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Phase I/II trial of combined chemotherapy of Nab-paclitaxel, S-1, and Oxaliplatin for gastric cancer patients with peritoneal metastasis (NSOX study) (NSOX study)

NSOX study (NSOX study)

6

Six patients were enrolled and evaluated for toxicity. Median age was 70 years, all patients had ill-defined macroscopic type and diffuse-type disease. No patients had definite distant metastasis except for peritoneal metastasis.

At dose level 0, DLTs were not observed in any patients. At dose level 1, two of the first 3 patients experienced grade 4 nonhematological toxicities as DLTs. One patient experienced acute myocardial infarction and was successfully treated by cardiac catheterization on day 19 from the start of treatment. The other patient developed jejunal perforation on day 8 from the start of chemotherapy and underwent emergent surgery. There was no treatment-related mortality during the study.The MTD and RD were consequently determined to be dose level 1 and dose level 0, respectively. No progression of disease was observed in any patients during the study.Since the registration of Phase I was very slow, we decided that it would be difficult to move to Phase II and canceled it on December 21, 2020.

There were no grade 3 or higher hematological toxicities. Common treatment-related adverse events were leukopenia (50.0%; n = 3), neutropenia (50.0%; n = 3), anorexia (83.3%; n = 5), fatigue (66.7%; n = 4), and peripheral sensory neuropathy (50.0%; n = 3).Only 1patient in dose level 1 could not receive protocol treatment after 8 days because of jejunal perforation.

The MTD was determined to be dose level 1, as 2 of 3 patients experienced dose-limiting toxicities (DLTs), grade 4 non-hematological toxicities. One patient experienced acute myocardial infarction, and the other patient developed jejunal perforation. There were no treatment-related deaths. Therefore, the RD was determined to be dose level 0.

The NSOX regimen was shown to be a tolerable regimen and may be a promising triplet therapy for patients with gastric cancer with peritoneal metastasis.

April. 07, 2021

Sept. 02, 2020

http://www.karger.com/ocl

No

We have no plan to share IPD.

https://jrct.mhlw.go.jp/latest-detail/jRCTs051180012

Nakamura Masaki

Wakayama Medical University Hospital

811-1 Kimiidera,Wakayama-shi,Wakayama, Japan

twins@wakayama-med.ac.jp

Nakamura Masaki

Wakayama Medical University Hospital

811-1 Kimiidera,Wakayama-shi,Wakayama, Japan

+81-73-441-0613

twins@wakayama-med.ac.jp

Complete

Jan. 11, 2018

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

treatment purpose

1. Histologically proven adenocarcinoma of gastric cancer and positive peritoneal dissemination by staging laparoscopy (except recurrent gastric cancer )
2. HER2 negative (or untested)
3. No non-curative factors except for peritoneal dissemination
4. No prior chemotherapy or radiation therapy (in case of previous adjuvant therapy, interval between end of chemotherapy and relapse must be > 6 months for S-1 therapy)
5. Age 20-75 years
6. ECOG PS 0 or 1
7. Able to ingest
8. Patients must have normal organ and marrow function as defined below within 14 days prior to enrollment :
Neutrophils (ANC) >= 1,500 /mm3
Platelets >=100,000 /mm3
Hemoglobin >= 8g/dL
Serum bilirubin <= 2.0 x upper normal limit (ULN)
AST/ALT <= 100 U/L
Serum creatinine level <= 1.2 mg/dL
CCR >= 60 mL/min
9. Life expectancy of at least 3 months
10.Signed and dated informed consent

1. History of hypersensitivity to nab-paclitaxel, S-1 or oxaliplatin
2. Contraindication for nab-paclitaxel, S-1 or oxaliplatin
(e.g. cases receiving severe bone marrow function suppression, severe renal disorder, severe liver disorder, administration of other pyrimidine-based antitumor agents, fluoride or flucytosine)
3. Active infectious disease
4. HBs-antigen positive
5. Severe complications, such as those listed below:
Uncontrolled heart failure/unstable angina pectoris/cardiac arrhythmia
Myocardial infarction (< 3 months prior to study entry)
Uncontrolled diabetes mellitus, uncontrolled hypertension
Interstitial pneumonia, pulmonary fibrosis
Complications that present serious obstacles to this study
6. Symptomatic neuropathy
7. Known brain metastasis with clinical symptoms
(if asymptomatic, examination is not required)
8. Watery diarrhea.
9. Active double cancer.
Synchronous or metachronous(within 5 years) malignancies except for carcinoma in situ or intramucosal tumors curatively treated with local therapy
10. Breast-feeding, pregnant or planning pregnancy
11. Patients who are otherwise judged to be ineligible for enrolment by investigators

Both

Gastric cancer with peritoneal metastasis

1. Nab-Paclitaxel:50-80 mg/m2 on days 1 and 8
2. Oxaliplatin: 100 mg/m2 on day 1
3. S-1:40mg/m2 bid (80mg/m2/day) between day 1 and 14
Patients receive five courses of No.1,2,3 therapies.

Phase I: Rate of dose limiting toxicity (DLT)
Phase II: Rate of negative conversion in peritoneal dissemination

Phase I:adverse events
Phase II:completion rate of chemotherapy, response rate, curative resection rate(R0 resection rate 0), rate of postoperative complications after the radical excision, pathological response rate , rate of adverse events, progression free survival, rate of disease control, relapse free survival after the radical excision, overall survival, time to treatment failure

+81-73-441-0896

Sept. 26, 2018

none