Pralatrexate and Docetaxel in Treating Patients With Stage IV Esophageal or Gastroesophageal Cancer Who Have Failed Platinum-Based Therapy
Primary Purpose
Adenocarcinoma of the Esophagus, Adenocarcinomas of the Gastroesophageal Junction, Recurrent Esophageal Cancer
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
pralatrexate
docetaxel
fludeoxyglucose F 18
positron emission tomography
Sponsored by
About this trial
This is an interventional treatment trial for Adenocarcinoma of the Esophagus focused on measuring Gastroesophageal Cancer, Gastroesophageal Carcinoma, Adenocarcinoma
Eligibility Criteria
Inclusion
- Pathologically confirmed unresectable advanced or metastatic carcinoma of the esophagus or gastroesophageal junction
- Established histological confirmation of squamous cell carcinoma or adenocarcinoma of the esophagus or gastroesophageal junction
- Stage IV disease
- Must have received platinum-based therapy; this includes definitive, adjuvant and metastatic treatments
- No more than 3 chemotherapeutic treatment regimens permitted; this includes concurrent chemoradiation
- Radiation therapy allowed if > 4 weeks have elapsed
- Must be off therapy for 4 weeks prior to enrollment
- Measurable disease as defined by RECIST v 1.1 criteria
- ECOG (Eastern Cooperative Oncology Group)PS(Performance status)of 0 to 2
- Predicted life expectancy of at least 12 weeks
- Patients with reproductive potential must use an effective method to avoid pregnancy for the duration of the trial and for three months after completion of treatment
- Marrow: ANC(absolute neutrophil count)> 1,000/mm^3
- Marrow: Hemoglobin > 9.0 g/dl
- Marrow: Platelet Count > 100,000/mm^3
- Renal: Serum creatinine =< 1.5 g/dL
- Hepatic: Serum bilirubin < 1.5 x ULN(upper limit of normal) and AST (aspartate aminotransferase) and ALT (Alanine aminotransferase)=< 2.5 x ULN
- Prior minor surgeries (such as laparoscopies) must have occurred at least 14 days prior to study enrollment; prior minor procedures such as biopsies and mediport placement must have occurred at least 48 hours prior to study enrollment
- All patients must have signed an informed consent indicating that they are aware of the neoplastic nature of their disease and have been informed of the procedures of the protocol, the experimental nature of the therapy, alternatives, potential benefits, side effects, risks, and discomforts
- History of allergic reactions attributed to compounds of similar chemical composition to agents used in the study
Exclusion
- Pregnant or lactating women
- Patients with any severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for study entry
- Any malignant condition for which one has received treatment in the last two years excluding squamous or basal cell carcinomas
- Patients with untreated brain metastases
- Patients must not have grade 2 or higher baseline peripheral neuropathy, according to CTCAE v 4.0
- Patients must have NO continuing acute toxic effects (except alopecia) of any prior radiotherapy, chemotherapy, or surgical procedures; all such effects must have resolved to Common Terminology Criteria for Adverse Events (CTCAE v 4.0) Grade =< 1 prior to study enrollment
Sites / Locations
- Ohio State University
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Arm I
Arm Description
Patients receive pralatrexate IV over 3-5 minutes and docetaxel IV on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Outcomes
Primary Outcome Measures
Overall Response
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
Secondary Outcome Measures
Progression-free Survival (PFS)
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Overall Survival (OS)
OS was determined from the date of start of therapy to death frm any cause.
Correlation of FDG PET Response With Response Rate
Radiological assessment of tumor response was performed by computed tomography (CT) and positron emission tomography (PET) every four cycles of therapy and responses were measured according to RECIST and PERCIST criteria.
Full Information
NCT ID
NCT01129206
First Posted
May 21, 2010
Last Updated
April 25, 2016
Sponsor
Ohio State University Comprehensive Cancer Center
Collaborators
National Comprehensive Cancer Network, Spectrum Pharmaceuticals, Inc
1. Study Identification
Unique Protocol Identification Number
NCT01129206
Brief Title
Pralatrexate and Docetaxel in Treating Patients With Stage IV Esophageal or Gastroesophageal Cancer Who Have Failed Platinum-Based Therapy
Official Title
Phase II Study of Pralatrexate and Docetaxel in Patients With Advanced Esophageal and Gastroesophageal Carcinoma Who Have Failed Prior Platinum-based Therapy.
Study Type
Interventional
2. Study Status
Record Verification Date
April 2016
Overall Recruitment Status
Completed
Study Start Date
July 2010 (undefined)
Primary Completion Date
September 2012 (Actual)
Study Completion Date
undefined (undefined)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Ohio State University Comprehensive Cancer Center
Collaborators
National Comprehensive Cancer Network, Spectrum Pharmaceuticals, Inc
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
RATIONALE: Pralatrexate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving pralatrexate together with docetaxel may kill more tumor cells.
PURPOSE: This phase II trial is studying how well giving pralatrexate together with docetaxel works in treating patients with stage IV esophageal or gastroesophageal cancer who have failed platinum-based therapy.
Detailed Description
PRIMARY OBJECTIVES:
I. To evaluate overall response rate CR & PR(Complete Response + Partial Response)as assessed by RECIST (Response Evaluation Criteria in Solid Tumors v 1.1) of the combination of pralatrexate and docetaxel in patients with advanced esophageal and gastroesophageal carcinomas.
SECONDARY OBJECTIVES:
I. Evaluation of progression free survival and overall survival. II. Correlation of FDG(fludeoxyglucose)PET(positron emission tomography)response defined as a 35% reduction in SUV(standard uptake value)during the early course of chemotherapy to progression free and overall survival in addition to radiographic response as measured by RECIST v 1.1 criteria on CT imaging.
OUTLINE:
Patients receive pralatrexate IV over 3-5 minutes and docetaxel IV on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Adenocarcinoma of the Esophagus, Adenocarcinomas of the Gastroesophageal Junction, Recurrent Esophageal Cancer, Squamous Cell Carcinoma of the Esophagus, Stage IV Esophageal Cancer
Keywords
Gastroesophageal Cancer, Gastroesophageal Carcinoma, Adenocarcinoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
6 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm I
Arm Type
Experimental
Arm Description
Patients receive pralatrexate IV over 3-5 minutes and docetaxel IV on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
pralatrexate
Other Intervention Name(s)
FOLOTYN, PDX
Intervention Description
IVP(intravenous push)over 3-5 minutes on day 1 at a dose of 120 mg/m2.
Intervention Type
Drug
Intervention Name(s)
docetaxel
Other Intervention Name(s)
RP 56976, Taxotere, TXT
Intervention Description
Given Intravenous Piggyback (IVPB)as one-hour infusion at a dose of 3 mg/m2 on day 1 of a cycle. cycle defined as 14 days.
Intervention Type
Radiation
Intervention Name(s)
fludeoxyglucose F 18
Other Intervention Name(s)
18FDG, FDG, Fluorine-18 2-Fluoro-2-deoxy-D-Glucose, fluorodeoxyglucose F 18
Intervention Description
Correlative studies
Intervention Type
Procedure
Intervention Name(s)
positron emission tomography
Other Intervention Name(s)
FDG-PET, PET, PET scan, tomography, emission computed
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Overall Response
Description
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
Time Frame
Approximately three years
Secondary Outcome Measure Information:
Title
Progression-free Survival (PFS)
Description
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Time Frame
Approximately three years
Title
Overall Survival (OS)
Description
OS was determined from the date of start of therapy to death frm any cause.
Time Frame
Approximately five years
Title
Correlation of FDG PET Response With Response Rate
Description
Radiological assessment of tumor response was performed by computed tomography (CT) and positron emission tomography (PET) every four cycles of therapy and responses were measured according to RECIST and PERCIST criteria.
Time Frame
Approximately three years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion
Pathologically confirmed unresectable advanced or metastatic carcinoma of the esophagus or gastroesophageal junction
Established histological confirmation of squamous cell carcinoma or adenocarcinoma of the esophagus or gastroesophageal junction
Stage IV disease
Must have received platinum-based therapy; this includes definitive, adjuvant and metastatic treatments
No more than 3 chemotherapeutic treatment regimens permitted; this includes concurrent chemoradiation
Radiation therapy allowed if > 4 weeks have elapsed
Must be off therapy for 4 weeks prior to enrollment
Measurable disease as defined by RECIST v 1.1 criteria
ECOG (Eastern Cooperative Oncology Group)PS(Performance status)of 0 to 2
Predicted life expectancy of at least 12 weeks
Patients with reproductive potential must use an effective method to avoid pregnancy for the duration of the trial and for three months after completion of treatment
Marrow: ANC(absolute neutrophil count)> 1,000/mm^3
Marrow: Hemoglobin > 9.0 g/dl
Marrow: Platelet Count > 100,000/mm^3
Renal: Serum creatinine =< 1.5 g/dL
Hepatic: Serum bilirubin < 1.5 x ULN(upper limit of normal) and AST (aspartate aminotransferase) and ALT (Alanine aminotransferase)=< 2.5 x ULN
Prior minor surgeries (such as laparoscopies) must have occurred at least 14 days prior to study enrollment; prior minor procedures such as biopsies and mediport placement must have occurred at least 48 hours prior to study enrollment
All patients must have signed an informed consent indicating that they are aware of the neoplastic nature of their disease and have been informed of the procedures of the protocol, the experimental nature of the therapy, alternatives, potential benefits, side effects, risks, and discomforts
History of allergic reactions attributed to compounds of similar chemical composition to agents used in the study
Exclusion
Pregnant or lactating women
Patients with any severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for study entry
Any malignant condition for which one has received treatment in the last two years excluding squamous or basal cell carcinomas
Patients with untreated brain metastases
Patients must not have grade 2 or higher baseline peripheral neuropathy, according to CTCAE v 4.0
Patients must have NO continuing acute toxic effects (except alopecia) of any prior radiotherapy, chemotherapy, or surgical procedures; all such effects must have resolved to Common Terminology Criteria for Adverse Events (CTCAE v 4.0) Grade =< 1 prior to study enrollment
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tony Saab, MD
Organizational Affiliation
Ohio State University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Ohio State University
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
26029462
Citation
Petullo B, Wei L, Yereb M, Neal A, Rose J, Bekaii-Saab T, Wu C. A phase II study of biweekly pralatrexate and docetaxel in patients with advanced esophageal and gastroesophageal carcinoma that have failed first-line platinum-based therapy. J Gastrointest Oncol. 2015 Jun;6(3):336-40. doi: 10.3978/j.issn.2078-6891.2015.011.
Results Reference
background
Links:
URL
http://cancer.osu.edu
Description
Jamesline
Learn more about this trial
Pralatrexate and Docetaxel in Treating Patients With Stage IV Esophageal or Gastroesophageal Cancer Who Have Failed Platinum-Based Therapy
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