Trial Outcomes & Findings for Testing AZD1775 inC Combination With Radiotherapy and Chemotherapy in Cervical, Upper Vaginal and Uterine Cancers (NCT NCT03345784)

NCT ID: NCT03345784

Last Updated: 2024-02-20

Results Overview

To determine the recommended phase II dose (RP2D) and safety profile of AZD1775 in combination with radiotherapy and concurrent cisplatin in patients with gynecological cancers.

• Recruitment status: TERMINATED
• Study phase: PHASE1
• Target enrollment: 10 participants
• Primary outcome timeframe: Up to week 5
• Results posted on: 2024-02-20

Participant Flow

This study was performed at 5 academic centers in the United States (four sites) and Canada (one site). It enrolled participants from May 2018 to July 2020.

Participant milestones

Measure	Treatment (Radiation Therapy, AZD1775 3 Days/Week, Cisplatin) Dose Level 1 Patients undergo external beam radiation therapy (45-50Gy) on days 1-5, receive 100mg AZD1775 PO on days 1, 3, and 5, and receive 40 mg/m2 cisplatin IV over 1 hour on day 1 or 3. Cycles repeat each week for up to 5 weeks in the absence of disease progression of unacceptable toxicity.	Treatment (Radiation Therapy, AZD1775 2 Days/Week, Cisplatin) Dose Level -1 Patients undergo external beam radiation therapy (45-50Gy) on days 1-5, receive 100mg AZD1775 PO on days 3 and 5, and receive 40 mg/m2 cisplatin IV over 1 hour on day 1 or 3. Cycles repeat each week for up to 5 weeks in the absence of disease progression of unacceptable toxicity.
Overall Study STARTED	5	5
Overall Study COMPLETED	3	4
Overall Study NOT COMPLETED	2	1

Reasons for withdrawal

Measure	Treatment (Radiation Therapy, AZD1775 3 Days/Week, Cisplatin) Dose Level 1 Patients undergo external beam radiation therapy (45-50Gy) on days 1-5, receive 100mg AZD1775 PO on days 1, 3, and 5, and receive 40 mg/m2 cisplatin IV over 1 hour on day 1 or 3. Cycles repeat each week for up to 5 weeks in the absence of disease progression of unacceptable toxicity.	Treatment (Radiation Therapy, AZD1775 2 Days/Week, Cisplatin) Dose Level -1 Patients undergo external beam radiation therapy (45-50Gy) on days 1-5, receive 100mg AZD1775 PO on days 3 and 5, and receive 40 mg/m2 cisplatin IV over 1 hour on day 1 or 3. Cycles repeat each week for up to 5 weeks in the absence of disease progression of unacceptable toxicity.
Overall Study Withdrawal by Subject	2	1

Baseline Characteristics

Testing AZD1775 inC Combination With Radiotherapy and Chemotherapy in Cervical, Upper Vaginal and Uterine Cancers

Baseline characteristics by cohort

Measure	Treatment (Radiation Therapy, AZD1775 3 Days/Week, Cisplatin) Dose Level 1 n=5 Participants Patients undergo external beam radiation therapy (45-50Gy) on days 1-5, receive 100mg AZD1775 PO on days 1, 3, and 5, and receive 40 mg/m2 cisplatin IV over 1 hour on day 1 or 3. Cycles repeat each week for up to 5 weeks in the absence of disease progression of unacceptable toxicity.	Treatment (Radiation Therapy, AZD1775 2 Days/Week, Cisplatin) Dose Level -1 n=5 Participants Patients undergo external beam radiation therapy (45-50Gy) on days 1-5, receive 100mg AZD1775 PO on days 3 and 5, and receive 40 mg/m2 cisplatin IV over 1 hour on day 1 or 3. Cycles repeat each week for up to 5 weeks in the absence of disease progression of unacceptable toxicity.	Total n=10 Participants Total of all reporting groups
Age, Continuous	48 years n=5 Participants	53 years n=7 Participants	50.5 years n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	5 Participants n=7 Participants	10 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	3 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment Canada	2 participants n=5 Participants	1 participants n=7 Participants	3 participants n=5 Participants
Region of Enrollment United States	3 participants n=5 Participants	4 participants n=7 Participants	7 participants n=5 Participants
ECOG Performance Status 0	1 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants
ECOG Performance Status 1	4 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants
Primary Site Cervical	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants
Primary Site Uterine	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Prior Therapy Surgery	5 Participants n=5 Participants	5 Participants n=7 Participants	10 Participants n=5 Participants
Prior Therapy Radiation	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
FIGO Stage IA	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
FIGO Stage IB	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
FIGO Stage IIA	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
FIGO Stage IIB	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
FIGO Stage IIIB	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Grade 1 - Low grade (well differentiated)	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Grade 2 - Intermediate grade (moderately differentiated)	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Grade 3 - High grade (poorly differentiated)	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Grade Unknown	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Histology Cervical squamous-cell carcinoma	3 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants
Histology Cervical adenocarcinoma	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Histology Uterine endometrioid adenocarcinoma	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to week 5

Population: Participants that were evaluable for response.

To determine the recommended phase II dose (RP2D) and safety profile of AZD1775 in combination with radiotherapy and concurrent cisplatin in patients with gynecological cancers.

Outcome measures

Measure	Treatment (Radiation Therapy, AZD1775 3 Days/Week, Cisplatin) Dose Level 1 n=3 Participants Patients undergo external beam radiation therapy on days 1-5, receive AZD1775 PO on days 1, 3, and 5, and receive cisplatin IV over 1 hour on day 1 or 3. Cycles repeat each week for up to 5 weeks in the absence of disease progression of unacceptable toxicity.	Treatment (Radiation Therapy, AZD1775 2 Days/Week, Cisplatin) Dose Level -1 n=4 Participants Patients undergo external beam radiation therapy on days 1-5, receive AZD1775 PO on days 3 and 5, and receive cisplatin IV over 1 hour on day 1 or 3. Cycles repeat each week for up to 5 weeks in the absence of disease progression of unacceptable toxicity.
Recommended Phase 2 Dose Defined as the Dose Level With < 1/6 Patients With Dose Limiting Toxicities	NA Participants Could not be determined due to early study closure (due to clinically significant toxicity, slow accrual and significant adverse events also reported with the combination of AZD1775 and chemoradiation in other studies)	NA Participants Could not be determined due to early study closure (due to clinically significant toxicity, slow accrual and significant adverse events also reported with the combination of AZD1775 and chemoradiation in other studies)

SECONDARY outcome

Timeframe: Up to 2 years

To determine the acute and late toxicity of AZD1775 when administered to patients with gynecological cancer in combination with standard radiotherapy and concurrent cisplatin. Frequency and severity of adverse events will be tabulated using counts and proportions detailing frequently occurring, serious and severe events of interest. Adverse events will be summarized using all adverse events experienced, although a subanalysis may be conducted including only those adverse events in which the treating physician deems possibly, probably or definitely attributable to one or both study treatments.

Outcome measures

Measure	Treatment (Radiation Therapy, AZD1775 3 Days/Week, Cisplatin) Dose Level 1 n=4 Participants Patients undergo external beam radiation therapy on days 1-5, receive AZD1775 PO on days 1, 3, and 5, and receive cisplatin IV over 1 hour on day 1 or 3. Cycles repeat each week for up to 5 weeks in the absence of disease progression of unacceptable toxicity.	Treatment (Radiation Therapy, AZD1775 2 Days/Week, Cisplatin) Dose Level -1 n=5 Participants Patients undergo external beam radiation therapy on days 1-5, receive AZD1775 PO on days 3 and 5, and receive cisplatin IV over 1 hour on day 1 or 3. Cycles repeat each week for up to 5 weeks in the absence of disease progression of unacceptable toxicity.
Frequency and Severity of AZD1775 Toxicity Events in Patients With Gynecological Cancer in Combination With Standard RT and Concurrent Cisplatin Related Grade 1-2 Toxicities	37 events	36 events
Frequency and Severity of AZD1775 Toxicity Events in Patients With Gynecological Cancer in Combination With Standard RT and Concurrent Cisplatin All Grade 1-2 Toxicities	46 events	53 events
Frequency and Severity of AZD1775 Toxicity Events in Patients With Gynecological Cancer in Combination With Standard RT and Concurrent Cisplatin All Grade 3-4 Toxicities	8 events	3 events
Frequency and Severity of AZD1775 Toxicity Events in Patients With Gynecological Cancer in Combination With Standard RT and Concurrent Cisplatin Related Grade 3-4 Toxicities	8 events	3 events

SECONDARY outcome

Timeframe: Up to 2 years

Population: Not analyzed as samples were not collected, therefore no data are available.

To evaluate the pharmacodynamic effects of AZD1775 drugs when administered in combination with radiotherapy and concurrent cisplatin. Pharmacodynamic biomarkers will include: pCDC2, Ki67, γH2AX, pH3, and CC3. Associations between pharmacokinetic data with toxicity profiles will be performed primarily using descriptive statistics; however, logistic regression may be used if warranted.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From start of treatment to time of progression or death, whichever occurs first, assessed up to 2 years

To obtain preliminary information about the progression-free survival of AZD1775 in combination with radiotherapy and concurrent cisplatin in women with locally advanced gynecological cancer. Progression is defined a clinical or radiological using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Outcome measures

Measure	Treatment (Radiation Therapy, AZD1775 3 Days/Week, Cisplatin) Dose Level 1 n=3 Participants Patients undergo external beam radiation therapy on days 1-5, receive AZD1775 PO on days 1, 3, and 5, and receive cisplatin IV over 1 hour on day 1 or 3. Cycles repeat each week for up to 5 weeks in the absence of disease progression of unacceptable toxicity.	Treatment (Radiation Therapy, AZD1775 2 Days/Week, Cisplatin) Dose Level -1 n=4 Participants Patients undergo external beam radiation therapy on days 1-5, receive AZD1775 PO on days 3 and 5, and receive cisplatin IV over 1 hour on day 1 or 3. Cycles repeat each week for up to 5 weeks in the absence of disease progression of unacceptable toxicity.
Progression-free Survival 4 Months Post Treatment · Alive and progression-free post-treatment	3 Participants	4 Participants
Progression-free Survival 4 Months Post Treatment · Lost to Follow-Up	0 Participants	0 Participants
Progression-free Survival 2 Years Post Treatment · Alive and progression-free post-treatment	3 Participants	3 Participants
Progression-free Survival 2 Years Post Treatment · Lost to Follow-Up	0 Participants	1 Participants

Adverse Events

Treatment (Radiation Therapy, AZD1775 3 Days/Week, Cisplatin) Dose Level 1

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

Treatment (Radiation Therapy, AZD1775 2 Days/Week, Cisplatin) Dose Level -1

Serious events: 1 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Measure	Treatment (Radiation Therapy, AZD1775 3 Days/Week, Cisplatin) Dose Level 1 n=4 participants at risk Patients undergo external beam radiation therapy (45-50Gy) on days 1-5, receive 100mg AZD1775 PO on days 1, 3, and 5, and receive 40 mg/m2 cisplatin IV over 1 hour on day 1 or 3. Cycles repeat each week for up to 5 weeks in the absence of disease progression of unacceptable toxicity.	Treatment (Radiation Therapy, AZD1775 2 Days/Week, Cisplatin) Dose Level -1 n=5 participants at risk Patients undergo external beam radiation therapy (45-50Gy) on days 1-5, receive 100mg AZD1775 PO on days 3 and 5, and receive 40 mg/m2 cisplatin IV over 1 hour on day 1 or 3. Cycles repeat each week for up to 5 weeks in the absence of disease progression of unacceptable toxicity.
Gastrointestinal disorders Grade 3 Diarrhea	25.0% 1/4 • Number of events 2 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.	0.00% 0/5 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.
Blood and lymphatic system disorders Grade 3 Lymphocyte Count Decreased	0.00% 0/4 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.	20.0% 1/5 • Number of events 1 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.

Other adverse events

Measure	Treatment (Radiation Therapy, AZD1775 3 Days/Week, Cisplatin) Dose Level 1 n=4 participants at risk Patients undergo external beam radiation therapy (45-50Gy) on days 1-5, receive 100mg AZD1775 PO on days 1, 3, and 5, and receive 40 mg/m2 cisplatin IV over 1 hour on day 1 or 3. Cycles repeat each week for up to 5 weeks in the absence of disease progression of unacceptable toxicity.	Treatment (Radiation Therapy, AZD1775 2 Days/Week, Cisplatin) Dose Level -1 n=5 participants at risk Patients undergo external beam radiation therapy (45-50Gy) on days 1-5, receive 100mg AZD1775 PO on days 3 and 5, and receive 40 mg/m2 cisplatin IV over 1 hour on day 1 or 3. Cycles repeat each week for up to 5 weeks in the absence of disease progression of unacceptable toxicity.
Gastrointestinal disorders Nausea	100.0% 4/4 • Number of events 5 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.	100.0% 5/5 • Number of events 7 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.
Gastrointestinal disorders Diarrhea	75.0% 3/4 • Number of events 6 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.	80.0% 4/5 • Number of events 4 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.
General disorders Fatigue	75.0% 3/4 • Number of events 3 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.	60.0% 3/5 • Number of events 4 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.
Metabolism and nutrition disorders Hypomagnesemia	75.0% 3/4 • Number of events 3 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.	0.00% 0/5 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.
Investigations Thrombocytopenia	75.0% 3/4 • Number of events 6 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.	0.00% 0/5 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.
Blood and lymphatic system disorders Anemia	75.0% 3/4 • Number of events 6 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.	0.00% 0/5 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.
Metabolism and nutrition disorders Anorexia	75.0% 3/4 • Number of events 3 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.	20.0% 1/5 • Number of events 1 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.
Gastrointestinal disorders Abdominal pain	50.0% 2/4 • Number of events 3 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.	20.0% 1/5 • Number of events 1 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.
Investigations Creatinine increased	50.0% 2/4 • Number of events 2 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.	20.0% 1/5 • Number of events 1 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.
Metabolism and nutrition disorders Hyponatremia	50.0% 2/4 • Number of events 3 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.	0.00% 0/5 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.
Investigations Neutropenia	25.0% 1/4 • Number of events 2 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.	20.0% 1/5 • Number of events 2 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.
Investigations Lymphopenia	25.0% 1/4 • Number of events 2 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.	40.0% 2/5 • Number of events 3 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.
Metabolism and nutrition disorders Hypoalbuminemia	25.0% 1/4 • Number of events 3 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.	20.0% 1/5 • Number of events 2 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.
Gastrointestinal disorders Vomiting	25.0% 1/4 • Number of events 1 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.	80.0% 4/5 • Number of events 4 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.
Injury, poisoning and procedural complications Dermatitis	0.00% 0/4 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.	60.0% 3/5 • Number of events 3 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.
Investigations Alanine aminotransferase increased	0.00% 0/4 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.	20.0% 1/5 • Number of events 1 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.
Investigations White blood cell decreased	50.0% 2/4 • Number of events 4 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.	0.00% 0/5 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.
Investigations Alkaline phosphatase increased	25.0% 1/4 • Number of events 1 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.	0.00% 0/5 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.
Skin and subcutaneous tissue disorders Blister Base Scalp	25.0% 1/4 • Number of events 1 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.	0.00% 0/5 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.
Injury, poisoning and procedural complications Bruising	25.0% 1/4 • Number of events 1 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.	0.00% 0/5 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.
Injury, poisoning and procedural complications Burn	25.0% 1/4 • Number of events 1 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.	0.00% 0/5 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.
General disorders Chills	25.0% 1/4 • Number of events 1 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.	0.00% 0/5 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.
Nervous system disorders Concentration impairment	25.0% 1/4 • Number of events 1 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.	0.00% 0/5 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.
Gastrointestinal disorders Constipation	25.0% 1/4 • Number of events 1 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.	20.0% 1/5 • Number of events 1 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.
Respiratory, thoracic and mediastinal disorders Cough	25.0% 1/4 • Number of events 1 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.	0.00% 0/5 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.
Nervous system disorders Dizziness	25.0% 1/4 • Number of events 1 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.	20.0% 1/5 • Number of events 1 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.
Gastrointestinal disorders Dry mouth	25.0% 1/4 • Number of events 1 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.	0.00% 0/5 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.
Nervous system disorders Headache	25.0% 1/4 • Number of events 1 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.	20.0% 1/5 • Number of events 1 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.
Vascular disorders Hot flashes	25.0% 1/4 • Number of events 1 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.	20.0% 1/5 • Number of events 1 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.
Metabolism and nutrition disorders Hypocalcemia	25.0% 1/4 • Number of events 2 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.	20.0% 1/5 • Number of events 1 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.
Metabolism and nutrition disorders Hypokalemia	25.0% 1/4 • Number of events 2 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.	20.0% 1/5 • Number of events 2 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.
Metabolism and nutrition disorders Hypophosphatemia	25.0% 1/4 • Number of events 1 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.	0.00% 0/5 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.
Psychiatric disorders Insomnia	25.0% 1/4 • Number of events 1 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.	0.00% 0/5 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.
General disorders Pain	25.0% 1/4 • Number of events 1 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.	0.00% 0/5 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.
Reproductive system and breast disorders Pelvic pain	25.0% 1/4 • Number of events 1 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.	20.0% 1/5 • Number of events 1 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.
Ear and labyrinth disorders Tinnitus	25.0% 1/4 • Number of events 1 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.	0.00% 0/5 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.
Investigations Weight loss	25.0% 1/4 • Number of events 1 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.	20.0% 1/5 • Number of events 1 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.
Investigations Aspartate aminotransferase increased	0.00% 0/4 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.	40.0% 2/5 • Number of events 2 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.
Metabolism and nutrition disorders Hyperglycemia	0.00% 0/4 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.	40.0% 2/5 • Number of events 2 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.
Renal and urinary disorders Urinary frequency	0.00% 0/4 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.	40.0% 2/5 • Number of events 2 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/4 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.	20.0% 1/5 • Number of events 1 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/4 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.	20.0% 1/5 • Number of events 1 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.
Metabolism and nutrition disorders Dehydration	0.00% 0/4 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.	20.0% 1/5 • Number of events 1 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.
Skin and subcutaneous tissue disorders Dry skin	0.00% 0/4 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.	20.0% 1/5 • Number of events 1 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.
Nervous system disorders Dysgeusia	0.00% 0/4 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.	20.0% 1/5 • Number of events 1 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.
Renal and urinary disorders Dysuria	0.00% 0/4 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.	20.0% 1/5 • Number of events 1 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.
Gastrointestinal disorders Gastroesophageal reflux disease	0.00% 0/4 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.	20.0% 1/5 • Number of events 1 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.
Vascular disorders Hypotension	0.00% 0/4 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.	20.0% 1/5 • Number of events 1 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.
Psychiatric disorders Paranoia thoughts	0.00% 0/4 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.	20.0% 1/5 • Number of events 1 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.
Psychiatric disorders Paranoid thoughts	0.00% 0/4 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.	20.0% 1/5 • Number of events 1 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.
Renal and urinary disorders Proteinuria	0.00% 0/4 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.	20.0% 1/5 • Number of events 1 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.
Skin and subcutaneous tissue disorders Rash acneiform	0.00% 0/4 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.	20.0% 1/5 • Number of events 1 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/4 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.	20.0% 1/5 • Number of events 1 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.
Renal and urinary disorders Urinary incontinence	0.00% 0/4 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.	20.0% 1/5 • Number of events 1 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.
Renal and urinary disorders Urinary tract pain	0.00% 0/4 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.	20.0% 1/5 • Number of events 1 • 2 years Through regular investigator assessment, regular laboratory testing, etc. Frequency and severity of adverse events were tabulated using counts and proportions.

Additional Information

Dr. Stephanie Lheureux, PI

University Health Network, Princess Margaret Cancer Centre

Phone: 416-946-2818

Email: stephanie.lheureux@uhnresearch.ca

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: LTE60