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Stage IB Esophageal AdenocarcinomaPhase 2NCT02392377

Molecular Phenotyping in Predicting Response in Patients With Stage IB-III Esophageal Cancer Receiving Combination Chemotherapy

A Phase 2 study testing Paclitaxel, Carboplatin and Oxaliplatin in people with Stage IB Esophageal Adenocarcinoma and Stage IIA Esophageal Adenocarcinoma, run by Case Comprehensive Cancer Center at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This randomized pilot phase II trial studies how well molecular phenotyping works in predicting response in patients with stage IB-III esophageal cancer who are receiving carboplatin and paclitaxel or oxaliplatin, leucovorin calcium, and fluorouracil. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Paclitaxel, Carboplatin and Oxaliplatin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1 participants
Where
1 siteUnited States
Study dates
Feb 2015to Dec 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

  • Patients must have histologically or cytologically confirmed localized (T1N1-3M0 or T2-4NanyM0, stage IB-III) Siewert type 1 or type 2 esophageal adenocarcinoma that is amenable to surgical resection as determined by a thoracic surgeon and for which all disease (primary tumor and involved lymph nodes) can be treated with radiation, as determined by a radiation oncologist
  • Patients may not have received any prior chemotherapy, biologic therapy or radiation therapy for management of their disease; chemotherapy or biologic therapy administered for treatment of another primary malignancy are permitted if treatment was greater than 5 years ago
  • Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Patients must have a life expectancy of > 3 months, in the opinion of and as documented by the investigator
  • Hemoglobin >= 10.0 g/dl
  • Absolute neutrophil count >= 1,500/mcL
Show all 15Show fewer
  • Platelet count >= 100,000/mcL
  • Total bilirubin within normal institutional limits
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =< 2.5 X institutional upper limit of normal
  • Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal
  • Serum creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal (as calculated by Cockcroft-Gault)
  • Patients must have an avid primary tumor with an standardized uptake value (SUV) of >= 5 on baseline (18F) FDG-PET/computed tomography (CT) imaging
  • Men must agree to use adequate contraception (double barrier method of birth control or abstinence) 1 week prior to study entry, for the duration of study participation and for 1 month after completing combined modality treatment with chemotherapy and radiation; should a male patient's female partner become pregnant or suspect that she is pregnant while her partner is participating in this study, the treating physician should be informed immediately
  • Patients must have the ability to understand and the willingness to sign a written informed consent document
  • This study will be limited to enrollment of Caucasian males only

Who cannot join

  • Patients who are receiving any chemotherapy, biologic therapy, radiation therapy or any investigational agent
  • Patients with metastatic disease
  • Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to platinums, taxanes or fluoropyrimidines
  • Patients who have previously received radiation therapy to the chest or abdomen such that there would be overlap between the previous and current radiation field
  • Patients with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Patients with human immunodeficiency virus (HIV) whom are not receiving antiretroviral therapy
  • Patients with another malignancy within the past 5 years

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Case Comprehensive Cancer Center

    Cleveland, Ohio, 44106-5065

Other trials in United States

About this study

Official title: Pilot Study of Correlation Between Molecular Phenotype and Response to Two Independent Treatment Regimens, Carboplatin and Paclitaxel vs. 5-Fluorouracil and Oxaliplatin Chemotherapy in Patients With Localized Esophageal Adenocarcinoma

This randomized pilot phase II trial studies how well molecular phenotyping works in predicting response in patients with stage IB-III esophageal cancer who are receiving carboplatin and paclitaxel or oxaliplatin, leucovorin calcium, and fluorouracil. Studying the genes in a patients tumor cells before and after chemotherapy may help in understanding if there are specific features of the tumor cells that make a person more or less likely to respond to treatment and how these features may be affected by treatment.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To evaluate gene and micro ribonucleic acid (miRNA) expression levels in patients with esophageal adenocarcinoma prior to receiving chemotherapy and identify relative expression differences between patients responding and not responding to treatment with carboplatin and paclitaxel or 5-fluorouracil (fluorouracil) and oxaliplatin as measured by fluorodeoxyglucose F-18 ([18F] FDG)-positron emission tomography (PET).

SECONDARY OBJECTIVES:

  1. To evaluate the impact of treatment on expression patterns of both genes and miRNAs in patients with esophageal adenocarcinoma following treatment with either carboplatin and paclitaxel or 5-fluorouracil and oxaliplatin, and identify expression patterns associated with treatment response and resistance as assessed by (18F) FDG-PET.

II. To evaluate the expression patterns of genes and miRNAs in patients with esophageal adenocarcinoma prior to and following a full neoadjuvant combined-modality treatment program with either carboplatin and paclitaxel or 5-fluorouracil and oxaliplatin chemotherapy plus radiation, and identify relative expression differences between patients achieving a pathologic complete response and patients not achieving a pathologic complete response.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I:

INDUCTION: Patients receive carboplatin (IV) and paclitaxel intravenously (IV) on days 1 and 8 of a 21 day cycle for two cycles (total of 6 weeks).

CHEMORADIATION THERAPY: Patients receive carboplatin (AUC=2) and paclitaxel (50 mg/m2) intravenously once weekly for five weeks throughout the duration of their radiation which is daily (Monday through Friday). This will be given in combination with radiation therapy to a total of 50.4Gy using 180cGy fractions.

ARM II:

INDUCTION: Patients receive mFOLFOX6 where they get oxaliplatin 85 mg/m2 intravenously on day 1, leucovorin 400 mg/m2 IV on day 1, 5-FU 400 mg/m2 IV on day 1 and then 5FU at 2400 mg/m2 IV to be administered over a 46 hour period. This is repeated every 2 weeks for 3 cycles (total of 6 weeks).

CHEMORADIATION THERAPY: Patients receive chemoradiation with oxaliplatin 85 mg/m2 IV on day 1 every 2 weeks for a total of 3 cycles (6 weeks) as well as 5FU 300 mg/m2/day over 96 hours via continuous infusion each week of radiation for a total of 6 weeks. This will be given in combination with radiation therapy to a total of 50.4Gy using 180cGy fractions.

SURGERY: In both arms, approximately 4-10 weeks after completion of chemoradiation therapy, patients undergo esophagectomy at the discretion of the treating team.

After completion of study treatment, patients are followed up at 30 days and then periodically thereafter.

Medical subject headings
Adenocarcinoma Of Esophagus

What participants receive

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

Study groups in NCT02392377
Study groupRoleWhat they receive
Arm I (paclitaxel, carboplatin, radiation therapy, surgery)ExperimentalINDUCTION: Patients receive chemotherapy with carboplatin and paclitaxel. Patients receive carboplatin (AUC=2) and paclitaxel (90 mg/m2) intravenously on days 1 and 8 of a 21 day treatment cycle for two cycles (total of 6 weeks). CHEMORADIATION THERAPY: Patients receive carboplatin (AUC=2) and paclitaxel (50 mg/m2) intravenously once weekly for five weeks throughout the duration of their radiation which is daily (Monday through Friday). SURGERY: Approximately 4-10 weeks after completion of chemoradiation therapy, patients undergo esophagectomy at the discretion of the treating team.
Receives: Drug: Paclitaxel; Drug: Carboplatin; Radiation: Radiation Therapy; Procedure: Therapeutic Conventional Surgery; Other: Laboratory Biomarker Analysis
Arm II (combination chemotherapy, radiation therapy, surgery)ExperimentalINDUCTION: Patients receive mFOLFOX6 where they get oxaliplatin 85 mg/m2 intravenously on day 1, leucovorin 400 mg/m2 IV on day 1, 5-FU 400 mg/m2 IV on day 1 and then 5FU at 2400 mg/m2 IV to be administered over a 46 hour period. This is repeated every 2 weeks for 3 cycles (total of 6 weeks). CHEMORADIATION THERAPY: Patients receive oxaliplatin 85 mg/m2 IV on day 1 every 2 weeks for a total of 3 cycles (6 weeks) as well as 5FU 300 mg/m2/day over 96 hours via continuous infusion each week of radiation for a total of 6 weeks. SURGERY: Approximately 4-10 weeks after completion of chemoradiation therapy, patients undergo esophagectomy at the discretion of the treating team.
Receives: Drug: Oxaliplatin; Drug: Leucovorin Calcium; Drug: Fluorouracil; Radiation: Radiation Therapy; Procedure: Therapeutic Conventional Surgery; Other: Laboratory Biomarker Analysis

What is being measured

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

  1. Relative Expression Differences in Individual Genes and Gene Profiles Between Patients Responding and Not Responding to Treatment, as Assessed by (18F) FDG-PET

    Baseline gene profiles will be compared for 10 (18F) FDG-PET responders vs. 15 (18F) FDG-PET non-responders per treatment regimen using a t-test and p-values will be corrected for multiple comparisons by calculating the false discovery rate (FDR) p-value (filtering on a FDR p-value < 0.05). Top genes identified will be tested in combination for their sensitivity and specificity using logistic regression models.

    Measured: Baseline

  2. Relative Expression Differences in Individual microRNAs and microRNA Profiles Between Patients Responding and Not Responding to Treatment, Assessed by (18F) FDG-PET

    Baseline microRNA profiles will be compared for 10 (18F) FDG-PET responders vs. 15 (18F) FDG-PET non-responders per treatment regimen using a t-test and p-values will be corrected for multiple comparisons by calculating the FDR p-value (filtering on a FDR p-value < 0.05). Top microRNAs identified will be tested in combination for their sensitivity and specificity using logistic regression models.

    Measured: Baseline

  3. Biological Pathway Perturbation Upon Exposure to Chemotherapy

    Predefined signatures of biological pathway activities will be evaluated in order to identify pathway perturbation upon exposure to chemotherapy. Significant pathway modulations upon brief exposure will then be evaluated for association with clinical response using non-parametric tests such as the Wilcoxon signed-rank test. In all cases, statistical correction to account for multiple hypothesis testing will be employed and pathways with a false discovery rate of 10% or lower will be considered as significant.

    Measured: Up to 6 weeks

Secondary outcomes (7)

  1. Relative Expression Differences Between Baseline and Post-induction Chemotherapy Specimens of Individual Genes and Gene Expression Profiles

    Changes in baseline and post-treatment gene expression levels will be calculated between (18F) FDG-PET responders and non-responders, filtering for expression level changes of >= 0.20. Differences in expression level change per treatment regimen will be calculated using a t-test and p-values will be corrected for multiple comparisons by calculating FDR p-value (filtering on a FDR p-value < 0.05). Top genes identified will be tested in combination for their sensitivity and specificity using logistic regression models to predict responsiveness or resistance to each individual treatment regimen.

    Measured: Baseline to post-induction (36-43 days)

  2. Relative Expression Differences Between Baseline and Post-induction Chemotherapy Specimens of Individual microRNAs and microRNA Profiles

    Changes in baseline and post-treatment microRNA levels will be calculated between (18F) FDG-PET responders and non-responders, filtering for expression level changes of >= 0.20. Differences in expression level change per treatment regimen will be calculated using a t-test and p-values will be corrected for multiple comparisons by calculating FDR p-value (filtering on a FDR p-value < 0.05). Top microRNAs identified will be tested in combination for their sensitivity and specificity using logistic regression models to predict responsiveness or resistance to each individual treatment regimen.

    Measured: Baseline to post-induction (36-43 days)

  3. Relative Expression Differences in Baseline Individual Genes and Gene Expression Profiles Between Patients Achieving and Not Achieving a Pathologic Complete Response Following Treatment

    Baseline gene expression profiles for 8 pathologic complete responders vs. 17 patients not achieving a pathologic complete response per treatment regimen using a t-test will be compared. Top genes will be tested in combination for their sensitivity and specificity using logistic regression models to predict achievement of a pathologic complete response vs. patients not achieving a pathologic complete response.

    Measured: Baseline

  4. Relative Expression Differences in Baseline Individual microRNAs and microRNA Profiles Between Patients Achieving and Not Achieving a Pathologic Complete Response Following Treatment

    Baseline microRNA profiles for 8 pathologic complete responders vs. 17 patients not achieving a pathologic complete response per treatment regimen using a t-test will be compared. Top microRNAs will be tested in combination for their sensitivity and specificity using logistic regression models to predict achievement of a pathologic complete response vs. patients not achieving a pathologic complete response.

    Measured: Baseline

  5. Relative Expression Differences Between Baseline and Post-induction Gene Expression Levels/Profiles Between Patients Achieving and Not Achieving a Pathologic Complete Response Following Treatment

    Changes in baseline and post-treatment gene expression level/profiles will be compared between 8 pathologic responders vs. 17 patients not achieving a pathologic complete response per treatment regimen, filtering for expression levels changes of 0.20 and above. Differences in expression level changes per treatment regimen will be calculated using a t-test. Top genes will be tested in combination for their sensitivity and specificity using logistic regression models to predict achievement of a pathologic complete response vs. patients not achieving a pathologic complete response.

    Measured: Baseline to post-induction (36-43 days)

  6. Relative Expression Differences Between Baseline and Post-induction microRNA Levels/Profiles Between Patients Achieving and Not Achieving a Pathologic Complete Response Following Treatment

    Changes in baseline and post-treatment microRNA level/profiles will be compared between 8 pathologic responders vs. 17 patients not achieving a pathologic complete response per treatment regimen, filtering for expression levels changes of 0.20 and above. Differences in expression level changes per treatment regimen will be calculated using a t-test. Top microRNAs will be tested in combination for their sensitivity and specificity using logistic regression models to predict achievement of a pathologic complete response vs. patients not achieving a pathologic complete response.

    Measured: Baseline to post-induction (36-43 days)

  7. Occurrence of Grade 3 or 4 Toxicity Per the National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.0

    Toxicities will be summarized as the percentage of patients experiencing each type and grade of event according to treatment group. Patients who receive at least one dose of treatment will be included in the analysis.

    Measured: Up to 30 days after the end of treatment

Timeline

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

  1. First posted19 Mar 2015 (estimated)
  2. Study startFeb 2015
  3. Primary completionDec 2015
  4. Study completionDec 2015

Why it stopped: Slow accrual

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
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
1 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02392377
Sponsor's protocol ID
CASE9314
Other IDs
NCI-2015-00034, CASE 9314, K12CA076917, P50CA150964, P30CA043703
Status last verified
Jan 2018
First submitted
13 Mar 2015
Last updated
13 Feb 2018
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Paclitaxel, Carboplatin and Oxaliplatin in people with Stage IB Esophageal Adenocarcinoma and Stage IIA Esophageal Adenocarcinoma, run by Case Comprehensive Cancer Center at 1 site 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 15 inclusion and 7 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: stopped early, as of the sponsor's last update on 13 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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 Feb 2018). 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?

Relative Expression Differences in Individual Genes and Gene Profiles Between Patients Responding and Not Responding to Treatment, as Assessed by (18F) FDG-PET (time frame: Baseline). The study lists 3 primary outcomes in all. 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 NCT02392377.

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 Feb 2018.

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