Clinical trial NCT00087685: RAD001 in Recurrent Endometrial Cancer Patients
Official title: A Phase II Study of RAD001 in Patients With Recurrent Endometrial Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Endometrial Cancer
Keywords: Recurrent Endometrial Cancer
Endometrial
Endometrioid
RAD001
Uterine Cancer
Lead sponsor: M.D. Anderson Cancer Center
Sponsor class: OTHER
First posted: 2004-07-14
Enrollment: 35
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The goal of this clinical research study is to learn if RAD001 can shrink or slow the growth of tumors in patients who have recurrent endometrial cancer. The safety of this drug will also be studied.

Objectives:

Primary Objective:

1. To determine the efficacy of RAD001 in patients with progressive or recurrent endometrial cancer.

Secondary Objective:

1. To determine the nature and degree of toxicity of RAD001 in this cohort of patients.
2. To characterize, in pre- and post- treatment tumor samples, when available, expression levels of total and phosphorylated mTOR (mammalian "target of rapamycin") as well as relevant upstream and downstream signaling components (optional).

Detailed description: RAD001 is a new drug that was designed to block proteins that are important in the development and growth of cancer.

Before treatment starts, you will have a complete physical exam, routine blood tests (about 2-3 teaspoons), a chest x-ray, and a CT scan or MRI of the abdomen and pelvis. Women who are able to have children must have a negative blood pregnancy test.

Routine blood tests (about 2 teaspoons) will be done weekly during treatment, and before each course of therapy, which is every 4 weeks. A complete checkup including evaluation of side effects, will also be done before each course of therapy and at the end of therapy (4 weeks after treatment ends).

You will take RAD001 10 mg by mouth every day. One course of therapy is 4 weeks long. RAD001 should be taken the same time every day on an empty stomach (fasting state) or after no more than a light, fat-free meal. You should wait at least 6 hours after a eating a regular (not fat-free meal) before taking RAD001. You should not eat fatty foods for at least one hour after taking RAD001.

If side effects occur at this dose, your doctor may lower the RAD001 dose, depending on the severity of the side effects. After an additional 4 weeks of therapy, if the dose was reduced and the side effects have resolved, your doctor may increase the dose back to the original dose, or you may continue at the reduced dose.

You will only be given the amount of drug needed for one course of therapy at a time. You will keep a diary during the study that will list when and how much drug you took. This diary will be reviewed after each course of therapy by the research nurse or physician and filed in your chart.

You will have CT or MRI scans and chest x-rays (only in patients with chest disease) to evaluate the response of your tumor to treatment. These scans will be done after the first two courses (eight weeks) and every third course (every 12 weeks) and at the end of therapy. Treatment will be stopped if the disease gets worse or intolerable side effects occur.

This is an investigational study. RAD001 has been authorized by the FDA for use in research only. Up to 35 patients will take part in this study. All will be enrolled at M. D. Anderson.

Eligibility criteria: Inclusion Criteria:

1. Histologically confirmed progressive or recurrent endometrial cancer (endometrioid or mixed with endometrioid component histology; any grade).
2. Patients may have failed no more than two prior chemotherapies for the recurrent disease (does not include chemosensitizing radiation).
3. All patients must have measurable disease. Measurable disease is defined as lesions that can be measured by physical examination or by means of imaging techniques. Ascites and pleural effusions are not considered measurable disease.
4. Patients must have a pretreatment granulocyte count (i.e., segmented neutrophils + bands) of \>/=1,500/Fl, a hemoglobin level of \>/=9.0 gm/dL and a platelet count of \>/=100,000/Fl.
5. Patients must have an adequate renal function as documented by serum creatinine \</=2.0 mg/dL.
6. Patients must have adequate hepatic function as documented by a serum bilirubin \</=1.5 mg/dL, regardless of whether patients have liver involvement secondary to tumor. Aspartate transaminase (SGOT) must be \</=3x institutional upper limit of normal unless the liver is involved with tumor, in that case the aspartate transaminase must be \</=5x institutional upper limit of normal.
7. Patients must have a Zubrod performance status of 0, 1, or 2.
8. Patients must have signed an approved informed consent.

Exclusion Criteria:

1. Patients who have previously received RAD001 or another mammalian target of rapamycin (mTOR) inhibitor.
2. Patients whose tumors have serous carcinomas, mixed malignant mullerian tumors (MMMT) components or uterine sarcomas.
3. Patients who have isolated recurrences (vaginal, pelvic, or para-aortic) that are amenable to potentially curative treatment with radiation therapy or surgery.
4. Patients with a history of psychiatric disorders that would interfere with consent or follow-up.
5. Patients with a history of myocardial infarction within the previous six months or congestive heart failure requiring therapy.
6. 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.
7. Pregnant or lactating women. Women of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.
8. Patients with a history of seizures are ineligible. Patients receiving phenytoin, phenobarbital, or other anti-epileptic prophylaxis are ineligible.
9. 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.
10. Patients with deep venous or arterial thrombosis (including pulmonary embolism) within 6 weeks of study entry.
11. Patients with \>/= grade 2 hypercholesterolemia or hypertriglyceridaemia (fasting state), despite lipid lowering therapy should be excluded from entering the study.
12. Patients currently taking any of the medications listed in Appendix A (Patients will be given a listing of these medications at the time of the informed consent).
13. Known hypersensitivity to everolimus, sirolimus or excipients including hydroxytoluene, magnesium stearate, hydroxypropylmethyl-cellulose, crospovidone and lactulose.

Primary outcomes:
measure: Number of Participants With Objective Response Plus Stable Disease Rate (CR + PR + SD)
timeFrame: 8 weeks
measure: Clinical Benefit Rate
timeFrame: 20 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Karen H. Lu, MD
role: PRINCIPAL_INVESTIGATOR
References: