prostate Specific Antigen (PSA) kinetics and objective responses (measurable disease), assessment of quality of life and assessment of bone bio-marker outcomes.

The study features a 4-week lead-in period with docetaxel monotherapy to assess for docetaxel intolerance. The lead-in period is then followed by combination therapy with Ra-223 every 4 weeks for 6 cycles in a traditional Phase I dose-escalation design.

A provision has been made to include prophylactic granulocyte colony stimulating factor (G-CSF) cohorts after the lead-in period if neutropenia is the dose limiting toxicity at either dose level.

The investigators hypothesize that the fractionated dosing of docetaxel will significantly mitigate the hematologic toxicity, preserve antineoplastic activity and allow for maintenance of the 4-weekly Ra-223 schedule.

Being tested
Docetaxel, Radium 223
Keywords
Prostate Cancer
Medical subject headings
Prostatic Neoplasms

What participants receive

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

  • DocetaxelDrug

    Also called Fractionated Docetaxel

    Docetaxel will be administered every 2 weeks (on Day 1 and Day 15 of a 28 day cycle). Fractionated dosing dependent on cohort.

  • Radium 223Radiation

    Also called Ra-223

    Radium 223 will be delivered every 28 days (on day 1) for 6 cycles.

Study groups in NCT03737370
Study groupRoleWhat they receive
Dose escalationExperimentalThere are four dose cohorts (1, 1a, 2, 2a) in this arm and two dose levels of docetaxel (40mg/m^2 [level 1] and 50mg/m^2 [level 2]). Dosing of Radium 223 remains the same in all cohorts (55 KBq/kg given every 28 days for 6 cycles). Maximum tolerated dose (MTD) of docetaxel will be assessed. MTD is defined as the highest dose-level, among those tested, associated with a rate of less than a 33% dose limiting toxicity (DLT).
Receives: Drug: Docetaxel; Radiation: Radium 223
Dose expansionExperimentalIf the maximum tolerated dose (MTD) of docetaxel is found in arm 1, this dose level will be expanded to include an additional 25 subjects to confirm the safety and explore the preliminary anti-cancer effect. If the MTD is not identified, the study will be stopped and the expansion cohort will not be accrued.
Receives: Drug: Docetaxel; Radiation: Radium 223

What is being measured

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

  1. Incidence of Dose Limiting Toxicities (DLT)

    DLT is defined as a subject in any cohort experiencing any of the following adverse events during cycle 1 of treatment, until cycle 2 day 1 of treatment: Thrombocytopenia (platelets < 75 x 10^9/L on C1D15 or < 100 x 10^9/L on C2D1), Neutropenia (ANC < 1000 K/mL on C1D15 or ANC < 1500 K/mL on C2D1), Grade 3 (by CTCAE v4) fatigue lasting ≥ 7 days, other non-hematologic toxicity ≥ grade 3, lasting ≥ 48 hours at least possibly related to treatment, or any toxicity (non-hematologic or hematologic) at least possibly related to treatment requiring dose reduction or dose interruption.

    Measured: Up to 29 Days

Secondary outcomes (8)

  1. Efficacy, assessed as non-progression/progression rate according to prostate cancer working group (PCWG2) criteria

    Time to progression of disease, calculated as a time-to-event endpoint

    Measured: From date of randomization until the date of first documented progression or death from any cause, whichever came first, assessed up to 25 years

  2. Progression Free Survival (PFS)

    Progression free survival is defined as the interval from first dose date of study drug to the earlier of the first documentation of definitive disease progression (assessed per PCWG2) or death from any cause

    Measured: Up to 25 years

  3. Time to Treatment Failure (TTTF)

    A measurement from the date of randomization to the first event which meets the criteria for disease progression (assessed per PCWG2 criteria) or death from any cause

    Measured: Up to 25 years

  4. Overall Survival

    Overall survival is defined as the interval from first dose date of study drug to death from any cause.

    Measured: Up to 25 years

  5. Proportion of Randomized Subjects to Complete Combination Therapy on Schedule per Protocol

    The number of subjects who were able to receive both lead-in doses of docetaxel and all 6 cycles of combination docetaxel and Ra223 on time (+/- 7 days).

    Measured: Up to 28 weeks

  6. Response to treatment, as assessed by prostate-specific antigen (PSA) Kinetics and Objective Responses

    Measurable disease calculated at each time point in which the data is collected. We will use mixed effect models to explore the temporal trajectories for the outcome changes over time in response to the treatment.

    Measured: From date of randomization until the date of first documented progression or death from any cause, whichever came first, assessed up to 25 years

  7. Satisfaction, as assessed by Quality of Life Questionnaires

    Measured by the Brief Pain Inventory (BPI) and Functional Assessment of Cancer Therapy (FACT-G) Questionnaires

    Measured: From date of randomization until the date of first documented progression or death from any cause, whichever came first, assessed up to 25 years

  8. Response to Treatment, as assessed by Bone Bio-marker Outcomes

    Measurement of bone-specific alkaline phosphatase and urine N-telopeptides (laboratory testing)

    Measured: Up to 28 weeks

Timeline

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

  1. First posted9 Nov 2018
  2. Study start30 Jan 2018
  3. Primary completion31 Dec 2024
  4. Study completion30 Sep 2025

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 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
43 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03737370
Sponsor's protocol ID
IIR-US-2016-3279
Status last verified
Oct 2025
First submitted
25 Oct 2018
Last updated
7 Oct 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Parker C, Nilsson S, Heinrich D, Helle SI, O'Sullivan JM, Fossa SD, Chodacki A, Wiechno P, Logue J, Seke M, Widmark A, Johannessen DC, Hoskin P, Bottomley D, James ND, Solberg A, Syndikus I, Kliment J, Wedel S, Boehmer S, Dall'Oglio M, Franzen L, Coleman R, Vogelzang NJ, O'Bryan-Tear CG, Staudacher K, Garcia-Vargas J, Shan M, Bruland OS, Sartor O; ALSYMPCA Investigators. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med. 2013 Jul 18;369(3):213-23. doi: 10.1056/NEJMoa1213755.

    PubMed 23863050

  • Antonarakis ES, Lu C, Wang H, Luber B, Nakazawa M, Roeser JC, Chen Y, Mohammad TA, Chen Y, Fedor HL, Lotan TL, Zheng Q, De Marzo AM, Isaacs JT, Isaacs WB, Nadal R, Paller CJ, Denmeade SR, Carducci MA, Eisenberger MA, Luo J. AR-V7 and resistance to enzalutamide and abiraterone in prostate cancer. N Engl J Med. 2014 Sep 11;371(11):1028-38. doi: 10.1056/NEJMoa1315815. Epub 2014 Sep 3.

    PubMed 25184630

  • Antonarakis ES, Lu C, Luber B, Wang H, Chen Y, Nakazawa M, Nadal R, Paller CJ, Denmeade SR, Carducci MA, Eisenberger MA, Luo J. Androgen Receptor Splice Variant 7 and Efficacy of Taxane Chemotherapy in Patients With Metastatic Castration-Resistant Prostate Cancer. JAMA Oncol. 2015 Aug;1(5):582-91. doi: 10.1001/jamaoncol.2015.1341.

    PubMed 26181238

  • Oudard S, Banu E, Beuzeboc P, Voog E, Dourthe LM, Hardy-Bessard AC, Linassier C, Scotte F, Banu A, Coscas Y, Guinet F, Poupon MF, Andrieu JM. Multicenter randomized phase II study of two schedules of docetaxel, estramustine, and prednisone versus mitoxantrone plus prednisone in patients with metastatic hormone-refractory prostate cancer. J Clin Oncol. 2005 May 20;23(15):3343-51. doi: 10.1200/JCO.2005.12.187. Epub 2005 Feb 28.

    PubMed 15738542

  • Kellokumpu-Lehtinen PL, Harmenberg U, Joensuu T, McDermott R, Hervonen P, Ginman C, Luukkaa M, Nyandoto P, Hemminki A, Nilsson S, McCaffrey J, Asola R, Turpeenniemi-Hujanen T, Laestadius F, Tasmuth T, Sandberg K, Keane M, Lehtinen I, Luukkaala T, Joensuu H; PROSTY study group. 2-Weekly versus 3-weekly docetaxel to treat castration-resistant advanced prostate cancer: a randomised, phase 3 trial. Lancet Oncol. 2013 Feb;14(2):117-24. doi: 10.1016/S1470-2045(12)70537-5. Epub 2013 Jan 4.

    PubMed 23294853

  • Kantoff PW, Higano CS, Shore ND, Berger ER, Small EJ, Penson DF, Redfern CH, Ferrari AC, Dreicer R, Sims RB, Xu Y, Frohlich MW, Schellhammer PF; IMPACT Study Investigators. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. 2010 Jul 29;363(5):411-22. doi: 10.1056/NEJMoa1001294.

    PubMed 20818862

  • Ryan CJ, Smith MR, de Bono JS, Molina A, Logothetis CJ, de Souza P, Fizazi K, Mainwaring P, Piulats JM, Ng S, Carles J, Mulders PF, Basch E, Small EJ, Saad F, Schrijvers D, Van Poppel H, Mukherjee SD, Suttmann H, Gerritsen WR, Flaig TW, George DJ, Yu EY, Efstathiou E, Pantuck A, Winquist E, Higano CS, Taplin ME, Park Y, Kheoh T, Griffin T, Scher HI, Rathkopf DE; COU-AA-302 Investigators. Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med. 2013 Jan 10;368(2):138-48. doi: 10.1056/NEJMoa1209096. Epub 2012 Dec 10.

    PubMed 23228172

  • Beer TM, Armstrong AJ, Rathkopf DE, Loriot Y, Sternberg CN, Higano CS, Iversen P, Bhattacharya S, Carles J, Chowdhury S, Davis ID, de Bono JS, Evans CP, Fizazi K, Joshua AM, Kim CS, Kimura G, Mainwaring P, Mansbach H, Miller K, Noonberg SB, Perabo F, Phung D, Saad F, Scher HI, Taplin ME, Venner PM, Tombal B; PREVAIL Investigators. Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med. 2014 Jul 31;371(5):424-33. doi: 10.1056/NEJMoa1405095. Epub 2014 Jun 1.

    PubMed 24881730

  • Scher HI, Halabi S, Tannock I, Morris M, Sternberg CN, Carducci MA, Eisenberger MA, Higano C, Bubley GJ, Dreicer R, Petrylak D, Kantoff P, Basch E, Kelly WK, Figg WD, Small EJ, Beer TM, Wilding G, Martin A, Hussain M; Prostate Cancer Clinical Trials Working Group. Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: recommendations of the Prostate Cancer Clinical Trials Working Group. J Clin Oncol. 2008 Mar 1;26(7):1148-59. doi: 10.1200/JCO.2007.12.4487.

    PubMed 18309951

  • Petrylak DP, Tangen CM, Hussain MH, Lara PN Jr, Jones JA, Taplin ME, Burch PA, Berry D, Moinpour C, Kohli M, Benson MC, Small EJ, Raghavan D, Crawford ED. Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med. 2004 Oct 7;351(15):1513-20. doi: 10.1056/NEJMoa041318.

    PubMed 15470214

  • Cessna JT, Zimmerman BE. Standardization of radium-223 by liquid scintillation counting. Appl Radiat Isot. 2010 Jul-Aug;68(7-8):1523-8. doi: 10.1016/j.apradiso.2009.11.068. Epub 2009 Dec 2.

    PubMed 20097568

  • Zimmerman BE, Bergeron DE, Cessna JT, Fitzgerald R, Pibida L. Revision of the NIST Standard for (223)Ra: New Measurements and Review of 2008 Data. J Res Natl Inst Stand Technol. 2015 Mar 11;120:37-57. doi: 10.6028/jres.120.004. eCollection 2015.

    PubMed 26958437

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Docetaxel and Radium 223 in people with Metastatic Castrate Resistant Prostate Cancer, run by Tufts Medical Center at 4 sites in United States.

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 17 inclusion and 14 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 7 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 4 sites in United States. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Incidence of Dose Limiting Toxicities (DLT) (time frame: Up to 29 Days). 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 NCT03737370, which also lists 12 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 7 Oct 2025.

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