Adenocarcinoma of the Gastroesophageal JunctionPhase 2NCT01178944
Pralatrexate and Oxaliplatin in Treating Patients With Unresectable or Metastatic Esophageal, Stomach, or Gastroesophageal Junction Cancer
A Phase 2 study testing Laboratory Biomarker Analysis, Oxaliplatin and Pralatrexate in people with Adenocarcinoma of the Gastroesophageal Junction and Esophageal Undifferentiated Carcinoma, run by Roswell Park Cancer Institute at 2 sites in United States.
Trial summary
This phase II trial studies how well pralatrexate and oxaliplatin work in treating patients with esophageal, stomach, or gastroesophageal junction cancer that cannot be removed by surgery or has spread from the primary site (place where it started) to other places in the body. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adenocarcinoma of the Gastroesophageal Junction, Esophageal Undifferentiated Carcinoma, Gastric Adenocarcinoma
- What is being tested?
- Laboratory Biomarker Analysis, Oxaliplatin and Pralatrexate
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 2 sitesUnited States
- Study dates
- Sep 2010to Nov 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed carcinoma of the esophagus, stomach or gastro-esophageal junction that is metastatic, or locally advanced and inoperable for cure; histological sub-types permitted include adenocarcinoma, squamous-cell carcinoma, or undifferentiated carcinoma; small-cell carcinoma variant is not eligible
- No previous systemic therapy for metastatic or recurrent disease; therapy (chemotherapy, radiotherapy, or both) administered in the neo-adjuvant, adjuvant, or definitive setting for previously localized disease is permitted, provided it was completed more than 6 months prior to enrollment; palliative radiotherapy is permitted provided it is completed >= 3 weeks prior to study therapy initiation
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Life expectancy >= 12 weeks
- Hemoglobin >= 9 g/dl
- Absolute neutrophil count >= 1500/mm^3
Show all 13Show fewer
- Platelet count >= 100,000/mm^3
- Serum creatinine =< institutional upper limit normal (ULN)
- Bilirubin =< 1.5 x ULN
- Transaminases =< 3 x ULN; for documented liver metastases, transaminases up to 5 x ULN is permitted
- No evidence of >= grade 2 peripheral neuropathy
- Patients with reproductive potential must be willing to use an adequate contraceptive method (e.g., abstinence, intrauterine device, oral contraceptives, barrier device with spermicide or surgical sterilization) during treatment and for three months after completing treatment; a negative pregnancy test is required for women of child-bearing potential; nursing women are ineligible
- Written, informed consent
Who cannot join
- Hypersensitivity to platinum compounds
- Uncontrolled inter-current illness including but not limited to active infection, symptomatic congestive heart failure, unstable angina, uncontrolled cardiac arrhythmia, or psychiatric illness that would limit compliance with study requirements
- Presence of brain metastases
- Patients with third-space (pleural, peritoneal) fluid not controllable with usual drainage methods are not eligible
- History of second primary malignancy within 3 years prior to enrollment, except for in-situ cervix carcinoma or non-melanoma skin cancer
- Undergone an allogeneic stem cell transplant
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Roswell Park Cancer Institute
Buffalo, New York, 14263
Rochester General Hospital
Rochester, New York, 14621
About this study
Official title: Pralatrexate in Combination With Oxaliplatin in Advanced Esophago-gastric Cancer: A Phase II Trial With Predictive Molecular Correlates
This phase II trial studies how well pralatrexate and oxaliplatin work in treating patients with esophageal, stomach, or gastroesophageal junction cancer that cannot be removed by surgery or has spread from the primary site (place where it started) to other places in the body. Pralatrexate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving pralatrexate with oxaliplatin may be an effective treatment for esophageal, stomach, or gastroesophageal junction cancer.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine the overall response rate in patients with advanced esophago-gastric cancer (EGC) to combination pralatrexate and oxaliplatin.
SECONDARY OBJECTIVES:
- To examine the toxicity and tolerability of this regimen. II. To determine the time-to-progression and overall survival using this regimen.
III. To examine whether functionally relevant polymorphisms of genes of the folate metabolism pathway correlate with efficacy and toxicity of pralatrexate.
IV. To examine whether response to pralatrexate can be predicted by micro-ribonucleic acid (microRNA) expression profiling of the epithelial component of the tumor.
OUTLINE:
Patients receive pralatrexate intravenously (IV) over 3-5 minutes and oxaliplatin IV over 2 hours on day 1. Courses repeat every 2 weeks in the absence of disease progression or unacceptable toxicity. Oxaliplatin will be discontinued after 12 courses.
After completion of study treatment, patients are followed up for 30 days and then periodically thereafter for up to 5 years.
- Conditions
- Adenocarcinoma of the Gastroesophageal Junction, Esophageal Undifferentiated Carcinoma, Gastric Adenocarcinoma, Gastric Squamous Cell Carcinoma, Recurrent Esophageal Adenocarcinoma, Recurrent Esophageal Squamous Cell Carcinoma
- Being tested
- Laboratory Biomarker Analysis, Oxaliplatin, Pralatrexate
- Medical subject headings
- Adenocarcinoma Of Esophagus, Esophageal Squamous Cell Carcinoma, Stomach Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Laboratory Biomarker AnalysisOther
Correlative studies
OxaliplatinDrug
Also called 1-OHP, Dacotin, Dacplat, Diaminocyclohexane Oxalatoplatinum
Given IV
PralatrexateDrug
Also called 10-propargyl-10-deazaaminopterin, Folotyn, PDX
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Treatment (pralatrexate, oxaliplatin) | Experimental | Patients receive pralatrexate IV over 3-5 minutes and oxaliplatin IV over 2 hours on day 1. Courses repeat every 2 weeks in the absence of disease progression or unacceptable toxicity. Oxaliplatin will be discontinued after 12 courses. Receives: Other: Laboratory Biomarker Analysis; Drug: Oxaliplatin; Drug: Pralatrexate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate
Overall response rate to combination pralatrexate and oxaliplatin as assessed by Response Evaluation Criteria in Solid Tumors version 1.1. Objective responses will be confirmed 4 weeks after first documentation of response. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) 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.
Measured: Up to 5 years
Secondary outcomes (3)
Number of Participants With an Adverse Event
Number of participants with an adverse event. Please refer to the adverse event reporting for more detail. Incidence of toxicity as assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
Measured: Up to 30 days after the last dose of study drug(s)
Overall Survival (OS)
Estimated using the Kaplan-Meier method and proportional hazards models.
Measured: From the date of study enrollment to the time of death from any cause, assessed up to 5 years
Time to Progression (TTP)
Estimated using the Kaplan-Meier method and proportional hazards models.
Measured: From the date of study enrollment to the first observation of progressive disease, assessed up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Aug 2010 (estimated)
- Study startSep 2010
- Primary completionJan 2015
- Study completionNov 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Adenocarcinoma of the Gastroesophageal JunctionStudies of the same condition, open and under way.
- More trials run by Roswell Park Cancer InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- Roswell Park Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI), National Comprehensive Cancer Network
- Responsible party
- Sponsor
- Investigators
- Nikhil Khushalani, Principal investigator, Roswell Park Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01178944
- Sponsor's protocol ID
- I 169210
- Other IDs
- NCI-2010-01583, I 169210, P30CA016056
- Status last verified
- Nov 2017
- First submitted
- 9 Aug 2010
- Last updated
- 13 Dec 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 13 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pralatrexate in Combination With Oxaliplatin in Advanced Esophago-gastric Cancer: A Phase II Trial With Predictive Molecular Correlates
- ClinicalTrials.gov ID
- NCT01178944
- Acronym / sponsor ID
- I 169210
- Conditions
- Adenocarcinoma of the Gastroesophageal Junction, Esophageal Undifferentiated Carcinoma, Gastric Adenocarcinoma, Gastric Squamous Cell Carcinoma, Recurrent Esophageal Adenocarcinoma, Recurrent Esophageal Squamous Cell Carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- Roswell Park Cancer InstituteUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI), National Comprehensive Cancer Network
- Study start
- Sep 2010
- Primary completion
- Jan 2015 (actual)
- Study completion
- Nov 2015 (actual)
- First posted
- 10 Aug 2010 (estimated)
- Results
- Posted 13 Dec 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II trial studies how well pralatrexate and oxaliplatin work in treating patients with esophageal, stomach, or gastroesophageal junction cancer that cannot be removed by surgery or has spread from the primary site (place where it started) to other places in the body. Pralatrexate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving pralatrexate with oxaliplatin may be an effective treatment for esophageal, stomach, or gastroesophageal junction cancer.
Detailed description
PRIMARY OBJECTIVES:
- To determine the overall response rate in patients with advanced esophago-gastric cancer (EGC) to combination pralatrexate and oxaliplatin.
SECONDARY OBJECTIVES:
- To examine the toxicity and tolerability of this regimen. II. To determine the time-to-progression and overall survival using this regimen.
III. To examine whether functionally relevant polymorphisms of genes of the folate metabolism pathway correlate with efficacy and toxicity of pralatrexate.
IV. To examine whether response to pralatrexate can be predicted by micro-ribonucleic acid (microRNA) expression profiling of the epithelial component of the tumor.
OUTLINE:
Patients receive pralatrexate intravenously (IV) over 3-5 minutes and oxaliplatin IV over 2 hours on day 1. Courses repeat every 2 weeks in the absence of disease progression or unacceptable toxicity. Oxaliplatin will be discontinued after 12 courses.
After completion of study treatment, patients are followed up for 30 days and then periodically thereafter for up to 5 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (pralatrexate, oxaliplatin) | Experimental | Other: Laboratory Biomarker Analysis, Drug: Oxaliplatin, Drug: PralatrexatePatients receive pralatrexate IV over 3-5 minutes and oxaliplatin IV over 2 hours on day 1. Courses repeat every 2 weeks in the absence of disease progression or unacceptable toxicity. Oxaliplatin will be discontinued after 12 courses. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Histologically confirmed carcinoma of the esophagus, stomach or gastro-esophageal junction that is metastatic, or locally advanced and inoperable for cure; histological sub-types permitted include adenocarcinoma, squamous-cell carcinoma, or undifferentiated carcinoma; small-cell carcinoma variant is not eligible
- No previous systemic therapy for metastatic or recurrent disease; therapy (chemotherapy, radiotherapy, or both) administered in the neo-adjuvant, adjuvant, or definitive setting for previously localized disease is permitted, provided it was completed more than 6 months prior to enrollment; palliative radiotherapy is permitted provided it is completed >= 3 weeks prior to study therapy initiation
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Life expectancy >= 12 weeks
- Hemoglobin >= 9 g/dl
Key exclusion criteria (6 listed)
- Hypersensitivity to platinum compounds
- Uncontrolled inter-current illness including but not limited to active infection, symptomatic congestive heart failure, unstable angina, uncontrolled cardiac arrhythmia, or psychiatric illness that would limit compliance with study requirements
- Presence of brain metastases
- Patients with third-space (pleural, peritoneal) fluid not controllable with usual drainage methods are not eligible
- History of second primary malignancy within 3 years prior to enrollment, except for in-situ cervix carcinoma or non-melanoma skin cancer
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Laboratory Biomarker AnalysisCorrelative studies | Other | Treatment (pralatrexate, oxaliplatin) |
| OxaliplatinAlso: 1-OHP, Dacotin, Dacplat, Diaminocyclohexane OxalatoplatinumGiven IV | Drug | Treatment (pralatrexate, oxaliplatin) |
| PralatrexateAlso: 10-propargyl-10-deazaaminopterin, Folotyn, PDXGiven IV | Drug | Treatment (pralatrexate, oxaliplatin) |
Primary outcome
Overall Response Rate
Time frame: Up to 5 years
Overall response rate to combination pralatrexate and oxaliplatin as assessed by Response Evaluation Criteria in Solid Tumors version 1.1. Objective responses will be confirmed 4 weeks after first documentation of response. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) 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.
3 secondary outcomes
Number of Participants With an Adverse Event
Time frame: Up to 30 days after the last dose of study drug(s)
Overall Survival (OS)
Time frame: From the date of study enrollment to the time of death from any cause, assessed up to 5 years
Time to Progression (TTP)
Time frame: From the date of study enrollment to the first observation of progressive disease, assessed up to 5 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Dec 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nikhil Khushalani principal investigator
Roswell Park Cancer Institute
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Laboratory Biomarker Analysis, Oxaliplatin and Pralatrexate in people with Adenocarcinoma of the Gastroesophageal Junction and Esophageal Undifferentiated Carcinoma, run by Roswell Park Cancer Institute at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Dec 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Dec 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Response Rate (time frame: Up to 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Dec 2017.