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CompletedNCT03379012FARETESUpdated Oct 22, 2019

Testosterone in Metastatic Renal Cell Carcinoma Patients

A Phase 2 interventional study of Testosterone undecanoate and sunitinib or pazopanib in Metastatic Renal Cell Carcinoma, sponsored by Kidney Cancer Research Bureau. Completed at 4 sites in Russian Federation. Open to male participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2019-10-22.

Sponsored by Kidney Cancer Research Bureau · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
60
Allocation
Randomized
Ages
18 Years and older
Sex
Male
01

Study summary

Purpose

To determine efficacy and safety of Testosterone in male patients with metastatic renal cell carcinoma and fatigue receiving targeted therapy or checkpoint inhibitors.

Read the detailed description

Fatigue is a frequent symptom of metastatic renal cell carcinoma (RCC), and most common adverse event of targeted and immunotherapy.

In Phase 3 pivotal studies, 56% (9%, grade 3-4), 54% (11%, grade 3), 37% (10%, grade 3-4) and 20% (2%, grade 3) of patients had fatigue during the therapy of cabozantinib, sunitinib, axitinib or pazopanib, respectively. 59% (14%, grade 3) and 31% (5%, grade 3) of patients treated with lenvatinib/everolimus and everolimus had fatigue in registrational trials. Finally, 33% (2%, grade 3-4) of patients that received nivolumab had fatigue in CheckMate 025 study.

Testosterone may help to relieve fatigue associated with the use of tyrosine kinase, mTOR or checkpoint inhibitors. Additionally, testosterone could impact on poor prognostic factors of RCC (anemia, ECOG performance status, serum calcium). This will be first clinical trial which evaluates safety and efficacy of Testosterone in RCC patients.

02

Conditions studied

  • Metastatic Renal Cell Carcinoma
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
Male
Accepts healthy volunteers
No

Inclusion criteria

  1. Histologically proven clear cell renal cell carcinoma;
  2. CT-confirmed metastatic measurable disease;
  3. First-line sunitinib or pazopanib treatment with fatigue;
  4. Low level of testosterone;
  1. Male, 18 years and older; 5. Normal PSA level

Exclusion criteria

Exclusion Criteria:

  1. Prostate and other cancers history
  2. Hypothyroidism
  3. History of serious cardiac arrhythmia, congestive heart failure, angina pectoris, or other severe cardiovascular disease (i.e., New York Heart Association class III or IV)
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
60 participants (actual)

Study arms

  • Experimental
    Testosterone and Targeted therapy

    Testosterone undecanoate (Nebido®) and Targeted therapy (sunitinib or pazopanib)

    Drug: Testosterone undecanoate and sunitinib or pazopanib

  • Active comparator
    Control

    Targeted therapy (sunitinib or pazopanib) only

    Drug: Testosterone undecanoate and sunitinib or pazopanib

Interventions

  • DrugTestosterone undecanoate and sunitinib or pazopanib

    Testosterone undecanoate (Nebido®) 1,000 mg (4 ml) intramuscular deeply, once before targeted therapy (sunitinib 50 mg 4/2 or pazopanib 800 mg daily)

05

What researchers measure

Primary outcomes

  1. Fatigue

    Difference in mean change of Fatigue from baseline score with testosterone vs. without testosterone.

    Time frame: 3 months

Secondary outcomes

  1. Safety and tolerability

    Safety and tolerability of testosterone (CTCAE v.4.03)

    Time frame: 3 months

  2. Quality of life

    Health-related quality of life (NCCN-FACT FKSI-19 (Version 2)

    Time frame: 3 months

  3. Overall rate of adverse events

    Overall rate of adverse events related with TKI treatment (CTCAE v.4.03)

    Time frame: 3 months

  4. Testosterone serum concentrations

    Maximum and minimum total testosterone serum concentrations following dose administration at week 12

    Time frame: 12 weeks

  5. Red blood cell count and Hemoglobin concentration

    Change in Red blood cell count and Hemoglobin concentration following dose administration at week 12

    Time frame: 12 weeks

  6. Serum calcium concentration

    Change in serum calcium concentration following dose administration at week 12

    Time frame: 12 weeks

  7. ECOG PS

    ECOG Performance status

    Time frame: 3 months

  8. Overall survival

    Time from randomization to death

    Time frame: 2 years

06

Study locations

4 sites
  • A.I. Kryzhanovsky Krasnoyarsk Cancer Center
    Krasnoyarsk, Russian Federation
  • Kidney Cancer Research Bureau
    Moscow, Russian Federation
  • RUDN University
    Moscow, Russian Federation
  • City Clinical Oncology Center
    Saint Petersburg, Russian Federation
07

References and documents

Publications

  • Choueiri TK, Escudier B, Powles T, Tannir NM, Mainwaring PN, Rini BI, Hammers HJ, Donskov F, Roth BJ, Peltola K, Lee JL, Heng DYC, Schmidinger M, Agarwal N, Sternberg CN, McDermott DF, Aftab DT, Hessel C, Scheffold C, Schwab G, Hutson TE, Pal S, Motzer RJ; METEOR investigators. Cabozantinib versus everolimus in advanced renal cell carcinoma (METEOR): final results from a randomised, open-label, phase 3 trial. Lancet Oncol. 2016 Jul;17(7):917-927. doi: 10.1016/S1470-2045(16)30107-3. Epub 2016 Jun 5. PubMed 27279544 ↗
  • Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Rixe O, Oudard S, Negrier S, Szczylik C, Kim ST, Chen I, Bycott PW, Baum CM, Figlin RA. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med. 2007 Jan 11;356(2):115-24. doi: 10.1056/NEJMoa065044. PubMed 17215529 ↗
  • Motzer RJ, Escudier B, Tomczak P, Hutson TE, Michaelson MD, Negrier S, Oudard S, Gore ME, Tarazi J, Hariharan S, Chen C, Rosbrook B, Kim S, Rini BI. Axitinib versus sorafenib as second-line treatment for advanced renal cell carcinoma: overall survival analysis and updated results from a randomised phase 3 trial. Lancet Oncol. 2013 May;14(6):552-62. doi: 10.1016/S1470-2045(13)70093-7. Epub 2013 Apr 16. Erratum In: Lancet Oncol. 2013 Jun;14(7):e254. PubMed 23598172 ↗
  • Sternberg CN, Hawkins RE, Wagstaff J, Salman P, Mardiak J, Barrios CH, Zarba JJ, Gladkov OA, Lee E, Szczylik C, McCann L, Rubin SD, Chen M, Davis ID. A randomised, double-blind phase III study of pazopanib in patients with advanced and/or metastatic renal cell carcinoma: final overall survival results and safety update. Eur J Cancer. 2013 Apr;49(6):1287-96. doi: 10.1016/j.ejca.2012.12.010. Epub 2013 Jan 12. PubMed 23321547 ↗
  • Motzer RJ, Hutson TE, Glen H, Michaelson MD, Molina A, Eisen T, Jassem J, Zolnierek J, Maroto JP, Mellado B, Melichar B, Tomasek J, Kremer A, Kim HJ, Wood K, Dutcus C, Larkin J. Lenvatinib, everolimus, and the combination in patients with metastatic renal cell carcinoma: a randomised, phase 2, open-label, multicentre trial. Lancet Oncol. 2015 Nov;16(15):1473-1482. doi: 10.1016/S1470-2045(15)00290-9. Epub 2015 Oct 22. Erratum In: Lancet Oncol. 2016 Jul;17(7):e270. doi: 10.1016/S1470-2045(16)30233-9. Lancet Oncol. 2018 Oct;19(10):e509. doi: 10.1016/S1470-2045(18)30672-7. PubMed 26482279 ↗
  • Motzer RJ, Escudier B, Oudard S, Hutson TE, Porta C, Bracarda S, Grunwald V, Thompson JA, Figlin RA, Hollaender N, Kay A, Ravaud A; RECORD-1 Study Group. Phase 3 trial of everolimus for metastatic renal cell carcinoma : final results and analysis of prognostic factors. Cancer. 2010 Sep 15;116(18):4256-65. doi: 10.1002/cncr.25219. PubMed 20549832 ↗
  • Tomita Y, Fukasawa S, Shinohara N, Kitamura H, Oya M, Eto M, Tanabe K, Kimura G, Yonese J, Yao M, Motzer RJ, Uemura H, McHenry MB, Berghorn E, Ozono S. Nivolumab versus everolimus in advanced renal cell carcinoma: Japanese subgroup analysis from the CheckMate 025 study. Jpn J Clin Oncol. 2017 Jul 1;47(7):639-646. doi: 10.1093/jjco/hyx049. PubMed 28419248 ↗

Individual participant data

Plan to share: No

08

Registry details

Key details

Study ID
NCT03379012
Lead sponsor
Kidney Cancer Research Bureau
Responsible party
Sponsor
First posted
Dec 20, 2017
Start date
Feb 8, 2016
Primary completion
Jan 30, 2018
Completion
Jul 30, 2019
Last update
Oct 22, 2019

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
View the source record on ClinicalTrials.gov ↗

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