Pharmacogenomic Study of Docetaxel and Cisplatin, Followed by Docetaxel, Cisplatin and Irradiation.

Adenocarcinomas of the Gastroesophageal Junction Clinical Trial

Official title:

Phase II Pharmacogenomic Study of Neoadjuvant Pre-irradiation Docetaxel and Cisplatin, Followed by Neoadjuvant Concomitant Docetaxel, Cisplatin and Irradiation, Followed by Surgery (CD-CDR-S) in Adult Patients With Operable Adenocarcinomas of the Esophagus or Gastroesophageal Junction

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00216008
• Other study ID #: MCC-13946
• Secondary ID: USFIRB#103493IIT
• Status: Terminated
• Phase: Phase 2
• First received: September 19, 2005
• Last updated: November 21, 2013
• Start date: July 2005
• Est. completion date: February 2007

Study information

• Verified date: July 2009
• Source: H. Lee Moffitt Cancer Center and Research Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this research study is to find out the effectiveness of the experimental combination of Docetaxel, Cisplatin, and radiation therapy administered prior to the surgical removal of your esophageal cancer.

Description:

This study seeks to determine the safety and efficacy (the latter based on pathologic response rate, three- and five-year survival rates) of a three-phase multi-modality approach to adenocarcinomas of the esophagus or gastroesophageal junction. This study also aims retrospectively to determine if a specific tumor gene array profile would predict for pathologic complete response. Study schema is as follows. Patients are first staged, next they receive induction Docetaxel and Cisplatin on days 1 and 22, patients are then restaged, next they will undergo radiation therapy combined with Cisplatin and Docetaxel for approximately days 42 thorough 84, patients are again restaged, and finally surgery at approximately days 100 to 150.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 42
• Est. completion date: February 2007
• Est. primary completion date: February 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients must have histological or cytological confirmed esophageal adenocarcinoma or adenocarcinoma of the gastroesophageal junction (this diagnosis will be rendered by the gastroenterology endoscopist, and refers to tumors at the junction of the esophagus and the stomach, where >50% of the tumor mass is above the diaphragm). Tumors must not have greater than 2cm extension into the the cardia.

• Stage T2N0M0, T3N0M0, T1-3N1M0, T1-3N0-1M1a as determined by imaging studies and endoscopic ultrasound staging. M1a disease (celiac nodal metastasis) is permitted if other eligibility criteria are met. Any lesion suspicious for metastasis should biopsied (either by tru cut or fine needle aspiration) to prove eligibility.

• The subject has been deemed an appropriate surgical candidate by one of the surgical subinvestigators (ie. Not T4).

• No medical comorbidity making the patient not a surgical candidate.

• Subject must be 18 years or older

• Subject must understand the consent and be willing to give written and informed consent to participate in this investigational protocol, and for a tumor biopsy to be performed for research purposes at the time of their staging endoscopic ultrasound (clinically required for their care), and for a portion of their resection specimen be subjected to experimental laboratory analysis

• ECOG performance status <1 (Karnofsky >80%; see Appendix A).

• Subjects must have adequate caloric intake, as determined by a nutrition evaluation by a registered dietician. Nutrition intake may be enteral, hyperalimentation by enteral feeding tube, or by parenteral nutrition.

• Patients must have normal organ and marrow function as defined as: leukocytes >3,000/mcL; absolute neutrophil count >1,500/mcL; platelets >100,000/mcL; hemoglobin > 8 g/dl; Creatinine clearance (estimated by Cockroft-Gault equation) >50-mL/min/1.73 m2 for patients with creatinine levels above institutional normal

• Hepatic: Total bilirubin must be < ULN; AST and ALT and alkaline phosphatase must both be less than 2.5 x ULN.

• Has a negative serum or urine pregnancy test within 7 days prior to initiation of therapy (female patients of childbearing potential).

Exclusion Criteria:

• Patients may not be receiving any other investigational agents.

• Common Toxicity Criteria Adverse Events version 3 (CTCAEv3) greater than grade 1 peripheral neuropathy.

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. Clinically significant cardiac disease (e.g. congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmias not well controlled with medication) or myocardial infarction within the last 12 months.

• Pregnant and nursing women are excluded from this study. Women / men of childbearing potential not using a reliable and appropriate contraceptive method. Woman of childbearing potential with either a positive or no pregnancy test at baseline. (Postmenopausal woman must have been amenorrheic for at least 12 months to be considered of non-childbearing potential). Patients will agree to continue contraception for 30 days from the date of the last study drug administration

• Patients with a history of severe hypersensitivity reaction to docetaxel, cisplatin, or drugs formulated with polysorbate (Tween) 80.

• Because patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy, HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with cisplatin and docetaxel or other agents administered during the study.

• Major surgery within 4 weeks of the start of study treatment, without complete recovery.

• History of clinically significant interstitial lung disease and/or pulmonary fibrosis.

• Treatment for other carcinomas within the last five years, except cured non-melanoma skin and treated in-situ cervical cancer.

• Clinical or radiographic evidence of a tracheobronchial fistula or invasion of the aorta (i.e. T4 disease).

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinomas of the Gastroesophageal Junction
• Esophageal Adenocarcinomas
• Esophageal Neoplasms

Intervention

Drug:
• docetaxel

• cisplatin

Procedure:
• radiation

• surgery

Locations

Country	Name	City	State
United States	H. Lee Moffitt Cancer Center & Research Institute	Tampa	Florida

Sponsors (2)

Lead Sponsor	Collaborator
H. Lee Moffitt Cancer Center and Research Institute	Aventis Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	response rate
Secondary	toxicity and tolerability of this induction strategy
Secondary	time to progression
Secondary	surgical complication rate

External Links

•   Moffiitt Cancer Center Clinical Trials website