Trial of XELOX Followed by Radiation Combined With Carboplatin and RAD001 for Esophageal Cancer

March 14, 2019 updated by: Nabil F. Saba, Emory University

Phase I/IIB Study of Induction Chemotherapy With XELOX, Followed by Radiation Therapy and Dose Escalation of RAD001 in Patients With Esophageal Cancer

The purpose of this study is to test the drug RAD001 in combination with another chemotherapy drug, Carboplatin, as well as radiation therapy in the treatment of esophageal cancer. Because RAD001 has not been used in this combination before, it is not clear which dose will be best when used in combination.

The standard of care for patients who have esophageal cancer that has not moved to other areas of the body (non-metastatic) includes a combination of chemotherapy, radiation therapy and possibly surgery. If the patient chooses to participate in this study, the patient will receive chemotherapy and radiation therapy. The patient will possibly also have surgery to have the cancer removed. This decision will be made by the treating physicians. All of the chemotherapy the patient will receive on the study is considered standard chemotherapy for esophagus cancer. The investigators do not know as of yet if the drug called RAD001 will help improve the treatment for patients with this disease. RAD001 is a pill that has been used in many other types of cancer and has been proven to be effective in other cancers such as kidney cancer.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Esophageal cancer is the sixth most common cause of cancer-related death worldwide. Recent medical advances have led to small improvements in survival, but the overall rate of survival remains low, making new treatment approaches necessary.

Chemotherapy drugs and radiation therapy are often both used in treating esophageal cancer. The combination of oxaliplatin and capecitabine (XELOX) is a commonly used chemotherapy combination. Sometimes chemotherapy is given as an "induction" therapy, before the radiation is given.

The drug RAD001 is a targeted drug that acts specifically on a protein inside cells (called mTOR), which is important for cancer development. The combination of RAD001 and radiation therapy has been shown to improve anti-cancer effects.

This study will look for the ideal dose of RAD001 when given in combination with radiation therapy after induction chemotherapy with XELOX, and test the anticancer effects of this treatment approach in patients with esophageal cancer.

Study Type

Interventional

Enrollment (Actual)

17

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Georgia
      • Atlanta, Georgia, United States, 30308
        • Emory University Hospital Midtown
      • Atlanta, Georgia, United States, 30322
        • Emory University Winship Cancer Institute
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients must have histologically or cytologically confirmed squamous cell carcinoma or adenocarcinoma of the esophagus or gastroesophageal (GE) junction.
  • Patients can have disease that is resectable or unresectable.
  • Patients must not have had prior chemotherapy or radiation therapy for esophageal cancer.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
  • Age ≥ 18.

  • Adequate bone marrow, liver and renal function as assessed by the following:

    • Absolute neutrophil count (ANC) ≥ 1500/mm³.
    • Platelet count ≥ 100,000/mm³.
    • Total bilirubin ≤ 1.5 x upper limit of normal (ULN).
    • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN (≤ 5 x ULN for patients with liver involvement).
    • Creatinine ≤ 1.5 x ULN.
  • Fasting serum cholesterol ≤ 300 mg/dL OR ≤ 7.75 mmol/L AND 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.
  • Women of childbearing potential must have a negative pregnancy test prior to first receiving investigational product. Sexually active women of childbearing potential (WOCBP) must use an effective method of birth control during the course of the study, in a manner such that risk of failure is minimized. All WOCBP should be instructed to contact the Investigator immediately if they suspect they might be pregnant (e.g., missed or late menstrual period) at any time during study participation.
  • Patient must be willing to sign informed consent.

Exclusion Criteria:

  • Patients currently receiving other investigational agents.
  • Patients with known distant metastases.
  • Patients who have received prior treatment with an mammalian target of rapamycin (mTOR) inhibitor (sirolimus, temsirolimus, everolimus).
  • Patients with a known hypersensitivity to RAD001 (everolimus) or other rapamycins (sirolimus, temsirolimus) or to its excipients.
  • Known hypersensitivity to oxaliplatin, other platinum-containing compounds.
  • Patients with known brain metastases.
  • Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as a known history of HIV seropositivity.
  • History of active hepatitis B or C.
  • Co-administration with strong inhibitors of cytochrome P450 3A4 isoenzyme (CYP3A4) (e.g., ketoconazole, itraconazole, ritonavir) or P-glycoprotein (PgP).
  • Patients with an active, bleeding diathesis.
  • Patients with significant intercurrent medical illness (including New York Heart Association [NYHA] class III or IV heart disease, significant arrhythmias requiring medication, symptomatic coronary artery disease, myocardial infarction) within the previous 6 months.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: XELOX/Radiation/Carboplatin/RAD001
Patients receive XELOX comprising oxaliplatin intravenously (IV) over 120 minutes on day 1 and capecitabine orally (PO) twice daily (BID) on days 1-14. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients then undergo radiotherapy (RT) 5 days a week for up to 6 weeks. Patients also receive carboplatin IV over 15 minutes to 24 hours once weekly for 5-6 weeks and RAD001 PO every other day (QOD) or once daily (QD) for 5-6 weeks during radiation therapy (RT). Patients with resectable disease undergo surgery.
Drug: RAD001
Dose escalation for Phase I; dose for Phase II to be determined after Phase I is completed.
Other Names:
  • Everolimus
Drug: XELOX
Patients will receive two cycles of XELOX.
Other Names:
  • Oxaliplatin and capecitabine
  • Eloxatin and Xeloda
Drug: Carboplatin
Given on a 3 weeks on and 1 week off schedule.
Other Names:
  • Paraplatin
Radiation: Radiation
1.8 Gy to 36 Gy; 3 fields or laterals to 50.4 Gy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Phase I portion to determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of RAD001 in combination with radiation
Time Frame: within one month after surgery
within one month after surgery

Secondary Outcome Measures

Outcome Measure
Time Frame
Rate of surgical pathologic complete remission (pCR) (absence of evidence of cancer after surgery)
Time Frame: within one month from surgery
within one month from surgery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Emory University

Collaborators

Novartis

Investigators

  • Principal Investigator: Nabil F. Saba, MD, Emory University Winship Cancer Institute

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 1, 2012

Primary Completion (Actual)

February 1, 2019

Study Completion (Actual)

February 1, 2019

Study Registration Dates

First Submitted

October 25, 2011

First Submitted That Met QC Criteria

December 12, 2011

First Posted (Estimate)

December 13, 2011

Study Record Updates

Last Update Posted (Actual)

March 15, 2019

Last Update Submitted That Met QC Criteria

March 14, 2019

Last Verified

March 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB00047026
  • WCI1871-10 (Other Identifier: Other)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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