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Adenocarcinoma of the EsophagusPhase 1/2NCT01231399

Everolimus and Combination Chemotherapy in Treating Patients With Metastatic Stomach or Esophageal Cancer

A Phase 1/2 study testing fluorouracil, leucovorin calcium and oxaliplatin in people with Adenocarcinoma of the Esophagus and Adenocarcinoma of the Gastroesophageal Junction, run by City of Hope Medical Center at 3 sites in United States.

Completed

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

Official record
Search all trials

Trial summary

RATIONALE: Everolimus may stop the growth of stomach or esophageal cancer by blocking blood flow to the tumor. Drugs used in chemotherapy, such as leucovorin calcium, fluorouracil, and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing… Read more about this study

Who is it for?
Ages 19 years and older
What is being tested?
fluorouracil, leucovorin calcium and oxaliplatin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
6 participants
Where
3 sitesUnited States
Study dates
Feb 2012to Jul 2016
Phase
Phase 1/2
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 19 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must have histologically confirmed diagnosis of gastric, esophageal, and GEJ adenocarcinoma
  • Patients must have metastatic disease
  • Patients must not have received any chemotherapy for metastatic disease
  • Patients may have received prior adjuvant chemotherapy; completion of chemotherapy must be greater than 6 months from date of recurrent disease
  • Patients must have computed tomography (CT) or magnetic resonance imaging (MRI) scan; patients must have at least one measurable site of disease according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria that has not been previously irradiated; if the patient has had previous radiation to the marker lesion(s), there must be evidence of progression since the radiation
  • Patients must have a ECOG Performance Status of 0-1
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  • Absolute neutrophil count (ANC) > 1,500/mcl
  • Platelet count > 100,000/mcl
  • Hemoglobin (Hg) > 9 g/dL
  • Serum creatinine < 1.5 mg/dl and/or Creatinine clearance > 60 cc/min
  • Bilirubin < 1.5 mg/dl
  • Serum glutamic oxaloacetic transaminase (SGOT) and/or serum glutamic pyruvic transaminase (SGPT) =< 2.5 x institutional upper limit of normal (IULN) (=< 5 x upper limit of normal [ULN] in patients with liver metastases)
  • Fasting serum cholesterol =< 300 mg/dL or =< 7.75 mmol/L
  • Fasting triglycerides =< 2.5 x ULN; NOTE: in case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication
  • Patients should have controlled diabetes as evidenced by hemoglobin (Hb)A1C =< 8%
  • International normalized ratio (INR) and partial thromboplastin time (PTT) =< 1.5; (anticoagulation is allowed if target INR =< 1.5 on a stable dose of warfarin or on a stable dose of low molecular weight [LMW] heparin for > 2 weeks at time of randomization)
  • Due to the possibility of harm to a fetus or nursing infant from this treatment regimen, patients must not be pregnant or nursing (or plan to become pregnant); women and men of reproductive potential must have agreed to use a highly effective contraceptive method for at least 8 weeks after treatment
  • Patients with risk factors for contraction hepatitis B or C should undergo screening prior to treatment on protocol. Patients with detectable viral titers are required to receive treatment for 4 weeks prior to starting protocol therapy.
  • Patients must be able to swallow pills
  • No other prior malignancy within the past 3 years is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for five years
  • All patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines
  • Patients must have pathology specimen available for submission

Who cannot join

  • Patients currently receiving anticancer therapies or who have received anticancer therapies within 4 weeks of the start of study drug (including chemotherapy, radiation therapy, antibody based therapy, etc)
  • Patients who have received prior treatment with an mammalian target of rapamycin (mTOR) inhibitor (sirolimus, temsirolimus, everolimus)
  • Patients with a known hypersensitivity to everolimus or other rapamycins (sirolimus, temsirolimus) or to its excipients
  • Patients, who have had a major surgery or significant traumatic injury within 4 weeks of start of study drug, patients who have not recovered from the side effects of any major surgery (defined as requiring general anesthesia) or patients that may require major surgery during the course of the study
  • Prior treatment with any investigational drug within the preceding 4 weeks
  • Patients receiving chronic, systemic treatment with corticosteroids (prednisone > 10 mg per day) or another immunosuppressive agent; topical or inhaled corticosteroids are allowed
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  • Patients should not receive immunization with attenuated live vaccines within one week of study entry or during study period
  • Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases
  • Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
  • Symptomatic congestive heart failure of New York heart Association Class III or IV
  • Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease
  • Severely impaired lung function as defined as spirometry and diffusion lung capacity of carbon monoxide (DLCO) that is 50% of the normal predicted value and/or 02 saturation that is 88% or less at rest on room air
  • Uncontrolled diabetes as defined by fasting serum glucose > 1.5 x ULN
  • Active (acute or chronic) or uncontrolled severe infections
  • Liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis
  • A known history of human immunodeficiency virus (HIV) seropositivity
  • Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of everolimus (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection)
  • Patients with an active, bleeding diathesis; history of noncompliance to medical regimens
  • Patients unwilling to or unable to comply with the protocol

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • City of Hope Medical Center

    Duarte, California, 91010

  • South Pasadena Cancer Center

    South Pasadena, California, 91030

  • H. Lee Moffitt Cancer Center and Research Institute

    Tampa, Florida, 33612

Other trials in United States

About this study

Official title: Phase Ib Trial of mFOLFOX6 and Everolimus (NSC-733504) in Patients With Metastatic Gastroesophageal Adenocarcinoma

RATIONALE: Everolimus may stop the growth of stomach or esophageal cancer by blocking blood flow to the tumor. Drugs used in chemotherapy, such as leucovorin calcium, fluorouracil, and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing, or by stopping them from spreading. Giving everolimus together with combination chemotherapy may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of everolimus when given together with combination chemotherapy in treating patients with metastatic stomach or esophageal cancer that has spread to other places in the body.

Read the detailed description

OBJECTIVES:

  1. To determine the maximum tolerated dose of everolimus to use in combination with mFOLFOX6 [oxaliplatin, leucovorin (leucovorin calcium), 5-FU (fluorouracil)].

II. To better describe the toxicities associated with the combination of everolimus with mFOLFOX6.

III. To assess response rate and progression-free survival in this patient population.

IV. To assess overall survival in patients with metastatic gastric, esophageal and gastroesophageal junction (GEJ) adenocarcinoma treated with the combination of mFOLFOX6 + everolimus.

OUTLINE: This is a dose-escalation study of everolimus. Patients receive fluorouracil intravenously (IV) continuously over 46 hours, leucovorin calcium IV over 2 hours, and oxaliplatin IV over 2 hours on day 1. Patients also receive oral everolimus once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically for 1 year.

Being tested
fluorouracil, leucovorin calcium, oxaliplatin, everolimus, laboratory biomarker analysis
Medical subject headings
Adenocarcinoma Of Esophagus, Esophageal Neoplasms, Stomach Neoplasms

What participants receive

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

  • fluorouracilDrug

    Also called 5-fluorouracil, 5-Fluracil, 5-FU, Adrucil

    Given IV

  • leucovorin calciumDrug

    Also called calcium folinate, CF, CFR, citrovorum factor

    Given IV

  • oxaliplatinDrug

    Also called 1-OHP, Dacotin, Dacplat, diaminocyclohexane oxalatoplatinum

    Given IV

  • everolimusDrug

    Also called 42-O-(2-hydroxy)ethyl rapamycin, Afinitor, RAD001

    Given orally

  • laboratory biomarker analysisOther

    Correlative studies

  • immunohistochemistry staining methodOther

    Also called immunohistochemistry

    Correlative studies

  • microarray analysisGenetic

    Also called gene expression profiling

    Correlative studies

Study groups in NCT01231399
Study groupRoleWhat they receive
Arm IExperimentalPatients receive fluorouracil IV continuously over 46 hours, leucovorin calcium IV over 2 hours, and oxaliplatin IV over 2 hours on day 1. Patients also receive oral everolimus once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: fluorouracil; Drug: leucovorin calcium; Drug: oxaliplatin; Drug: everolimus; Other: laboratory biomarker analysis; Other: immunohistochemistry staining method; Genetic: microarray analysis

What is being measured

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

  1. Maximum Tolerated Dose (MTD) of Everolimus

    The highest dose tested in which fewer than 33% of patients experience an attributable DLT to the study drug, when at least 6 patients are treated at that dose and are evaluable for toxicity. Toxicities will be assessed using Common Terminology Criteria for Adverse Events (CTCAE) v4.0.

    Measured: Course 1 (first 28 days)

  2. Number of Subject With 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

    Measured: Up to 5 years

  3. Progression-free Survival

    Estimated using the product-limit method of Kaplan and Meier. From the date treatment started until the date of first documented progression or date of death from any cause, whichever came first. 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.

    Measured: up to 5 years

  4. Overall Survival

    Estimated using the product-limit method of Kaplan and Meier. From the date treatment started until the date of death from any cause.

    Measured: 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.

  1. First posted1 Nov 2010 (estimated)
  2. Study startFeb 2012
  3. Primary completionJul 2016
  4. Study completionJul 2016

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
6 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01231399
Sponsor's protocol ID
10064
Other IDs
NCI-2010-02168
Status last verified
Apr 2017
First submitted
28 Oct 2010
Last updated
31 May 2017
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing fluorouracil, leucovorin calcium and oxaliplatin in people with Adenocarcinoma of the Esophagus and Adenocarcinoma of the Gastroesophageal Junction, run by City of Hope Medical Center at 3 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 22 inclusion and 19 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 31 May 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 31 May 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?

Maximum Tolerated Dose (MTD) of Everolimus (time frame: Course 1 (first 28 days)). The study lists 4 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 NCT01231399.

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 31 May 2017; AzTrials last refreshed its copy on 8 Nov 2026.

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