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

NCT03737370 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: IIR-US-2016-3279
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 4

Brief 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. 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.

Conditions

Metastatic Castrate Resistant Prostate Cancer

Keywords

Prostate Cancer

Outcome Measures

Primary Outcomes (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.

  Up to 29 Days

Secondary Outcomes (8)

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

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

• Progression Free Survival (PFS)

  Up to 25 years

• Time to Treatment Failure (TTTF)

  Up to 25 years

• Overall Survival

  Up to 25 years

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

  Up to 28 weeks

Study Arms (2)

Dose escalation

EXPERIMENTAL

There 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).

Drug: Docetaxel; Radiation: Radium 223

Dose expansion

EXPERIMENTAL

If 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.

Drug: Docetaxel; Radiation: Radium 223

Interventions

Docetaxel DRUG

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

Also known as: Fractionated Docetaxel

Dose escalation; Dose expansion

Radium 223 RADIATION

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

Also known as: Ra-223

Dose escalation; Dose expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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.

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• Tufts Medical Center: lead
• Bayer: collaborator
• Lahey Clinic: collaborator
• Henry Ford Hospital: collaborator
• Ohio State University Comprehensive Cancer Center: collaborator

Study Sites (4)

Lahey Hospital & Medical Center

Boston, Massachusetts, 01805, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Related Publications (12)

• 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.

  PMID: 23863050 BACKGROUND

• 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.

  PMID: 25184630 BACKGROUND

• 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.

  PMID: 26181238 BACKGROUND

• 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.

  PMID: 15738542 BACKGROUND

• 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.

  PMID: 23294853 BACKGROUND

• 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.

  PMID: 20818862 BACKGROUND

• 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.

  PMID: 23228172 BACKGROUND

• 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.

  PMID: 24881730 BACKGROUND

• 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.

  PMID: 18309951 BACKGROUND

• 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.

  PMID: 15470214 BACKGROUND

• 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.

  PMID: 20097568 BACKGROUND

• 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.

  PMID: 26958437 BACKGROUND

Related Links

• Citation
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MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Docetaxel; radium Ra 223 dichloride; Radium-223

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Paul Mathew, MD

  Tufts Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 25, 2018
• First Posted: November 9, 2018
• Study Start: January 30, 2018
• Primary Completion: December 31, 2024
• Study Completion: September 30, 2025
• Last Updated: October 7, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)