Clinical Trial VICCGI1211
Phase IB/II Study of Induction Chemotherapy with XELOX, followed by Radiation Therapy, Carboplatin and RAD001 in Patients with Esophageal Cancer
- Protocol No. VICCGI1211
- Open Date: 03/08/2013
- Staging: Phase I/II
- Age Group: Adults
- Scope: National
- Objective: Phase I - Determine the MTD and DLT of RAD001 in combination with fixed dose weekly carboplatin administered for up to 6 weekly treatments, and radiation therapy after induction therapy with XELOX Phase II - Determine the rate of pathologic complete remission after the same treatment.
- Disease Sites: Esophageal
- Therapies: Chemotherapy - cytotoxic; Molecular Targeted Agents / Immunotherapy / Biologics; Radiotherapy
- Drugs: Carboplatin; Oxaliplatin; RAD001; Xeloda (Capecitabine)
- Participating Institutions: Vanderbilt University
- National Clinical Trial ID: NCT01490749
- Secondary Protocol No: CRAD001CUS159T
|Ages Eligible for Study:||18 Years and older|
|Genders Eligible for Study:||Both|
|Accepts Healthy Volunteers:||No|
• Patients must have histologically or cytologically confirmed squamous cell carcinoma or esophageal adenocarcinoma.
• The patient must have locally advanced disease without distant metastases.
• For the Phase I study, patients can have disease that is resectable or unresectable
• For the Phase II study, patients must have disease that is resectable
• Patients must not have had prior chemotherapy or radiation therapy for esophageal cancer.
• ECOG performance status ≤ 2 (Karnofsky ≥ 60%)
• Life expectancy of greater than 12 weeks.
• Age ≥ 18.
• Adequate bone marrow, liver and renal function as assessed by the following:
• Hemoglobin ≥ 9.0/dl
• Absolute-neutrophil count (ANC ) ≥ 1000/mm3
• Platelet count ≥ 100,000/mm3
• Total bilirubin ≤ 1.5 x ULN
• ALT and AST ≤ 2.5 x ULN (≤ 5 x ULN for patients with liver involvement)
• INR ≤ 1.5 or a PT and PTT within normal limits (Anticoagulation is allowed if target INR ≤ 1.5 on a stable dose of warfarin or on a stable dose of LMW heparin for >2 weeks at time of enrollment)
• 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 within 7 days 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. Prior to study enrollment, WOCBP must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy. In addition, men enrolled on this study should understand the risks to any sexual partner of childbearing potential and should practice an effective method of birth control. 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.
• Signed informed consent prior to beginning protocol specific procedures. Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care. Patients or their legal representatives must be able to read, understand and provide informed consent to participate in the trial
• No significant intercurrent medical illness (including NYHA class III or IV heart disease, significant arrhythmias requiring medication, symptomatic coronary artery disease, myocardial infarction) within the previous 6 months.
• Men and women of childbearing potential must be willing to consent to using effective contraception prior to study entry, while on treatment and for at least 3 months thereafter.
• All histologic types other than squamous cell carcinoma or adenocarcinoma
• Patients currently receiving other investigational agents.
• Patients who have received prior treatment with an 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 with neurological symptoms must undergo a CT scan/MRI of the brain to exclude brain metastasis.
• 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 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 (Note: A detailed assessment of Hepatitis B/C medical history and risk factors must be done at screening for all patients. HBV DNA and HCV RNA PCR testing are required at screening for all patients with a positive medical history based on risk factors and/or confirmation of prior HBV/HCV infection.)
• Abnormal LFTs as follows: total bilirubin (TB) > 1.5x IULN, alanine aminotransferase (ALT) > 1.25x IULN, and/or alkaline phosphatase > 2.5 x IULN (except when LFTs attributed to metastatic SCCHN, in which case, TB, ALT and alkaline phosphatase must be ≤ NCI-CTCAE, v3.0 grade 1).
• Absolute neutrophil count < 1000/mm3 or platelets < 100,000/mm3.
• A known history of HIV seropositivity
• Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001 (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection)
• Patients with an active, bleeding diathesis
• Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods. If barrier contraceptives are being used, these must be continued throughout the trial by both sexes. Hormonal contraceptives are not acceptable as a sole method of contraception. (WOCBP must have a negative urine or serum pregnancy test within 7 days prior to administration of RAD001)
• History of noncompliance to medical regimens
• Patients unwilling to or unable to comply with the protocol
• Women who are breast-feeding.
• Chronic treatment with systemic steroids or another immunosuppressive agents.