OCTASUR: Total Neoadjuvant Chemotherapy in Locally Advanced Gastric and Gastroesophageal Junction Cancer
Study Details
Study Description
Brief Summary
The main goal of this study is to investigate the histopathological regression rate in patients with locally advanced gastric and gastroesophageal adenocarcinoma without previous treatment who will be prospectively randomized into two groups to undergo one of two chemotherapy regimens, followed by surgery:
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8 cycles of Total Neoadjuvant ChemoTherapy (TNT) with 5-Fluorouracil (5-FU), Leucovorin, Oxaliplatin and Docetaxel (FLOT) followed by surgery.
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4 cycles of Neoadjuvant FLOT chemotherapy scheme preoperatively and 4 adjuvant FLOT cycles postoperatively.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2/Phase 3 |
Detailed Description
758 participants with resectable locally advanced gastric and gastroesophageal (Siewert 2, 3) adenocarcinoma (T3-4b, N1-3, M0) with no history of previous treatment will be included in this study after reading and signing the informed consent. After the initial diagnostic laparoscopy, patients will be randomized into two groups in a 1:1 ratio, with allocation to one of the two study groups.
Patients who will be randomized to the first (control) group will receive 8 cycles of perioperative FLOT chemotherapy scheme: 4 cycles before surgical treatment and 4 cycles after surgical intervention. Patients who will be randomized to the second (study) group will receive 8 cycles of FLOT total neoadjuvant chemotherapy, followed by surgery.
Primary endpoint of the study is pathomorphological tumor response rate. Secondary endpoints are: perioperative morbidity and mortality (surgical and chemotherapeutic complications); disease-free survival (DFS) and 1-, 3- and 5-years overall survival (OS); quality of life during and after the treatment; correlation between the pathohistological response and chemotherapy regimen.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Perioperative 4+4 FLOT cycles 4 cycles of neoadjuvant FLOT chemotherapy scheme, followed by surgery and 4 cycles of adjuvant FLOT chemotherapy scheme. |
Drug: Docetaxel
50mg/m2, d1, i.v., every 2 weeks
Drug: Oxaliplatin
85 mg/m², d1, i.v., every 2 weeks
Drug: Leucovorin
200 mg/m², d1, i.v., every 2 weeks
Drug: Fluorouracil
2600 mg/m²d1 i.v. every 2 weeks
|
| Experimental: Total Neoadjuvant ChemoTherapy (TNT) 8 FLOT cycles 8 cycles of total neoadjuvant FLOT chemotherapy scheme, followed by surgery. |
Drug: Docetaxel
50mg/m2, d1, i.v., every 2 weeks
Drug: Oxaliplatin
85 mg/m², d1, i.v., every 2 weeks
Drug: Leucovorin
200 mg/m², d1, i.v., every 2 weeks
Drug: Fluorouracil
2600 mg/m²d1 i.v. every 2 weeks
|
Outcome Measures
Primary Outcome Measures
- Histopathological tumor response rate (Becker regression criteria). [14 days after surgery]
To determine the pathohistological regression rate after 8 FLOT cycles in total neoadjuvant regimen compared to 4 FLOT cycles in neoadjuvant regimen.
Secondary Outcome Measures
- Surgical complications rate. [30 days after surgery.]
To determine postoperative surgical complications rate and profile after the different chemotherapy regimens, according to Clavien-Dindo classification.
- Chemotherapy toxicity rate and profile. [At the end of each FLOT cycle (each cycle is 14 days), up to 14 days after the last cycle.]
To determine chemotherapeutic toxicity profile, according to Common Terminology Criteria for Adverse Events (CTCEA 5.0).
- Quality of patients' life, according to the European Organisation for Research and Treatment of Cancer core quality of life questionnaire (EORTC QLQ-30, QLQ-OG25). [24 months.]
To determine quality of life during the chemotherapy in both groups, after the surgery and 2 years follow-up after the completion of treatment, using EORTC QLQ-30, QLQ-OG25 questionnaires.
- Disease-free survival. [1 year after the last intervention.]
To determine the efficacy of total neoadjuvant FLOT regimen compared to perioperative FLOT regimen.
- Median overall survival. [5 years follow-up after the last intervention.]
To determine the efficacy of TNT FLOT regimen compared to perioperative FLOT regimen by assessment of overall survival.
- Correlation between the pathohistological response and overall and disease-free survival. [14 days after surgery.]
To determine the correlation between the pathohistological response and overall and disease-free survival.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Tumor spread: сT3, сT4a, сТ4b (except of invasion of the common hepatic artery, celiac trunk, proximal part of the splenic artery, aorta, head of the pancreas); сN1, сN2, сN3; сM0;
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Performance status by Eastern Cooperative Oncology Group (ECOG): 0 - 1;
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Histological type of tumor: adenocarcinoma;
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Differentiation grade: G0 - G4;
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Tumor localization: cardio-esophageal junction (Siewert 2, 3), cardiac part of the stomach, body of the stomach, antral part of the stomach, pyloric part of the stomach;
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Tumor extension: esophagus, diaphragm, liver, body and tail of the pancreas, anterior abdominal wall, small and large intestine, distal part of the splenic artery, spleen;
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No history of cancer in the past 5 years;
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Absence of previous chemotherapeutic, surgical or radiation treatment for oncological disease;
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No concomitant severe comorbidity;
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Patient willing to participate.
Exclusion Criteria:
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M1 (distant metastases);
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ECOG 2 - 4;
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Age over 80 and under 18;
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Concomitant severe comorbidity;
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Refusal of the patient to participate in the study.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | National Cancer Institute | Kyiv | Ukraine | 03022 |
Sponsors and Collaborators
- Ukrainian Society of Clinical Oncology
Investigators
- Principal Investigator: Mykyta Pepenin, MD, National Cancer Institute (NCI)
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 241/4