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

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2015 by Emory University
Sponsor:
Collaborator:
Novartis
Information provided by (Responsible Party):
Nabil F. Saba, Emory University
ClinicalTrials.gov Identifier:
NCT01490749
First received: October 25, 2011
Last updated: February 19, 2015
Last verified: February 2015
  Purpose

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.


Condition Intervention Phase
Esophageal Cancer
Neoplasms, Esophageal
Drug: RAD001
Drug: XELOX
Drug: Carboplatin
Radiation: Radiation
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/IIB Study of Induction Chemotherapy With XELOX, Followed by Radiation Therapy and Dose Escalation of RAD001 in Patients With Esophageal Cancer

Resource links provided by NLM:


Further study details as provided by Emory University:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Rate of surgical pathologic complete remission (pCR) (absence of evidence of cancer after surgery) [ Time Frame: within one month from surgery ] [ Designated as safety issue: No ]

Estimated Enrollment: 63
Study Start Date: February 2012
Estimated Study Completion Date: May 2016
Estimated Primary Completion Date: February 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: Paraplatin
Radiation: Radiation
1.8 Gy to 36 Gy; 3 fields or laterals to 50.4 Gy.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01490749

Contacts
Contact: Nabil F. Saba, MD 404-778-1842 nfsaba@emory.edu

Locations
United States, Georgia
Emory University Hospital Midtown Recruiting
Atlanta, Georgia, United States, 30308
Contact: Rachel Lowrie    404-778-1842    ralowri@emory.edu   
Emory University Winship Cancer Institute Recruiting
Atlanta, Georgia, United States, 30322
Contact: Rachel Lowrie    404-778-1842    ralowri@emory.edu   
Principal Investigator: Nabil F. Saba, MD         
United States, Tennessee
Vanderbilt University Recruiting
Nashville, Tennessee, United States, 37232
Contact: Anuradha Chakravarthy, MD    615-322-2555      
Principal Investigator: Anuradha Chakravarthy, MD         
Sponsors and Collaborators
Emory University
Novartis
Investigators
Principal Investigator: Nabil F. Saba, MD Emory University Winship Cancer Institute
  More Information

No publications provided

Responsible Party: Nabil F. Saba, Principal Investigator, Emory University
ClinicalTrials.gov Identifier: NCT01490749     History of Changes
Other Study ID Numbers: IRB00047026, WCI1871-10
Study First Received: October 25, 2011
Last Updated: February 19, 2015
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by Emory University:
Esophageal Cancer
Neoplasms, Esophageal

Additional relevant MeSH terms:
Esophageal Neoplasms
Digestive System Diseases
Digestive System Neoplasms
Esophageal Diseases
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Head and Neck Neoplasms
Neoplasms
Neoplasms by Site
Carboplatin
Antineoplastic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on March 26, 2015