Endoxifen in Adults With Hormone Receptor-Positive Solid Tumors
- Some types of cancer cells that have hormone receptors on their surfaces need the hormone estrogen to grow. The drug tamoxifen blocks estrogen from binding to the tumor cells, which helps to slow or stop the growth of cancer. Tamoxifen has been approved for treatment of certain types of estrogen-linked cancers, such as breast and ovarian cancer.
- The experimental drug Z-Endoxifen HCl (endoxifen) is related to tamoxifen, and has been shown to work against similar estrogen-linked cancers. In many cancer patients, tamoxifen is turned into endoxifen by enzymes in the liver; however, not all people have the liver enzymes that can turn tamoxifen into endoxifen, which means that the drug cannot work properly. Taking certain other drugs at the same time as tamoxifen can also keep it from turning into endoxifen. Researchers are interested in determining whether endoxifen tablets are effective in slowing or stopping tumor growth in individuals whose hormone-linked tumors have not responded to standard treatment.
- To test the safety and effectiveness of daily endoxifen in individuals with hormone receptor-positive solid tumors that have not responded to standard treatment.
- Individuals at least 18 years of age who have been diagnosed with hormone receptor-positive solid tumors (breast or other tumors), desmoid tumors, or gynecologic tumors that have not responded to standard treatment.
Individuals with breast cancer must have had at least one prior chemotherapy regimen and one prior hormonal regimen for metastatic disease.
- Participants will be screened with a full medical history (including prior hormone use) and physical examination, as well as blood and urine tests, tumor imaging studies, and an eye examination.
- Participants will take endoxifen tablets daily for 28-day cycles of treatment, and will be asked to keep a medication diary to record any side effects.
- Participants will have regular clinic visits with blood and urine samples and imaging studies to evaluate the cancer's response to treatment.
- Participants will continue to take endoxifen for as long as the cancer responds to the treatment.
Hormone Receptor-Positive Breast
Hormone Receptor-Positive Neoplasms
Drug: [(18)F] Fluoroestradiol
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Trial of Z-Endoxifen in Adults With Refractory Hormone Receptor-Positive Breast Cancer, Desmoid Tumors, Gynecologic Tumors, or Other Hormone Receptor-Positive Solid Tumors|
- Establish the safety and tolerability of oral endoxifen (Z Endoxifen HCI) administered on a daily schedule to patients with refractory receptor-positive solid tumors (breast or other tumors), desmoid tumors, or gynecologic tumors.
- Determine the pharmacokinetics of oral Z-endoxifen.
|Study Start Date:||December 2010|
- Genetic polymorphisms in CYP2D6 and concomitant medications alter tamoxifen metabolism, limiting exposure to the active metabolite endoxifen. These factors are associated with a higher rate of recurrence and shorter disease-free survival in breast cancer patients receiving tamoxifen.
- Administration of endoxifen directly to patients is anticipated to bypass the effects of CYP2D6 polymorphisms and concomitant medications and provide adequate active drug levels in all treated patients, resulting in clinical benefit.
- 16 alpha-[(18)F]-fluoro-17 beta estradiol (FES) is an investigational radiolabeled imaging agent used with positron emission tomography (PET) to investigate tumor estrogen receptor activity
- Establish the safety and tolerability of oral endoxifen (Z-Endoxifen HCl) administered on a daily schedule to patients with refractory hormone receptor-positive solid tumors (breast or other tumors), desmoid tumors, or gynecologic tumors.
- Establish the maximum tolerated dose (MTD) of oral Z-endoxifen administered on a daily schedule.
- Determine the pharmacokinetics of oral Z-endoxifen.
- Evaluate the change in [(18)F]FES uptake using PET/CT in hormone receptor-positive tumors before and after treatment with oral Z-endoxifen.
- Adults with histologically documented hormone receptor-positive solid tumors (breast or other tumors), desmoid tumors, or gynecologic tumors.
- Patients with breast cancer must have had at least one prior chemotherapy regimen and one prior hormonal regimen for metastatic disease. All other patients must have disease that has progressed following at least one line of standard therapy.
- No major surgery, radiation, hormonal, or chemotherapy within 4 weeks prior to study enrollment, and recovered from toxicities of prior therapies to at least eligibility levels.
- Patients in the 6-patient expansion cohort at the MTD will be asked to undergo optional tumor biopsies for research purposes.
- Z-endoxifen will be administered orally once a day in 28-day cycles.
- Dose escalation will proceed until the MTD is established. Six additional patients will be entered at the MTD to assess pharmacodynamics.
- When imaging agent is available, optional FES PET/CT scans will be performed at baseline and 1-3 hours after Z-endoxifen treatment once during week 1 of cycle 1.
A) Z-Endoxifen (Z-Endoxifen HCl) will be given orally once a day on a continuous schedule in 28-day cycles.
B) Blood and urine samples for PK will be collected from all patients during cycle 1 only. Blood samples will be collected on days 1 and 28 before drug administration and at the following times after administering Z-endoxifen: 0.5, 1, 2, 3, 4, 6, 8, and 24 (before next dose) hours. Urine will be collected for 24 hours after dosing on day 1.
C) Tumor biopsies collected at baseline and at the end of cycle 1 (+/- 2 days). Tumor biopsies are optional for patients enrolled in the dose escalation phase and in the 6-patient expansion cohort at the MTD.
Dose -Level Dose
|Contact: Jennifer H Zlott||(301) email@example.com|
|Contact: Shivaani Kummar, M.D.||(301) firstname.lastname@example.org|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office (888) NCI-1937|
|Principal Investigator:||Shivaani Kummar, M.D.||National Cancer Institute (NCI)|