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Letrozole and RAD001 With Advanced or Recurrent Endometrial Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Novartis
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01068249
First received: February 11, 2010
Last updated: February 14, 2014
Last verified: February 2014
  Purpose

The goal of this clinical research study is to learn if the combination of RAD001 (everolimus) and Femara (letrozole) can help to control recurrent or progressive endometrial cancer. The safety of this drug combination will also be studied.


Condition Intervention Phase
Endometrial Cancer
Drug: Letrozole
Drug: RAD001 (Everolimus)
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Letrozole and RAD001 (Everolimus) in Patients With Advanced or Recurrent Endometrial Cancer

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Objective Response or Stable Disease Rate (CR + PR + SD) [ Time Frame: Evaluation within approximately 8 weeks of treatment, then every 12 weeks. ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 42
Study Start Date: April 2010
Estimated Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Letrozole + RAD001
Letrozole and RAD001 (Everolimus)
Drug: Letrozole
2.5 mg daily by mouth every day, at same time as Everolimus.
Other Name: Femara
Drug: RAD001 (Everolimus)
10 mg by mouth daily
Other Name: Afinitor

  Show Detailed Description

  Eligibility

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

Inclusion Criteria:

  1. Patients must have signed an approved informed consent.
  2. Histologically confirmed endometrial cancer (endometrioid, serous, or clear cell, or mixed histology; any grade) which is considered progressive or recurrent.
  3. Patients may have failed no more than two prior chemotherapeutic regimens for recurrent or advanced disease (including adjuvant therapy). Chemotherapy administered in conjunction with radiation as a radio-sensitizer is not counted as a prior treatment for recurrent or advanced disease.
  4. All patients must have measurable disease as defined by RECIST 1.1.
  5. Patients must have at least one "target lesion" to be used to assess response on this protocol as defined by RECIST. Tumors within a previously irradiated field will be designated as "non-target" lesions, unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy.
  6. Patients must have a Zubrod performance status of 0, 1, or 2.
  7. Patients must not be of child bearing potential. Patients are considered not of child bearing potential if they are surgically sterile (they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are postmenopausal for greater than 12 months. Patients in whom ovaries are present and were not previously menopausal at the time of hysterectomy, should have a serum estradiol < 10 pg/mL to confirm ovarian senescence.
  8. Patients must have a pretreatment granulocyte count (i.e., segmented neutrophils + bands) of >1,500/Fl, a hemoglobin level of >/=9gm/dL and a platelet count of >100,000/Fl. Close contact with those who have received attenuated live vaccines should be avoided during treatment with everolimus. Examples of live vaccines include intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever, varicella and TY21a typhoid vaccines.
  9. Patients must have an adequate renal function of >50cc/min as documented by the Cockcroft Gault creatinine clearance formula: Estimated GFR = (140 - age) x (weight kg) divided by 72 x serum Creatinine (non-IDMS) x 0.85 (female)
  10. Patients must have adequate hepatic function as documented by a serum bilirubin </=2.5 mg/dL, regardless of whether patients have liver involvement secondary to tumor. 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.
  11. Alanine aminotransferase (SGPT) must be </= 3x institutional upper limit of normal unless the liver is involved with tumor, in that case, the alanine aminotransferase must be </= 5 x institutional upper limit of normal.
  12. Prior to beginning therapy, at least 4 weeks must have elapsed since prior chemotherapy, surgery, radiation therapy, hormonal therapy or investigational therapy. Patients receiving palliative radiation therapy are exempt from the 4 week waiting period.
  13. Baseline lipid levels (triglycerides, cholesterol) must be </= grade 1. Patients are allowed to be on lipid lowering drugs.
  14. Patients must be >/= 18 years of age.

Exclusion Criteria:

  1. Patients with intact ovarian function.
  2. Patients who have previously received RAD001 or another mTOR inhibitor or letrozole or another aromatase inhibitor. Use of progestational or other hormonal agents are permitted provided they have not been administered within the previous 4 weeks.
  3. Patients who have uterine sarcomas or mixed malignant mullerian tumors.
  4. Patients who have isolated recurrences (vaginal, pelvic, or paraaortic) that are amenable to potentially curative treatment with radiation therapy or surgery.
  5. Patients with any other severe concurrent disease, which would make the patient inappropriate for entry into this study, including significant hepatic, renal, or gastrointestinal diseases.
  6. Patients currently receiving chemotherapy or radiotherapy or those in whom anti-cancer treatment has occurred within the preceding 4 weeks.
  7. Chronic treatment with systemic steroids or another immuno-suppressive agent.
  8. Patients should not receive immunization with attenuated live vaccines within one week of study entry or during study period.
  9. Patients with a history of prior malignancy except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease-free for at least five years
  10. Patients with active infection that requires systemic antibiotics.
  11. Patients with a known history of cardiac disease; i.e., uncontrolled hypertension (systolic B/P >/= 140 mm Hg and/or diastolic B/P >/= 90 mm Hg) or unstable angina. Patients with a history of myocardial infarct within 6 months before enrollment, New York Heart Association (NYHA) Class II or greater heart failure, or symptoms suspicious for congestive heart failure are not eligible unless a left ventricular ejection fraction in the past 6 months is documented to be 50% or greater. Patients who have had a LVEF (performed for any reason) of less than 50% in the past 6 months are ineligible.
  12. Patients with a known history severely impaired lung function (patients who are oxygen dependent).
  13. Patients with a known hypersensitivity to RAD001 (everolimus) or other rapamycins (sirolimus, temsirolimus) or to its excipients.
  14. Patients who are pregnant or breast-feeding.
  15. Presence of clinically apparent untreated central nervous system metastases.
  16. Patients with carcinomatous meningitis.
  17. Patients with deep venous or arterial thrombosis (including pulmonary embolism) within 6 weeks of study entry. Patients may be on maintenance anticoagulation therapy.
  18. Patients with previously documented human immunodeficiency virus (HIV) infection.
  19. Patients with an 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).
  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: NCT01068249

Locations
United States, New Jersey
Morristown Memorial Hospital, Women's Cancer Center
Morristown, New Jersey, United States, 07962
United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Novartis
Investigators
Study Chair: Robert Coleman, MD UT MD Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01068249     History of Changes
Other Study ID Numbers: 2009-0059, NCI-2011-03639
Study First Received: February 11, 2010
Last Updated: February 14, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
Advanced
Recurrent
Progressive
Endometrial Cancer
Letrozole
RAD001
Afinitor
Everolimus
Femara

Additional relevant MeSH terms:
Endometrial Neoplasms
Genital Diseases, Female
Genital Neoplasms, Female
Neoplasms
Neoplasms by Site
Urogenital Neoplasms
Uterine Diseases
Uterine Neoplasms
Everolimus
Letrozole
Sirolimus
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antineoplastic Agents
Aromatase Inhibitors
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 24, 2014