Induction Chemotherapy Followed by Chemoradiotherapy in Esophageal Cancer

• ClinicalTrials.gov Identifier: NCT02403531
• Recruitment Status: Completed
• First Posted: March 31, 2015
• Last Update Posted: June 2, 2020
• Sponsor: Mian XI
• Information provided by (Responsible Party): Mian XI, Sun Yat-sen University

Tracking Information

• First Submitted Date: March 19, 2015
• First Posted Date: March 31, 2015
• Last Update Posted Date: June 2, 2020
• Actual Study Start Date: May 1, 2015
• Actual Primary Completion Date: September 6, 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 31, 2018)

overall response rate (clinical complete response and partial response) [ Time Frame: 3 months after chemoradiotherapy (plus or minus 7 days) ]

RECIST (Response Evaluation Criteria in Solid Tumors) criteria was used to determine the tumor response. Tumor response was evaluated 3 months after the completion of treatment based on barium esophagography, CT scans, and endoscopy with biopsies.

Original Primary Outcome Measures (submitted: March 25, 2015)

overall response rate [ Time Frame: 3 months after the treatment (plus or minus 7 days) ]

RECIST (Response Evaluation Criteria in Solid Tumors) criteria was used to determine the tumor response. Tumor response was evaluated 3 months after the completion of treatment based on barium esophagography, CT scans, and endoscopy with biopsies.

Current Secondary Outcome Measures (submitted: December 31, 2018)

• Overall survival [ Time Frame: 3 years ]
  Three years follow-up from the enrollment to the date of death from any cause or date of lost follow-up
• Progression-free survival [ Time Frame: 3 years ]
  From the date of randomization to the date of disease progression or last follow-up

Original Secondary Outcome Measures (submitted: March 25, 2015)

• Overall survival [ Time Frame: 3 years ]
  Three years follow-up from the enrollment to the date of death from any cause or date of lost follow-up
• Progression-free survival [ Time Frame: 3 years ]
  From the date of randomization to the date of disease progression or last follow-up
• Quality of life [ Time Frame: 3 years ]
  EORTC QLQ-C30 questionnaire was used to assess the quality of life.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Induction Chemotherapy Followed by Chemoradiotherapy in Esophageal Cancer
• Official Title: A Phase II Randomized Trial of Induction Chemotherapy Versus no Induction Chemotherapy Followed by Definitive Chemoradiotherapy in Patients With Inoperable Thoracic Esophageal Cancer
• Brief Summary: The contribution of induction chemotherapy before definitive chemoradiotherapy is unknown. The purpose of this study was to compare the efficacy and toxicity of induction chemotherapy followed by definitive chemoradiotherapy versus no induction chemotherapy in patients with inoperable thoracic esophageal squamous cell carcinoma.
• Detailed Description: 108 patients were randomized to receive no induction chemotherapy (IC, Arm A) or IC (Arm B) before definitive chemoradiotherapy in patients with inoperable thoracic esophageal squamous cell carcinoma. Patients assigned to Arm B first received two cycles of 3-weekly schedule of IC, consisting of docetaxel 75 mg/m2 on day 1 and cisplatin 75 mg/m2 on day 1. The prescribed dose of radiotherapy is generally 50-60 Gy/25-28fr. The concomitant chemotherapy is docetaxel 20 mg/m2 on day 1, cisplatin 25 mg/m2 on day 1, repeated weekly during radiation.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Neoplasms

Intervention

• Drug: Docetaxel
  Include brand names, serial numbers and code names to improve search results on the ClinicalTrials.gov web site.
  Other Name: taxotere
• Drug: Cisplatin
  Include brand names, serial numbers and code names to improve search results on the ClinicalTrials.gov web site.
  Other Name: DDP
• Radiation: Radiotherapy
  definitive radiotherapy
  Other Name: radiation

Study Arms

• Active Comparator: Concurrent chemoradiotherapy
  Patients assigned to this Arm received concurrent chemoradiotherapy. The prescribed dose of radiotherapy is generally 50-60 Gy/25-28fr. The concomitant chemotherapy is docetaxel 20 mg/m2 on day 1, cisplatin 25 mg/m2 on day 1, repeated weekly during radiation.
  Interventions:

  • Drug: Docetaxel
  • Drug: Cisplatin
  • Radiation: Radiotherapy
• Experimental: Induction chemotherapy plus chemoradiotherapy
  Patients assigned to this Arm first received two cycles of 3-weekly schedule of IC before definitive chemoradiotherapy, consisting of docetaxel 75 mg/m2 on day 1 and cisplatin 75 mg/m2 on day 1. The prescribed dose of radiotherapy is generally 50-60 Gy/25-28fr. The concomitant chemotherapy is docetaxel 20 mg/m2 on day 1, cisplatin 25 mg/m2 on day 1, repeated weekly during radiation.
  Interventions:

  • Drug: Docetaxel
  • Drug: Cisplatin
  • Radiation: Radiotherapy

Publications *

• 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 preoperative induction chemotherapy followed by chemoradiation with docetaxel and cisplatin for locally advanced esophageal carcinoma (SAKK 75/02). Ann Oncol. 2009 Sep;20(9):1522-1528. doi: 10.1093/annonc/mdp045. Epub 2009 May 22.
• Koo DH, Park SI, Kim YH, Kim JH, Jung HY, Lee GH, Choi KD, Song HJ, Song HY, Shin JH, Cho KJ, Yoon DH, Kim SB. Phase II study of use of a single cycle of induction chemotherapy and concurrent chemoradiotherapy containing capecitabine/cisplatin followed by surgery for patients with resectable esophageal squamous cell carcinoma: long-term follow-up data. Cancer Chemother Pharmacol. 2012 Mar;69(3):655-63. doi: 10.1007/s00280-011-1750-5. Epub 2011 Oct 4.
• Ilson DH, Minsky BD, Ku GY, Rusch V, Rizk N, Shah M, Kelsen DP, Capanu M, Tang L, Campbell J, Bains M. Phase 2 trial of induction and concurrent chemoradiotherapy with weekly irinotecan and cisplatin followed by surgery for esophageal cancer. Cancer. 2012 Jun 1;118(11):2820-7. doi: 10.1002/cncr.26591. Epub 2011 Oct 11.
• Ajani JA, Xiao L, Roth JA, Hofstetter WL, Walsh G, Komaki R, Liao Z, Rice DC, Vaporciyan AA, Maru DM, Lee JH, Bhutani MS, Eid A, Yao JC, Phan AP, Halpin A, Suzuki A, Taketa T, Thall PF, Swisher SG. A phase II randomized trial of induction chemotherapy versus no induction chemotherapy followed by preoperative chemoradiation in patients with esophageal cancer. Ann Oncol. 2013 Nov;24(11):2844-9. doi: 10.1093/annonc/mdt339. Epub 2013 Aug 23.
• Liu S, Luo L, Zhao L, Zhu Y, Liu H, Li Q, Cai L, Hu Y, Qiu B, Zhang L, Shen J, Yang Y, Liu M, Xi M. Induction chemotherapy followed by definitive chemoradiotherapy versus chemoradiotherapy alone in esophageal squamous cell carcinoma: a randomized phase II trial. Nat Commun. 2021 Jun 29;12(1):4014. doi: 10.1038/s41467-021-24288-1.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 30, 2020): 110
• Original Estimated Enrollment (submitted: March 25, 2015): 108
• Actual Study Completion Date: May 30, 2020
• Actual Primary Completion Date: September 6, 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Histologically confirmed squamous cell carcinoma of the esophagus;
2. Localized, nonmetastatic disease (T1-4, N0-1) confirmed by endoscopic ultrasound (EUS) and CT scan (according to UICC TNM version 6);
3. Absence of distant metastasis of solid organ;
4. Not suitable for surgery (either for medical reasons or patient's choice);
5. Age at diagnosis 18 to 70 years;
6. Eastern Cooperative Oncology Group performance status ≤ 2
7. No prior cancer therapy;
8. No history of concomitant or previous malignancy;
9. Hematologic function: WBC ≥ 4.0×109/L, PLT ≥ 80×109/L, Hb ≥ 10mg/dL;
10. Renal function: Cr ≤ 1.25×UNL;
11. Hepatic function: BIL ≤ 1.5×UNL, ALT/AST ≤ 2.5×UNL;
12. Documented informed consent to participate in the trial.

Exclusion Criteria:

1. Younger than 18 or older than 70 years of age;
2. ECOG performance status of 3 or above;
3. Other cancer history;
4. Previous radiotherapy history;
5. Subjects with distant metastases;
6. Pregnancy or breast feeding. Women of childbearing age must use effective contraception;
7. Serious cardiovascular disease (congestive heart failure, uncontrollable arrhythmia, unstable angina, myocardial infarction, serious heart valve disease, resistant hypertension);
8. Evidence of bleeding diathesis or serious infection.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT02403531
• Other Study ID Numbers: ICCRTEC
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Mian XI, Sun Yat-sen University
• Original Responsible Party: Same as current
• Current Study Sponsor: Mian XI
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Chair: Meng-Zhong Liu, MD; Sun Yat-sen University

• PRS Account: Sun Yat-sen University
• Verification Date: May 2020