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A Phase II Trial of PF-00299804 in Patients With Metastatic or Recurrent Squamous Cell Carcinoma of Esophagus

Primary Purpose

Esophageal Squamous Cell Carcinoma

Status

Completed

Phase

Phase 2

Locations

Korea, Republic of

Study Type

Interventional

Intervention

PF804

About this trial

This is an interventional treatment trial for Esophageal Squamous Cell Carcinoma

Eligibility Criteria

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

Inclusion Criteria:

Histologically confirmed squamous cell carcinoma of esophagus
Age >= 18
ECOG PS 0-2
Ineligibility for local therapy (surgery or radiotherapy)
Not more than one prior palliative therapy
At least one bidimensionally measurable disease as defined by RECIST ver 1.1
Adequate organ function for treatment
- Absolute neutrophil count (ANC)>=1000cells/mm3
- Platelets >=100000 cells/mm3
- Estimated creatinine clearance>=50mL/min, or serum creatinine<1.5 x institution upper limit of normal
- Bilirubin=<1.5 x upper limit of normal(ULN)
- AST(SGOT)=<2.5 x ULN (5.0xULN if hepatic metastases)
- ALT(SGPT)=<2.5 x ULN (5.0xULN if hepatic metastases)
- 12-Lead electrocardiogram(ECG) with normal tracing or non-clinically significant changes that do not require medical intervention
- QTc interval =<470 msec and without history of Torsades de Points or other symptomatic QTc abnormality
- LVEF (by MUGA or echocardiogram) of >=50%.
The patient has provided signed informed consent and is amenable to compliance with protocol schedules and testing.

Exclusion Criteria:

Previous treatment with small molecule EGFR tyrosine kinase inhibitors
Two or more previous systemic cytotoxic chemotherapy (Chemotherapy administered with concurrent radiotherapy for local control is not counted)
Any major operation or irradiation within 4 weeks of baseline disease assessment
Any clinically significant gastrointestinal abnormalities which may impair intake or absorption of the study drug
CNS metastasis with continuous corticosteroid use within 4 weeks of baseline disease assessment
Patients with known interstitial lung disease
Patients with uncontrolled or significant cardiovascular disease (AMI within 12 months,Unstable angina within 6 months, NYHA Class III, IV Congestive heart failure or left ventricular ejection fraction below local institutional lower limit of normal or below 45%, Congenital long QT syndrome, Any significant ventricular arrhythmia, Any uncontrolled second or third degree heart block, Uncontrolled hypertension)
Previous or concurrent malignancy except for basal or squamous cell skin cancer and/or in situ carcinoma of the cervix, or other solid tumors treated curatively and without evidence of recurrence for at least 5 years prior to study entry.
Pregnant or breast-feeding women
Other severe acute or chronic medical condition or laboratory abnormality that may increase the risk associated with trial participation or investigational product administration or may interfere with the interpretation of trial results and, in the judgment of the investigator, would make the patient inappropriate for entry into this trial.

Sites / Locations

Severance hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

PF804

Arm Description

Outcomes

Primary Outcome Measures

Overall Response Rate

Objective Tumor Response will be performed according to the Response Evaluation in Solid Tumor Criteria (RECIST).

Secondary Outcome Measures

Full Information

NCT ID

NCT01608022

First Posted

May 18, 2012

Last Updated

September 5, 2016

Sponsor

Yonsei University

1. Study Identification

Unique Protocol Identification Number

NCT01608022

Brief Title

A Phase II Trial of PF-00299804 in Patients With Metastatic or Recurrent Squamous Cell Carcinoma of Esophagus

Study Type

Interventional

2. Study Status

Record Verification Date

September 2016

Overall Recruitment Status

Completed

Study Start Date

July 2012 (undefined)

Primary Completion Date

April 2015 (Actual)

Study Completion Date

October 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Yonsei University

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

Esophageal cancer (EC) is the eighth most common cause of cancer-related death in the worldwide. Systemic chemotherapy in patients with metastatic EC has limited effectiveness, resulting in a median survival of 8 months to 10months. The low activity and brief duration of benefit for chemotherapy to palliate advanced disease make clear need to identify new active agents. Epidermal growth factor receptor (EGFR) is often over-expressed, and have been related to poor prognosis in patients with EC. The association between EGFR-activated signaling pathways and tumor cell survival are well documented in many studies. Some EGFR tyrosine kinase inhibitors (TKIs) already showed clinical efficacy against EC. A study with erlotinib showed objective response rate of 15% (2 of 13 patients), but activity was limited to squamous cell type.8 In another study, thirty patients with malignant solid tumor were treated with BIBW2992, irreversible inhibitor of EGFR and HER2, and one of four EC patients achieved partial response. PF-00299804 is a second-generation quinazoline-based irreversible pan-HER inhibitor. In preclinical studies, PF-00299804 has much lower IC50 values than gefitinib in cell lines engineered to express EGFRvIII mutations (1.2 nM versus 2,700 nM) and produces tumor growth inhibition in gefitinib-resistant xenografts. PF-00299804 reportedly have clinical anti-tumor activity in patients with non-small cell lung cancer and head and neck squamous cell carcinoma with manageable toxicity. The aim of current trial is to evaluate the antitumor efficacy and safety profile of PF-00299804 and to identify biomarker to predict the tumor response to PF-00299804.

6. Conditions and Keywords

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

Esophageal Squamous Cell Carcinoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

48 (Actual)

8. Arms, Groups, and Interventions

Arm Title

PF804

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

PF804

Intervention Description

45 mg p.o. daily and continuously (28-day treatment as one treatment cycle)

Primary Outcome Measure Information:

Title

Overall Response Rate

Description

Objective Tumor Response will be performed according to the Response Evaluation in Solid Tumor Criteria (RECIST).

Time Frame

28th day of every chemotherapy cycle

10. Eligibility

Sex

All

Minimum Age & Unit of Time

20 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Histologically confirmed squamous cell carcinoma of esophagus Age >= 18 ECOG PS 0-2 Ineligibility for local therapy (surgery or radiotherapy) Not more than one prior palliative therapy At least one bidimensionally measurable disease as defined by RECIST ver 1.1 Adequate organ function for treatment Absolute neutrophil count (ANC)>=1000cells/mm3 Platelets >=100000 cells/mm3 Estimated creatinine clearance>=50mL/min, or serum creatinine<1.5 x institution upper limit of normal Bilirubin=<1.5 x upper limit of normal(ULN) AST(SGOT)=<2.5 x ULN (5.0xULN if hepatic metastases) ALT(SGPT)=<2.5 x ULN (5.0xULN if hepatic metastases) 12-Lead electrocardiogram(ECG) with normal tracing or non-clinically significant changes that do not require medical intervention QTc interval =<470 msec and without history of Torsades de Points or other symptomatic QTc abnormality LVEF (by MUGA or echocardiogram) of >=50%. The patient has provided signed informed consent and is amenable to compliance with protocol schedules and testing. Exclusion Criteria: Previous treatment with small molecule EGFR tyrosine kinase inhibitors Two or more previous systemic cytotoxic chemotherapy (Chemotherapy administered with concurrent radiotherapy for local control is not counted) Any major operation or irradiation within 4 weeks of baseline disease assessment Any clinically significant gastrointestinal abnormalities which may impair intake or absorption of the study drug CNS metastasis with continuous corticosteroid use within 4 weeks of baseline disease assessment Patients with known interstitial lung disease Patients with uncontrolled or significant cardiovascular disease (AMI within 12 months,Unstable angina within 6 months, NYHA Class III, IV Congestive heart failure or left ventricular ejection fraction below local institutional lower limit of normal or below 45%, Congenital long QT syndrome, Any significant ventricular arrhythmia, Any uncontrolled second or third degree heart block, Uncontrolled hypertension) Previous or concurrent malignancy except for basal or squamous cell skin cancer and/or in situ carcinoma of the cervix, or other solid tumors treated curatively and without evidence of recurrence for at least 5 years prior to study entry. Pregnant or breast-feeding women Other severe acute or chronic medical condition or laboratory abnormality that may increase the risk associated with trial participation or investigational product administration or may interfere with the interpretation of trial results and, in the judgment of the investigator, would make the patient inappropriate for entry into this trial.

Facility Information:

Facility Name

Severance hospital

City

Seoul

ZIP/Postal Code

120-752

Country

Korea, Republic of

12. IPD Sharing Statement

Learn more about this trial

A Phase II Trial of PF-00299804 in Patients With Metastatic or Recurrent Squamous Cell Carcinoma of Esophagus

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