Endoxifen in Adults With Hormone Receptor Positive Solid Tumors
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT01273168|
Recruitment Status : Active, not recruiting
First Posted : January 10, 2011
Last Update Posted : September 24, 2021
- 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.
|Condition or disease||Intervention/treatment||Phase|
|Hormone Receptor-Positive Breast Gynecologic Desmoid Hormone Receptor-Positive Neoplasms||Drug: Z-Endoxifen||Phase 1|
- 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 HCl administered on a daily schedule.
-Determine the pharmacokinetics of oral Z-endoxifen (HCl form).
-Evaluate the change in [(18)F]FES uptake using PET/CT in hormone receptor-positive tumors before and after treatment with oral Z-endoxifen-HCI.
- 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 or targeted maximum dose (DL8) reached. Six additional patients will then be entered in an expansion cohort to assess pharmacodynamics and pharmacokinetics
- 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.
- As a relative bioavailability study, 6 patients in the expansion cohort will be given a single dose of the free base form of Z-endoxifen on day 1 and will then continue on study taking Z-endoxifen HCl; blood and urine will be collected for PK at baseline, on cycle 1 days 1 and 2, and on cycle 2 day 1. Please note: As of Febuary 2017, we will no longer evaluate the free base form of Z-endoxifen in the expansion cohort due to drug supply issues.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||40 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Actual Study Start Date :||March 1, 2011|
|Actual Primary Completion Date :||June 1, 2020|
|Estimated Study Completion Date :||June 1, 2022|
Z-endoxifen will be administered orally once a day in 28-day cycles
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
- Establish safety and MTD of Z-endoxifen [ Time Frame: 28 days (1 cycle) ]Adverse events will be graded as described in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
- Determine the pharmacokinetics of Zendoxifen (free base and HClforms) [ Time Frame: 28 days (1 cycle) ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01273168
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Naoko Takebe, M.D.||National Cancer Institute (NCI)|