Clinical trial NCT00022139: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Esophageal Cancer
Gastric Cancer
Keywords: stage III gastric cancer
stage II esophageal cancer
stage III esophageal cancer
adenocarcinoma of the stomach
squamous cell carcinoma of the esophagus
adenocarcinoma of the esophagus
Lead sponsor: Alliance for Clinical Trials in Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-03-07
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Proportion of successes
timeFrame: Up to 4 years
Secondary outcomes:
measure: Toxicity-free rate
timeFrame: Up to 4 years
measure: Clinical tumor response
timeFrame: Up to 4 years
measure: Pathologic tumor response
timeFrame: Up to 4 years
measure: Time to disease progression
timeFrame: Up to 4 years
measure: Surgical outcome
timeFrame: Up to 4 years
measure: Survival
timeFrame: Up to 4 years
measure: Time to treatment failure
timeFrame: Up to 4 years
measure: Quality of life
timeFrame: Up to 4 years
Other outcomes:
Locations:
city: Chanute
country: United States
facility: Cancer Center of Kansas, PA - Chanute
state: Kansas
city: Dodge City
country: United States
facility: Cancer Center of Kansas, PA - Dodge City
state: Kansas
city: El Dorado
country: United States
facility: Cancer Center of Kansas, PA - El Dorado
state: Kansas
city: Kingman
country: United States
facility: Cancer Center of Kansas, PA - Kingman
state: Kansas
city: Liberal
country: United States
facility: Southwest Medical Center
state: Kansas
city: Newton
country: United States
facility: Cancer Center of Kansas, PA - Newton
state: Kansas
city: Parsons
country: United States
facility: Cancer Center of Kansas, PA - Parsons
state: Kansas
city: Pratt
country: United States
facility: Cancer Center of Kansas, PA - Pratt
state: Kansas
city: Salina
country: United States
facility: Cancer Center of Kansas, PA - Salina
state: Kansas
city: Wellington
country: United States
facility: Cancer Center of Kansas, PA - Wellington
state: Kansas
city: Wichita
country: United States
facility: Associates in Womens Health, PA - North Review
state: Kansas
city: Wichita
country: United States
facility: Cancer Center of Kansas, PA - Medical Arts Tower
state: Kansas
city: Wichita
country: United States
facility: Cancer Center of Kansas, PA - Wichita
state: Kansas
city: Wichita
country: United States
facility: CCOP - Wichita
state: Kansas
city: Wichita
country: United States
facility: Via Christi Cancer Center at Via Christi Regional Medical Center
state: Kansas
city: Wichita
country: United States
facility: Wesley Medical Center
state: Kansas
city: Winfield
country: United States
facility: Cancer Center of Kansas, PA - Winfield
state: Kansas
city: Burnsville
country: United States
facility: Fairview Ridges Hospital
state: Minnesota
city: Coon Rapids
country: United States
facility: Mercy and Unity Cancer Center at Mercy Hospital
state: Minnesota
city: Duluth
country: United States
facility: Duluth Clinic Cancer Center - Duluth
state: Minnesota
city: Duluth
country: United States
facility: CCOP - Duluth
state: Minnesota
city: Duluth
country: United States
facility: Miller - Dwan Medical Center
state: Minnesota
city: Edina
country: United States
facility: Fairview Southdale Hospital
state: Minnesota
city: Fridley
country: United States
facility: Mercy and Unity Cancer Center at Unity Hospital
state: Minnesota
city: Maplewood
country: United States
facility: Minnesota Oncology Hematology, PA - Maplewood
state: Minnesota
city: Minneapolis
country: United States
facility: Virginia Piper Cancer Institute at Abbott - Northwestern Hospital
state: Minnesota
city: Robbinsdale
country: United States
facility: Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center
state: Minnesota
city: Saint Louis Park
country: United States
facility: CCOP - Metro-Minnesota
state: Minnesota
city: St. Louis Park
country: United States
facility: Park Nicollet Cancer Center
state: Minnesota
city: St. Paul
country: United States
facility: United Hospital
state: Minnesota
city: Waconia
country: United States
facility: Ridgeview Medical Center
state: Minnesota
city: Woodbury
country: United States
facility: Minnesota Oncology Hematology, PA - Woodbury
state: Minnesota
city: Sioux Falls
country: United States
facility: Avera Cancer Institute
state: South Dakota
city: Sioux Falls
country: United States
facility: Medical X-Ray Center, PC
state: South Dakota
city: Sioux Falls
country: United States
facility: Sanford Cancer Center at Sanford USD Medical Center
state: South Dakota
Study officials:
affiliation: Mayo Clinic
name: Aminah Jatoi, MD
role: STUDY_CHAIR
References:
citation: 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. doi: 10.1053/j.seminoncol.2003.11.013.
citation: 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. doi: 10.1097/COC.0b013e31805c139a.
citation: 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. doi: 10.1186/1477-7800-1-9.