Orteronel as Monotherapy in Patients With Metastatic Breast Cancer (MBC) That Expresses the Androgen Receptor (AR)
Study Details
Study Description
Brief Summary
The androgen receptor (AR) is expressed in 70-90 percent of primary breast tumors and in 75 percent of breast metastases. There is evidence to suggest that Androgen Receptor (AR) may be a target in patients with advanced breast cancer. Breast cancer patients whose tumors do not express the ER, PR or HER2 (triple negative) have very few options for treatment. Orteronel is being developed as an endocrine therapy for relevant hormone-sensitive cancers such as prostrate cancer and breast cancer. Triple-negative metastatic breast cancer patients with AR expression could potentially benefit from anti-androgen therapy like orteronel.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Detailed Description
This open-label multicenter study will be conducted in 2 stages.
-
Lead-in Phase: The first 6 patients treated will be evaluated to confirm the safety and feasibility of this regimen. After all 6 patients complete at least 4 weeks of treatment, and if no prohibitive toxicities are identified, continuous study treatment will begin.
-
Continuous Study Treatment: Patients will continue to be enrolled into both cohorts based on their tumor specificities with an anticipated total of 31 patients in Cohort 1 (ER-/PR-/HER2-/AR+) and an anticipated total of 55 patients in Cohort 2 (ER+ and/or PR+/AR+).
Patients will be evaluated every eight weeks for response to treatment. All patients who respond to treatment (complete response [CR] or partial response [PR]) or have stable disease (SD) will continue to receive orteronel until they develop progressive disease (PD) or unacceptable toxicity.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Orteronel The planned dose of orteronel is 300mg orally (PO) twice daily (BID), for a total daily dose of 600mg. |
Drug: Orteronel
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Response Rate (RR) [upto 36 months]
Response rate (RR) will be estimated as the percentage of patients exhibiting complete response or partial response out of all evaluable cases. Complete Response is defined per RECIST as the disappearance of all target/non-target lesions and normalization of tumor markers. Partial Response is defined per RECIST as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Complete and partial responses were confirmed at least 4 weeks after the initial response.
- Disease Control Rate (DCR) [6 months]
Defined as the percentage of patients who do not exhibit progression (CR+PR+SD) at 6 months among those patients who are evaluable for response by RECIST V1.1. Complete Response is defined per RECIST as the disappearance of all target/non-target lesions and normalization of tumor markers. Partial Response is defined per RECIST as At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Stable disease is defined per RECIST as Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest (nadir) sum LD since the treatment started.
Secondary Outcome Measures
- Number of Participants With Treatment-Related Adverse Events as a Measure of Safety [weekly for 4 weeks then every 8 weeks until end of study treatment, up to 36 months.]
Assessments will be made through analysis of the reported incidence of treatment-related Adverse Events as determined by the investigator and assessed by NCI CTCAE, Version 4.0.
- Progression-free Survival (PFS) [Every 8 weeks during treatment then every 6 months for 2 years, annually thereafter up to 5 years.]
Progression-free survival is defined as the time from the first day of treatment until the day tumor progression or date of death was documented. The response was evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST v1.1). Progressive Disease (PD): Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.
- Overall Survival (OS) [After disease progression is documented, survival was monitored every 6 months for 2 years and annually thereafter up to 5 years.]
OS is defined as the time from the first treatment until the date of death due to any cause. In the absence of confirmation of death or lack of data beyond the follow-up period, the survival time was censored to the last date the participant was known to be alive.
- Measurement of Serum Hormone Levels - Estradiol [At baseline, at day 1 of cycle 2 and 4 (treatment cycle repeated every 4 weeks), and at end of treatment visit, up to 36 months]
Blood samples collected At baseline, at day 1 of cycle 2 and 4, and at end of treatment visit to test for serum estradiol levels
- Measurement of Serum Hormone Levels - Total Testosterone [At baseline, at day 1 of cycle 2 and 4 (treatment cycle repeated every 4 weeks), and at end of treatment visit, up to 36 months]
Blood samples were collected at baseline, on day 1 of cycles 2 and 4, and at end of treatment visit to test total testosterone levels
- Measurement of Serum Hormone Levels - Free Testosterone [At baseline, at day 1 of cycle 2 and 4 (treatment cycle repeated every 4 weeks), and at end of treatment visit, up to 36 months]
Blood samples were collected At baseline, at day 1 of cycle 2 and 4, and at end of treatment visit to test free testosterone levels
- Measurement of Serum Hormone Levels - Sex Hormone-binding Globulin [At baseline, at day 1 of cycle 2 and 4 (treatment cycle repeated every 4 weeks), and at end of treatment visit, up to 36 months]
Blood samples were collected at baseline, on day 1 of cycles 2 and 4, and at end of the treatment visit for sex hormone-binding globulin (SHBG) levels
- Measurement of Serum Hormone Levels - Adrenocorticotropic Hormone [At baseline, at day 1 of cycle 2 and 4 (treatment cycle repeated every 4 weeks), and at end of treatment visit, up to 36 months]
Blood samples were collected at baseline, on day 1 of cycles 2 and 4, and at end of the treatment visit to test for adrenocorticotropic hormone (ACTH) levels
- Measurement of Serum Hormone Levels - Dehydroepiandrosterone Sulfate (DHEA-S) [At baseline, at day 1 of cycle 2 and 4 (treatment cycle repeated every 4 weeks), and at end of treatment visit, up to 36 months]
Blood samples were collected at baseline, on day 1 of cycles 2 and 4, and at end of the treatment visit dehydroepiandrosterone sulfate (DHEA-S) levels
- Measurement of Serum Hormone Levels - Cortisol [At baseline, at day 1 of cycle 2 and 4 (treatment cycle repeated every 4 weeks), and at end of treatment visit, up to 36 months]
Blood samples to test for serum cortisol levels
Other Outcome Measures
- Number of Participants With PTEN Gene Expression Status of Positive, Weak Positive, or Negative [At pre-screening]
Archived tumor tissue was assayed for loss of phosphatase and tensin homolog (PTEN) biomarker. PTEN loss was determined by immunohistochemistry (IHC) staining. pTEN Positive by IHC is defined as strongly positive (2+ intensity) staining for PTEN protein expression in the entire tumor or the vast majority of the tumor cells. pTEN Negative by IHC is defined as no staining (0+intensity) in entire tumor cells for pTEN protein expression. pTEN Weakly positive(1+intensity) by IHC is defined as tumor cells showing weak pTEN protein expression.
- Number of Participants With PIK3CA Gene Mutation Status of Mutated or No Mutation [At pre-screening]
Archived tumor tissue was assayed for the phosphatidylinositol 3-kinase (PIK3CA) biomarker. PIK3CA hotspot mutations at codons 88, 539-549, 1020-1025, 1043-1049 were tested by pyrosequencing. 'PIK3CA-'mutated' is defined as the presence of mutation in one of the codons 88, 539-549, 1020-1025, 1043-1049 of the PIK3CA gene. PIK3CA-'no mutation' is defined as the absence of mutation in codons 88, 539-549, 1020-1025, 1043-1049 of the PIK3CA gene.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Voluntary written informed consent before performance of any study-related procedure not part of normal medical care
-
Patients must have MBC that is measurable or evaluable as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. Patients with metastases limited to the bones are eligible.
-
Patients with breast tumors that are AR+ (≥10% staining by immunohisto-chemistry). Archived tumor tissue from a primary biopsy or metastatic lesion for centralized determination of AR expression is mandatory. If tissue is limited, the additional correlative testing is optional. If tissue is not available, a patient will not be eligible for enrollment into the study. Patients may enroll based on local laboratory AR assessment, but will need to submit tissue for confirmation at the central laboratory.
-
In addition to having AR+ tumors, patients must fit into 1 of the 2 following categories:
-
Triple negative (ER-/PR-/HER2-) (Note: This group of patients must have received at least 1 and up to 3 prior chemotherapy regimens in the advanced setting.)
-
ER+ and/or PR+ (Note: This group of patients must have received at least 1 and up to 3 prior hormonal therapies and at least one prior chemotherapy treatment in the advanced setting. HER2+ patients in this group must have received a minimum of 2 lines of HER2-directed therapy in the advanced setting.) This group of patients may be pre-menopausal with ovarian suppression or post-menopausal. LHRH agonists maybe used to render ovarian suppression with post-menopausal ranges of estradiol or FSH per institutional guidelines.
-
Female or male patients ≥18 years-of-age
-
Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
-
Patient has recovered (to Grade ≤1) from all clinically significant toxicities related to prior antineoplastic therapies (with the exception of alopecia)
-
Adequate hematological function, defined as:
-
Absolute neutrophil count (ANC) ≥1.25 x 109/L
-
Platelets ≥75 x 109/L
-
Hemoglobin ≥9 g/dL
- Adequate liver function, defined as:
-
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 x the upper limit of normal (ULN), if no liver involvement or ≤5 x ULN with liver involvement
-
Total bilirubin ≤1.5 times the upper limit of normal (ULN) (in patients with known Gilbert Syndrome, a total bilirubin ≤3.0 x ULN, with direct bilirubin ≤1.5 x ULN)
- Adequate renal function, defined as:
- Creatinine ≤1.5 x ULN or creatinine clearance ≥40 mL/min as calculated by the Cockcroft-Gault method
-
Screening calculated LVEF of ≥50% by echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scan
-
Ability to swallow and retain oral medication
-
Male patients (even those post vasectomy) who are willing to use adequate contraceptive measures or abstain from heterosexual intercourse during the entire study treatment period and for 4 months after the last dose of study drug
-
Female patients who are not of child-bearing potential and female patients of child-bearing potential who agree to use adequate contraceptive measures or abstain from heterosexual intercourse during the entire study treatment period and for 4 months after the last dose of study drug, who are not breastfeeding, and who have had a negative serum/urine pregnancy test ≤7 days prior to dosing
-
Life expectancy of ≥3 months
-
Willingness and ability to understand the nature of this study and to comply with the study and follow-up procedures.
Exclusion Criteria:
-
Known hypersensitivity to orteronel or to orteronel excipients, which are listed by formulation in the Investigator Brochure
-
Patients receiving other treatment for breast cancer (includes standard hormonal therapy, chemotherapy, biologic therapy, immunotherapy, or radiation therapy). Patients receiving chronic bisphosphonate or denosumab therapy are eligible.
-
Female patients who are both lactating and breastfeeding or have a positive serum pregnancy test during the screening period.
-
Prior anti-androgen therapy
-
Use of an investigational drug ≤21 days or 5 half-lives (whichever is shorter) prior to the first dose of orteronel, or concurrent treatment. For investigational drugs for which 5 half-lives is less than 21 days, a minimum of 10 days between termination of the investigational drug and administration of orteronel is required.
-
Active brain metastases or leptomeningeal disease. Previously treated brain metastases are allowed provided lesions are stable for at least 3 months as documented by head CT scan or magnetic resonance imaging (MRI) of the brain. Patients must be off steroids, but anti-convulsants are allowed.
-
Patients with known adrenal insufficiency, or patients receiving treatment with ketoconazole, abiraterone, or aminoglutethimide.
-
Wide field radiotherapy (including therapeutic radioisotopes such as strontium 89) administered ≤28 days or limited field radiation for palliation ≤7 days prior to starting study drug or has not recovered from side effects of such therapy.
-
Major surgical procedures ≤28 days of beginning study treatment or minor surgical procedures ≤7 days. No waiting is required following port-a-cath placement.
-
Presence of active gastrointestinal (GI) disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of oral therapy (eg, ulcerative disease, uncontrolled nausea, vomiting, diarrhea ≥ Grade 2, and malabsorption syndrome).
-
History of myocardial infarction, unstable symptomatic ischemic heart disease, ongoing arrhythmias > Grade 2 (National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE], Version 4.0), thromboembolic events (eg, deep vein thrombosis, pulmonary embolism, or symptomatic cerebrovascular events), or any other cardiac condition (eg, pericardial effusion restrictive cardiomyopathy) within 6 months prior to first dose of study drug. Chronic stable atrial fibrillation on stable anticoagulant therapy is allowed.
-
New York Heart Association (NYHA) Class III or IV heart failure
-
Electrocardiogram (ECG) abnormalities of Q-wave infarction, unless identified 6 or more months prior to screening or QTc Fridericia (F) interval >460 msec
-
Inadequately controlled hypertension (ie, systolic blood pressure [SBP] >160 mmHg or diastolic BP [DBP] >90 mmHg) at 2 separate measurements no more than 60 minutes apart during the Screening visit. Note: patients may be rescreened after adjustment of antihypertensive medications.
-
Known diagnosis of human immunodeficiency virus, active chronic hepatitis B, or C, life-threatening illness unrelated to cancer, or any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with participation in this study
-
Uncontrolled diabetes mellitus. Patients with Type II diabetes are eligible if they require only oral hypoglycemic agents and fasting blood glucose level is ≤120. Patients with Type I diabetes are eligible if their glycosylated hemoglobin (HbAlc) is ≤7.
-
Diagnosis or treatment for another malignancy within 2 years of enrollment, with the exception of adequately treated in-situ carcinoma of the cervix, uteri, basal or squamous cell carcinoma or non-melanomatous skin cancer
-
Inability or unwillingness (including psychological, familial, sociological, or geographical conditions) to comply with study and/or follow-up procedures as outlined in the protocol.
-
Use of a prohibited concomitant medication that cannot be safely discontinued or substituted.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Yale School of Medicine | New Haven | Connecticut | United States | 06520 |
| 2 | Northeast Georgia Medical Center | Gainesville | Georgia | United States | 30501 |
| 3 | Hope Cancer Center | Terre Haute | Indiana | United States | 47802 |
| 4 | Baptist Hospital East | Louisville | Kentucky | United States | 40207 |
| 5 | Center for Cancer and Blood Disorders | Bethesda | Maryland | United States | 20817 |
| 6 | Cancer Research Consortium of West Michigan | Grand Rapids | Michigan | United States | 49503 |
| 7 | Cancer Centers of SW Oklahoma | Lawton | Oklahoma | United States | 73505 |
| 8 | Tennessee Oncology PLLC | Chattanooga | Tennessee | United States | 37404 |
| 9 | Tennessee Oncology PLLC | Nashville | Tennessee | United States | 37203 |
| 10 | Center for Cancer and Blood Disorders | Fort Worth | Texas | United States | 76104 |
Sponsors and Collaborators
- SCRI Development Innovations, LLC
- Millennium Pharmaceuticals, Inc.
Investigators
- Study Chair: Howard A Burris, III, MD, SCRI Development Innovations, LLC
Study Documents (Full-Text)
More Information
Publications
None provided.- SCRI BRE 203
Study Results
Participant Flow
| Recruitment Details | 71 participants were enrolled |
|---|---|
| Pre-assignment Detail | In this study, the first 6 participants enrolled in cohorts 1 and 2 were evaluated as part of a safety lead-in phase following pre-screening for AR expression. The lead-in did not affect the cohort assignments; the assignment was decided by Inclusion Criteria. After these 6 patients completed at least 4 weeks of treatment without any prohibitive toxicities, the study continued to enroll the rest of the study participants. |
| Arm/Group Title | Cohort 1: Patients With AR+/ER-/PR-/HER2- Tumors | Cohort 2: AR+/HR+/HER2 +/- Tumors |
|---|---|---|
| Arm/Group Description | Patients with estrogen receptor-negative (ER-)/progesterone receptor negative (PR-)/ human epidermal growth factor receptor 2 negative (HER2-)/Androgen receptor-positive (AR +) MBC with 1 to 3 previous treatments for metastatic disease | Postmenopausal women with hormone receptor (HR) positive (ER+ and/or PR+) /AR-positive (+) refractory MBC who have progressed after at least one and up to 3 previous hormonal treatments for metastatic disease. |
| Period Title: Overall Study | ||
| STARTED | 27 | 44 |
| COMPLETED | 0 | 0 |
| NOT COMPLETED | 27 | 44 |
Baseline Characteristics
| Arm/Group Title | Cohort 1: Patients With AR+/ER-/PR-/HER2- Tumors | Cohort 2: AR+/HR+/HER2 +/- Tumors | Total |
|---|---|---|---|
| Arm/Group Description | Patients with estrogen receptor-negative (ER-)/progesterone receptor negative (PR-)/ human epidermal growth factor receptor 2 negative (HER2-)/Androgen receptor-positive (AR +) MBC with 1 to 3 previous treatments for metastatic disease | Postmenopausal women with hormone receptor (HR) positive (ER+ and/or PR+) /AR-positive (+) refractory MBC who have progressed after at least one and up to 3 previous hormonal treatments for metastatic disease. | Total of all reporting groups |
| Overall Participants | 27 | 44 | 71 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
57.9
(13.73)
|
63.1
(11.34)
|
61.1
(12.47)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
27
100%
|
44
100%
|
71
100%
|
| Male |
0
0%
|
0
0%
|
0
0%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
4
14.8%
|
1
2.3%
|
5
7%
|
| Not Hispanic or Latino |
23
85.2%
|
43
97.7%
|
66
93%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
1
3.7%
|
1
2.3%
|
2
2.8%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
2
7.4%
|
4
9.1%
|
6
8.5%
|
| White |
22
81.5%
|
39
88.6%
|
61
85.9%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
2
7.4%
|
0
0%
|
2
2.8%
|
| Region of Enrollment (participants) [Number] | |||
| United States |
27
100%
|
44
100%
|
71
100%
|
| Patients with Bone-only disease (Count of Participants) | |||
| Count of Participants [Participants] |
4
14.8%
|
8
18.2%
|
12
16.9%
|
| HER2 positive patients (Count of Participants) | |||
| Count of Participants [Participants] |
0
0%
|
5
11.4%
|
5
7%
|
Outcome Measures
| Title | Response Rate (RR) |
|---|---|
| Description | Response rate (RR) will be estimated as the percentage of patients exhibiting complete response or partial response out of all evaluable cases. Complete Response is defined per RECIST as the disappearance of all target/non-target lesions and normalization of tumor markers. Partial Response is defined per RECIST as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Complete and partial responses were confirmed at least 4 weeks after the initial response. |
| Time Frame | upto 36 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| One participant in cohort 1 was found to be ineligible after starting treatment and was excluded from the analysis. Participants with bone-only metastases (4 in cohort 1 and 8 in cohort 2) were excluded from the analysis as they are not evaluable by RECIST V1.1. 14 participants, 1 in cohort 1 and 13 in cohort 2 who discontinued treatment prior to having a post-baseline scan were excluded. Participants who received at least one dose of study drug and with one post-baseline scan were included. |
| Arm/Group Title | Cohort 1: Patients With AR+/ER-/PR-/HER2- Tumors | Cohort 2: AR+/HR+/HER2 +/- Tumors |
|---|---|---|
| Arm/Group Description | Patients with estrogen receptor-negative (ER-)/progesterone receptor negative (PR-)/ human epidermal growth factor receptor 2 negative (HER2-)/Androgen receptor-positive (AR +) MBC with 1 to 3 previous treatments for metastatic disease | Postmenopausal women with hormone receptor (HR) positive (ER+ and/or PR+) /AR-positive (+) refractory MBC who have progressed after at least one and up to 3 previous hormonal treatments for metastatic disease. |
| Measure Participants | 21 | 23 |
| Number (95% Confidence Interval) [percentage of participants] |
4.8
17.8%
|
0
0%
|
| Title | Disease Control Rate (DCR) |
|---|---|
| Description | Defined as the percentage of patients who do not exhibit progression (CR+PR+SD) at 6 months among those patients who are evaluable for response by RECIST V1.1. Complete Response is defined per RECIST as the disappearance of all target/non-target lesions and normalization of tumor markers. Partial Response is defined per RECIST as At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Stable disease is defined per RECIST as Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest (nadir) sum LD since the treatment started. |
| Time Frame | 6 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| One participant in cohort 1 was found to be ineligible after starting treatment and was excluded from the analysis. Participants with bone-only metastases (4 in cohort 1 and 8 in cohort 2) were excluded from the analysis as they are not evaluable by RECIST V1.1. 14 participants, 1 in cohort 1 and 13 in cohort 2 who discontinued treatment prior to having a post-baseline scan were excluded. Participants who received at least one dose of study drug and with one post-baseline scan were included. |
| Arm/Group Title | Cohort 1: Patients With AR+/ER-/PR-/HER2- Tumors | Cohort 2: AR+/HR+/HER2 +/- Tumors |
|---|---|---|
| Arm/Group Description | Patients with estrogen receptor-negative (ER-)/progesterone receptor negative (PR-)/ human epidermal growth factor receptor 2 negative (HER2-)/Androgen receptor-positive (AR +) MBC with 1 to 3 previous treatments for metastatic disease | Postmenopausal women with hormone receptor (HR) positive (ER+ and/or PR+) /AR-positive (+) refractory MBC who have progressed after at least one and up to 3 previous hormonal treatments for metastatic disease. |
| Measure Participants | 21 | 23 |
| Number (95% Confidence Interval) [percentage of participants] |
4.8
17.8%
|
8.7
19.8%
|
| Title | Number of Participants With Treatment-Related Adverse Events as a Measure of Safety |
|---|---|
| Description | Assessments will be made through analysis of the reported incidence of treatment-related Adverse Events as determined by the investigator and assessed by NCI CTCAE, Version 4.0. |
| Time Frame | weekly for 4 weeks then every 8 weeks until end of study treatment, up to 36 months. |
Outcome Measure Data
| Analysis Population Description |
|---|
| One participant in cohort 1 was found to be ineligible after starting treatment and hence was excluded from the analysis. |
| Arm/Group Title | Cohort 1: Patients With AR+/ER-/PR-/HER2- Tumors | Cohort 2: AR+/HR+/HER2 +/- Tumors |
|---|---|---|
| Arm/Group Description | Patients with estrogen receptor-negative (ER-)/progesterone receptor negative (PR-)/ human epidermal growth factor receptor 2 negative (HER2-)/Androgen receptor-positive (AR +) MBC with 1 to 3 previous treatments for metastatic disease | Postmenopausal women with hormone receptor (HR) positive (ER+ and/or PR+) /AR-positive (+) refractory MBC who have progressed after at least one and up to 3 previous hormonal treatments for metastatic disease. |
| Measure Participants | 26 | 44 |
| Count of Participants [Participants] |
20
74.1%
|
38
86.4%
|
| Title | Progression-free Survival (PFS) |
|---|---|
| Description | Progression-free survival is defined as the time from the first day of treatment until the day tumor progression or date of death was documented. The response was evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST v1.1). Progressive Disease (PD): Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. |
| Time Frame | Every 8 weeks during treatment then every 6 months for 2 years, annually thereafter up to 5 years. |
Outcome Measure Data
| Analysis Population Description |
|---|
| One participant in cohort 1 was found to be ineligible after starting treatment and hence was excluded from the analysis. |
| Arm/Group Title | Cohort 1: Patients With AR+/ER-/PR-/HER2- Tumors | Cohort 2: AR+/HR+/HER2 +/- Tumors |
|---|---|---|
| Arm/Group Description | Patients with estrogen receptor-negative (ER-)/progesterone receptor negative (PR-)/ human epidermal growth factor receptor 2 negative (HER2-)/Androgen receptor-positive (AR +) MBC with 1 to 3 previous treatments for metastatic disease | Postmenopausal women with hormone receptor (HR) positive (ER+ and/or PR+) /AR-positive (+) refractory MBC who have progressed after at least one and up to 3 previous hormonal treatments for metastatic disease. |
| Measure Participants | 26 | 44 |
| Median (95% Confidence Interval) [months] |
2
|
1.8
|
| Title | Overall Survival (OS) |
|---|---|
| Description | OS is defined as the time from the first treatment until the date of death due to any cause. In the absence of confirmation of death or lack of data beyond the follow-up period, the survival time was censored to the last date the participant was known to be alive. |
| Time Frame | After disease progression is documented, survival was monitored every 6 months for 2 years and annually thereafter up to 5 years. |
Outcome Measure Data
| Analysis Population Description |
|---|
| One participant in cohort 1 was found to be ineligible after starting treatment and hence was excluded from the analysis. |
| Arm/Group Title | Cohort 1: Patients With AR+/ER-/PR-/HER2- Tumors | Cohort 2: AR+/HR+/HER2 +/- Tumors |
|---|---|---|
| Arm/Group Description | Patients with estrogen receptor-negative (ER-)/progesterone receptor negative (PR-)/ human epidermal growth factor receptor 2 negative (HER2-)/Androgen receptor-positive (AR +) MBC with 1 to 3 previous treatments for metastatic disease | Postmenopausal women with hormone receptor (HR) positive (ER+ and/or PR+) /AR-positive (+) refractory MBC who have progressed after at least one and up to 3 previous hormonal treatments for metastatic disease. |
| Measure Participants | 26 | 44 |
| Median (95% Confidence Interval) [months] |
10.2
|
7.6
|
| Title | Measurement of Serum Hormone Levels - Estradiol |
|---|---|
| Description | Blood samples collected At baseline, at day 1 of cycle 2 and 4, and at end of treatment visit to test for serum estradiol levels |
| Time Frame | At baseline, at day 1 of cycle 2 and 4 (treatment cycle repeated every 4 weeks), and at end of treatment visit, up to 36 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| One participant in cohort 1 was found to be ineligible after starting treatment and hence was excluded from the analysis. Available data from the samples collected at each timepoint is reported. |
| Arm/Group Title | Cohort 1: Patients With AR+/ER-/PR-/HER2- Tumors | Cohort 2: AR+/HR+/HER2 +/- Tumors |
|---|---|---|
| Arm/Group Description | Patients with estrogen receptor-negative (ER-)/progesterone receptor negative (PR-)/ human epidermal growth factor receptor 2 negative (HER2-)/Androgen receptor-positive (AR +) MBC with 1 to 3 previous treatments for metastatic disease | Postmenopausal women with hormone receptor (HR) positive (ER+ and/or PR+) /AR-positive (+) refractory MBC who have progressed after at least one and up to 3 previous hormonal treatments for metastatic disease. |
| Measure Participants | 26 | 44 |
| Baseline |
31.99
|
29.16
|
| Cycle 2 Day 1 |
22.29
|
26.99
|
| Cycle 4 Day 1 |
20.86
|
33
|
| End of Treatment |
25.46
|
28.15
|
| Title | Measurement of Serum Hormone Levels - Total Testosterone |
|---|---|
| Description | Blood samples were collected at baseline, on day 1 of cycles 2 and 4, and at end of treatment visit to test total testosterone levels |
| Time Frame | At baseline, at day 1 of cycle 2 and 4 (treatment cycle repeated every 4 weeks), and at end of treatment visit, up to 36 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| One participant in cohort 1 was found to be ineligible after starting treatment and hence was excluded from the analysis. Available data from the samples collected at each timepoint is reported |
| Arm/Group Title | Cohort 1: Patients With AR+/ER-/PR-/HER2- Tumors | Cohort 2: AR+/HR+/HER2 +/- Tumors |
|---|---|---|
| Arm/Group Description | Patients with estrogen receptor-negative (ER-)/progesterone receptor negative (PR-)/ human epidermal growth factor receptor 2 negative (HER2-)/Androgen receptor-positive (AR +) MBC with 1 to 3 previous treatments for metastatic disease | Postmenopausal women with hormone receptor (HR) positive (ER+ and/or PR+) /AR-positive (+) refractory MBC who have progressed after at least one and up to 3 previous hormonal treatments for metastatic disease. |
| Measure Participants | 26 | 44 |
| Baseline |
16.36
|
24.79
|
| Cycle 2 Day 1 |
4.23
|
4.35
|
| Cycle 4 Day 1 |
3.71
|
2.4
|
| End of Treatment |
6.11
|
8.5
|
| Title | Measurement of Serum Hormone Levels - Free Testosterone |
|---|---|
| Description | Blood samples were collected At baseline, at day 1 of cycle 2 and 4, and at end of treatment visit to test free testosterone levels |
| Time Frame | At baseline, at day 1 of cycle 2 and 4 (treatment cycle repeated every 4 weeks), and at end of treatment visit, up to 36 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| One participant in cohort 1 was found to be ineligible after starting treatment and hence was excluded from the analysis. Available data from the samples collected at each timepoint is reported. |
| Arm/Group Title | Cohort 1: Patients With AR+/ER-/PR-/HER2- Tumors | Cohort 2: AR+/HR+/HER2 +/- Tumors |
|---|---|---|
| Arm/Group Description | Patients with estrogen receptor-negative (ER-)/progesterone receptor negative (PR-)/ human epidermal growth factor receptor 2 negative (HER2-)/Androgen receptor-positive (AR +) MBC with 1 to 3 previous treatments for metastatic disease | Postmenopausal women with hormone receptor (HR) positive (ER+ and/or PR+) /AR-positive (+) refractory MBC who have progressed after at least one and up to 3 previous hormonal treatments for metastatic disease. |
| Measure Participants | 26 | 44 |
| Baseline |
1.62
|
4.13
|
| Cycle 2 Day 1 |
0.31
|
0.39
|
| Cycle 4 Day 1 |
0.36
|
0.16
|
| End of treatment |
0.6
|
1.01
|
| Title | Measurement of Serum Hormone Levels - Sex Hormone-binding Globulin |
|---|---|
| Description | Blood samples were collected at baseline, on day 1 of cycles 2 and 4, and at end of the treatment visit for sex hormone-binding globulin (SHBG) levels |
| Time Frame | At baseline, at day 1 of cycle 2 and 4 (treatment cycle repeated every 4 weeks), and at end of treatment visit, up to 36 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| One participant in cohort 1 was found to be ineligible after starting treatment and hence was excluded from the analysis. Available data from the samples collected at each timepoint is reported |
| Arm/Group Title | Cohort 1: Patients With AR+/ER-/PR-/HER2- Tumors | Cohort 2: AR+/HR+/HER2 +/- Tumors |
|---|---|---|
| Arm/Group Description | Patients with estrogen receptor-negative (ER-)/progesterone receptor negative (PR-)/ human epidermal growth factor receptor 2 negative (HER2-)/Androgen receptor-positive (AR +) MBC with 1 to 3 previous treatments for metastatic disease | Postmenopausal women with hormone receptor (HR) positive (ER+ and/or PR+) /AR-positive (+) refractory MBC who have progressed after at least one and up to 3 previous hormonal treatments for metastatic disease. |
| Measure Participants | 26 | 44 |
| Baseline |
81.95
|
72.88
|
| Cycle 2 Day 1 |
82.7
|
91.93
|
| Cycle 4 Day 1 |
67.17
|
118.54
|
| End of Treatment |
77.69
|
73.48
|
| Title | Measurement of Serum Hormone Levels - Adrenocorticotropic Hormone |
|---|---|
| Description | Blood samples were collected at baseline, on day 1 of cycles 2 and 4, and at end of the treatment visit to test for adrenocorticotropic hormone (ACTH) levels |
| Time Frame | At baseline, at day 1 of cycle 2 and 4 (treatment cycle repeated every 4 weeks), and at end of treatment visit, up to 36 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| One participant in cohort 1 was found to be ineligible after starting treatment and hence was excluded from the analysis. Available data from the samples collected at each timepoint is reported |
| Arm/Group Title | Cohort 1: Patients With AR+/ER-/PR-/HER2- Tumors | Cohort 2: AR+/HR+/HER2 +/- Tumors |
|---|---|---|
| Arm/Group Description | Patients with estrogen receptor-negative (ER-)/progesterone receptor negative (PR-)/ human epidermal growth factor receptor 2 negative (HER2-)/Androgen receptor-positive (AR +) MBC with 1 to 3 previous treatments for metastatic disease | Postmenopausal women with hormone receptor (HR) positive (ER+ and/or PR+) /AR-positive (+) refractory MBC who have progressed after at least one and up to 3 previous hormonal treatments for metastatic disease. |
| Measure Participants | 26 | 44 |
| Baseline |
16.86
|
18.61
|
| Cycle 2 Day 1 |
62.82
|
58.04
|
| Cycle 4 Day 1 |
56.55
|
214.94
|
| End of treatment |
42.14
|
40.26
|
| Title | Measurement of Serum Hormone Levels - Dehydroepiandrosterone Sulfate (DHEA-S) |
|---|---|
| Description | Blood samples were collected at baseline, on day 1 of cycles 2 and 4, and at end of the treatment visit dehydroepiandrosterone sulfate (DHEA-S) levels |
| Time Frame | At baseline, at day 1 of cycle 2 and 4 (treatment cycle repeated every 4 weeks), and at end of treatment visit, up to 36 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| One participant in cohort 1 was found to be ineligible after starting treatment and hence was excluded from the analysis. Available data from the samples collected at each timepoint is reported |
| Arm/Group Title | Cohort 1: Patients With AR+/ER-/PR-/HER2- Tumors | Cohort 2: AR+/HR+/HER2 +/- Tumors |
|---|---|---|
| Arm/Group Description | Patients with estrogen receptor-negative (ER-)/progesterone receptor negative (PR-)/ human epidermal growth factor receptor 2 negative (HER2-)/Androgen receptor-positive (AR +) MBC with 1 to 3 previous treatments for metastatic disease | Postmenopausal women with hormone receptor (HR) positive (ER+ and/or PR+) /AR-positive (+) refractory MBC who have progressed after at least one and up to 3 previous hormonal treatments for metastatic disease. |
| Measure Participants | 26 | 44 |
| Baseline |
74.63
|
54.8
|
| Cycle 2 Day 1 |
16.54
|
14.48
|
| cycle 4 Day 1 |
23.29
|
10.3
|
| End of Treatment |
36.85
|
34.31
|
| Title | Measurement of Serum Hormone Levels - Cortisol |
|---|---|
| Description | Blood samples to test for serum cortisol levels |
| Time Frame | At baseline, at day 1 of cycle 2 and 4 (treatment cycle repeated every 4 weeks), and at end of treatment visit, up to 36 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| One participant in cohort 1 was found to be ineligible after starting treatment and hence was excluded from the analysis. Available data from the samples collected at each timepoint is reported |
| Arm/Group Title | Cohort 1: Patients With AR+/ER-/PR-/HER2- Tumors | Cohort 2: AR+/HR+/HER2 +/- Tumors |
|---|---|---|
| Arm/Group Description | Patients with estrogen receptor-negative (ER-)/progesterone receptor negative (PR-)/ human epidermal growth factor receptor 2 negative (HER2-)/Androgen receptor-positive (AR +) MBC with 1 to 3 previous treatments for metastatic disease | Postmenopausal women with hormone receptor (HR) positive (ER+ and/or PR+) /AR-positive (+) refractory MBC who have progressed after at least one and up to 3 previous hormonal treatments for metastatic disease. |
| Measure Participants | 26 | 44 |
| Baseline |
10.45
|
12.89
|
| Cycle 2 Day 1 |
7.08
|
6.91
|
| cycle 4 Day 1 |
7.14
|
11
|
| End of Treatment |
8.16
|
12.34
|
| Title | Number of Participants With PTEN Gene Expression Status of Positive, Weak Positive, or Negative |
|---|---|
| Description | Archived tumor tissue was assayed for loss of phosphatase and tensin homolog (PTEN) biomarker. PTEN loss was determined by immunohistochemistry (IHC) staining. pTEN Positive by IHC is defined as strongly positive (2+ intensity) staining for PTEN protein expression in the entire tumor or the vast majority of the tumor cells. pTEN Negative by IHC is defined as no staining (0+intensity) in entire tumor cells for pTEN protein expression. pTEN Weakly positive(1+intensity) by IHC is defined as tumor cells showing weak pTEN protein expression. |
| Time Frame | At pre-screening |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent to treat analysis set. All enrolled participants' tissue was analyzed for loss of gene expression. Results are not reported for 6 participants in cohort 1, and 10 participants in cohort 2 who could not be assayed because of insufficient tissue available for testing or because their assay had indeterminate results. |
| Arm/Group Title | Cohort 1: Patients With AR+/ER-/PR-/HER2- Tumors | Cohort 2: AR+/HR+/HER2 +/- Tumors |
|---|---|---|
| Arm/Group Description | Patients with estrogen receptor-negative (ER-)/progesterone receptor negative (PR-)/ human epidermal growth factor receptor 2 negative (HER2-)/Androgen receptor-positive (AR +) MBC with 1 to 3 previous treatments for metastatic disease | Postmenopausal women with hormone receptor (HR) positive (ER+ and/or PR+) /AR-positive (+) refractory MBC who have progressed after at least one and up to 3 previous hormonal treatments for metastatic disease. |
| Measure Participants | 20 | 34 |
| Positive |
6
22.2%
|
18
40.9%
|
| Weak Positive |
1
3.7%
|
7
15.9%
|
| Negative |
13
48.1%
|
9
20.5%
|
| Title | Number of Participants With PIK3CA Gene Mutation Status of Mutated or No Mutation |
|---|---|
| Description | Archived tumor tissue was assayed for the phosphatidylinositol 3-kinase (PIK3CA) biomarker. PIK3CA hotspot mutations at codons 88, 539-549, 1020-1025, 1043-1049 were tested by pyrosequencing. 'PIK3CA-'mutated' is defined as the presence of mutation in one of the codons 88, 539-549, 1020-1025, 1043-1049 of the PIK3CA gene. PIK3CA-'no mutation' is defined as the absence of mutation in codons 88, 539-549, 1020-1025, 1043-1049 of the PIK3CA gene. |
| Time Frame | At pre-screening |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent to treat analysis set. All enrolled participants' tissue was analyzed for loss of gene expression. Results are not reported for 8 participants in cohort 1, and 11 participants in cohort 2 who could not be assayed because of insufficient tissue or because of their assay had indeterminate results. |
| Arm/Group Title | Cohort 1: Patients With AR+/ER-/PR-/HER2- Tumors | Cohort 2: AR+/HR+/HER2 +/- Tumors |
|---|---|---|
| Arm/Group Description | Patients with estrogen receptor-negative (ER-)/progesterone receptor negative (PR-)/ human epidermal growth factor receptor 2 negative (HER2-)/Androgen receptor-positive (AR +) MBC with 1 to 3 previous treatments for metastatic disease | Postmenopausal women with hormone receptor (HR) positive (ER+ and/or PR+) /AR-positive (+) refractory MBC who have progressed after at least one and up to 3 previous hormonal treatments for metastatic disease. |
| Measure Participants | 18 | 33 |
| Mutated |
3
11.1%
|
12
27.3%
|
| No mutation |
15
55.6%
|
21
47.7%
|
Adverse Events
| Time Frame | Up to 36 months for Serious Adverse Events and Other Adverse Events. Up to 5 years for All-Cause Mortality. | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | All patients who received at least one dose of protocol treatment were followed for safety. Adverse events and serious adverse events were collected from the day of the first dose to 30 days after the last dose of the study medication and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. One participant in cohort 1 was found to be ineligible after starting with study treatment and hence excluded from further analyses. | |||
| Arm/Group Title | Cohort 1: Patients With AR+/ER-/PR-/HER2- Tumors | Cohort 2: AR+/HR+/HER2 +/- Tumors | ||
| Arm/Group Description | Patients with estrogen receptor-negative (ER-)/progesterone receptor negative (PR-)/ human epidermal growth factor receptor 2 negative (HER2-)/AR-positive (+) MBC with 1 to 3 previous treatments for metastatic disease | Postmenopausal women with hormone receptor (HR) positive (ER+ and/or PR+) /AR-positive (+) refractory MBC who have progressed after at least one and up to 3 previous hormonal treatments for metastatic disease. | ||
All Cause Mortality |
||||
| Cohort 1: Patients With AR+/ER-/PR-/HER2- Tumors | Cohort 2: AR+/HR+/HER2 +/- Tumors | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 23/26 (88.5%) | 39/44 (88.6%) | ||
Serious Adverse Events |
||||
| Cohort 1: Patients With AR+/ER-/PR-/HER2- Tumors | Cohort 2: AR+/HR+/HER2 +/- Tumors | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 11/26 (42.3%) | 11/44 (25%) | ||
| Ear and labyrinth disorders | ||||
| Vertigo | 0/26 (0%) | 0 | 1/44 (2.3%) | 1 |
| Endocrine disorders | ||||
| Adrenal insufficiency | 0/26 (0%) | 0 | 1/44 (2.3%) | 1 |
| Diabetes insipidus | 0/26 (0%) | 0 | 1/44 (2.3%) | 1 |
| Gastrointestinal disorders | ||||
| Abdominal pain | 0/26 (0%) | 0 | 1/44 (2.3%) | 1 |
| Nausea | 0/26 (0%) | 0 | 1/44 (2.3%) | 1 |
| Vomiting | 0/26 (0%) | 0 | 1/44 (2.3%) | 1 |
| General disorders | ||||
| Chest pain | 1/26 (3.8%) | 1 | 0/44 (0%) | 0 |
| Fatigue | 1/26 (3.8%) | 1 | 0/44 (0%) | 0 |
| Non-cardiac chest pain | 1/26 (3.8%) | 1 | 0/44 (0%) | 0 |
| Oedema peripheral | 1/26 (3.8%) | 1 | 0/44 (0%) | 0 |
| Pyrexia | 1/26 (3.8%) | 1 | 0/44 (0%) | 0 |
| Hepatobiliary disorders | ||||
| Hepatic failure | 0/26 (0%) | 0 | 2/44 (4.5%) | 2 |
| Infections and infestations | ||||
| Urinary tract infection | 0/26 (0%) | 0 | 1/44 (2.3%) | 1 |
| Injury, poisoning and procedural complications | ||||
| Femur fracture | 0/26 (0%) | 0 | 1/44 (2.3%) | 1 |
| Subdural haematoma | 1/26 (3.8%) | 1 | 0/44 (0%) | 0 |
| Investigations | ||||
| Electrocardiogram QT prolonged | 0/26 (0%) | 0 | 1/44 (2.3%) | 1 |
| Metabolism and nutrition disorders | ||||
| Dehydration | 0/26 (0%) | 0 | 1/44 (2.3%) | 2 |
| Hypercalcaemia | 0/26 (0%) | 0 | 1/44 (2.3%) | 1 |
| Hypokalaemia | 0/26 (0%) | 0 | 1/44 (2.3%) | 1 |
| Nervous system disorders | ||||
| Haemorrhage intracranial | 0/26 (0%) | 0 | 1/44 (2.3%) | 1 |
| Intracranial mass | 1/26 (3.8%) | 1 | 0/44 (0%) | 0 |
| Transient ischaemic attack | 1/26 (3.8%) | 1 | 0/44 (0%) | 0 |
| Psychiatric disorders | ||||
| Delirium | 0/26 (0%) | 0 | 1/44 (2.3%) | 1 |
| Suicide attempt | 1/26 (3.8%) | 1 | 0/44 (0%) | 0 |
| Renal and urinary disorders | ||||
| Renal failure | 0/26 (0%) | 0 | 1/44 (2.3%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Dyspnoea | 1/26 (3.8%) | 1 | 1/44 (2.3%) | 1 |
| Pneumonitis | 1/26 (3.8%) | 1 | 0/44 (0%) | 0 |
| Pneumothorax | 1/26 (3.8%) | 1 | 0/44 (0%) | 0 |
| Vascular disorders | ||||
| Hypertension | 1/26 (3.8%) | 2 | 1/44 (2.3%) | 1 |
| Superior vena cava syndrome | 1/26 (3.8%) | 1 | 0/44 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||
| Cohort 1: Patients With AR+/ER-/PR-/HER2- Tumors | Cohort 2: AR+/HR+/HER2 +/- Tumors | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 20/26 (76.9%) | 38/44 (86.4%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 3/26 (11.5%) | 4 | 3/44 (6.8%) | 3 |
| Eosinophilia | 1/26 (3.8%) | 1 | 0/44 (0%) | 0 |
| Leukopenia | 1/26 (3.8%) | 2 | 0/44 (0%) | 0 |
| Neutropenia | 1/26 (3.8%) | 1 | 3/44 (6.8%) | 5 |
| Cardiac disorders | ||||
| Left ventricular hypertrophy | 0/26 (0%) | 0 | 1/44 (2.3%) | 1 |
| Palpitations | 1/26 (3.8%) | 1 | 3/44 (6.8%) | 4 |
| Sinus tachycardia | 1/26 (3.8%) | 1 | 0/44 (0%) | 0 |
| Tachycardia | 0/26 (0%) | 0 | 1/44 (2.3%) | 1 |
| Ear and labyrinth disorders | ||||
| Tinnitus | 0/26 (0%) | 0 | 1/44 (2.3%) | 1 |
| Endocrine disorders | ||||
| Adrenal insufficiency | 0/26 (0%) | 0 | 1/44 (2.3%) | 1 |
| Eye disorders | ||||
| Blepharitis | 1/26 (3.8%) | 1 | 0/44 (0%) | 0 |
| Eyelid margin crusting | 1/26 (3.8%) | 1 | 0/44 (0%) | 0 |
| Gastrointestinal disorders | ||||
| Abdominal distension | 0/26 (0%) | 0 | 1/44 (2.3%) | 1 |
| Abdominal pain | 3/26 (11.5%) | 3 | 5/44 (11.4%) | 7 |
| Abdominal pain lower | 0/26 (0%) | 0 | 1/44 (2.3%) | 2 |
| Abdominal pain upper | 0/26 (0%) | 0 | 1/44 (2.3%) | 1 |
| Constipation | 7/26 (26.9%) | 8 | 12/44 (27.3%) | 14 |
| Dental paraesthesia | 1/26 (3.8%) | 1 | 0/44 (0%) | 0 |
| Diarrhoea | 5/26 (19.2%) | 5 | 7/44 (15.9%) | 9 |
| Dry mouth | 2/26 (7.7%) | 2 | 1/44 (2.3%) | 1 |
| Dyspepsia | 1/26 (3.8%) | 1 | 1/44 (2.3%) | 1 |
| Dysphagia | 1/26 (3.8%) | 1 | 1/44 (2.3%) | 1 |
| Gastrooesophageal reflux disease | 1/26 (3.8%) | 1 | 1/44 (2.3%) | 1 |
| Hypoaesthesia oral | 0/26 (0%) | 0 | 1/44 (2.3%) | 1 |
| Lip exfoliation | 1/26 (3.8%) | 1 | 0/44 (0%) | 0 |
| Nausea | 14/26 (53.8%) | 15 | 19/44 (43.2%) | 24 |
| Pancreatitis | 1/26 (3.8%) | 1 | 0/44 (0%) | 0 |
| Stomatitis | 1/26 (3.8%) | 1 | 1/44 (2.3%) | 1 |
| Toothache | 0/26 (0%) | 0 | 1/44 (2.3%) | 1 |
| Vomiting | 5/26 (19.2%) | 5 | 10/44 (22.7%) | 14 |
| General disorders | ||||
| Asthenia | 0/26 (0%) | 0 | 3/44 (6.8%) | 3 |
| Chest pain | 0/26 (0%) | 0 | 2/44 (4.5%) | 2 |
| Chills | 2/26 (7.7%) | 2 | 0/44 (0%) | 0 |
| Early satiety | 1/26 (3.8%) | 1 | 0/44 (0%) | 0 |
| Facial pain | 1/26 (3.8%) | 1 | 0/44 (0%) | 0 |
| Fatigue | 13/26 (50%) | 16 | 21/44 (47.7%) | 34 |
| Gait disturbance | 0/26 (0%) | 0 | 1/44 (2.3%) | 1 |
| Localised oedema | 0/26 (0%) | 0 | 1/44 (2.3%) | 3 |
| Malaise | 1/26 (3.8%) | 1 | 2/44 (4.5%) | 2 |
| Oedema peripheral | 3/26 (11.5%) | 3 | 3/44 (6.8%) | 4 |
| Pain | 3/26 (11.5%) | 3 | 3/44 (6.8%) | 3 |
| Peripheral swelling | 1/26 (3.8%) | 1 | 1/44 (2.3%) | 1 |
| Pyrexia | 2/26 (7.7%) | 2 | 0/44 (0%) | 0 |
| Swelling | 0/26 (0%) | 0 | 1/44 (2.3%) | 1 |
| Tenderness | 1/26 (3.8%) | 1 | 0/44 (0%) | 0 |
| Thirst | 1/26 (3.8%) | 1 | 0/44 (0%) | 0 |
| Hepatobiliary disorders | ||||
| Biliary dilatation | 1/26 (3.8%) | 1 | 0/44 (0%) | 0 |
| Infections and infestations | ||||
| Bronchitis | 1/26 (3.8%) | 1 | 0/44 (0%) | 0 |
| Nasopharyngitis | 0/26 (0%) | 0 | 1/44 (2.3%) | 2 |
| Oral candidiasis | 0/26 (0%) | 0 | 1/44 (2.3%) | 1 |
| Sinusitis | 2/26 (7.7%) | 2 | 3/44 (6.8%) | 3 |
| Upper respiratory tract infection | 1/26 (3.8%) | 2 | 1/44 (2.3%) | 2 |
| Vulvovaginal mycotic infection | 0/26 (0%) | 0 | 1/44 (2.3%) | 1 |
| Injury, poisoning and procedural complications | ||||
| Contusion | 1/26 (3.8%) | 1 | 0/44 (0%) | 0 |
| Fall | 0/26 (0%) | 0 | 1/44 (2.3%) | 1 |
| Femur fracture | 0/26 (0%) | 0 | 1/44 (2.3%) | 1 |
| Subdural haematoma | 1/26 (3.8%) | 1 | 0/44 (0%) | 0 |
| Investigations | ||||
| Alanine aminotransferase | 0/26 (0%) | 0 | 1/44 (2.3%) | 1 |
| Alanine aminotransferase increased | 3/26 (11.5%) | 4 | 5/44 (11.4%) | 5 |
| Amylase | 0/26 (0%) | 0 | 2/44 (4.5%) | 2 |
| Amylase increased | 3/26 (11.5%) | 5 | 3/44 (6.8%) | 7 |
| Aspartate aminotransferase | 0/26 (0%) | 0 | 1/44 (2.3%) | 1 |
| Aspartate aminotransferase increased | 5/26 (19.2%) | 6 | 6/44 (13.6%) | 7 |
| Blood albumin decreased | 1/26 (3.8%) | 1 | 0/44 (0%) | 0 |
| Blood alkaline phosphatase | 0/26 (0%) | 0 | 1/44 (2.3%) | 1 |
| Blood alkaline phosphatase increased | 4/26 (15.4%) | 6 | 4/44 (9.1%) | 5 |
| Blood bilirubin increased | 0/26 (0%) | 0 | 5/44 (11.4%) | 7 |
| Blood lactate dehydrogenase increased | 1/26 (3.8%) | 1 | 1/44 (2.3%) | 1 |
| Blood sodium decreased | 1/26 (3.8%) | 3 | 0/44 (0%) | 0 |
| Ejection fraction decreased | 1/26 (3.8%) | 1 | 0/44 (0%) | 0 |
| Haematocrit decreased | 2/26 (7.7%) | 3 | 0/44 (0%) | 0 |
| Haemoglobin | 0/26 (0%) | 0 | 1/44 (2.3%) | 3 |
| Haemoglobin decreased | 1/26 (3.8%) | 3 | 0/44 (0%) | 0 |
| Lipase | 0/26 (0%) | 0 | 2/44 (4.5%) | 3 |
| Lipase increased | 2/26 (7.7%) | 6 | 6/44 (13.6%) | 11 |
| Neutrophil count | 0/26 (0%) | 0 | 1/44 (2.3%) | 2 |
| Neutrophil count decreased | 2/26 (7.7%) | 2 | 0/44 (0%) | 0 |
| Neutrophil count increased | 1/26 (3.8%) | 1 | 0/44 (0%) | 0 |
| Platelet count | 0/26 (0%) | 0 | 1/44 (2.3%) | 4 |
| Platelet count decreased | 2/26 (7.7%) | 4 | 3/44 (6.8%) | 4 |
| Protein total increased | 1/26 (3.8%) | 1 | 0/44 (0%) | 0 |
| Transaminases increased | 1/26 (3.8%) | 1 | 0/44 (0%) | 0 |
| Weight decreased | 3/26 (11.5%) | 3 | 5/44 (11.4%) | 5 |
| White blood cell count | 0/26 (0%) | 0 | 1/44 (2.3%) | 2 |
| White blood cell count decreased | 2/26 (7.7%) | 3 | 1/44 (2.3%) | 1 |
| Metabolism and nutrition disorders | ||||
| Decreased appetite | 5/26 (19.2%) | 6 | 9/44 (20.5%) | 11 |
| Dehydration | 0/26 (0%) | 0 | 4/44 (9.1%) | 8 |
| Fluid retention | 0/26 (0%) | 0 | 1/44 (2.3%) | 1 |
| Hypercalcaemia | 0/26 (0%) | 0 | 3/44 (6.8%) | 3 |
| Hyperglycaemia | 1/26 (3.8%) | 1 | 1/44 (2.3%) | 2 |
| Hyperkalaemia | 0/26 (0%) | 0 | 1/44 (2.3%) | 1 |
| Hypoalbuminaemia | 0/26 (0%) | 0 | 4/44 (9.1%) | 4 |
| Hypocalcaemia | 1/26 (3.8%) | 2 | 0/44 (0%) | 0 |
| Hypokalaemia | 4/26 (15.4%) | 4 | 3/44 (6.8%) | 3 |
| Hypomagnesaemia | 1/26 (3.8%) | 1 | 0/44 (0%) | 0 |
| Hypophosphataemia | 0/26 (0%) | 0 | 1/44 (2.3%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 6/26 (23.1%) | 6 | 1/44 (2.3%) | 2 |
| Back pain | 0/26 (0%) | 0 | 2/44 (4.5%) | 3 |
| Bone pain | 0/26 (0%) | 0 | 2/44 (4.5%) | 2 |
| Exostosis | 1/26 (3.8%) | 1 | 0/44 (0%) | 0 |
| Flank pain | 0/26 (0%) | 0 | 1/44 (2.3%) | 1 |
| Groin pain | 0/26 (0%) | 0 | 1/44 (2.3%) | 1 |
| Muscle discomfort | 1/26 (3.8%) | 1 | 0/44 (0%) | 0 |
| Muscle spasms | 0/26 (0%) | 0 | 1/44 (2.3%) | 1 |
| Muscular weakness | 0/26 (0%) | 0 | 2/44 (4.5%) | 3 |
| Musculoskeletal chest pain | 1/26 (3.8%) | 1 | 3/44 (6.8%) | 3 |
| Musculoskeletal discomfort | 1/26 (3.8%) | 1 | 0/44 (0%) | 0 |
| Musculoskeletal pain | 0/26 (0%) | 0 | 1/44 (2.3%) | 2 |
| Myalgia | 0/26 (0%) | 0 | 2/44 (4.5%) | 3 |
| Neck pain | 1/26 (3.8%) | 1 | 4/44 (9.1%) | 4 |
| Pain in extremity | 1/26 (3.8%) | 1 | 5/44 (11.4%) | 5 |
| Pain in jaw | 0/26 (0%) | 0 | 1/44 (2.3%) | 2 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Tumour pain | 1/26 (3.8%) | 2 | 0/44 (0%) | 0 |
| Nervous system disorders | ||||
| Dizziness | 2/26 (7.7%) | 3 | 3/44 (6.8%) | 3 |
| Dysgeusia | 2/26 (7.7%) | 2 | 0/44 (0%) | 0 |
| Dyskinesia | 0/26 (0%) | 0 | 1/44 (2.3%) | 1 |
| Headache | 6/26 (23.1%) | 7 | 10/44 (22.7%) | 13 |
| Horner's syndrome | 0/26 (0%) | 0 | 1/44 (2.3%) | 1 |
| Hypoaesthesia | 1/26 (3.8%) | 1 | 0/44 (0%) | 0 |
| Migraine | 1/26 (3.8%) | 1 | 0/44 (0%) | 0 |
| Neuralgia | 0/26 (0%) | 0 | 1/44 (2.3%) | 1 |
| Neuropathy peripheral | 1/26 (3.8%) | 1 | 3/44 (6.8%) | 3 |
| Peripheral sensory neuropathy | 0/26 (0%) | 0 | 1/44 (2.3%) | 1 |
| Taste disorder | 0/26 (0%) | 0 | 1/44 (2.3%) | 1 |
| Tremor | 0/26 (0%) | 0 | 1/44 (2.3%) | 1 |
| Psychiatric disorders | ||||
| Anxiety | 0/26 (0%) | 0 | 3/44 (6.8%) | 3 |
| Confusional state | 0/26 (0%) | 0 | 2/44 (4.5%) | 2 |
| Depression | 2/26 (7.7%) | 5 | 3/44 (6.8%) | 3 |
| Hallucination | 1/26 (3.8%) | 1 | 0/44 (0%) | 0 |
| Insomnia | 2/26 (7.7%) | 2 | 2/44 (4.5%) | 4 |
| Restlessness | 1/26 (3.8%) | 1 | 1/44 (2.3%) | 1 |
| Suicidal ideation | 1/26 (3.8%) | 2 | 0/44 (0%) | 0 |
| Renal and urinary disorders | ||||
| Chromaturia | 0/26 (0%) | 0 | 1/44 (2.3%) | 1 |
| Haematuria | 0/26 (0%) | 0 | 1/44 (2.3%) | 1 |
| Nocturia | 0/26 (0%) | 0 | 1/44 (2.3%) | 1 |
| Proteinuria | 1/26 (3.8%) | 1 | 0/44 (0%) | 0 |
| Reproductive system and breast disorders | ||||
| Pelvic pain | 0/26 (0%) | 0 | 1/44 (2.3%) | 1 |
| Vulvovaginal dryness | 1/26 (3.8%) | 1 | 0/44 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Acute respiratory failure | 1/26 (3.8%) | 1 | 0/44 (0%) | 0 |
| Cough | 1/26 (3.8%) | 1 | 4/44 (9.1%) | 6 |
| Dysphonia | 0/26 (0%) | 0 | 1/44 (2.3%) | 1 |
| Dyspnoea | 5/26 (19.2%) | 6 | 8/44 (18.2%) | 8 |
| Dyspnoea exertional | 0/26 (0%) | 0 | 2/44 (4.5%) | 3 |
| Epistaxis | 1/26 (3.8%) | 1 | 1/44 (2.3%) | 1 |
| Pleural effusion | 1/26 (3.8%) | 1 | 0/44 (0%) | 0 |
| Pneumonitis | 1/26 (3.8%) | 1 | 0/44 (0%) | 0 |
| Productive cough | 0/26 (0%) | 0 | 2/44 (4.5%) | 2 |
| Rhinitis allergic | 0/26 (0%) | 0 | 1/44 (2.3%) | 1 |
| Sinus congestion | 0/26 (0%) | 0 | 2/44 (4.5%) | 2 |
| Skin and subcutaneous tissue disorders | ||||
| Alopecia | 0/26 (0%) | 0 | 1/44 (2.3%) | 1 |
| Erythema | 0/26 (0%) | 0 | 3/44 (6.8%) | 3 |
| Night sweats | 0/26 (0%) | 0 | 2/44 (4.5%) | 2 |
| Pain of skin | 1/26 (3.8%) | 1 | 0/44 (0%) | 0 |
| Palmar-plantar erythrodysaesthesia syndrome | 0/26 (0%) | 0 | 1/44 (2.3%) | 1 |
| Pruritus | 1/26 (3.8%) | 1 | 0/44 (0%) | 0 |
| Rash | 1/26 (3.8%) | 1 | 3/44 (6.8%) | 5 |
| Skin atrophy | 0/26 (0%) | 0 | 1/44 (2.3%) | 1 |
| Vascular disorders | ||||
| Deep vein thrombosis | 0/26 (0%) | 0 | 1/44 (2.3%) | 1 |
| Flushing | 0/26 (0%) | 0 | 1/44 (2.3%) | 1 |
| Hot flush | 6/26 (23.1%) | 6 | 4/44 (9.1%) | 4 |
| Hypertension | 3/26 (11.5%) | 8 | 6/44 (13.6%) | 10 |
| Hypotension | 0/26 (0%) | 0 | 2/44 (4.5%) | 2 |
| Lymphoedema | 0/26 (0%) | 0 | 1/44 (2.3%) | 1 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | Sarah Cannon Development Innovations, LLC |
|---|---|
| Organization | Sarah Cannon Development Innovations, LLC |
| Phone | 844-710-6157 |
| CANN.InnovationsMedical@sarahcannon.com |
- SCRI BRE 203