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 May 2014 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: May 20, 2014
Last verified: May 2014
  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: Everolimus
Drug: Paclitaxel
Drug: carboplatin
Drug: cetuximab
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 II to assess the rate of pathologic CR in patients with resectable esophageal carcinoma receiving induction therapy followed by surgical resection; [ Time Frame: within one month after surgery ] [ Designated as safety issue: No ]
  • 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: 52
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/Carbo/RAD001 Drug: Everolimus
Dose escalation for Phase I; dose for Phase II to be determined after Phase I is completed
Other Names:
  • RAD001
  • Everolimus
Drug: Paclitaxel
fixed dose of paclitaxel
Drug: carboplatin
given on a 3 weeks on and 1 week off schedule
Drug: cetuximab
given weekly

  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 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
  • 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.

Exclusion Criteria:

  • 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.
  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 1-888-946-7447 nfsaba@emory.edu

Locations
United States, Georgia
Emory University Winship Cancer Institute Recruiting
Atlanta, Georgia, United States, 30322
Principal Investigator: Nabil F Saba, MD         
United States, Tennessee
Vanderbilt University Not yet 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: May 20, 2014
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:
Neoplasms
Esophageal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Carboplatin
Paclitaxel
Sirolimus
Everolimus
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents

ClinicalTrials.gov processed this record on September 18, 2014