Study of TRC105 and Bevacizumab in Patients With Refractory Gestational Trophoblastic Neoplasia (GTN)

• Sponsor: Tracon Pharmaceuticals Inc. (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02664961
• Collaborator: (none)
• Enrollment: 3
• Locations: 3
• Arm: 1
• Actual Duration (Months): 32
• Patient Per Site: 1
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The purpose of the study is to determine the overall response rate of single agent TRC105 and the combination of TRC105 and bevacizumab in patients with refractory GTN (including choriocarcinoma, placental site trophoblastic tumor (PSTT), and epithelioid trophoblastic tumor (ETT)). Up to 30 patients will be treated.

Condition or Disease	Intervention/Treatment	Phase
Gestational Trophoblastic Neoplasia; Choriocarcinoma; Placental Site Trophoblastic Tumor; Epithelioid Trophoblastic Tumor	Drug: TRC105; Drug: Bevacizumab	Phase 2

Detailed Description

TRC105 is a monoclonal antibody that binds to endoglin, an angiogenic target highly expressed on the tumor vessels and tumor cells in gestational trophoblastic neoplasia (GTN). Bevacizumab is a monoclonal antibody to vascular endothelial growth factor (VEGF) that inhibits angiogenesis and extends survival in patients with a wide variety of solid tumor types. TRC105 has been well tolerated as a single agent and when combined with bevacizumab. These antibodies may be efficacious in refractory GTN, a tumor type that is highly vascular and has been shown to densely express endoglin.

Study Design

• Study Type: Interventional
• Actual Enrollment: 3 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2A Study of TRC105 (With Option to Add Bevacizumab) in Patients With Refractory Gestational Trophoblastic Neoplasia (GTN)
• Actual Study Start Date: Mar 1, 2016
• Actual Primary Completion Date: Apr 1, 2018
• Actual Study Completion Date: Nov 1, 2018

Arms and Interventions

Arm

Intervention/Treatment

Experimental: TRC105 and/or bevacizumab All subjects will begin by receiving single agent TRC105 weekly. In the case of a complete response to single agent TRC105, subjects will continue to receive single agent TRC105 for at least 3 months following complete response. In the case of a partial response (without a complete response) to single agent TRC105, bevacizumab every two weeks will be added. In the absence of a partial or complete response to single agent TRC105, subjects will receive single agent bevacizumab every two weeks. In the absence of a complete response to single agent bevacizumab, or for subjects who have documented disease progression on a prior bevacizumab containing regimen, subjects will receive TRC105 weekly and bevacizumab every two weeks.

Drug: TRC105; Subjects will begin by receiving TRC105 weekly. Subjects who achieve a complete response on single agent TRC105 may transition to every two week dosing.; Other Names: Chimeric Antibody (TRC105) to CD105 ; Drug: Bevacizumab; Bevacizumab will be dosed every two weeks.; Other Names: Avastin

Outcome Measures

Primary Outcome Measures

1. Overall Response Rate on TRC105 Alone and on the Combination of TRC105 and Bevacizumab [8 weeks]

   Antitumor Activity of Single Agent TRC105 and the Combination of TRC105 and Bevacizumab will be assessed via RECIST 1.1 and by measuring circulating bHCG. Disease progression is defined as >20% increase (the absolute increase must be ≥10 IU/L) above the nadir on consecutive measurements separated by at least two weeks; Partial response is defined as a hCG decrease of 50% or more from starting value on consecutive measurements; Complete response will be defined as normalization of hCG on consecutive measurements separated by at least two weeks; Stable disease will be defined as the absence of response or progression on 3 consecutive measurements separated by at least two weeks.

Secondary Outcome Measures

1. Progression-Free Survival (PFS) [8 weeks]

   Median Progression-Free Survival (PFS) via Serum hCG levels and response evaluation according to RECIST version 1.1 as a preliminary measure of the antitumor activity of TRC105. Disease progression is defined as >20% increase (the absolute increase must be ≥10 IU/L) above the nadir on consecutive measurements separated by at least two weeks; Partial response is defined as a hCG decrease of 50% or more from starting value on consecutive measurements; Complete response will be defined as normalization of hCG on consecutive measurements separated by at least two weeks; Stable disease will be defined as the absence of response or progression on 3 consecutive measurements separated by at least two weeks. Patients must have screening (baseline) and at least one on study CT scan to be considered evaluable.

2. Overall Response Rate on Bevacizumab Alone [8 weeks]

   Overall Response Rate on bevacizumab alone according to RECIST 1.1 in combination with serum hCG levels. Disease progression is defined as >20% increase (the absolute increase must be ≥10 IU/L) above the nadir on consecutive measurements separated by at least two weeks; Partial response is defined as a hCG decrease of 50% or more from starting value on consecutive measurements; Complete response will be defined as normalization of hCG on consecutive measurements separated by at least two weeks; Stable disease will be defined as the absence of response or progression on 3 consecutive measurements separated by at least two weeks.

3. Maximum Plasma Concentration (Cmax) of TRC105. [cycle 2 day 1 (28 days after initiation of dosing)]

   Mean serum TRC105 concentrations were assessed at cycle 1 and cycle 2 on day 1, 8, 15, and 22 and on day 1 of every subsequent cycle using validated methods in order to determine the Cmax of TRC105

4. TRC105 Immunogenicity as Assessed by Anti-Product Antibody (APA). [8 weeks]

   Anti-Product Antibody (APA) concentrations will be measured using validated ELISA methods at the time points specified in the protocol. APA concentrations will be evaluated in the context of pharmacokinetic parameters and AE profiles. Number of patients with positive APA titers on study will be reported.

5. Frequency and Severity of Adverse Events [20 months]

   Determine frequency and severity of adverse events as assessed by NCI CTCAE (Version 4.03)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 16 Years to 99 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Willingness and ability to consent for self to participate in study

2. Willingness and ability to comply with study procedures

3. Elevated serum hCG (in cases of choriocarcinoma); elevated hCG or measurable disease (in cases of PSTT or ETT)

4. Histologically proven trophoblastic neoplasia, or clinically demonstrated trophoblastic neoplasia that has progressed following treatment with at least one chemotherapy regimen that included 2 or more chemotherapy agents.

5. Age of 16 years or older

6. ECOG performance status ≤ 1

7. Resolution of all acute adverse events resulting from prior cancer therapies to NCI CTCAE grade ≤ 1 or baseline

8. Adequate organ function

Exclusion Criteria:

1. Male

2. Prior treatment with TRC105

3. . Current treatment on another therapeutic clinical trial

4. Uncontrolled chronic hypertension defined as systolic > 150 or diastolic > 90 despite optimal therapy

5. Significant pericardial effusion, pleural effusion, or ascites

6. Active bleeding or pathologic condition that carries a high risk of bleeding

7. Tumors located in the central chest or other location where bleeding is associated with high morbidity

8. Thrombolytic use (except to maintain i.v. catheters) within 10 days prior to first day of study therapy

9. Angina, MI, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, arterial embolism, pulmonary embolism, percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass graft (CABG) within the past 6 months. Deep venous thrombosis within 6 months, unless the patient is therapeutically anti-coagulated for at least 2 weeks. In this situation, low molecular weight heparin is preferred

10. Known active viral or nonviral hepatitis

11. Pregnant or actively breastfeeding without intention to discontinue prior to initiation of study

12. Open wounds or unhealed fractures within 28 days of starting study treatment

13. History of peptic ulcer disease or erosive gastritis within the past 6 months, unless treated for the condition and complete resolution has been documented by esophagogastroduodenoscopy (EGD) within 28 days of starting study treatment

14. History of gastrointestinal perforation or fistula in the past 6 months, or while previously on antiangiogenic therapy, unless underlying risk has been resolved

15. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness

16. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient inappropriate for this study

17. History of brain involvement with cancer, spinal cord compression, or carcinomatous meningitis, or new evidence of brain or leptomeningeal disease. Patients with radiated or resected lesions are permitted, provided the lesions are fully treated and inactive, patients are asymptomatic, and no steroids have been administered for brain edema for at least 28 days

18. Receipt of systemic anticancer therapy, including investigational agents, within 28 days of starting study treatment. If anticancer therapy was given within 28 days of starting study treatment, patients may be included if 5 times the elimination half-life of the drug has passed

19. Patients who have received wide field radiotherapy ≤ 28 days (defined as > 50% of volume of pelvic bones or equivalent) or limited field radiation for palliation < 14 days prior to starting study treatment or those patients who have not recovered adequately from side effects of such therapy

20. Major surgical procedure or significant traumatic injury within 6 weeks prior to study registration or not fully recovered from any such procedure

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02215
2	Ohio State University	Columbus	Ohio	United States	43210
3	UT Southwestern	Dallas	Texas	United States	75390

Sponsors and Collaborators

• Tracon Pharmaceuticals Inc.

Investigators

• Study Director: Charles Theuer, MD, PhD, Tracon Pharmaceuticals Inc.

Study Documents (Full-Text)

• Statistical Analysis Plan - Aug 7, 2018
• Study Protocol - Sep 27, 2016

More Information

Publications

None provided.

• Responsible Party: Tracon Pharmaceuticals Inc.
• ClinicalTrials.gov Identifier: NCT02664961
• Other Study ID Numbers: 105GTN201
• First Posted: Jan 27, 2016
• Last Update Posted: Jul 23, 2019
• Last Verified: May 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Tracon Pharmaceuticals Inc.: TRC105; CD105; Endoglin; Angiogenesis inhibitor; GTN; Bevacizumab; Avastin
• Additional relevant MeSH terms: Neoplasms; Choriocarcinoma; Trophoblastic Neoplasms; Gestational Trophoblastic Disease; Trophoblastic Tumor, Placental Site; Bevacizumab

Study Results

Participant Flow

Arm/Group Title	TRC105 and/or Bevacizumab
Arm/Group Description	All subjects will begin by receiving single agent TRC105 weekly. In the case of a complete response to single agent TRC105, subjects will continue to receive single agent TRC105 for at least 3 months following complete response. In the case of a partial response (without a complete response) to single agent TRC105, bevacizumab every two weeks will be added. In the absence of a partial or complete response to single agent TRC105, subjects will receive single agent bevacizumab every two weeks. In the absence of a complete response to single agent bevacizumab, or for subjects who have documented disease progression on a prior bevacizumab containing regimen, subjects will receive TRC105 weekly and bevacizumab every two weeks. TRC105: Subjects will begin by receiving TRC105 weekly. Subjects who achieve a complete response on single agent TRC105 may transition to every two week dosing. Bevacizumab: Bevacizumab will be dosed every two weeks.
Period Title: Overall Study
STARTED	3
COMPLETED	3
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	TRC105 and/or Bevacizumab
Arm/Group Description	All subjects will begin by receiving single agent TRC105 weekly. In the case of a complete response to single agent TRC105, subjects will continue to receive single agent TRC105 for at least 3 months following complete response. In the case of a partial response (without a complete response) to single agent TRC105, bevacizumab every two weeks will be added. In the absence of a partial or complete response to single agent TRC105, subjects will receive single agent bevacizumab every two weeks. In the absence of a complete response to single agent bevacizumab, or for subjects who have documented disease progression on a prior bevacizumab containing regimen, subjects will receive TRC105 weekly and bevacizumab every two weeks. TRC105: Subjects will begin by receiving TRC105 weekly. Subjects who achieve a complete response on single agent TRC105 may transition to every two week dosing. Bevacizumab: Bevacizumab will be dosed every two weeks.
Overall Participants	3
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	48
Sex: Female, Male (Count of Participants)
Female	3 100%
Male	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	3 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 33.3%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	0 0%
More than one race	0 0%
Unknown or Not Reported	2 66.7%
Region of Enrollment (Count of Participants)
United States	3 100%
Number of Prior Regimens (prior regimens) [Median (Full Range) ]
Median (Full Range) [prior regimens]	6

Outcome Measures

1. Primary Outcome

Title	Overall Response Rate on TRC105 Alone and on the Combination of TRC105 and Bevacizumab
Description	Antitumor Activity of Single Agent TRC105 and the Combination of TRC105 and Bevacizumab will be assessed via RECIST 1.1 and by measuring circulating bHCG. Disease progression is defined as >20% increase (the absolute increase must be ≥10 IU/L) above the nadir on consecutive measurements separated by at least two weeks; Partial response is defined as a hCG decrease of 50% or more from starting value on consecutive measurements; Complete response will be defined as normalization of hCG on consecutive measurements separated by at least two weeks; Stable disease will be defined as the absence of response or progression on 3 consecutive measurements separated by at least two weeks.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

All patients who had a baseline scan and at least 1 on study assessment

Arm/Group Title	TRC105 and/or Bevacizumab
Arm/Group Description	All subjects will begin by receiving single agent TRC105 weekly. In the case of a complete response to single agent TRC105, subjects will continue to receive single agent TRC105 for at least 3 months following complete response. In the case of a partial response (without a complete response) to single agent TRC105, bevacizumab every two weeks will be added. In the absence of a partial or complete response to single agent TRC105, subjects will receive single agent bevacizumab every two weeks. In the absence of a complete response to single agent bevacizumab, or for subjects who have documented disease progression on a prior bevacizumab containing regimen, subjects will receive TRC105 weekly and bevacizumab every two weeks. TRC105: Subjects will begin by receiving TRC105 weekly. Subjects who achieve a complete response on single agent TRC105 may transition to every two week dosing. Bevacizumab: Bevacizumab will be dosed every two weeks.
Measure Participants	3
Number of patients with best response of PR	0 0%
Number of patients with best response of SD	0 0%
Number of patients with best response of PD	3 100%
Number of patients with best response of CR	0 0%

2. Secondary Outcome

Title	Progression-Free Survival (PFS)
Description	Median Progression-Free Survival (PFS) via Serum hCG levels and response evaluation according to RECIST version 1.1 as a preliminary measure of the antitumor activity of TRC105. Disease progression is defined as >20% increase (the absolute increase must be ≥10 IU/L) above the nadir on consecutive measurements separated by at least two weeks; Partial response is defined as a hCG decrease of 50% or more from starting value on consecutive measurements; Complete response will be defined as normalization of hCG on consecutive measurements separated by at least two weeks; Stable disease will be defined as the absence of response or progression on 3 consecutive measurements separated by at least two weeks. Patients must have screening (baseline) and at least one on study CT scan to be considered evaluable.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

Progression Free Survival

Arm/Group Title	TRC105 and/or Bevacizumab
Arm/Group Description	All subjects will begin by receiving single agent TRC105 weekly. In the case of a complete response to single agent TRC105, subjects will continue to receive single agent TRC105 for at least 3 months following complete response. In the case of a partial response (without a complete response) to single agent TRC105, bevacizumab every two weeks will be added. In the absence of a partial or complete response to single agent TRC105, subjects will receive single agent bevacizumab every two weeks. In the absence of a complete response to single agent bevacizumab, or for subjects who have documented disease progression on a prior bevacizumab containing regimen, subjects will receive TRC105 weekly and bevacizumab every two weeks. TRC105: Subjects will begin by receiving TRC105 weekly. Subjects who achieve a complete response on single agent TRC105 may transition to every two week dosing. Bevacizumab: Bevacizumab will be dosed every two weeks.
Measure Participants	1
Median (Full Range) [weeks]	6

3. Secondary Outcome

Title	Overall Response Rate on Bevacizumab Alone
Description	Overall Response Rate on bevacizumab alone according to RECIST 1.1 in combination with serum hCG levels. Disease progression is defined as >20% increase (the absolute increase must be ≥10 IU/L) above the nadir on consecutive measurements separated by at least two weeks; Partial response is defined as a hCG decrease of 50% or more from starting value on consecutive measurements; Complete response will be defined as normalization of hCG on consecutive measurements separated by at least two weeks; Stable disease will be defined as the absence of response or progression on 3 consecutive measurements separated by at least two weeks.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

No patients received bevacizumab alone.

Arm/Group Title	TRC105 and/or Bevacizumab
Arm/Group Description	All subjects will begin by receiving single agent TRC105 weekly. In the case of a complete response to single agent TRC105, subjects will continue to receive single agent TRC105 for at least 3 months following complete response. In the case of a partial response (without a complete response) to single agent TRC105, bevacizumab every two weeks will be added. In the absence of a partial or complete response to single agent TRC105, subjects will receive single agent bevacizumab every two weeks. In the absence of a complete response to single agent bevacizumab, or for subjects who have documented disease progression on a prior bevacizumab containing regimen, subjects will receive TRC105 weekly and bevacizumab every two weeks. TRC105: Subjects will begin by receiving TRC105 weekly. Subjects who achieve a complete response on single agent TRC105 may transition to every two week dosing. Bevacizumab: Bevacizumab will be dosed every two weeks.
Measure Participants	0

4. Secondary Outcome

Title	Maximum Plasma Concentration (Cmax) of TRC105.
Description	Mean serum TRC105 concentrations were assessed at cycle 1 and cycle 2 on day 1, 8, 15, and 22 and on day 1 of every subsequent cycle using validated methods in order to determine the Cmax of TRC105
Time Frame	cycle 2 day 1 (28 days after initiation of dosing)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	TRC105 and/or Bevacizumab
Arm/Group Description	All subjects will begin by receiving single agent TRC105 weekly. In the case of a complete response to single agent TRC105, subjects will continue to receive single agent TRC105 for at least 3 months following complete response. In the case of a partial response (without a complete response) to single agent TRC105, bevacizumab every two weeks will be added. In the absence of a partial or complete response to single agent TRC105, subjects will receive single agent bevacizumab every two weeks. In the absence of a complete response to single agent bevacizumab, or for subjects who have documented disease progression on a prior bevacizumab containing regimen, subjects will receive TRC105 weekly and bevacizumab every two weeks. TRC105: Subjects will begin by receiving TRC105 weekly. Subjects who achieve a complete response on single agent TRC105 may transition to every two week dosing. Bevacizumab: Bevacizumab will be dosed every two weeks.
Measure Participants	2
Mean (Full Range) [ng/mL]	232500

5. Secondary Outcome

Title	TRC105 Immunogenicity as Assessed by Anti-Product Antibody (APA).
Description	Anti-Product Antibody (APA) concentrations will be measured using validated ELISA methods at the time points specified in the protocol. APA concentrations will be evaluated in the context of pharmacokinetic parameters and AE profiles. Number of patients with positive APA titers on study will be reported.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	TRC105 and/or Bevacizumab
Arm/Group Description	All subjects will begin by receiving single agent TRC105 weekly. In the case of a complete response to single agent TRC105, subjects will continue to receive single agent TRC105 for at least 3 months following complete response. In the case of a partial response (without a complete response) to single agent TRC105, bevacizumab every two weeks will be added. In the absence of a partial or complete response to single agent TRC105, subjects will receive single agent bevacizumab every two weeks. In the absence of a complete response to single agent bevacizumab, or for subjects who have documented disease progression on a prior bevacizumab containing regimen, subjects will receive TRC105 weekly and bevacizumab every two weeks. TRC105: Subjects will begin by receiving TRC105 weekly. Subjects who achieve a complete response on single agent TRC105 may transition to every two week dosing. Bevacizumab: Bevacizumab will be dosed every two weeks.
Measure Participants	3
Number of patients with negative APA	1 33.3%
Number of patients with positive APA	2 66.7%

6. Secondary Outcome

Title	Frequency and Severity of Adverse Events
Description	Determine frequency and severity of adverse events as assessed by NCI CTCAE (Version 4.03)
Time Frame	20 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	TRC105 and/or Bevacizumab
Arm/Group Description	All subjects will begin by receiving single agent TRC105 weekly. In the case of a complete response to single agent TRC105, subjects will continue to receive single agent TRC105 for at least 3 months following complete response. In the case of a partial response (without a complete response) to single agent TRC105, bevacizumab every two weeks will be added. In the absence of a partial or complete response to single agent TRC105, subjects will receive single agent bevacizumab every two weeks. In the absence of a complete response to single agent bevacizumab, or for subjects who have documented disease progression on a prior bevacizumab containing regimen, subjects will receive TRC105 weekly and bevacizumab every two weeks. TRC105: Subjects will begin by receiving TRC105 weekly. Subjects who achieve a complete response on single agent TRC105 may transition to every two week dosing. Bevacizumab: Bevacizumab will be dosed every two weeks.
Measure Participants	3
Participants who experienced an SAE	1 33.3%
Participants who experienced a TRC105 related SAE	0 0%

Adverse Events

Time Frame	Patients were followed for at least 28 days after the last dose of TRC105 study drug for adverse events, up to approximately 2 years.
Arm/Group Title	TRC105 and/or Bevacizumab
Arm/Group Description	All subjects will begin by receiving single agent TRC105 weekly. In the case of a complete response to single agent TRC105, subjects will continue to receive single agent TRC105 for at least 3 months following complete response. In the case of a partial response (without a complete response) to single agent TRC105, bevacizumab every two weeks will be added. In the absence of a partial or complete response to single agent TRC105, subjects will receive single agent bevacizumab every two weeks. In the absence of a complete response to single agent bevacizumab, or for subjects who have documented disease progression on a prior bevacizumab containing regimen, subjects will receive TRC105 weekly and bevacizumab every two weeks. TRC105: Subjects will begin by receiving TRC105 weekly. Subjects who achieve a complete response on single agent TRC105 may transition to every two week dosing. Bevacizumab: Bevacizumab will be dosed every two weeks.
All Cause Mortality
	TRC105 and/or Bevacizumab
	Affected / at Risk (%)	# Events
Total	0/3 (0%)
Serious Adverse Events
	TRC105 and/or Bevacizumab
	Affected / at Risk (%)	# Events
Total	1/3 (33.3%)
Infections and infestations
Urinary Tract Infection	1/3 (33.3%)	1
Other (Not Including Serious) Adverse Events
	TRC105 and/or Bevacizumab
	Affected / at Risk (%)	# Events
Total	3/3 (100%)
Blood and lymphatic system disorders
Anaemia	2/3 (66.7%)	7
Cardiac disorders
Sinus Tachycardia	1/3 (33.3%)	1
Eye disorders
Visual Impairment	1/3 (33.3%)	1
Gastrointestinal disorders
Ascites	1/3 (33.3%)	1
Constipation	1/3 (33.3%)	2
Diarrhoea	1/3 (33.3%)	1
Dry Mouth	1/3 (33.3%)	1
Dyspepsia	1/3 (33.3%)	1
Faecal Incontinence	1/3 (33.3%)	2
Gingival Bleeding	1/3 (33.3%)	1
Intestinal Obstruction	1/3 (33.3%)	1
Nausea	2/3 (66.7%)	2
Oesophagitis	1/3 (33.3%)	1
Small Intestinal Obstruction	1/3 (33.3%)	2
Vomiting	3/3 (100%)	4
General disorders
Fatigue	1/3 (33.3%)	2
Localised Oedema	1/3 (33.3%)	1
Pyrexia	1/3 (33.3%)	3
Infections and infestations
Candiduria	1/3 (33.3%)	1
Device Related Infection	1/3 (33.3%)	2
Pelvic Abscess	1/3 (33.3%)	3
Urinary Tract Infection	1/3 (33.3%)	2
Investigations
Blood Amylase Increased	1/3 (33.3%)	2
Fungal Test Positive	1/3 (33.3%)	1
Lipase Increased	1/3 (33.3%)	2
Metabolism and nutrition disorders
Decreased Appetite	1/3 (33.3%)	1
Dehydration	1/3 (33.3%)	1
Hypomagnesaemia	1/3 (33.3%)	1
Musculoskeletal and connective tissue disorders
Myalgia	1/3 (33.3%)	1
Nervous system disorders
Headache	3/3 (100%)	6
Spinal Cord Compression	1/3 (33.3%)	1
Reproductive system and breast disorders
Vaginal Haemorrhage	1/3 (33.3%)	1
Respiratory, thoracic and mediastinal disorders
Cough	1/3 (33.3%)	1

Limitations/Caveats

[Not Specified]

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 less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.