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

Primary Purpose

Esophageal Cancer, Neoplasms, Esophageal

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

RAD001

XELOX

Carboplatin

Radiation

About this trial

This is an interventional treatment trial for Esophageal Cancer focused on measuring Esophageal Cancer, Neoplasms, Esophageal

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Emory University Hospital Midtown
Emory University Winship Cancer Institute
Vanderbilt University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

XELOX/Radiation/Carboplatin/RAD001

Arm Description

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.

Outcomes

Primary Outcome Measures

Phase I portion to determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of RAD001 in combination with radiation

Secondary Outcome Measures

Rate of surgical pathologic complete remission (pCR) (absence of evidence of cancer after surgery)

Full Information

NCT ID

NCT01490749

First Posted

October 25, 2011

Last Updated

March 14, 2019

Sponsor

Emory University

Collaborators

Novartis

1. Study Identification

Unique Protocol Identification Number

NCT01490749

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2019

Overall Recruitment Status

Completed

Study Start Date

February 2012 (Actual)

Primary Completion Date

February 2019 (Actual)

Study Completion Date

February 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Emory University

Collaborators

Novartis

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Esophageal Cancer, Neoplasms, Esophageal

Keywords

Esophageal Cancer, Neoplasms, Esophageal

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

17 (Actual)

8. Arms, Groups, and Interventions

Arm Title

XELOX/Radiation/Carboplatin/RAD001

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

RAD001

Other Intervention Name(s)

Everolimus

Intervention Description

Dose escalation for Phase I; dose for Phase II to be determined after Phase I is completed.

Intervention Type

Drug

Intervention Name(s)

XELOX

Other Intervention Name(s)

Oxaliplatin and capecitabine, Eloxatin and Xeloda

Intervention Description

Patients will receive two cycles of XELOX.

Intervention Type

Drug

Intervention Name(s)

Carboplatin

Other Intervention Name(s)

Paraplatin

Intervention Description

Given on a 3 weeks on and 1 week off schedule.

Intervention Type

Radiation

Intervention Name(s)

Radiation

Intervention Description

1.8 Gy to 36 Gy; 3 fields or laterals to 50.4 Gy.

Primary Outcome Measure Information:

Title

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

Secondary Outcome Measure Information:

Title

Rate of surgical pathologic complete remission (pCR) (absence of evidence of cancer after surgery)

Time Frame

within one month from surgery

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Nabil F. Saba, MD

Organizational Affiliation

Emory University Winship Cancer Institute

Official's Role

Principal Investigator

Facility Information:

Facility Name

Emory University Hospital Midtown

City

Atlanta

State/Province

Georgia

ZIP/Postal Code

30308

Country

United States

Facility Name

Emory University Winship Cancer Institute

City

Atlanta

State/Province

Georgia

ZIP/Postal Code

30322

Country

United States

Facility Name

Vanderbilt University

City

Nashville

State/Province

Tennessee

ZIP/Postal Code

37232

Country

United States

12. IPD Sharing Statement

Learn more about this trial

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

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