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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. Identifier: NCT01273168
Recruitment Status : Active, not recruiting
First Posted : January 10, 2011
Last Update Posted : August 12, 2022
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

Brief Summary:


  • 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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 40 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (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
Actual Study Start Date : March 1, 2011
Actual Primary Completion Date : June 1, 2020
Estimated Study Completion Date : June 1, 2023

Arm Intervention/treatment
Experimental: 1
Z-endoxifen will be administered orally once a day in 28-day cycles
Drug: Z-Endoxifen
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.

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. Determine the pharmacokinetics of Z-endoxifen (free base and HCl forms) [ Time Frame: 28 days (1 cycle) ]

Information from the National Library of Medicine

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, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Patients with the following types of histologically documented solid tumors:

  • ER +/PR+, ER+/PR-, or ER-/PR+ breast cancer
  • Gynecologic tumors (endometrial, ovarian, uterine, fallopian tube, peritoneal, etc.)
  • Desmoid tumors
  • Tumors that are ER+ or PR+ by immunohistochemistry (including low-level expression) such as non-small cell lung, colorectal, and prostate

Patients with breast cancer must have had at least one prior chemotherapy regimen for metastatic disease. Additionally, patients with breast cancer must have received prior tamoxifen and/or aromatase inhibitor therapy (if postmenopausal) with at least one hormonal regimen in the metastatic setting. Patients with HER2+ breast cancer must have progressed after at least one prior HER2-directed regimen (trastuzumab, lapatinib) for metastatic disease.

All other patients must have disease that has progressed following at least one line of standard therapy. Prior therapy with tamoxifen is allowed.

Patients enrolled based on tumor ER/PR status must have ER/PR status confirmed by the Laboratory of Pathology, NIH. ER/PR status will be determined on a metastatic site, if possible; otherwise, the original site or available tissue will be acceptable.

Patients must have recovered to at least eligibility levels following any display of adverse events and/or toxicity due to prior chemotherapy or biologic therapy. They must not have had hormonal therapy, chemotherapy or biologic therapy within 4 weeks prior to entering the study (6 weeks for nitrosoureas or mitomycin C, or UCN-01). Patients must be greater than or equal 2 weeks since any prior administration of study drug in a Phase 0 study (also referred to as an "early Phase I study" or "pre-Phase I study" where a sub-therapeutic dose of drug is administered) at the PI's discretion. Patients must be greater than or equal to 4 weeks since any prior radiation or major surgery. However, patients receiving bisphosphonates or therapeutic anticoagulation are eligible for this trial.

Age greater than or equal 18 years

The Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2

Life expectancy > 3 months

Patients must have normal or adequate organ and marrow function as defined below:

Absolute neutrophil count greater than or equal to 1,500/microL

Platelets greater than or equal to 100,000/micorL

Total bilirubin within less than or equal to 1.5 times institutional upper limit of normal

AST (SGOT)/ALT (SGPT) less than or equal to 2.5 times institutional upper limit of normal

Creatinine < 1.5 times upper limit of normal


Creatinine clearance greater than or equal to 60 mL/min/1.73 m(2) for patients with creatinine levels greater than or equal to 1.5 times upper limit of normal.

The effects of Z-endoxifen on the developing human fetus are unknown. For this reason, women of childbearing potential and men must agree to use adequate nonhormonal contraception (barrier method of birth control or abstinence) prior to study entry, for the duration of study participation, and for 2 months after discontinuation from the study. Women of childbearing potential must have a negative pregnancy test in order to be eligible. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with Z-endoxifen, breastfeeding should be discontinued if the mother is treated with Z-endoxifen.

Ability to understand and the willingness to sign a written informed consent document.


Patients receiving any other investigational agents.

Patients with known brain metastases are excluded from this clinical trial, with the exception of patients whose brain metastatic disease status has remained stable for greater than or equal to 3 months after treatment of the brain metastases, without steroids or anti-seizure medications. These patients may be enrolled at the discretion of the principal investigator.

Patients with clinically significant illnesses which could compromise participation in the study, including, but not limited to, uncontrolled infection, uncontrolled diabetes, uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, myocardial infarction within the past 6 months, uncontrolled cardiac arrhythmia, stroke/cerebrovascular accident within the past 6 months, or psychiatric illness/social situations that in the investigator s opinion would make it undesirable for the patient to participate in the trial, or which would jeopardize compliance with the protocol.

Patients with untreated spinal cord metastases or metastases close to vital organs (as determined by the principal investigator) are excluded because of the risk of hormonal flare.

Patients with a history of deep vein thrombosis must be on anti-coagulation therapy prior to enrollment. Patients requiring prophylactic anti-coagulation are eligible.

Information from the National Library of Medicine

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 identifier (NCT number): NCT01273168

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United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Cancer Institute (NCI)
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Principal Investigator: Naoko Takebe, M.D. National Cancer Institute (NCI)
Additional Information:
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Responsible Party: National Cancer Institute (NCI) Identifier: NCT01273168    
Other Study ID Numbers: 110061
First Posted: January 10, 2011    Key Record Dates
Last Update Posted: August 12, 2022
Last Verified: December 21, 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: .All IPD recorded in the medical record will be shared with intramural investigators upon request.@@@@@@All collected IPD will be shared with collaborators under the terms of collaborative agreements.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Time Frame: Clinical data will be available during the study and indefinitely.
Access Criteria: Clinical data will be made available via subscription to BTRIS and with the permission of the study PI.@@@@@@Requests for all collected IPD data from clinical trials, conducted under a binding collaborative agreement between NCI/DCTD and a pharmaceutical/biotechnology company, that are not under DSMB monitoring must be in compliance with the terms of the binding collaborative agreement and must be approved by NCI/DCTD and the Pharmaceutical Collaborator.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ):
Advanced Cancer
Gynecologic Cancer
Breast Cancer
Desmoid Tumor
Endometrial Cancer
Ovarian Cancer
Uterine Cancer
Fallopian Tube Cancer
Peritoneal Cancer
Cytochrome P450
Selective Estrogen Receptor Modulator
Tamoxifen Metabolite
Additional relevant MeSH terms:
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Fibromatosis, Aggressive
Neoplasms, Fibrous Tissue
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type