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Stomach NeoplasmsPhase 2NCT00515216

Pharmacogenomically Selected Treatment for Gastric and Gastroesophageal Junction (GEJ) Tumors

A Phase 2 study testing 5-fluorouracil, Oxaliplatin and Leucovorin in people with Stomach Neoplasms and Esophageal Neoplasms, run by Vanderbilt University at 4 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This study is for patients who have stomach cancer or cancer of the lower part of the esophagus that has spread to other organs. There are many different chemotherapy treatments for this type of cancer. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Stomach Neoplasms, Esophageal Neoplasms
What is being tested?
5-fluorouracil, Oxaliplatin and Leucovorin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
26 participants
Where
4 sitesUnited States
Study dates
Aug 2007to Nov 2013
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

  • Patients must have histologically or cytologically confirmed adenocarcinoma of the stomach or gastroesophageal junction.
  • Patients must have measurable disease.
  • No prior therapy for metastatic disease. Prior neo-adjuvant or adjuvant therapy is permitted if the disease free interval has been longer than 6 months.
  • Age ≥18 years.
  • Life expectancy of greater than 3 months.
  • ECOG (Eastern Cooperative Oncology Group) performance status greater than 2 (Karnofsky greater than 60%).
Show all 9Show fewer
  • Patients must have normal organ and marrow function.
  • Not pregnant. Not breast feeding.
  • Ability to understand and the willingness to sign a written informed consent document.

Who cannot join

  • Patients may not be receiving any other chemotherapy agents.
  • Patients with known active brain metastases. Patients with treated brain metastases are permitted if stable off steroids for at least 30 days.
  • History of allergic reactions to 5-FU or oxaliplatin.
  • Uncontrolled intercurrent illness.
  • Patients with immune deficiency.

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35294

  • University of North Carolina

    Chapel Hill, North Carolina, 27599

  • Vanderbilt University Medical Center

    Nashville, Tennessee, 37232

  • Washington University School of Medicine

    St Louis, Missouri, 63110

Other trials in United States

About this study

Official title: Pharmacogenomically Selected Treatment for Gastric and Gastroesophageal (GEJ) Tumors: A Phase II Study

This study is for patients who have stomach cancer or cancer of the lower part of the esophagus that has spread to other organs. There are many different chemotherapy treatments for this type of cancer. At the present time, there is no general agreement on the way to choose the most beneficial therapy for an individual patient. Patients with different genetic backgrounds may respond differently to the same chemotherapy treatments. In this study the investigators will use a certain genetic difference in an important gene (thymidylate synthase or TS gene) to see whether treating patients who have a particular type of that gene will respond better to a standard chemotherapy regimen. The investigators are hoping that by treating patients according to their genes, that they may respond to treatment of their cancer better and it will help the investigators choose cancer treatments better in the future.

Read the detailed description

Gastric and gastroesophageal junction (GEJ) cancers are a leading cause of cancer mortality. Despite the development of newer chemotherapies, the response rates and median survival in patients with these tumors has remained essentially stagnant. Defining host and molecular/biologic tumor characteristics to customize treatment may lead to improved survival outcomes. Retrospective studies have identified genetic markers that predict treatment outcome. However, there have been no prospective studies in gastric and GEJ cancer evaluating the clinical utility of these genetic factors. We hypothesize that genomically based treatment will improve the expected response rate in patients with gastric and GEJ cancers. We propose a prospective, multi-institutional Phase II clinical trial testing a germline polymorphism in the thymidylate synthase (TS) gene, the number of tandem repeats in the TS enhancer region (TSER) as a treatment selection marker. The polymorphic variant conferring three tandem repeats (TSER*3) has been associated with 5-FU resistance due to high tumor TS expression in comparison to the TSER*2 variant (two tandem repeats). The TSER*3 polymorphism is common (allelic frequency of 0.5-0.8). In the proposed study, we will prospectively genotype patients with gastric and GEJ cancers. Patients who are expected to be 5-FU sensitive (carrying a TSER*2 allele) will receive a 5-FU containing regimen (5-FU, leucovorin, oxaliplatin). Patients who are expected to be 5-FU resistant (homozygous for TSER*3) will not be included in the study. In completing this study, we will determine whether treatment selection based on germline TSER polymorphism status improves the response rate in patients with metastatic gastric and GEJ tumors. Additional correlative studies are proposed to identify confounding factors that may alter the expected outcomes of this treatment approach.

Keywords
Phase II, Gastric cancer, Gastroesophageal cancer, Metastatic, FOLFOX, Thymidylate synthase, Pharmacogenomic
Medical subject headings
Stomach Neoplasms, Esophageal Neoplasms, Neoplasm Metastasis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 5-fluorouracilDrug

    Also called 5-FU, Fluorouracil

  • OxaliplatinDrug

    Also called Eloxatin

  • LeucovorinDrug

    Also called Wellcovorin, citrovorum factor, folinic acid, 5-formyl tetrahydrofolate

Study groups in NCT00515216
Study groupRoleWhat they receive
Oxaliplatin/Leucovorin/5-FUExperimental"Good risk" patients with the TSER*2/*2 or *2/*3 genotype or low TS expression genotype received treatment of oxaliplatin, leucovorin given over 2 hours along with 5-FU given as intravenous push followed by 5-FU given as intravenous infusion of 46 hours. This treatment was repeated every 2 weeks.
Receives: Drug: 5-fluorouracil; Drug: Oxaliplatin; Drug: Leucovorin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall Response Rate (ORR)

    • ORR = complete response + partial response
    • Complete response - disappearance of all target and non-target lesions
    • Partial response - at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter

    Measured: 2 years

Secondary outcomes (18)

  1. Overall Survival

    Measured: 4 years

  2. Progression-free Survival (PFS)

    Progressive disease - at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions

    Measured: 4 years

  3. Disease Control Rate (DCR)

    DCR - complete response, partial response, and stable disease

    • Complete response - disappearance of all target and non-target lesions
    • Partial response - at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter
    • Stable disease - neither sufficient shrinkage to qualify for partial response not sufficient increase to qualify for progressive disease

    Measured: 2 years

  4. Tumor Specific Changes That May Alter Treatment Outcomes

    Measured: 4 years

  5. Genetic Polymorphisms That May Alter Treatment Outcomes (Partial Response)

    This outcome looks at what genotypes of the TYMS 5'-UTR TSER + G>C (rs34743033) gene had a partial tumor response.

    Measured: 4 years

  6. Genetic Polymorphisms That May Alter Treatment Outcomes (Partial Response)

    This outcome looks at what genotypes of the TYMS 3'-UTR 1494delTTAAAG(6 bp) (rs34489327) gene had a partial tumor response.

    Measured: 4 years

  7. Genetic Polymorphisms That May Alter Treatment Outcomes (Partial Response)

    This outcome looks at what genotypes of the ERCC1 c.354C>T (rs11615) gene had a partial tumor response.

    Measured: 4 years

  8. Genetic Polymorphisms That May Alter Treatment Outcomes (Partial Response)

    This outcome looks at what genotypes of the ERCC2 c.2251A>C (rs13181) gene had a partial response.

    Measured: 4 years

  9. Genetic Polymorphisms That May Alter Treatment Outcomes (Partial Response)

    This outcome looks at what genotypes of the GSTP1 c.313A>G (rs1695) gene had a partial response.

    Measured: 4 years

  10. Genetic Polymorphisms That May Alter Treatment Outcomes (Partial Response)

    This outcome looks at what genotypes of the XRCC1 c.1196G>A (rs25487) gene had a partial response.

    Measured: 4 years

  11. Genetic Polymorphisms That May Alter Treatment Outcomes (Partial Response)

    This outcome looks at what genotypes of the MDR1 c.3435C>T (rs1045642) gene had a partial response.

    Measured: 4 years

  12. Genetic Polymorphisms That May Alter Treatment Outcomes (Stable Disease)

    This outcome looks at what genotypes of the TYMS 5'-UTR TSER + G>C (rs34743033) gene had stable disease.

    Measured: 4 years

  13. Genetic Polymorphisms That May Alter Treatment Outcomes (Stable Disease)

    This outcome looks at what genotypes of the TYMS 3'-UTR 1494delTTAAAG(6 bp) (rs34489327) gene had stable disease.

    Measured: 4 years

  14. Genetic Polymorphisms That May Alter Treatment Outcomes (Stable Disease)

    This outcome looks at what genotypes of the ERCC1 c.354C>T (rs11615) gene had stable disease.

    Measured: 4 years

  15. Genetic Polymorphisms That May Alter Treatment Outcomes (Stable Disease)

    This outcome looks at what genotypes of the ERCC2 c.2251A>C (rs13181) gene had stable disease.

    Measured: 4 years

  16. Genetic Polymorphisms That May Alter Treatment Outcomes (Stable Disease)

    This outcome looks at what genotypes of the GSTP1 c.313A>G (rs1695) gene had stable disease.

    Measured: 4 years

  17. Genetic Polymorphisms That May Alter Treatment Outcomes (Stable Disease)

    This outcome looks at what genotypes of the XRCC1 c.1196G>A (rs25487) gene had stable disease.

    Measured: 4 years

  18. Genetic Polymorphisms That May Alter Treatment Outcomes (Stable Disease)

    This outcome looks at what genotypes of the MDR1 c.3435C>T (rs1045642) gene had stable disease.

    Measured: 4 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Aug 2007 (estimated)
  2. Study startAug 2007
  3. Primary completionAug 2011
  4. Study completionNov 2013

Resources

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
26 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00515216
Sponsor's protocol ID
070433
Other IDs
R21CA123881
Status last verified
Dec 2015
First submitted
9 Aug 2007
Last updated
7 Jan 2016
Data monitoring committee
No

Publications

  • Goff LW, Thakkar N, Du L, Chan E, Tan BR, Cardin DB, McLeod HL, Berlin JD, Zehnbauer B, Fournier C, Picus J, Wang-Gillam A, Lee W, Lockhart AC. Thymidylate synthase genotype-directed chemotherapy for patients with gastric and gastroesophageal junction cancers. PLoS One. 2014 Sep 18;9(9):e107424. doi: 10.1371/journal.pone.0107424. eCollection 2014.

    PubMed 25232828

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing 5-fluorouracil, Oxaliplatin and Leucovorin in people with Stomach Neoplasms and Esophageal Neoplasms, run by Vanderbilt University at 4 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 9 inclusion and 5 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 7 Jan 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 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 27 Feb 2015). 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 (ORR) (time frame: 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00515216, which also lists 1 linked publication.

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 7 Jan 2016.

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