A phase II trial of ramucirumab plus irinotecan for patients with early relapced gastric cancer

JRCT ID: jRCTs051190071

Registered date:06/11/2019

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Gastric cancer
• Date of first enrollment: 05/12/2019
• Target sample size: 40
• Study type: Interventional

Intervention(s)

Irinotecan 150 mg/m^2 day 1 div
Ramucirumab 8 mg/kg day 1 div
Continued for 2-week courses until the subject becomes refractory.

Outcome(s)

• Primary Outcome: overall survival
• Secondary Outcome: progression free survival (PFS), time to treatment failure (TTF), response rate (RR), disease control rate (DCR), safety (rate of occurence of grade 3/4 adverse events), relative dose intensity (RDI)

Key inclusion & exclusion criteria

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

Include criteria

1) A histopathological diagnosis of adenocarcinoma.
2) Patients who are on DS adjuvant chemotherapy after the confirmation of pathological stage III (including ypIII) after radical gastrectomy*1.
3) Early recurrence postsurgery: during DS adjuvant chemotherapy*2 or a recurrence within*3 six months after completing therapy*4.
4) Age of >20 years.
5) Performance status 0 or 1
6) Lesions that can be evaluated by imaging according to RECIST 1.1 guidelines or nonmeasurable lesions.
7) Laboratory results with the following values within 14 days prior to clinical study registration. Of all values within this 14day period, the most recent will be used for registration. Using the day of registration as the reference point, laboratory results 2 weeks prior to registration can be used as long as the results reflect samples collected on the same day as the registration day.
Absolute neutrophil count (ANC): =>1,500/mm3
Hemoglobin: =>9.0 g/dL
Platelet count: =>100000/mm3
AST, ALT: =<100 IU/L
(=<200 IU/L in patients with liver metastasis)
Total bilirubin: =<1.5 mg/dL (elevated bilirubin associated with grade1 Gilbert's syndrome will be exempted)
Serum creatinine: =<1.5 mg/dL, or creatinine clearance: =>40ml/min
(estimated creatinine clearance rate using the Cockcroft-Gault formula or creatinine concentration measured after 24-hour urine collection)
Urinary protein: =< (1+) on dipstick or routine urinalysis or =>2 g/24 hours after 24-hour urine collection, or urinary protein/creatinine ratio <2
PT-INR: =<1.5
PTT: =<5 seconds above the ULN
(APTT: =<5 seconds above the ULN)
8) Written informed consent was obtained from patient after providing a detailed explanation of the clinical study prior to registration.
9) HER2 undectable or negative.
10) No history of receiving irinotecan or ramucirumab.
11) Ability to tolerate chemotherapy or radiation prior to surgery.
12) Oral intake possible

*1 Gastroesophageal junction adenocarcinoma with R0 resection is also eligible.
*2 During adjuvant therapy: After the beginning of the second course of DS therapy (a history of more than one course of DOC).
*3 CT scan at 6 months: If CT scan is taken >6 months after the initiation of the final course, because of patient circumstances or the facility, and the patient was diagnosed with recurrence within 4 weeks after the 6-month time point, then the patient was included in the study.
*4 After the completion of adjuvant therapy: the end date of adjuvant therapy is defined as 6 weeks after the start date of the final course.

Exclude criteria

1.Active multiple primary cancers (synchronous and heterogeneous multiple primary cancers within a 5-year disease-free interval). However, localized treatment resulting in a cure of pathological lesions such as carcinoma in situ or equivalent to intramucosal cancer would not be considered as active multiple primary cancers.
2.Symptomatic interstitial pneumonia or pulmonary fibrosis is observed.
3.An infection requiring systemic treatment; however, even if HBsAg positive, if the infection is being controlled by nucleoside/nucleotide analogs and serum is confirmed as HBV-DNA negative, then the subject is eligible for registration.
4.Body temperature of 38C at the time of registration.
5.Pregnant, lactating women, those who may be currently pregnant, or are unwilling to use contraceptives.
6.Diagnosed with or manifestations of mental illness demonstrated such that the subject has difficulty in participating in the clinical study.
7.Continued systemic steroid administration.
8.Presence of a serious complication.
9.Anticoagulants are being administered for thromboembolism treatment.
10.Uncontrolled hypertension (for example, even with standard oral agents, blood pressure exceeds 150/90 mm Hg).
11.Uncontrolled diarrhea affecting daily activities despite adequate treatment.
12.Evidence of active bleeding (a history of grade 3 or 4 bleeding within 3 months of receiving the first adjuvant treatment).
13.No symptoms consistent with evidence of metastasis to the central nervous system (brain, spinal cord, and meninges).
14.Blood transfusion treament within 2 weeks of registration.
15.Presence of more than moderate pleural effusion with ascites accumulation.
16.Is in the process of enrolling in another interventional clinical study at the time of registration for this clinical study.
17.Currently on medication with ataznavir sulfate, for which co-administration with IRI is contraindicated.
18.Other situations in which the clinical study physician determines that the subject is an unsuitable candidate.

Related Information

• Primary Sponsor: YAMAGUCHI Toshifumi
• Source(s) of Monetary Support: Eli Lilly Japan K.K.