Salvage Chemoradiation Therapy for Recurrence After Radical Surgery or Palliative Surgery in Esophageal Cancer Patients

• ClinicalTrials.gov Identifier: NCT03731442
• Recruitment Status: Recruiting
• First Posted: November 6, 2018
• Last Update Posted: December 12, 2018
• Sponsor: Chinese Academy of Medical Sciences
• Collaborators: The First Affiliated Hospital with Nanjing Medical University; Tianjin Medical University Cancer Institute and Hospital; Anyang Tumor Hospital; Fujian Cancer Hospital; Peking University Cancer Hospital & Institute; Hebei Medical University Fourth Hospital
• Information provided by (Responsible Party): Zefen Xiao, Chinese Academy of Medical Sciences

Tracking Information

• First Submitted Date: October 31, 2018
• First Posted Date: November 6, 2018
• Last Update Posted Date: December 12, 2018
• Actual Study Start Date: November 1, 2018
• Estimated Primary Completion Date: October 31, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 5, 2018)

1-, 2-, 3-year overall survival [ Time Frame: From treatment initiation to death from any cause or censor, assessed up to 36 months ]

Overall survival

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 5, 2018)

• 1-, 2-, 3-year local progression-free survival [ Time Frame: From treatment initiation to first documented local progression or death or censor, assessed up to 36 months ]
  Local progression-free survival
• 1-, 2-, 3-year progression-free survival [ Time Frame: From treatment initiation to first documented progression or death or censor, assessed up to 36 months ]
  Progression-free survival
• Simultaneously integrated boost radiation therapy completion rate [ Time Frame: During chemoradation, assessed up to 60 days ]
  Radiation therapy completion rate
• Toxicities according to RTOG and CTCAE criteria, including hematological and non-hematological toxicities [ Time Frame: Assessed within 3 months from initiation of chemoradiaiton (acute), and 3 months after initiation of chemoradiation (late), according to RTOG and CTCAE criteria, including hematological and non-hematological toxicities ]
  Toxicities of chemoradiation therapy

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Salvage Chemoradiation Therapy for Recurrence After Radical Surgery or Palliative Surgery in Esophageal Cancer Patients
• Official Title: Salvage Chemoradiation Therapy for Recurrence After Radical Surgery or Palliative Surgery in Esophageal Cancer Patients: A Prospective, Multicenter Clinical Trial
• Brief Summary: Currently, adjuvant therapy is not recommended for patients with esophageal squamous cell carcinoma who received radical surgery. However, the recurrence rate is as high as 23.8%-58%, and the median time-to-recurrence is about 10.5 months. In patients who had residual tumor after surgery, evidence lacks for chemoradiation. The aim of the study is to evaluate the efficacy and safety of chemoradiation therapy in patients with recurrences after radical surgery or palliative surgery.

Detailed Description

Currently, adjuvant therapy is not recommended for patients with esophageal squamous cell carcinoma who received surgery as their first treatment. However, the recurrence rate is as high as 23.8%-58%, and the median time-to-recurrence is about 10.5 months. In patients who had residual tumor after surgery, evidence lacks for chemoradiation.

Retrospective data of 218 cases in our hospital indicated patients underwent salvage chemoradiation had significantly improved survival compared with chemotherapy, radiotherapy or best supportive care. For patients with locoregional recurrence, the 1-, 3-year overall survival (OS) rates were statistically higher in patients received salvage chemoradiation than radiotherapy (1-year OS, 70.0% vs. 55.2%, 3-year OS, 41.9% vs. 23.5%, p=0.045). Patients received chemotherapy had 1-year OS of 0%.

Data of 218 cases of our hospital indicated patients received radiation dose > 54Gy had a significantly longer median overall survival time of 21.2 months compared with 11.3 months in patients had <54Gy. The optimal radiation dose should be further investigated.

The recurrence pattern of patients with esophageal cancer after esophagectomy mainly consist of supraclavicular and mediastinal lymph nodes. For patients recurred after radical surgery, prophylactic irradiation to high-risk lymph node regions should be considered. The study use simultaneously integrated boost (SIB) intensity-modulated radiation therapy (IMRT) in this trial, which made different radiation dose to recurrent tumor and high-risk lymph node regions possible.

The aim of the study is to evaluate the efficacy and safety of chemoradiation therapy in patients with recurrences after radical surgery or palliative surgery. Patients were further assigned to receive elective field irradiation (ENI) or involved field irradiation (IFI) according to tumor size, tumor location and time-to-recurrence.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: Single (Outcomes Assessor); Primary Purpose: Treatment
• Condition: Esophageal Cancer

Intervention

• Radiation: Involved field irradiation
  Involved field irradiation; intensity-modulated radiation therapy
• Radiation: Elective field irradiation
  Elective field irradiation; intensity-modulated radiation therapy
• Drug: Paclitaxel
  Paclitaxel 135-150mg/m2, d1, every 3 weeks
• Drug: Platinum
  for lobaplatin, 30mg/m2, d1-2, total dose should not exceed 50mg,every 3 weeks; for nedaplatin 50mg/m2, d1-2, every 3 weeks;
• Drug: PEG-rhG-CSF
  PEG-rhG-CSF 3-6mg, 48 hours after chemotherapy

Study Arms

• Experimental: Involved field irradiation
  Patients after R0 surgery whose recurrence lesion larger than 5cm in diameter, or largest diameter was less than 5cm but with skip metastasis far from primary tumor or their time-to-recurrence longer than 16 months were assigned to involved field irradiation group. For lesions far from the thoracic stomach, the prescribed dose is 60Gy/2Gy/30f, and for lesions close to the thoracic stomach, the prescribed dose is 59.4-61.2Gy/1.8Gy/33-34f. Chest CT scan is planned at 50Gy. Radiation field should be modified according to the tumor response. Concurrent chemotherapy of paclitaxel and platinum was delivered every 3 weeks. PEG-rhG-CSF (3-6mg) should be given after 48 hours of chemotherapy.If patients received postoperative chemotherapy of paclitaxel and platinum and went through local-regional recurrence within six months, it is allowed to deliver chemotherapy regimens in the second line. Consolidate chemotherapy were adjusted to the patients after radiation therapy.
  Interventions:

  • Radiation: Involved field irradiation
  • Drug: Paclitaxel
  • Drug: Platinum
  • Drug: PEG-rhG-CSF
• Experimental: Elective field irradiation
  Patients after R1/R2 surgery or R0 surgery with the recurrence lesion whose diameter was less than 5cm without skip metastasis far from primary tumor and time-to-recurrence shorter than 16 months were assigned to elective field irradiation group. For lesions far from the thoracic stomach, the prescribed dose is 50.4Gy/1.8Gy/28f with a simultaneously integrated boost up to 59.92-62.16Gy/2.14-2.22Gy/28f. For lesions close to the thoracic stomach, the prescribed dose is 50.4Gy/1.8Gy/28f with a sequential boost of 10-12Gy/1.8-2Gy/5-7f. For patients whose planned thoracic stomach V50>50%, the dose should be lowered to 45Gy/1.8Gy/25f. Concurrent chemotherapy of paclitaxel and platinum was delivered every 3 weeks. PEG-rhG-CSF should be given in need. If patients received postoperative chemotherapy of TP and went through local-regional recurrence within 6 months, chemotherapy regimens delivered in the second line. Consolidate chemotherapy were adjusted to the patients after radiation therapy.
  Interventions:

  • Radiation: Elective field irradiation
  • Drug: Paclitaxel
  • Drug: Platinum
  • Drug: PEG-rhG-CSF

• Publications *: Chang X, Deng L, Ni W, Li C, Han W, Gao LR, Wang S, Zhou Z, Chen D, Feng Q, Liang J, Bi N, Lv J, Gao S, Mao Y, Xue Q, Xiao Z. Salvage chemoradiation therapy for recurrence after radical surgery or palliative surgery in esophageal cancer patients: a prospective, multicenter clinical trial protocol. BMC Cancer. 2020 Sep 14;20(1):877. doi: 10.1186/s12885-020-07315-0.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 5, 2018): 300
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: October 31, 2027
• Estimated Primary Completion Date: October 31, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Locoregional recurrence after radical surgery;
• Positive resection margin (R1/R2) after surgery;
• Out-of-field recurrence after adjuvant chemoradiation or radiotherapy;
• Recurrence after adjuvant chemotherapy;
• No prior therapy after recurrence;
• Age 16-70 years;
• KPS>70;
• No history of drug allergy;
• Sufficient liver and kidney functions;
• White blood cell count > 4.0*10^9/L.

Exclusion Criteria:

• Age>70 or <16 years;
• Pregnancy or lactation;
• History of drug allergy;
• Declining informed consent;
• Insufficient liver or kidney functions, or abnormal CBC test;
• Severe cardiovascular diseases, infections, active ulcerations, diabetes mellitus with unstable blood sugar, mental disorders.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 16 Years to 70 Years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Zefen Xiao, MD; +86-13621018159; xiaozefen@sina.com

Contact: Lei Deng, MD; +86-18611766429; dengleipumc@163.com

• Listed Location Countries: China

Administrative Information

• NCT Number: NCT03731442
• Other Study ID Numbers: 18-175/1753
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Zefen Xiao, Chinese Academy of Medical Sciences
• Original Responsible Party: Same as current
• Current Study Sponsor: Chinese Academy of Medical Sciences
• Original Study Sponsor: Same as current

Collaborators

• The First Affiliated Hospital with Nanjing Medical University
• Tianjin Medical University Cancer Institute and Hospital
• Anyang Tumor Hospital
• Fujian Cancer Hospital
• Peking University Cancer Hospital & Institute
• Hebei Medical University Fourth Hospital

• Investigators: Not Provided
• PRS Account: ChineseAMS
• Verification Date: December 2018