Study of Docetaxel or Vinorelbine Plus Cisplatin in Neoadjuvant Chemoradiotherapy for Esophageal Cancer (NEOCRTEC308)

Esophageal Cancer Clinical Trial

Official title:

A Phase III Clinical Trial of Docetaxel Plus Cisplatin Versus Vinorelbine Plus Cisplatin in Neoadjuvant Chemoradiotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma (NEOCRTEC308)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02465736
• Other study ID #: NEOCRTEC-2.0
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: July 2015
• Est. completion date: July 2025

Study information

• Verified date: January 2024
• Source: Sun Yat-sen University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective is to compare docetaxel plus cisplatin (DP) versus vinorelbine plus cisplatin (NP) in neoadjuvant chemoradiotherapy, in terms of the overall survival and toxicity in patients with Stage IIB or III squamous cell esophageal carcinoma.

Description:

Esophageal cancer (EC) is the eighth most common cancers in the world, with more than 456,000 new cases and 400,000 deaths occurred annually worldwide. Every year in China, no matter new cases or deaths account for more than half of the world. Besides, over 90% of Chinese patients have esophageal squamous cell carcinoma (ESCC).

Preoperative chemoradiotherapy (CRT) followed by surgery can hopefully improve the survival of ESCC. The CROSS trial has demonstrated that preoperative chemoradiotherapy can significantly increase the overall survival of patients with EC compared with surgery alone. The therapeutic effects were also found in 84 ESCC cases enrolled in this trial. Previously, the investigators performed a phase III, randomized clinical trial (NCT01216527) to compare the overall survival of stage IIB-III ESCC patients treated with or without neoadjuvant CRT, in which vinorelbine plus cisplatin was used as chemotherapy regime. The enrollment was completed in 2014. The outcomes will hopefully prove the survival benefit of neoadjuvant CRT to ESCC.

However, the investigators also observed that some patients suffer from the toxic response of neoadjuvant therapy, such as myelosuppression (45.2%), pulmonary toxicity (42.9%), and esophagitis (59.5%). The toxicity caused by CRT will decrease the patient compliance; moreover increase the perioperative complications and deaths, which may totally offset the survival benefit. Therefore, it is important to improve chemoradiotherapy effect and reduce toxicity, so as to achieve better survival in ESCC patients.

Docetaxel draws increasing attentions with its high effective rate and low toxicity. Several Phase II clinical trials and retrospective studies suggested that docetaxel showed better survival benefits in both monotherapy and combined-therapy in EC patients. Therefore, the investigators intended to conduct a phase III, randomized clinical trial to further explore whether docetaxel plus cisplatin would be an effective therapy with lower toxicity.

The investigators are to carry out a phased III clinical trial to compare the effect and toxicity of docetaxel plus cisplatin with vinorelbine plus cisplatin in neoadjuvant chemoradiotherapy for esophageal squamous cell carcinoma.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 610
• Est. completion date: July 2025
• Est. primary completion date: July 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

1. Histologic diagnosis of squamous cell thoracic esophageal carcinoma of Stage T1-4aN1-3M0 or T4aN0M0, according to 7th edition of Union for International Cancer Control (UICC) staging system.

2. Patients must not have received any prior anticancer therapy.

3. More than 6 months of expected survival

4. Age ranges from 18 to 70 years

5. Absolute white blood cells count =4.0×109/L, neutrophil =1.5×109/L, platelets =100.0×109/L, hemoglobin =90g/L, and normal functions of liver and kidney.

6. WHO performance status (PS) of 0-1

7. Signed informed consent document on file

Exclusion Criteria:

1. Patients have received any prior anticancer therapy

2. Patients with advanced inoperable or metastatic esophageal carcinoma

3. Patients with concomitant hemorrhagic disease

4. Patients with other uncontrollable status that cannot tolerate surgery

5. Pregnant or breast feeding

6. Patients cannot signed the informed consent document because of psychological quality, family and social factors

7. Patients with concomitant peripheral neuropathy, whose CTC status is 2 or even more

8. Have a prior malignancy other than esophageal carcinoma, carcinoma in situ of the cervix, nonmelanoma skin cancer or cured early stage of prostate cancer

9. Have a history of diabetes over 10 years and with poorly controlled blood sugar level

10. patients with serious cardiac, respiratory, hepatic, renal, hematologic, immunological disease or cachexy, who cannot tolerate chemoradiotherapy or surgery

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Esophageal Cancer
• Esophageal Neoplasms
• Esophageal Squamous Cell Carcinoma
• Oesophageal Cancer

Intervention

Drug:
• Docetaxel
25mg/ m2 Docetaxel dose administered on days 1, 8, 15, and 22.
• Cisplatin
25mg/ m2 on days 1, 8, 15 and 22.

Radiation:
• Radiation
Patient will receive 4 weeks of radiation therapy (44 Gy/20 fractions).

Procedure:
• Surgery
McKeown esophagectomy, Ivor Lewis esophagectomy or minimally invasive esophagectomy will be performed 4-8 weeks after chemoradiotherapy. Two-field lymphadenectomy with total mediastinal lymph node dissection is performed during surgery.

Drug:
• Vinorelbine
25mg/ m2 on days 1, 8 of each cycle (i.e. every 21 days).
• Cisplatin
75mg/ m2 on day 1 of each cycle only (i.e. every 21 days).

Locations

Country	Name	City	State
China	Sun Yat-sen University Cancer Center	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Sun Yat-sen University

Country where clinical trial is conducted

China, 

References & Publications (10)

Arnott SJ, Duncan W, Gignoux M, Hansen HS, Launois B, Nygaard K, Parmar MK, Rousell A, Spilopoulos G, Stewart G, Tierney JF, Wang M, Rhugang Z; Oeosphageal Cancer Collaborative Group. Preoperative radiotherapy for esophageal carcinoma. Cochrane Database S — View Citation

Bhansali MS, Vaidya JS, Bhatt RG, Patil PK, Badwe RA, Desai PB. Chemotherapy for carcinoma of the esophagus: a comparison of evidence from meta-analyses of randomized trials and of historical control studies. Ann Oncol. 1996 Apr;7(4):355-9. doi: 10.1093/o — View Citation

Kushida T, Nohara S, Yoshino K, Fujiwara D, Ouchi K, Amano T, Isayama F, Tomita N, Iwanuma Y, Sasai K, Tsurumaru M, Kajiyama Y. Utility of weekly docetaxel combined with preoperative radiotherapy for locally advanced esophageal cancer from pathological an — View Citation

Lin SH, Wang L, Myles B, Thall PF, Hofstetter WL, Swisher SG, Ajani JA, Cox JD, Komaki R, Liao Z. Propensity score-based comparison of long-term outcomes with 3-dimensional conformal radiotherapy vs intensity-modulated radiotherapy for esophageal cancer. — View Citation

Mariette C, Dahan L, Mornex F, Maillard E, Thomas PA, Meunier B, Boige V, Pezet D, Robb WB, Le Brun-Ly V, Bosset JF, Mabrut JY, Triboulet JP, Bedenne L, Seitz JF. Surgery alone versus chemoradiotherapy followed by surgery for stage I and II esophageal can — View Citation

Pasini F, de Manzoni G, Zanoni A, Grandinetti A, Capirci C, Pavarana M, Tomezzoli A, Rubello D, Cordiano C. Neoadjuvant therapy with weekly docetaxel and cisplatin, 5-fluorouracil continuous infusion, and concurrent radiotherapy in patients with locally a — View Citation

Ruhstaller T, Widmer L, Schuller JC, Roth A, Hess V, Mingrone W, von Moos R, Borner M, Pestalozzi BC, BalmerMajno S, Koberle D, Terraciano L, Schnider A, Bodis S, Popescu R; Swiss Group for Clinical Cancer Research (SAKK). Multicenter phase II trial of pr — View Citation

Sjoquist KM, Burmeister BH, Smithers BM, Zalcberg JR, Simes RJ, Barbour A, Gebski V; Australasian Gastro-Intestinal Trials Group. Survival after neoadjuvant chemotherapy or chemoradiotherapy for resectable oesophageal carcinoma: an updated meta-analysis. — View Citation

Wang J, Wei C, Tucker SL, Myles B, Palmer M, Hofstetter WL, Swisher SG, Ajani JA, Cox JD, Komaki R, Liao Z, Lin SH. Predictors of postoperative complications after trimodality therapy for esophageal cancer. Int J Radiat Oncol Biol Phys. 2013 Aug 1;86(5):885-91. doi: 10.1016/j.ijrobp.2013.04.006. — View Citation

Zanoni A, Verlato G, Giacopuzzi S, Weindelmayer J, Casella F, Pasini F, Zhao E, de Manzoni G. Neoadjuvant concurrent chemoradiotherapy for locally advanced esophageal cancer in a single high-volume center. Ann Surg Oncol. 2013 Jun;20(6):1993-9. doi: 10.12 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival	Overall survival will be calculated from the date of randomisation and an event registered on the date of death from any cause. Patients lost to follow up, or those with no death recorded on the day the database is frozen, will be censored on the date of last follow up.	At end of trial- up to 3 years in follow up
Primary	Toxicities of neo-adjuvant chemoradiotherapy	All symptoms of toxicity will be evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE) Version. 3.0.	Within the first 56 days after the start of chemoradiotherapy
Secondary	Disease free survival		At end of trial- up to 3 years in follow up
Secondary	Clinical response rate		4-6 weeks after completion of chemoradiotherapy
Secondary	R0 resection rate		One week after the operation
Secondary	Number of Participants who withdraw the treatment		Within the first 84 days after the start of chemoradiotherapy
Secondary	Perioperative complication		Within the first 90 days after the start of surgery
Secondary	Pathological complete response rate		One week after the operation
Secondary	Health Related Quality of Life		Within the first 84 days after the start of chemoradiotherapy