Endoxifen in Adults With Hormone Receptor Positive Solid Tumors
|First Received Date ICMJE||January 7, 2011|
|Last Updated Date||November 27, 2013|
|Start Date ICMJE||December 2010|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE
||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.|
|Original Primary Outcome Measures ICMJE||Not Provided|
|Change History||Complete list of historical versions of study NCT01273168 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
||Determine the pharmacokinetics of oral Z-endoxifen.|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Endoxifen in Adults With Hormone Receptor Positive Solid Tumors|
|Official Title ICMJE||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|
- 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.
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
|Study Type ICMJE||Interventional|
|Study Phase||Phase 1|
|Study Design ICMJE||Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Study Arm (s)||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Recruiting|
|Estimated Enrollment ICMJE||72|
|Completion Date||Not Provided|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
Patients with the following types of histologically documented solid tumors:
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 an aromatase inhibitor (if post-menopausal) 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.
Patients with hypertension not controlled by medical therapy (hypertension defined as systolic blood pressure > 150 mmHg or diastolic pressure > 90 mmHg despite optimal medical management).
|Ages||18 Years and older|
|Accepts Healthy Volunteers||No|
|Location Countries ICMJE||United States|
|NCT Number ICMJE||NCT01273168|
|Other Study ID Numbers ICMJE||110061, 11-C-0061|
|Has Data Monitoring Committee||Not Provided|
|Responsible Party||Not Provided|
|Study Sponsor ICMJE||National Cancer Institute (NCI)|
|Collaborators ICMJE||Not Provided|
|Information Provided By||National Institutes of Health Clinical Center (CC)|
|Verification Date||July 2013|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP