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Oct. 01, 2018

April. 01, 2023

jRCTs031180022

WJOG10617G Randomized phase II trial of weekly paclitaxel + ramucirumab versus weekly nab-paclitaxel + ramucirumab for unresectable advanced or recurrent gastric/esophagogastric junction adenocarcinoma with peritoneal dissemination refractory to first-line therapy including a fluoropyrimidine (P-SELECT)
(P-SELECT)

Selection trial of paclitaxel in gastric cancer with peritoneal dissemination (P-SELECT)

Jan. 27, 2021

105

Fifty-three patients were assigned to Arm A (weekly PTX plus ramucirumab) and 52 to Arm B (weekly nab-PTX plus ramucirumab). Median age was 69 years in Arm A and 66 years in Arm B. The male ratio was 60.4% in Arm A and 65.4% in Arm B. All patients had peritoneal dissemination, with none/small/moderate/large ascites in 22.6%/41.5%/7.5%/28.3% of patients in Arm A and 23.1%/36.5%/21.2%/19.2% of patients in Arm B. The Lauren classification of intestinal type was 35.8% in Arm A and 34.6% in Arm B, and diffuse type was 62.3% in Arm A and 65.4% in Arm B.

Enrollment began on October 2, 2018, and although the initial plan was for a three-year enrollment period, the pace of enrollment exceeded expectations. The last patient was enrolled on January 27, 2020, completing enrollment of 105 cases in 1 year and 4 months. Fifty-eight facilities participated in the study, 30 of which registered at least one case. The top 5 registered centers were Keio University Hospital (13 cases), National Cancer Center Hospital (11 cases), Saitama Cancer Center (10 cases), Toranomon Hospital (8 cases), and Kobe City Medical Center General Hospital (6 cases); the remaining centers registered 5 or fewer cases. Efficacy analysis was performed by ITT analysis. Safety analysis was performed on all patients in group A and 51 patients in group B except one who did not receive protocol treatment.

Adverse events were evaluated based on CTCAE version 4.0. One case of treatment-related death (TRD) was observed, which was a case of gastrointestinal perforation from colorectal ileus due to progression of the primary disease, and a causal relationship with ramucirumab could not be ruled out. There were 52 serious adverse events reported, all of which were unrelated or known adverse events. 62.3% of patients in Arm A and 78.4% in Arm B had Grade 3 or higher neutropenia, while 11.3% of patients in Arm A and 5.9% of patients in Arm B had Grade 3 or higher febrile neutropenia. Other G3 or higher adverse events in Arm A and B included anorexia in 13.2% and 15.7% of patients; peripheral sensory neuropathy in 7.5% and 17.6%; and hypertension in 5.7% and 7.8%, respectively.

Median OS was 8.1 months in Arm A and 7.2 months in Arm B (HR 1.04, 95% confidence interval [CI] 0.67 - 1.61, P = 0.63). Median PFS was 5.1 months in Arm A and 3.9 months in Arm B (HR 1.04, 95% CI 0.69 - 1.56, P = 0.89). The ORR and DCR for Arm A and Arm B were 20.7% vs. 20.0% (P = 0.99) and 77.4% vs. 63.5% (P = 0.15), respectively. The ascites control rate was 86.1% in Arm A and 70.3% in Arm B (P = 0.07). The incidence of grade 3/4 neuropathy was higher in Arm B (7.5% vs 17.6%, P = 0.14), whereas there was no difference in neuropathy-specific quality of life between the two groups. The incidence of febrile neutropenia was higher in Arm A (11.3% vs 5.9%, P = 0.49). SPARC expression in tumor tissue was not significantly correlated with efficacy, while caveolin-1 expression in tumor stroma was significantly correlated with efficacy in Arm B. Trough values of blood ramucirumab levels tended to correlate with efficacy in Arm A, but not in Arm B.

The potential difference in efficacies between nab-PTX+RAM and PTX-RAM was not shown in advanced gastric cancer with peritoneal dissemination.

April. 01, 2023

Feb. 01, 2022

https://ascopubs.org/doi/abs/10.1200/JCO.2022.40.4_suppl.280

No

-

https://jrct.niph.go.jp/latest-detail/jRCTs031180022

Hirata Kenro

Keio University Hospital

35, Shinanomachi, Shinjuku, Tokyo

+81-3-3353-1211

kenro916@gmail.com

Yukawa Naomi

Keio University Hospital

35, Shinanomachi, Shinjuku, Tokyo

+81-3-5363-3288

yukawa703@keio.jp

Complete

Oct. 01, 2018

Oct. 11, 2018
105

Interventional

randomized controlled trial

open(masking not used)

active control

parallel assignment

treatment purpose

1) age >= 20 years old.
2) Informed consent.
3) Histological diagnosis of primary gastric or esophagogastric junction adenocarcinoma.
4) Unresectable gastric or esophagogastric junction cancer or recurrent gastric or esophagogastric junction cancer.
5) At least one of i) to iv) below present as a sign indicating peritoneal metastasis.
i) Contrast enema/enterography: Obvious malignant intestinal stenosis or deformation of the intestinal wall.
ii) CT: Obvious peritoneal mass or ascites, hydronephrosis not attributable to a cause other than peritoneal metastasis, increased density of peritoneal adipose tissue, thickening of the intestinal wall.
iii) Clinical signs: Palpable metastasis in the pouch of Douglas, board-like rigidity of the abdomen not attributable to a cause other than peritoneal metastasis.
iv) Operative findings (including exploratory laparoscopy): Lesions suggestive of peritoneal metastasis, confirmed by pathological diagnosis of peritoneal metastasis.
6) Patients without massive pleural effusion.
7) Patients without advanced central nervous system (CNS) metastases.
8) Patients with lesions which can be evaluated (Whether or not lesions are measurable is irrelevant.).
9) Intolerant or refractory to first-line therapy including a fluoropyrimidine.
10) Patient without history of use of taxane or angiogenesis inhibitors.
11) Patients without history of radiotherapy including irradiation of the abdominal region.
12) ECOG performance status: 0, 1, 2
13) Adequate organ function.

1) Active multiple cancer (synchronous multiple cancer or metachronous multiple cancer in which the patient has been disease-free for less than 3 years). However, lesions corresponding to carcinoma in situ (intraepithelial carcinoma) or intramucosal cancer assessed as cured by local treatment are not classed as active multiple cancers.
2) History of sensitivity to any of the drugs used in this study (including alcohol or albumin sensitivity).
3) Patients with the history of surgery under general anesthesia within 28 days.
4) Patients who have had deep vein thrombosis, pulmonary embolism, or some other major form of thromboembolism up to 12 weeks prior to enrollment.
5) Palliative ascites aspiration (excluding diagnostic puncture for laboratory tests) within the past 2 weeks.
6) Active infection requiring systemic treatment.
7) Uncontrolled hypertension despite hypotensive drug therapy.
8) Diabetes under treatment with continuous insulin use or uncontrolled diabetes.
9) Patients with severe pulmonary disease.
10) Unstable angina (attacks occurring or exacerbated within the past 3 weeks), or myocardial infarction within the past 3 months.
11) Serious hemorrhagic disorder or vasculitis, or an episode of serious gastrointestinal bleeding.
12) Grade 2 or worse peripheral sensory neuropathy.
13) Patients with liver cirrhosis (Child Pugh B or C) or previous hepatic encephalopathy.
14) Patients with intestinal obstruction.
15) Patients receiving continuous systemic administration of steroids.
16) Patients receiving antiplatelet drugs.
17) Mental illness or mental symptoms that would interfere with participation in the study.
18) Pregnant, breast-feeding, with chance of pregnancy, or expecting to give birth.
19) Patients deemed by an investigator to be unsuitable as study subjects for any other reason.

20age old over
No limit

Both

Unresectable advanced gastric/esophagogastric junction adenocarcinoma with peritoneal dissemination

Arm A (Standard Treatment)
Paclitaxel 80 mg/m^2 day 1, 8, 15 div
Ramucirumab 8 mg/kg day 1, 15 div
Continued for 4-week courses until the subject becomes refractory.

Arm B (Investigational Treatment)
Nab-paclitaxel 100 mg/m^2 day 1, 8, 15 div
Ramucirumab 8 mg/kg day 1, 15 div
Continued for 4-week courses until the subject becomes refractory.

Overall survival: OS

Progression-free survival: PFS
Objective response rate: ORR
Disease control rate: DCR
Proportion of ascites response
Proportion of ascites control
Time to treatment failure: TTF
Rate of adverse events
Quality of life: QOL
Biomarkers for nab-PTX and RAM

TAIHO PHARMACEUTICAL CO., LTD.
Not applicable
Certified Review Board of Keio
35, Shinanomachi, Shinjuku, Tokyo, Tokyo

+81-3-5363-3503

med-nintei-jimu@adst.keio.ac.jp
Approval

Aug. 09, 2018

なし
None

None

History of Changes

No Publication date
12 April. 01, 2023 (this page) Changes
11 Oct. 27, 2022 Detail Changes
10 Aug. 08, 2022 Detail Changes
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7 June. 17, 2022 Detail Changes
6 Sept. 15, 2021 Detail Changes
5 Aug. 20, 2020 Detail Changes
4 April. 26, 2019 Detail Changes
3 Dec. 10, 2018 Detail Changes
2 Oct. 19, 2018 Detail Changes
1 Oct. 01, 2018 Detail