Dose Escalation Study in Female Subjects With Breast Cancer Receiving Aromatase Inhibitor or Tamoxifen

Que Oncology21 enrolled

Overview

Open-label, two dose study of Q-122, over a 4 week treatment period to explore the effects of Q-122 in a population of women with a history of breast cancer taking an aromatase inhibitor or tamoxifen.

Vasomotor symptoms are significant in postmenopausal women with the most effective medications for relief being hormonal preparations. Non-hormonal medications have demonstrated efficacy but at a far lower level than estrogen replacement therapy. For women with a history of breast cancer hormone replacement therapy is problematic especially if their therapeutic regime involves an aromatase inhibitor. Therefore, this study will explore the effect of Q-122 in a population of women with a history of breast cancer taking an aromatase inhibitor or tamoxifen. The study is an open-label, two dose study (Group 1: 100 mg once daily and Group 2: 200 mg once daily) of Q-122, over a 4 week treatment period. As eligible subjects are enrolled, they will be assigned to Group 1 until Group 1 is fully enrolled. Dose escalation to the 200 mg level will only occur following a review of the safety experience of at least 6 subjects treated with 100 mg Q-122 once daily for at least 2 weeks. Once Group 1 is fully enrolled, eligible subjects will be enrolled into Group 2. A two-week screening phase will be used to establish a stable baseline of vasomotor symptoms and to establish study eligibility. Qualified subjects will be treated with Q-122 for four weeks either at 100 mg/day dose or the 200 mg/day dose, during which time they will be evaluated for safety, tolerability, and pharmacokinetics of Q-122 and tamoxifen levels; subjects will continue to record their hot flashes in identical fashion to the screening period. Following the 28 day treatment, period subjects who complete the study will continue to record their hot flashes for a two week follow up period.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Vasomotor Symptoms (VMS)

Interventions

oral capsule of Q-122DRUG

Eligibility

Sex: FEMALEMin age: 30 YearsMax age: 70 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Be a female of any race between the ages of 30-70 years. * History of breast cancer and presently taking an aromatase inhibitor or tamoxifen. * Naturally menopausal: ≥ 12 months spontaneous amenorrhea or \> 6 but \< 12 months amenorrhea with a serum follicle stimulating hormone (FSH) level of \> 40 mIU/mL (Milli-international Units Per Milliliter). * Surgically menopausal with an FSH level \> 40 mIU/mL. * Have a minimum of 7 moderate to severe hot flushes/day or 50 moderate to severe hot flushes per week, as verified for both weeks during the 14-day Screening Phase, prior to enrollment into the treatment phase of the study. * Able to read, understand and complete the required subject diary. * Willing and able to complete the daily subject diary, attend all study visits, and participate in all study procedures, including PK blood draws. Exclusion Criteria: * Childbearing potential, including pregnancy, or lactation. * Undiagnosed abnormal genital bleeding. * Significant day-to-day variability in hot flushes. * Participation in another clinical trial within 30 days prior to screening or during the study. * Legal incapacity or limited legal capacity. * Chronic renal (serum creatinine \> 2.0 mg/dL) or hepatic disease \[SGPT (ALT) or SGOT (AST) \> 2X normal limits\]. * Gastrointestinal, liver, kidney or other conditions which could interfere with the absorption, distribution, metabolism or excretion of Q-122. * Untreated overt hyperthyroidism. * Use of thyroid medication of less than 12 weeks on a stable dose. * Any clinically important systemic disease in the judgement of the investigator. * Inability to complete all study visits and study assessments for scheduling or other reasons. * Any other reason which in the investigator's opinion makes the subject unsuitable for a clinical trial. * Abnormal laboratory findings including: 1. Hematocrit \< 30% or hemoglobin \< 9.5 gm/dL 2. Fasting blood sugar \> 140 mg/dL 3. Fasting serum triglycerides \> 300 mg/dL 4. Fasting SGOT, SGPT, GGT, or bilirubin greater than twice the upper limit of normal (a subject will not be excluded if a second measurement is less than twice the upper limit of normal) 5. Creatinine \> 2.0 mg/dL

Outcomes

Primary Outcomes

Adverse Event (AE) Reporting of Q-122

Number of participants with indicated AE receiving Q-122

Time frame: 4 weeks

Serious Adverse Event (SAE) Reporting of Q-122

Number of participants with indicated SAE receiving Q-122

Time frame: 4 weeks

Change in Frequency of Moderate to Severe Vasomotor Symptoms.

Mean change in frequency of moderate to severe vasomotor symptoms. Daily patient (paper) diaries will be used as the primary efficacy collection tool. Change from baseline represents the mean change from the daily average frequency calculated at baseline to the daily average frequency calculated for the last week the subject was on drug. The hot flash severity categories are defined clinically as follow: mild, sensation of heat without perspiration; moderate, sensation of heat with perspiration, but subject is able to continue with activity; and severe. sensation of heat with sweating, sufficiently severe to result in discontinuation of activity.

Time frame: Baseline to 4 weeks

Percent Change in Frequency of Moderate to Severe Vasomotor Symptoms.

Percent reduction in frequency of moderate to severe vasomotor symptoms. Daily patient (paper) diaries will be used as the primary efficacy collection tool. The hot flash severity categories are defined clinically as follows: mild, sensation of heat without perspiration; moderate, sensation of heat with perspiration, but subject is able to continue with activity; and severe, sensation of heat with sweating, sufficiently severe to result in discontinuation of activity.

Time frame: Baseline to 4 weeks

Secondary Outcomes

Change in Hot Flash Severity Score

For moderate-to-severe (mod/sev) hot flashes (HF), a score will be calculated by multiplying the number of moderate-to-severe HFs by their severity to determine the HF (mod/sev) index score, using the following formula: HFSSmod/sev = (number of moderate hot flashes/day × 2) + (number of severe hot flashes/day x 3). The Average Daily HFSSmod/sev for each week will be calculated by dividing the total of daily HFSSmod/sev by the number of days observations will be recorded in that week. The change in score is of clinical significance, with a lower score representing less moderate to severe hot flashes and a higher score representing a greater number of moderate to severe hot flashes.

Data from ClinicalTrials.gov

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