Phase I study of pevonedistat in combination with capecitabine and oxaliplatin (CapeOX) in patients with advanced gastric cancer refractory to platinum

JRCT ID: jRCT2031190020

Registered date:10/05/2019

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: stomach cancer
• Date of first enrollment: 28/08/2019
• Target sample size: 23
• Study type: Interventional
• Intervention(s): In a 21-day-administration cycle, pevonedistat at 15 mg/m^2 (level 0: initiation dose) will be administered on days 1, 3, and 5. Oxaliplatin at 130 g/m^2 will be administered on day 1, and capecitabine will be orally administered at 2000 mg/m^2 split in 2 approximately every 12 hour for 14 days and then it was withdrawn for 7 days.

Outcome(s)

Primary Outcome

The safety and tolerability of the combination of pevonedistat and CapeOX in Japanese patients with unresectable advanced/recurrent gastric cancer who are refractory or intolerant to platinum (cisplatin or oxaliplatin) in order to determine the recommended dose (RD).
The pharmacokinetics (PK) of pevonedistat under its combined administration with CapeOX in Japanese patients with unresectable advanced/recurrent gastric cancer who are refractory or intolerant to platinum (cisplatin or oxaliplatin).

• Secondary Outcome: The therapeutic effect of the combination of pevonedistat and CapeOX on gastric cancer.

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1) Patients who are diagnosed as having any of adenocarcinoma (pupillary adenocarcinoma, tubular adenocarcinoma, or poorly differentiated adenocarcinoma), signet-ring cell carcinoma and mucinous carcinoma.
2) Patients with unresectable advanced gastric cancer or those with recurrent gastric cancer (including those with carcinoma of gastroesophageal junction).
3) Patients whose CT images show no massive ascites toward the upper abdomen over the pelvic cavity, and patients without massive ascites requiring drainage.
4) Patients who can take food orally.
5) Patients who are 20 years old or older at the registration.
6) Patients with ECOG performance status (PS) of 0 or 1.
7) Patients in whom at least 1 measurable lesion* was proven with thoracic-abdominal-pelvic CT scan.
8) Patients who are refractory or intolerant to fluoropyrimidines (at least one of 5-FU, capecitabine or S-1), first-line chemotherapy containing cisplatin or oxaliplatin, or second-line chemotherapy containing taxanes for gastric cancer and have been treated with two or more regimens of anticancer therapy previously.
9) Peripheral sensory neuropathy and peripheral motor neuropathy
less than Grade 1 defined by CTCAE v5.0
10) Patients who were not treated with systemic antineoplastic therapy (including investigational drugs) within 14 days before the registration.
11) Patients who were not radiated to their spinal cord or pelvis within 28 days before the registration, and those who did not receive radiation to the organs other than the spinal cord and pelvis within 14 days before the registration.
12) Patient whose clinical laboratory test values obtained within 3 days before the registration meet the following criteria.
13) Female patients who agree to practice 1 highly effective method and 1 additional effective (barrier) method of contraception, at the same time, from the time of signing the informed consent through 4 months after the last dose of study drug or 6 months after the last dose of capecitabine, whichever comes later.
14) Male patients, even if surgically sterilized (ie, status postvasectomy), who agree to practice effective barrier contraception during the entire study treatment period and through 4 months after the last dose of study drug or 3 months after the last dose of capecitabine, whichever comes later.
15) Patients who have provided a written informed consent to participate in the trial.

Exclude criteria

1) Synchronous or metachronous (within 5 years) malignancies except for carcinoma in situ or mucosal tumors curatively treated with local therapy.
2) Patients with an infectious disease requiring systemic treatment.
3) Intorelant to capecitabine and/or oxaliplatin.
4) Prothrombin time (PT) or activated partial thromboplastin time (APTT) exceeds 1.5 times the institution standard value or has poorly controlled active coagulopathy or hemorrhagic disease
5) Known cardiopulmonary disease.
6) Left ventricular ejection fraction (LVEF) measured using echocardiography (ECHO), less than 50%
7) Major surgery or laparotomized biopsy under general anesthesia within 14 days prior to registration
8) Metastasis to the central nervous system (brain, spinal cord, meningeal) is evident
9) Patients with Liver cirrhosis or severe hepatic disorder
10) Have a life-threatening disease not related to gastric cancer
11) A positive test result for any of the followings: Human immunodeficiency virus antibody, hepatitis B surfaces (HBs) antigen, or hepatitis C virus antibody.
12) Positive test result for either HBs antibody or hepatitis B core antibody, with a detectable level of hepatitis B virus-deoxyribonucleic acid (HBV-DNA) even in case of negative HBs antigen test
13) Female patients who are both lactating and breastfeeding or have a positive serum pregnancy test during the screening period or a positive urine pregnancy test on Day 1 before first dose of study drug.
14) Female patients who intend to donate eggs (ova) during the course of this study or 4 months after receiving their last dose of study drug(s) or 6 months following the last dose of capecitabine, whichever comes later.
15) Male patients who intend to donate sperm during the course of this study or 4 months after receiving their last dose of study drug(s) or 3 months following the last dose of capecitabine, whichever comes later.
16) Judged to be incapable of providing consent for certain reasons, such as concurrent dementia
17) Require or have received systemic corticosteroids or immunosuppressants
18) Uncontrolled high blood pressure (ie, systolic blood pressure > 180 mm Hg, diastolic blood pressure > 95 mm Hg).
19) Prolonged rate corrected QT (QTc) interval more than 500 msec, calculated according to institutional guidelines.
20) Known moderate to severe chronic obstructive pulmonary disease, interstitial lung disease, and pulmonary fibrosis.
21) Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of study procedures.

Related Information

• Primary Sponsor: Shoji Hirokazu
• Source(s) of Monetary Support: Takeda Pharmaceutical Company Limited