Pralatrexate and Docetaxel in Treating Patients With Stage IV Esophageal or Gastroesophageal Cancer Who Have Failed Platinum-Based Therapy

• Sponsor: Ohio State University Comprehensive Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT01129206
• Collaborator: National Comprehensive Cancer Network (Other), Spectrum Pharmaceuticals, Inc (Industry)
• Enrollment: 6
• Location: 1
• Arm: 1

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Adenocarcinoma of the Esophagus; Adenocarcinomas of the Gastroesophageal Junction; Recurrent Esophageal Cancer; Squamous Cell Carcinoma of the Esophagus; Stage IV Esophageal Cancer	Drug: pralatrexate; Drug: docetaxel; Radiation: fludeoxyglucose F 18; Procedure: positron emission tomography	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. 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:

1. 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 6 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Start Date: Jul 1, 2010
• Actual Primary Completion Date: Sep 1, 2012

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Arm I 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.

Drug: pralatrexate; IVP(intravenous push)over 3-5 minutes on day 1 at a dose of 120 mg/m2.; Other Names: FOLOTYN PDX ; Drug: docetaxel; 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.; Other Names: RP 56976 Taxotere TXT ; Radiation: fludeoxyglucose F 18; Correlative studies; Other Names: 18FDG FDG Fluorine-18 2-Fluoro-2-deoxy-D-Glucose fluorodeoxyglucose F 18 ; Procedure: positron emission tomography; Correlative studies; Other Names: FDG-PET PET PET scan tomography, emission computed

Outcome Measures

Primary Outcome Measures

1. Overall Response [Approximately three years]

   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

1. Progression-free Survival (PFS) [Approximately three years]

   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

2. Overall Survival (OS) [Approximately five years]

   OS was determined from the date of start of therapy to death frm any cause.

3. Correlation of FDG PET Response With Response Rate [Approximately three years]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ohio State University	Columbus	Ohio	United States	43210

Sponsors and Collaborators

• Ohio State University Comprehensive Cancer Center
• National Comprehensive Cancer Network
• Spectrum Pharmaceuticals, Inc

Investigators

• Principal Investigator: Tony Saab, MD, Ohio State University

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Jamesline

Publications

• 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.

• Responsible Party: Tony Bekaii-Saab, Principal Investigator, Ohio State University Comprehensive Cancer Center
• ClinicalTrials.gov Identifier: NCT01129206
• Other Study ID Numbers: OSU-10018; NCI-2010-01225
• First Posted: May 24, 2010
• Last Update Posted: Jun 1, 2016
• Last Verified: Apr 1, 2016

• Keywords provided by Tony Bekaii-Saab, Principal Investigator, Ohio State University Comprehensive Cancer Center: Gastroesophageal Cancer; Gastroesophageal Carcinoma; Adenocarcinoma
• Additional relevant MeSH terms: Carcinoma; Adenocarcinoma; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Deoxyglucose; Docetaxel; Fluorodeoxyglucose F18

Study Results

Participant Flow

Recruitment Details	This was a phase II single-arm, open label trial performed at The Ohio State University James Cancer Hospital.

Arm/Group Title	Arm I: Pralatrexate and Docetaxel
Arm/Group 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. pralatrexate: IVP(intravenous push)over 3-5 minutes on day 1 at a dose of 120 mg/m2. docetaxel: 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. fludeoxyglucose F 18: Correlative studies positron emission tomography: Correlative studies
Period Title: Overall Study
STARTED	6
COMPLETED	6
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Arm I
Arm/Group 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. pralatrexate: IVP(intravenous push)over 3-5 minutes on day 1 at a dose of 120 mg/m2. docetaxel: 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. fludeoxyglucose F 18: Correlative studies positron emission tomography: Correlative studies
Overall Participants	6
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	63.5
Sex: Female, Male (Count of Participants)
Female	1 16.7%
Male	5 83.3%
Region of Enrollment (participants) [Number]
United States	6 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I: Pralatrexate and Docetaxel
Arm/Group 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. pralatrexate: IVP(intravenous push)over 3-5 minutes on day 1 at a dose of 120 mg/m2. docetaxel: 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. fludeoxyglucose F 18: Correlative studies positron emission tomography: Correlative studies
Measure Participants	6
Stable disease	2
Progressive disease	4

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I: Pralatrexate and Docetaxel
Arm/Group 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. pralatrexate: IVP(intravenous push)over 3-5 minutes on day 1 at a dose of 120 mg/m2. docetaxel: 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. fludeoxyglucose F 18: Correlative studies positron emission tomography: Correlative studies
Measure Participants	6
Median (95% Confidence Interval) [months]	1.9

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I
Arm/Group 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. pralatrexate: IVP(intravenous push)over 3-5 minutes on day 1 at a dose of 120 mg/m2. docetaxel: 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. fludeoxyglucose F 18: Correlative studies positron emission tomography: Correlative studies
Measure Participants	6
Median (95% Confidence Interval) [months]	5.5

4. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

2 patients not evaluable for response applying the PERCIST criteria per PET

Arm/Group Title	PERCIST Criteria Per PET	RECIST Criteria Per CT
Arm/Group Description
Measure Participants	4	6
Progressive Disease	0	4
Stable Disease	2	2
Partial Response	2	0

Adverse Events

Adverse Event Reporting Description	Toxicities were defined by the National Cancer Institutes CTCAE version 3.0
Arm/Group Title	Arm I
Arm/Group 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. pralatrexate: IVP(intravenous push)over 3-5 minutes on day 1 at a dose of 120 mg/m2. docetaxel: 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. fludeoxyglucose F 18: Correlative studies positron emission tomography: Correlative studies
All Cause Mortality
	Arm I
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Arm I
	Affected / at Risk (%)	# Events
Total	0/6 (0%)
Other (Not Including Serious) Adverse Events
	Arm I
	Affected / at Risk (%)	# Events
Total	6/6 (100%)
Blood and lymphatic system disorders
Anemia	2/6 (33.3%)	2
Gastrointestinal disorders
Mucocitis	2/6 (33.3%)	2
Investigations
Lymphopenia	6/6 (100%)	6
Leukopenia	2/6 (33.3%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.