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Chemotherapy & Erlotinib in Treating Patients w/ Esophageal or Gastroesophageal Cancer That Cannot Be Removed by Surgery

Primary Purpose

Esophageal Cancer

Status

Terminated

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Erlotinib

5-fluorouracil

Leucovorin

Oxaliplatin

About this trial

This is an interventional treatment trial for Esophageal Cancer focused on measuring metastatic esophageal cancer, erlotinib, folfox, advanced esophageal cancer, unresectable esophageal cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Histologically confirmed esophageal carcinoma (squamous or adenocarcinoma)
Surgically unresectable disease and/or metastatic disease; endoscopic accessibility of the primary tumor is preferred but not a prerequisite
No prior chemotherapy therapy except for neoadjuvant treatment (radiation and/or chemotherapy); prior treatment with EGFR-inhibiting agents is not allowed
Life expectancy > 12 weeks
Patients must have the ability to take and retain oral medications or have an appropriate percutaneous feeding tube in place
Patients must have Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 (Karnofsky Performance Status (KPS) >= 50%)
Patients must have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria and radiographic imaging performed within 28 days prior to registration
Absolute neutrophil count (ANC) >= 1500/mL
Platelet count >= 100,000/mL
Hemoglobin level >= 10.0 gm/dL
Serum creatinine =< 1.5 x IULN (institutional upper limits of normal); OR measured creatinine clearance >= 60 mL/min
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase (SGOT)) or alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase (SGPT)) =< 2.5 x IULN (unless the liver is involved by tumor, in which case it must be =< 5.0 x IULN)
Total bilirubin =< 1.5 x IULN
Provision of written informed consent
Women of childbearing potential (WOCBP) must be willing to practice acceptable methods of birth control to prevent pregnancy; WOCBP are any females who have experienced menarche and who have not undergone surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy), who are not postmenopausal (defined as amenorrhea >= 12 consecutive months), or are on hormone replacement therapy; acceptable methods of birth control include oral or hormonal contraceptives and barrier methods (e.g., condom, diaphragm) used in combination with other methods (e.g., spermicide)
Male patients who are capable of fathering a child must avoid doing so while participating in this study through the use of acceptable methods of birth control; this is a precautionary measure because this study involves chemotherapy agents

Exclusion Criteria:

Presence of a Kras mutation
Lack of expression of EGFR (tumors that do not have detectable EGFR staining in at least 10% of tumor cells will not be considered EGFR-positive)
Prior treatment with EGFR-inhibiting agents, chemotherapy, or radiotherapy for esophagogastric carcinomas (other than neoadjuvant treatment as noted in inclusion criteria)
Patients must not be receiving any other investigational agents; use of erythropoietin is allowable; secondary prophylaxis with granulocyte colony stimulating factor (G-CSF) (Filgrastim) is allowable
The patient concomitantly uses phenytoin, carbamazepine, barbiturates, rifampicin, phenobarbital, or St. John's wort
Uncontrolled brain metastases
Patients must not have uncontrolled intercurrent illness at the time of registration 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
Patients must not have current New York Heart Association Class III or IV heart disease
Known human immunodeficiency virus (HIV) infection
Pregnant or breast-feeding women
Patients who have had prior malignancies, except non-melanoma skin cancer (basal or squamous cell carcinoma) are not eligible for this study; unless greater than 5 years has passed since the event
Known severe hypersensitivity to Tarceva
Treatment with a non-approved or investigational drug within 30 days before day 1 of trial treatment
Incomplete healing from previous oncologic or other major surgery
Serum creatinine level greater than Common Toxicity Criteria (CTC) grade 2

Sites / Locations

University of California, San Francisco

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Tarceva and FOLFOX

Arm Description

COMBINATION THERAPY PHASE: Patients receive erlotinib hydrochloride orally (PO) once daily (QD) on days 1-56. Patients also receive FOLFOX6 therapy comprising oxaliplatin intravenously (IV) over 2 hours, leucovorin calcium IV over 2 hours, and fluorouracil IV over 46-48 hours on days 1, 15, 29, and 43. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity. Patients with stable disease or no evidence of disease after course 2 or subsequent courses continue on to maintenance phase. MAINTENANCE PHASE: Patients receive erlotinib hydrochloride PO QD on days 1-42. Treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

Progression Free Survival (PFS)

PFS is defined as the duration of time from enrollment into the run-in period of the study to objective tumor progression as determined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria. The proportion of patients with PFS will be reported and evaluated using Kaplan-Meier survival curves with median survival and 95% confidence interval.

Secondary Outcome Measures

Objective Response Rate (RR)

The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for Progressive Disease (PD) the smallest measurements recorded since the treatment started). Best response assignment will depend on the achievement of both measurement and confirmation criteria using RECIST for both target and non-target lesions. For target lesions, response is defined as follows: Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): >= 30% decrease in sum of the LD, taking as reference the baseline sum LD; PD: >=20% increase in sum of the LD of target lesions, taking as reference smallest sum LD recorded since treatment started or appearance of one or more new lesions , Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.

Time to Progression (TTP)

Patient with objective tumor response or stable disease will be treated with single agent Tarceva until tumor progression. For this study, time to progression will be determined as the number of days following the first day of single agent treatment with Tarceva following the last and completed cycle of Tarcerva/FOLFOX combination therapy. TTP will be calculated for the entire patient population as well as for patients that objectively responded to the combination therapy versus those that did not.

Full Information

NCT ID

NCT00539617

First Posted

October 2, 2007

Last Updated

March 5, 2020

Sponsor

University of California, San Francisco

Collaborators

Genentech, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT00539617

Brief Title

Chemotherapy & Erlotinib in Treating Patients w/ Esophageal or Gastroesophageal Cancer That Cannot Be Removed by Surgery

Official Title

A Single-Arm, Phase II Study of Tarceva Plus FOLFOX6 in Patients With Unresectable or Metastatic Cancer of Esophagus or Gastroesophageal Junction

Study Type

Interventional

2. Study Status

Record Verification Date

March 2020

Overall Recruitment Status

Terminated

Why Stopped

For slow accrual

Study Start Date

October 5, 2007 (Actual)

Primary Completion Date

May 12, 2011 (Actual)

Study Completion Date

May 12, 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of California, San Francisco

Collaborators

Genentech, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The purpose of this study is to test the safety and effectiveness of erlotinib and FOLFOX in patients with esophageal or gastro-esophageal cancer that cannot be removed by surgery.

Detailed Description

More than 50% of patients with advanced esophageal cancer present with disease that cannot be removed by surgery or has spread to other parts of the body. Improved therapies for patients with advanced esophageal cancer are therefore urgently needed. The epidermal growth factor receptor (EGFR) inhibitor erlotinib (in combination with chemotherapy) has lead to improved survival in patients with pancreatic and lung cancer. EGFR is a target in esophageal cancer therapy since its overexpression is associated with more aggressive disease and poor survival. Early studies have shown some clinical activity of EGFR inhibitors in this disease alone or in combination with chemotherapy. This study aims to explore how safe and effective treatment with erlotinib and FOLFOX is in patients with advanced esophageal or gastro-esophageal cancer.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Esophageal Cancer

Keywords

metastatic esophageal cancer, erlotinib, folfox, advanced esophageal cancer, unresectable esophageal cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

7 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Tarceva and FOLFOX

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Erlotinib

Other Intervention Name(s)

Tarceva

Intervention Description

Tarceva single agent therapy: 150 mg/day PO

Intervention Type

Drug

Intervention Name(s)

5-fluorouracil

Other Intervention Name(s)

5-FU, Adrucil

Intervention Description

5-FU bolus: 400 mg/m2 IV once every 2 weeks for 16 weeks 5-FU infusion: 2400 mg/m2 IV over 46-48 hours, once every 2 weeks for 16 weeks

Intervention Type

Drug

Intervention Name(s)

Leucovorin

Other Intervention Name(s)

Folinic acid

Intervention Description

400 mg/m2 IV once every 2 weeks for 16 weeks

Intervention Type

Drug

Intervention Name(s)

Oxaliplatin

Other Intervention Name(s)

Eloxatin

Intervention Description

85 mg/m2 IV once every 2 weeks for 16 weeks

Primary Outcome Measure Information:

Title

Progression Free Survival (PFS)

Description

Time Frame

Up to 2 years

Secondary Outcome Measure Information:

Title

Objective Response Rate (RR)

Description

Time Frame

Up to 2 years

Title

Time to Progression (TTP)

Description

Time Frame

Up to 2 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Histologically confirmed esophageal carcinoma (squamous or adenocarcinoma) Surgically unresectable disease and/or metastatic disease; endoscopic accessibility of the primary tumor is preferred but not a prerequisite No prior chemotherapy therapy except for neoadjuvant treatment (radiation and/or chemotherapy); prior treatment with EGFR-inhibiting agents is not allowed Life expectancy > 12 weeks Patients must have the ability to take and retain oral medications or have an appropriate percutaneous feeding tube in place Patients must have Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 (Karnofsky Performance Status (KPS) >= 50%) Patients must have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria and radiographic imaging performed within 28 days prior to registration Absolute neutrophil count (ANC) >= 1500/mL Platelet count >= 100,000/mL Hemoglobin level >= 10.0 gm/dL Serum creatinine =< 1.5 x IULN (institutional upper limits of normal); OR measured creatinine clearance >= 60 mL/min Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase (SGOT)) or alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase (SGPT)) =< 2.5 x IULN (unless the liver is involved by tumor, in which case it must be =< 5.0 x IULN) Total bilirubin =< 1.5 x IULN Provision of written informed consent Women of childbearing potential (WOCBP) must be willing to practice acceptable methods of birth control to prevent pregnancy; WOCBP are any females who have experienced menarche and who have not undergone surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy), who are not postmenopausal (defined as amenorrhea >= 12 consecutive months), or are on hormone replacement therapy; acceptable methods of birth control include oral or hormonal contraceptives and barrier methods (e.g., condom, diaphragm) used in combination with other methods (e.g., spermicide) Male patients who are capable of fathering a child must avoid doing so while participating in this study through the use of acceptable methods of birth control; this is a precautionary measure because this study involves chemotherapy agents Exclusion Criteria: Presence of a Kras mutation Lack of expression of EGFR (tumors that do not have detectable EGFR staining in at least 10% of tumor cells will not be considered EGFR-positive) Prior treatment with EGFR-inhibiting agents, chemotherapy, or radiotherapy for esophagogastric carcinomas (other than neoadjuvant treatment as noted in inclusion criteria) Patients must not be receiving any other investigational agents; use of erythropoietin is allowable; secondary prophylaxis with granulocyte colony stimulating factor (G-CSF) (Filgrastim) is allowable The patient concomitantly uses phenytoin, carbamazepine, barbiturates, rifampicin, phenobarbital, or St. John's wort Uncontrolled brain metastases Patients must not have uncontrolled intercurrent illness at the time of registration 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 Patients must not have current New York Heart Association Class III or IV heart disease Known human immunodeficiency virus (HIV) infection Pregnant or breast-feeding women Patients who have had prior malignancies, except non-melanoma skin cancer (basal or squamous cell carcinoma) are not eligible for this study; unless greater than 5 years has passed since the event Known severe hypersensitivity to Tarceva Treatment with a non-approved or investigational drug within 30 days before day 1 of trial treatment Incomplete healing from previous oncologic or other major surgery Serum creatinine level greater than Common Toxicity Criteria (CTC) grade 2

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

W. Michael Korn, MD

Organizational Affiliation

University of California, San Francisco

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of California, San Francisco

City

San Francisco

State/Province

California

ZIP/Postal Code

94115

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Chemotherapy & Erlotinib in Treating Patients w/ Esophageal or Gastroesophageal Cancer That Cannot Be Removed by Surgery

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