Clinical trial NCT03701373: Maintenance Treatment With S-1 in Gastric Cancer Patients
Official title: Maintenance Treatment With S-1 Versus Observation After First-line Chemotherapy in Patients With Advanced Gastric Cancer: a Randomized Phase II Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Gastric Cancer Stage IV
Cancer of Stomach
Keywords: Advanced Gastric Cancer
Maintenance
S-1
First-line treatment
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2018-10-10
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Gastric cancer remains the third leading cause of cancer-related death worldwide and is especially frequent in East Asia. Fluoropyrimidines are the backbone of first-line chemotherapy for advanced gastric cancer (AGC), and S-1 provides new option with its simplicity and convenience.

5-Fluorouracil (5-FU) was the only efficacious treatment for AGC before the nineties of the 20th century, and afterwards with the discovery of chemotherapy such as cisplatin, oxaliplatin, S-1 and capecitabine, response rate as well as survival had been improved greatly.

Most of AGC will progress after first-line treatment; therefore, seeking an efficient and low toxic maintaining regimen to prolong progression-free survival (PFS) becomes a hot topic in oncologic field. Some clinical researches demonstrated maintenance treatment for advanced colorectal cancer (CRC) and lung cancer. The investigators had conducted a phase III clinical trial that demonstrated capecitabine maintenance versus observation prolonged PFS significantly after first-line chemotherapy with FOLFOX or XELOX regimens in advanced CRC. In AGC, several retrospective studies revealed patients receiving 5-FU/leucovorin(LV), capecitabine, or trastuzumab maintaining therapy experienced significantly longer PFS than that stopped chemotherapy after first-line chemotherapy. Some one-arm phase II clinical trials found 5-FU/LV, capecitabine, S-1, capecitabine plus bevacirumab, or capecitabine plus bevacirumab plus trastuzumab maintenance seemed to yield sound PFS and good tolerance. However, there were no randomized controlled clinical trials for maintenance treatment of these regimens in AGC, except that a phase II Chinese randomized controlled trial of Uracil and Tegafur (UFT) versus observation experienced early termination.

Above all, so far, there is no data to demonstrate that regular 2-6 months of chemotherapy followed by maintenance treatment could prolong PFS and OS for AGC. S-1 is effective for gastric cancer, and was approved as palliative treatment for advanced gastric cancer and adjuvant treatment; in addition, with its relative less frequency of side effects and convenient oral administration, S-1 as maintenance regimen could be prone to be accepted by patients. Therefore, the current study is designed to investigate that S-1 as maintenance treatment after first-line palliative chemotherapy could improve PFS and OS for patients with advanced gastric cancer through a perspective randomized clinical study.

Detailed description: Patients with AGC who achieved objective response or stable disease after 2-6 months of first-line chemotherapy were randomly assigned to one of two groups, to receive either S-1 (40 mg for BSA\<1.25 m2, 50 mg for 1.25≤BSA\<1.50 m2 and 60 mg for BSA≥1.50 m2 b.i.d. on days 1-14, q3w) as maintenance therapy or observation. The treatment will continue until disease progression or unacceptable toxicity.

Eligibility criteria: Inclusion Criteria:

* Age older than 18 years
* Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1
* At least one measurable lesion according to the Response Evaluation Criteria in Solid Tumor (RECIST version 1.0)
* Histologically confirmed gastric cancer with inoperable locally advanced or recurrent and/or metastatic disease, not amenable to curative therapy
* No previous chemotherapy for metastatic GC was allowed, the interval after the end of adjuvant/neoadjuvant chemotherapy beyond 6 months was allowable
* Life expectancy of at least 3 months
* Adequate hematologic, hepatic and renal function. Neutrophil count ≥ 1.5 × 109/L; platelet count ≥ 100 × 109/L; Serum bilirubin ≤ 1.5 × upper limit of normal (ULN), AST or ALT ≤ 2.5 × ULN (or ≤ 5 × ULN in patients with liver metastases), alkaline phosphatase ≤ 2.5 × ULN (or ≤ 5 × ULN in patients with liver metastases, or ≤ 10 × ULN in patients with bone but no liver metastases); serum creatinine ≤ 1.5 × ULN；and albumin ≥ 25 g/L
* Patients who achieved objective response or stable disease after 2-6 month first-line chemotherapy
* The first-line chemotherapy regimens were doublets including platinum (cisplatin or oxaliplatin) plus fluoropyrimidine (5-FU, capecitabine, or S-1)
* Signed informed consent

Exclusion Criteria:

* Known hypersensitivity to platinum (cisplatin or oxaliplatin) or fluoropyrimidine (5-FU, capecitabine, or S-1)
* History or clinical evidence of brain metastases
* Previous chemotherapy for metastatic disease
* Positive serum pregnancy test in women of childbearing potential
* Subjects with reproductive potential not willing to use an effective method of contraception
* Received any investigational drug treatment within 4 weeks of start of study treatment
* Other prior malignancies in the past 5 years
* Unresolved bowel obstruction or malabsorption syndrome

Primary outcomes:
measure: maintenance progression-free survival (PFS)
timeFrame: from date of randomization to maintenance or observation until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years
Secondary outcomes:
measure: progression-free survival from induction treatment (PFS2)
timeFrame: from induction treatment (the initiation date of first-line chemotherapy) until the date of first documented progression or date of death from any cause after maintenance treatment or observation, whichever came first, assessed up to 2 years
measure: overall survival (OS)
timeFrame: from induction treatment (the initiation date of first-line chemotherapy) until death from any cause or the last follow-up date, assessed up to 2 years.
measure: toxicity relevant to S-1 maintenance/observation
timeFrame: from date of randomization to maintenance or observation until the date of first documented progression or unaccepted toxicities, assessed up to 30 days after the last oral administration of S-1.
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
Study officials:
affiliation: Sun Yat-sen University
name: Rui-hua Xu
role: PRINCIPAL_INVESTIGATOR
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