Radiation Therapy and Paclitaxel, Carboplatin, and Fluorouracil Followed by Esophagectomy in Treating Patients With Locally Advanced Cancer of the Esophagus or Gastroesophageal Junction

• ClinicalTrials.gov Identifier: NCT00022139
• Recruitment Status: Completed
• First Posted: March 7, 2003
• Last Update Posted: December 7, 2016
• Sponsor: Alliance for Clinical Trials in Oncology
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Alliance for Clinical Trials in Oncology

Tracking Information

• First Submitted Date: August 10, 2001
• First Posted Date: March 7, 2003
• Last Update Posted Date: December 7, 2016
• Study Start Date: January 2002
• Actual Primary Completion Date: July 2005 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: July 7, 2015): Proportion of successes [ Time Frame: Up to 4 years ]
• Original Primary Outcome Measures: Not Provided

Current Secondary Outcome Measures (submitted: July 7, 2015)

• Toxicity-free rate [ Time Frame: Up to 4 years ]
• Clinical tumor response [ Time Frame: Up to 4 years ]
• Pathologic tumor response [ Time Frame: Up to 4 years ]
• Time to disease progression [ Time Frame: Up to 4 years ]
• Surgical outcome [ Time Frame: Up to 4 years ]
• Survival [ Time Frame: Up to 4 years ]
• Time to treatment failure [ Time Frame: Up to 4 years ]
• Quality of life [ Time Frame: Up to 4 years ]

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

Descriptive Information

• Brief Title: Radiation Therapy and Paclitaxel, Carboplatin, and Fluorouracil Followed by Esophagectomy in Treating Patients With Locally Advanced Cancer of the Esophagus or Gastroesophageal Junction
• Official Title: A Phase II Trial of Preoperative Radiation and Chemotherapy (Paclitaxel, Carboplatin, and Continuous Infusion 5-FU) for Locally Advanced Esophageal Cancer

Brief Summary

RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy, such as paclitaxel, carboplatin, and fluorouracil, work in different ways to stop tumor cells from dividing so they stop growing or die. Giving radiation therapy with chemotherapy and giving them before surgery may shrink the tumor so that it can be removed during surgery.

PURPOSE: This phase II trial is studying how well giving radiation therapy together with combination chemotherapy followed by esophagectomy works in treating patients with locally advanced cancer of the esophagus or gastroesophageal junction.

Detailed Description

OBJECTIVES:

• Determine the pathologic complete response rate in patients with locally advanced cancer of the esophagus or gastroesophageal junction treated with radiotherapy administered concurrently with paclitaxel, carboplatin, and fluorouracil before esophagectomy.
• Determine the tolerability of this regimen in these patients.
• Determine the tumor response rate in patients treated with this regimen.
• Determine the quality of life of patients treated with this regimen.
• Assess the relationship between the presence of genetic polymorphisms in these patients and the toxicity of this regimen.

OUTLINE: This is a multicenter study.

Patients receive carboplatin IV and paclitaxel IV over 3 hours on days 1 and 22 and fluorouracil IV continuously on days 1-42. Beginning on day 1 of chemotherapy, patients undergo radiotherapy to the esophagus 5 days a week for 5 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease at 4-8 weeks after completion of radiotherapy undergo esophagectomy and complete dissection of the mediastinal and perigastric lymph nodes. Beginning 8 weeks after surgery, patients who underwent curative resection may receive a maximum of 2 additional courses of paclitaxel and carboplatin in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, before chemotherapy on days 1 and 22, and within 2 weeks before surgery.

Patients are followed every 3 months for 4 years.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Esophageal Cancer
• Gastric Cancer

Intervention

• Drug: carboplatin
• Drug: fluorouracil
• Drug: paclitaxel
• Procedure: conventional surgery
• Radiation: radiation therapy

Study Arms

Experimental: carboplatin + paclitaxel + fluorouracil + radiation + surgery

Patients receive carboplatin IV and paclitaxel IV over 3 hours on days 1 and 22 and fluorouracil IV continuously on days 1-42. Beginning on day 1 of chemotherapy, patients undergo radiotherapy to the esophagus 5 days a week for 5 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease at 4-8 weeks after completion of radiotherapy undergo esophagectomy and complete dissection of the mediastinal and perigastric lymph nodes. Beginning 8 weeks after surgery, patients who underwent curative resection may receive a maximum of 2 additional courses of paclitaxel and carboplatin in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, before chemotherapy on days 1 and 22, and within 2 weeks before surgery.

Patients are followed every 3 months for 4 years.

Interventions:

• Drug: carboplatin
• Drug: fluorouracil
• Drug: paclitaxel
• Procedure: conventional surgery
• Radiation: radiation therapy

Publications *

• Jatoi A. Aggressive multimodality therapy for patients with locally advanced esophageal cancer: is there a role for amifostine? Semin Oncol. 2003 Dec;30(6 Suppl 18):72-5. Review.
• Jatoi A, Martenson JA, Foster NR, McLeod HL, Lair BS, Nichols F, Tschetter LK, Moore DF Jr, Fitch TR, Alberts SR; North Central Cancer Treatment Group (N0044). Paclitaxel, carboplatin, 5-fluorouracil, and radiation for locally advanced esophageal cancer: phase II results of preliminary pharmacologic and molecular efforts to mitigate toxicity and predict outcomes: North Central Cancer Treatment Group (N0044). Am J Clin Oncol. 2007 Oct;30(5):507-13.
• Jatoi A, Martenson J, Mahoney MR, Lair BS, Brindle JS, Nichols F, Caron N, Rowland K, Tschetter L, Alberts S. Results of a planned interim toxicity analysis with trimodality therapy, including carboplatin AUC = 4, paclitaxel, 5-fluorouracil, amifostine, and radiation for locally advanced esophageal cancer: preliminary analyses and treatment recommendations from the North Central Cancer Treatment Group. Int Semin Surg Oncol. 2004 Nov 8;1(1):9.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 7, 2015): 56
• Original Enrollment: Not Provided
• Actual Study Completion Date: January 2009
• Actual Primary Completion Date: July 2005 (Final data collection date for primary outcome measure)

Eligibility Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed squamous cell carcinoma or adenocarcinoma of the thoracic esophagus (below 20 cm) or gastroesophageal junction

  • Surgically resectable disease (T1-3; NX, N0, or N1; M1a)
  • T4 tumors that are not unequivocally unresectable allowed
  • Celiac lymph node (stations 15-20) involvement allowed
• Must be considered a potential surgical candidate by a thoracic or general surgeon
• No supraclavicular lymph node involvement by palpation, biopsy, or radiograph (greater than 1.5 cm)
• No distant metastases

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

  • Patients with ECOG 2 must be considered good candidates for study by treating oncologists

Life expectancy

• At least 12 weeks

Hematopoietic

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• AST no greater than 3 times ULN

Renal

• Creatinine no greater than 1.5 times ULN

Cardiovascular

• No New York Heart Association class III or IV heart disease

Other

• No uncontrolled infection
• No other severe underlying disease that would preclude study participation
• No grade 2 or greater peripheral neuropathy
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• No prior chemotherapy for esophageal cancer

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy to anticipated fields of study radiotherapy

Surgery

• Not specified

Other

• No concurrent diuretics
• No concurrent amifostine

Sex/Gender

• Sexes Eligible for Study: All

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

Administrative Information

• NCT Number: NCT00022139
• Other Study ID Numbers: NCCTG-N0044; NCI-2012-02394 ( Registry Identifier: CTRP (Clinical Trials Reporting System) ); CDR0000068789 ( Registry Identifier: PDQ (Physician Data Query) )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Alliance for Clinical Trials in Oncology
• Study Sponsor: Alliance for Clinical Trials in Oncology
• Collaborators: National Cancer Institute (NCI)

Investigators

• Study Chair: Aminah Jatoi, MD; Mayo Clinic

• PRS Account: Alliance for Clinical Trials in Oncology
• Verification Date: December 2016