Back to resultsDose Escalation Study in Female Subjects With Breast Cancer Receiving Aromatase Inhibitor or Tamoxifen
Primary Purpose
Vasomotor Symptoms (VMS)
Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
oral capsule of Q-122
Sponsored by
About this trial
This is an interventional treatment trial for Vasomotor Symptoms (VMS) focused on measuring Vasomotor Symptoms, Breast Cancer, Hot Flashes, Tamoxifen, Aromatase Inhibitors, Estrogen Antagonists, Hormone Antagonists, Hormones, Hormone Substitutes, Hormone Antagonists, Physiological Effects of Drugs, Antineoplastic Agents, Hormonal Antineoplastic, Selective Estrogen Receptor Modulators, Estrogen Receptor Modulators, Bone Density Conservation Agents, Steroid Synthesis Inhibitors, Enzyme Inhibitors, Molecular Mechanisms of Pharmacological Action
Eligibility Criteria
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:
- Hematocrit < 30% or hemoglobin < 9.5 gm/dL
- Fasting blood sugar > 140 mg/dL
- Fasting serum triglycerides > 300 mg/dL
- 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)
- Creatinine > 2.0 mg/dL
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
100 mg Q-122
200 mg Q-122
Arm Description
10 patients treated with Q-122, 100 mg. Dosage was 100 mg Q-122 administered orally as two 50 mg capsules once daily for 28 days.
11 patients treated with Q-122, 200 mg. Dosage was 200 mg Q-122 administered orally as four 50 mg capsules once daily for 28 days.
Outcomes
Primary Outcome Measures
Adverse Event (AE) Reporting of Q-122
Number of participants with indicated AE receiving Q-122
Serious Adverse Event (SAE) Reporting of Q-122
Number of participants with indicated SAE receiving Q-122
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.
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.
Secondary Outcome Measures
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.
Percent 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.
Symptoms Associated With Postmenopausal Status
Greene Climacteric Scale: A comprehensive assessment divided into psychological, physical and vasomotor areas. The scale includes 21 symptoms, subject will score the severity of each symptom with the following score system: 0 = not at all; 1 = a little; 2 = quite a bit; and 3 = extremely. The results represent the total combined score, which can range from 0 to 63. A lower score represents a better outcome.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04080297
Brief Title
Dose Escalation Study in Female Subjects With Breast Cancer Receiving Aromatase Inhibitor or Tamoxifen
Official Title
A Two Dose, Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Effect on Vasomotor Symptoms of Q-122 in Female Subjects With Breast Cancer and Receiving an Aromatase Inhibitor or Tamoxifen
Study Type
Interventional
2. Study Status
Record Verification Date
February 2020
Overall Recruitment Status
Completed
Study Start Date
January 10, 2014 (Actual)
Primary Completion Date
July 28, 2014 (Actual)
Study Completion Date
July 28, 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Que Oncology
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
Detailed Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Vasomotor Symptoms (VMS)
Keywords
Vasomotor Symptoms, Breast Cancer, Hot Flashes, Tamoxifen, Aromatase Inhibitors, Estrogen Antagonists, Hormone Antagonists, Hormones, Hormone Substitutes, Hormone Antagonists, Physiological Effects of Drugs, Antineoplastic Agents, Hormonal Antineoplastic, Selective Estrogen Receptor Modulators, Estrogen Receptor Modulators, Bone Density Conservation Agents, Steroid Synthesis Inhibitors, Enzyme Inhibitors, Molecular Mechanisms of Pharmacological Action
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Model Description
open-label, two dose study
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
21 (Actual)
8. Arms, Groups, and Interventions
Arm Title
100 mg Q-122
Arm Type
Experimental
Arm Description
10 patients treated with Q-122, 100 mg. Dosage was 100 mg Q-122 administered orally as two 50 mg capsules once daily for 28 days.
Arm Title
200 mg Q-122
Arm Type
Experimental
Arm Description
11 patients treated with Q-122, 200 mg. Dosage was 200 mg Q-122 administered orally as four 50 mg capsules once daily for 28 days.
Intervention Type
Drug
Intervention Name(s)
oral capsule of Q-122
Primary Outcome Measure Information:
Title
Adverse Event (AE) Reporting of Q-122
Description
Number of participants with indicated AE receiving Q-122
Time Frame
4 weeks
Title
Serious Adverse Event (SAE) Reporting of Q-122
Description
Number of participants with indicated SAE receiving Q-122
Time Frame
4 weeks
Title
Change in Frequency of Moderate to Severe Vasomotor Symptoms.
Description
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
Title
Percent Change in Frequency of Moderate to Severe Vasomotor Symptoms.
Description
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 Outcome Measure Information:
Title
Change in Hot Flash Severity Score
Description
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.
Time Frame
Baseline to 4 weeks
Title
Percent Change in Hot Flash Severity Score
Description
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.
Time Frame
Baseline to 4 weeks
Title
Symptoms Associated With Postmenopausal Status
Description
Greene Climacteric Scale: A comprehensive assessment divided into psychological, physical and vasomotor areas. The scale includes 21 symptoms, subject will score the severity of each symptom with the following score system: 0 = not at all; 1 = a little; 2 = quite a bit; and 3 = extremely. The results represent the total combined score, which can range from 0 to 63. A lower score represents a better outcome.
Time Frame
Baseline and 4 weeks
10. Eligibility
Sex
Female
Gender Based
Yes
Minimum Age & Unit of Time
30 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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:
Hematocrit < 30% or hemoglobin < 9.5 gm/dL
Fasting blood sugar > 140 mg/dL
Fasting serum triglycerides > 300 mg/dL
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)
Creatinine > 2.0 mg/dL
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rob Crombie
Organizational Affiliation
Que Oncology
Official's Role
Study Chair
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
Dose Escalation Study in Female Subjects With Breast Cancer Receiving Aromatase Inhibitor or Tamoxifen
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