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

BMC Cancer

Study Protocol

Yasutaka Chiba¹  Yoichi Otake²  Masato Terashima³  Yoshihiko Fujita³  Kazuto Nishio³  Kazuhiko Nakagawa⁴  Junji Tsurutani⁴  Kiyohiro Sakai⁵  Takeshi Yoshida⁶  Atsuko Koyama⁶  Hiromichi Matsuoka⁷ 

[1] Clinical Research Center, Kindai University Hospital, 377-2 Ohno-higashi, Osakasayama City, 589-8511, Osaka, Japan;Department of General Internal Medicine, Sakai City Medical Center, 377-2 Ohno-higashi, Osakasayama City, 589-8511, Osaka, Japan;Department of Genome Biology, Kindai University Faculty of Medicine, 377-2 Ohno-higashi, Osakasayama City, 589-8511, Osaka, Japan;Department of Medical Oncology, Kindai University Faculty of Medicine, 377-2 Ohno-higashi, Osakasayama City, 589-8511, Osaka, Japan;Department of Psychosomatic Medicine, Kindai University Faculty of Medicine, 377-2 Ohno-higashi, Osakasayama City, 589-8511, Osaka, Japan;Palliative Care Center, Cancer Center, Kindai University Hospital, 377-2 Ohno-higashi, Osakasayama City, 589-8511, Osaka, Japan;Department of Medical Oncology, Kindai University Faculty of Medicine, 377-2 Ohno-higashi, Osakasayama City, 589-8511, Osaka, Japan;Palliative Care Center, Cancer Center, Kindai University Hospital, 377-2 Ohno-higashi, Osakasayama City, 589-8511, Osaka, Japan;Department of Psychosomatic Medicine, Kindai University Faculty of Medicine, 377-2 Ohno-higashi, Osakasayama City, 589-8511, Osaka, Japan;

关键词: Opioid;    Biomarker;    Cancer pain;    Randomized controlled trial;   

DOI  :  10.1186/s12885-017-3664-z

 received in 2016-06-17, accepted in 2017-09-28,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundCancer 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.MethodsThe 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.DiscussionA 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 registrationUMIN000015579 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.

【 授权许可】

CC BY   
© The Author(s). 2017