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Randomized Controlled Trial
. 2017 Oct 6;17(1):674.
doi: 10.1186/s12885-017-3664-z.

Selection of opioids for cancer-related pain using a biomarker: a randomized, multi-institutional, open-label trial (RELIEF study)

Hiromichi Matsuoka  1   2 , Junji Tsurutani  3 , Yasutaka Chiba  4 , Yoshihiko Fujita  5 , Masato Terashima  5 , Takeshi Yoshida  6   3 , Kiyohiro Sakai  7 , Yoichi Otake  8 , Atsuko Koyama  6   3 , Kazuto Nishio  5 , Kazuhiko Nakagawa  3
Affiliations
Randomized Controlled Trial

Selection of opioids for cancer-related pain using a biomarker: a randomized, multi-institutional, open-label trial (RELIEF study)

Hiromichi Matsuoka et al. BMC Cancer. .

Abstract

Background: Cancer patients experience pain that has physiological, sensory, affective, cognitive, behavioral, and sociocultural dimensions. Opioids are used in treatment of pain in patients with various types of cancer. We previously showed that the catechol-O-methyltransferase (COMT) genotype is related to the plasma level of morphine and the required dose of morphine in an exploratory prospective study. The findings showed that a group of patients with a GG single nucleotide polymorphism (SNP) rs4680 in COMT required a significantly higher dose of morphine than a non-GG group. A biomarker for selection of opioids for cancer pain relief would be particularly useful clinically, and therefore we have planned a randomized comparative study of morphine and oxycodone, using the COMT rs4680 SNP as a biomarker. This study is aimed at verifying the assumption that patients in the GG group require an increased morphine dose for pain relief.

Methods: The RELIEF study is a randomized, multi-institutional, open-label trial with a primary endpoint of the proportion of subjects requiring high-dose opioids, as calculated from the dose of a rescue preparation administered on day 0. Secondary endpoints include the Hospital Anxiety and Depression Scale, Short form McGill Pain Questionnaire-2, European Organization for Research and Treatment of Cancer QLQ-C15-PAL, Pain Catastrophizing Scale, and adverse events, Eligibility criteria are patients with advanced carcinoma with non-daily use of opioids in initial screening for registration; and cancer pain targeted for daily opioid treatment, NSAIDs or acetaminophen, NRS ≥3(average over 24 h), opioid-treatment naive within 30 h, no chemotherapy, radiotherapy, or bisphosphonate administration newly started within 2 weeks, and written informed consent at the time of second registration. Between November 2014 and June 2017, an estimated 110 patients from two sites in Japan were randomized (1:1) to morphine or oxycodone in GG and non-GG groups.

Discussion: A method for selection of appropriate opioids in cancer patients is a high unmet medical need. This study was designed to evaluate the efficacy of different opioids in patients with cancer based on gene polymorphism, as the first potential multi-institutional registration trial to be conducted in cancer patients with pain.

Trial registration: UMIN000015579 Date of registration: 4 November 2014. It is updated once every six months, the latest update is 30 June 2017. Trial status. The enrollment started in November 2014. At the time of manuscript submission (July 2017), Three-quarters of patients have participated. We thus expect to complete the recruitment by March 2018.

Keywords: Biomarker; Cancer pain; Opioid; Randomized controlled trial.

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Conflict of interest statement

Ethics approval and consent to participate

Institutional review board approvals were obtained from the ethical committee of the Kindai University Faculty of Medicine and Sakai City Medical Center. (reference numbers 26–130 and 1604, respectively). The RELIEF study is published under UMIN000015579. All patients are required to provide written informed consent. The study will be performed in accordance with the Declaration of Helsinki and the International Conference on Harmonization and Good Clinical Practice.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Design of the study
Fig. 2
Fig. 2
Methods for dose titration
See this image and copyright information in PMC

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