Docetaxel-based Chemoradiotherapy Plus Periradiation Chemotherapy Compared With INT 0116 Adjuvant Arm in Gastric Cancer

NCT ID: NCT02640898

Last Updated: 2020-10-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

500 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-12-31

Study Completion Date

2022-12-31

Brief Summary

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Although the intergroup 0116 trial was the first to demonstrate that adjuvant chemoradiotherapy offers a significant survival benefit in completely resected gastric cancer,it is more toxic and less effective. It is reasonable to optimize this regimen.

Detailed Description

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The intergroup 0116 trial was the first to demonstrate that adjuvant chemoradiotherapy offers a significant survival benefit. In this study, 556 patients with R0 resected gastric cancer were randomly assigned to surgery plus postoperative chemoradiotherapy or to surgery alone. The adjuvant treatment consisted of 425 mg per square meter of bolus fluorouracil per day, 20 mg per square meter of leucovorin , per day, for 5 days, followed by 45 Gy of radiation with current fluorouracil ( 400mg per square meter ) and leucovorin (20mg per square meter) as an intravenous bolus on each of of the first four days and the last three days of irradiation. One month after the completion of radiotherapy, two 5-day cycles of fluorouracil and leucovorin chemotherapy were given one month apart. Patients in the adjuvant arm achieved a significant 3-year overall and relapse-free survival benefit of 9% and 17%, respectively.

Despite the improvement in outcome, up to 120 of 281 patients in the chemoradiotherapy arm relapsed in local regional or/and distant sites within 3 years of potentially curative resection. Notably, the patients receiving chemoradiotherapy had a higher rate of distant metastasis compared with the control arm (40/281 vs 32/275), indicating that bolus 5-FU/LV was not suboptimal to control the development of distant metastases. Furthermore, the toxicity in INT 0116 trial was substantial, with grade 3 or higher overall toxicities observed in 73% of the cases. As a result, only 64% of the patients were able to complete protocol therapy. Obviously, it is reasonable to optimize the Intergroup 0116 chemoradiotherapy regimen.

Docetaxel, as a monotherapy, is active in both first- and second-line treatment of advanced stage gastric cancer. In addition, in vitro and in vivo studies have demonstrated that docetaxel is a potent radiosensitizer in human cancer cell lines, making it an attractive agent combined with radiation. A phase I study has identified the phase II recommended dose of docetaxel as 20mg/m2 weekly for six weeks when administered with concurrent chest radiation of 60 Gy.

Furthermore, docetaxel when added to standard cisplatin and infused fluorouracil (DCF regimen) demonstrated an advantage in survival, time to progression, and response rate (RR) over cisplatin and fluorouracil (CF) in a randomized phase Ⅲ trial, but the toxicity profile associated with the DCF regimen was significant. In addition, a favorable RR and median overall survival for DCF over epirubicin, cisplatin, protracted venous infusion fluorouracil (ECF) has been seen in a randomized phase Ⅱ trial.

Two large phase III trials has demonstrated that the addition of perioperative chemotherapy (ECF) or adjuvant chemotherapy (S1) to radical surgery could significantly improve surgical outcomes in localized gastric cancer as compared with surgery alone in terms of progression-free and overall survival. These results suggest that adjuvant and neoadjuvant chemotherapy may have excellent effects on both the primary tumor and micrometasatsis.

Based on these important findings, we designed a phase 3 trial to compared our novel docetaxel-based chemoradiotherapy regimen with the Intergroup 0116 adjuvant arm in patients with curatively resected gastric cancer

Conditions

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Gastric Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Participants
open label

Study Groups

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FU-based chemoradiotherapy

patients will be treated with the INT0116 regimen.

Group Type ACTIVE_COMPARATOR

FU-based chemoradiotherapy

Intervention Type RADIATION

The adjuvant treatment consisted of 425mg/m2 of bolus fluorouracil(5-FU) per day, 20 mg/m2 of leucovorin (LV), per day, for 5 days, followed by 45Gy of radiation with current 5-FU ( 400mg/m2 ) and LV (20mg/m2) as an intravenous bolus on each of of the first four days and the last three days of irradiation. One month after the completion of radiotherapy, two 5-day cycles of 5-FU and FV chemotherapy were given one month apart.

docetaxel-based chemoradiotherapy

patients will be treated with modified DCF chemotherapy in combination with docetaxel-based chemoradiotherapy.

Group Type EXPERIMENTAL

docetaxel-based chemoradiotherapy

Intervention Type RADIATION

experimental:Patients with Zubrod performance status (PS) of 0-2 received up to 2 21-day cycles of pre- and post-radiation chemotherapy (docetaxel 37.5 mg/m2 on days 1 and 8, cisplatin 25 mg/m2 on days 1-3, and a continuous infusion of fluorouracil (FU) 750 mg/m2 on days 1-5), respectively. CCRT between pre- and post-radiation chemotherapy was initiated on day 43 and consisted of 3-dimensional conformal intensity-modulated radiation therapy (45 Gy) plus concurrent docetaxel 20 mg/m2 weekly for 6 weeks;

Interventions

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docetaxel-based chemoradiotherapy

experimental:Patients with Zubrod performance status (PS) of 0-2 received up to 2 21-day cycles of pre- and post-radiation chemotherapy (docetaxel 37.5 mg/m2 on days 1 and 8, cisplatin 25 mg/m2 on days 1-3, and a continuous infusion of fluorouracil (FU) 750 mg/m2 on days 1-5), respectively. CCRT between pre- and post-radiation chemotherapy was initiated on day 43 and consisted of 3-dimensional conformal intensity-modulated radiation therapy (45 Gy) plus concurrent docetaxel 20 mg/m2 weekly for 6 weeks;

Intervention Type RADIATION

FU-based chemoradiotherapy

The adjuvant treatment consisted of 425mg/m2 of bolus fluorouracil(5-FU) per day, 20 mg/m2 of leucovorin (LV), per day, for 5 days, followed by 45Gy of radiation with current 5-FU ( 400mg/m2 ) and LV (20mg/m2) as an intravenous bolus on each of of the first four days and the last three days of irradiation. One month after the completion of radiotherapy, two 5-day cycles of 5-FU and FV chemotherapy were given one month apart.

Intervention Type RADIATION

Other Intervention Names

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a docetaxel arm the INT 0116 adjuvant arm

Eligibility Criteria

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Inclusion Criteria

* Patients with microscopically confirmed stages IB through IIIB adenocarcinoma of the stomach or gastroesophageal junction, who underwent a potentially curative resection (ie, R0 resection);
* Zubrod performance status 0 to 1;
* No prior chemotherapy or prior radiation therapy to the treatment field;
* Age 20-75;
* Absolute granulocyte count (AGC) ≥2 × 109 cells/L, platelets ≥ 100× 109 cells/L, hemoglobin ≥ 10.0 g/dl (Note: The use of transfusion or other intervention to achieve Hgb ≥ 10.0 g/dl is acceptable)
* Adequate renal and hepatic function (serum creatinine ≤1.5 × upper limit of normal \[ULN\], bilirubin and AST ≤1.5 × ULN).

Exclusion Criteria

* A history of prior upper abdominal radiotherapy or chemotherapy;
* Evidence of metastatic disease to distant organs, peritoneal carcinoma by computed tomography or positive cytology of peritoneal effusion;
* Prior malignancies (except cured cervical carcinoma in situ, non-melanoma skin cancer, or other curatively treated cancer with no evidence of disease for ≥5 years);
* active inflammatory bowel disease;
* Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months;
* Transmural myocardial infarction within the last 6 months;
* uncontrolled hypertension;
* Chronic Obstructive Pulmonary Disease(COPD) exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 60 days before registration;
* Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects;
* Patients with Acquired Immune Deficiency Syndrome were excluded from the study because the treatments involved in this protocol may be significantly immunosuppressive.
* Hypersensitivity reaction to docetaxel;
* Uncontrolled neuropathy grade 2 or greater regardless of cause;
* Conditions precluding medical follow-up and protocol compliance;
* Pregnant or lactating women are excluded from study entry due to the embryotoxic effects of the protocol treatment.
Minimum Eligible Age

20 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine

OTHER

Sponsor Role lead

Responsible Party

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Chen tingfeng

Docetaxel-based chemoradiotherapy plus periradiation chemotherapy in R0 gastric cancer

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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tingfeng chen, MD

Role: PRINCIPAL_INVESTIGATOR

the ethic committee of shanghai genernal hospital

Locations

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the Ethic Committee of Shanghai General Hospital

Shanghai, Shanghai Municipality, China

Site Status RECRUITING

Countries

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China

Central Contacts

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yong liu, MD

Role: CONTACT

37798364 ext. 8119

tiening zhang, MD

Role: CONTACT

37798364 ext. 8119

Facility Contacts

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zhixiao chen, MD

Role: primary

021-63240090 ext. 6218

References

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Macdonald JS, Smalley SR, Benedetti J, Hundahl SA, Estes NC, Stemmermann GN, Haller DG, Ajani JA, Gunderson LL, Jessup JM, Martenson JA. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med. 2001 Sep 6;345(10):725-30. doi: 10.1056/NEJMoa010187.

Reference Type BACKGROUND
PMID: 11547741 (View on PubMed)

Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, Scarffe JH, Lofts FJ, Falk SJ, Iveson TJ, Smith DB, Langley RE, Verma M, Weeden S, Chua YJ, MAGIC Trial Participants. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006 Jul 6;355(1):11-20. doi: 10.1056/NEJMoa055531.

Reference Type BACKGROUND
PMID: 16822992 (View on PubMed)

Sulkes A, Smyth J, Sessa C, Dirix LY, Vermorken JB, Kaye S, Wanders J, Franklin H, LeBail N, Verweij J. Docetaxel (Taxotere) in advanced gastric cancer: results of a phase II clinical trial. EORTC Early Clinical Trials Group. Br J Cancer. 1994 Aug;70(2):380-3. doi: 10.1038/bjc.1994.310.

Reference Type BACKGROUND
PMID: 7914428 (View on PubMed)

Choy H, Rodriguez FF, Koester S, Hilsenbeck S, Von Hoff DD. Investigation of taxol as a potential radiation sensitizer. Cancer. 1993 Jun 1;71(11):3774-8. doi: 10.1002/1097-0142(19930601)71:113.0.co;2-0.

Reference Type BACKGROUND
PMID: 8098270 (View on PubMed)

Mauer AM, Masters GA, Haraf DJ, Hoffman PC, Watson SM, Golomb HM, Vokes EE. Phase I study of docetaxel with concomitant thoracic radiation therapy. J Clin Oncol. 1998 Jan;16(1):159-64. doi: 10.1200/JCO.1998.16.1.159.

Reference Type BACKGROUND
PMID: 9440738 (View on PubMed)

Van Cutsem E, Moiseyenko VM, Tjulandin S, Majlis A, Constenla M, Boni C, Rodrigues A, Fodor M, Chao Y, Voznyi E, Risse ML, Ajani JA; V325 Study Group. Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: a report of the V325 Study Group. J Clin Oncol. 2006 Nov 1;24(31):4991-7. doi: 10.1200/JCO.2006.06.8429.

Reference Type BACKGROUND
PMID: 17075117 (View on PubMed)

Other Identifiers

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SGH201510

Identifier Type: -

Identifier Source: org_study_id