Trial Outcomes & Findings for Study of TRC105 and Bevacizumab in Patients With Refractory Gestational Trophoblastic Neoplasia (GTN) (NCT NCT02664961)
NCT ID: NCT02664961
Last Updated: 2019-07-23
Results Overview
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.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
3 participants
Primary outcome timeframe
8 weeks
Results posted on
2019-07-23
Participant Flow
Participant milestones
| Measure |
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.
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 Study
STARTED
|
3
|
|
Overall Study
COMPLETED
|
3
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Study of TRC105 and Bevacizumab in Patients With Refractory Gestational Trophoblastic Neoplasia (GTN)
Baseline characteristics by cohort
| Measure |
TRC105 and/or Bevacizumab
n=3 Participants
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.
|
|---|---|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
3 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
3 Participants
n=5 Participants
|
|
Number of Prior Regimens
|
6 prior regimens
n=5 Participants
|
|
Age, Continuous
|
48 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 8 weeksPopulation: All patients who had a baseline scan and at least 1 on study assessment
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.
Outcome measures
| Measure |
TRC105 and/or Bevacizumab
n=3 Participants
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.
|
|---|---|
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Overall Response Rate on TRC105 Alone and on the Combination of TRC105 and Bevacizumab
Number of patients with best response of PR
|
0 Participants
|
|
Overall Response Rate on TRC105 Alone and on the Combination of TRC105 and Bevacizumab
Number of patients with best response of SD
|
0 Participants
|
|
Overall Response Rate on TRC105 Alone and on the Combination of TRC105 and Bevacizumab
Number of patients with best response of PD
|
3 Participants
|
|
Overall Response Rate on TRC105 Alone and on the Combination of TRC105 and Bevacizumab
Number of patients with best response of CR
|
0 Participants
|
SECONDARY outcome
Timeframe: 8 weeksPopulation: Progression Free Survival
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.
Outcome measures
| Measure |
TRC105 and/or Bevacizumab
n=1 Participants
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.
|
|---|---|
|
Progression-Free Survival (PFS)
|
6 weeks
Interval 6.0 to 6.0
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SECONDARY outcome
Timeframe: 8 weeksPopulation: No patients received bevacizumab alone.
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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 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
Outcome measures
| Measure |
TRC105 and/or Bevacizumab
n=2 Participants
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.
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|---|---|
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Maximum Plasma Concentration (Cmax) of TRC105.
|
232500 ng/mL
Interval 199000.0 to 266000.0
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SECONDARY outcome
Timeframe: 8 weeksAnti-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.
Outcome measures
| Measure |
TRC105 and/or Bevacizumab
n=3 Participants
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.
|
|---|---|
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TRC105 Immunogenicity as Assessed by Anti-Product Antibody (APA).
Number of patients with negative APA
|
1 Participants
|
|
TRC105 Immunogenicity as Assessed by Anti-Product Antibody (APA).
Number of patients with positive APA
|
2 Participants
|
SECONDARY outcome
Timeframe: 20 monthsDetermine frequency and severity of adverse events as assessed by NCI CTCAE (Version 4.03)
Outcome measures
| Measure |
TRC105 and/or Bevacizumab
n=3 Participants
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.
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|---|---|
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Frequency and Severity of Adverse Events
Participants who experienced an SAE
|
1 Participants
|
|
Frequency and Severity of Adverse Events
Participants who experienced a TRC105 related SAE
|
0 Participants
|
Adverse Events
TRC105 and/or Bevacizumab
Serious events: 1 serious events
Other events: 3 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
TRC105 and/or Bevacizumab
n=3 participants at risk
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.
|
|---|---|
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Infections and infestations
Urinary Tract Infection
|
33.3%
1/3 • Number of events 1 • Patients were followed for at least 28 days after the last dose of TRC105 study drug for adverse events, up to approximately 2 years.
|
Other adverse events
| Measure |
TRC105 and/or Bevacizumab
n=3 participants at risk
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.
|
|---|---|
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Blood and lymphatic system disorders
Anaemia
|
66.7%
2/3 • Number of events 7 • Patients were followed for at least 28 days after the last dose of TRC105 study drug for adverse events, up to approximately 2 years.
|
|
Gastrointestinal disorders
Ascites
|
33.3%
1/3 • Number of events 1 • Patients were followed for at least 28 days after the last dose of TRC105 study drug for adverse events, up to approximately 2 years.
|
|
Investigations
Blood Amylase Increased
|
33.3%
1/3 • Number of events 2 • Patients were followed for at least 28 days after the last dose of TRC105 study drug for adverse events, up to approximately 2 years.
|
|
Infections and infestations
Candiduria
|
33.3%
1/3 • Number of events 1 • Patients were followed for at least 28 days after the last dose of TRC105 study drug for adverse events, up to approximately 2 years.
|
|
Gastrointestinal disorders
Constipation
|
33.3%
1/3 • Number of events 2 • Patients were followed for at least 28 days after the last dose of TRC105 study drug for adverse events, up to approximately 2 years.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
33.3%
1/3 • Number of events 1 • Patients were followed for at least 28 days after the last dose of TRC105 study drug for adverse events, up to approximately 2 years.
|
|
Metabolism and nutrition disorders
Decreased Appetite
|
33.3%
1/3 • Number of events 1 • Patients were followed for at least 28 days after the last dose of TRC105 study drug for adverse events, up to approximately 2 years.
|
|
Metabolism and nutrition disorders
Dehydration
|
33.3%
1/3 • Number of events 1 • Patients were followed for at least 28 days after the last dose of TRC105 study drug for adverse events, up to approximately 2 years.
|
|
Infections and infestations
Device Related Infection
|
33.3%
1/3 • Number of events 2 • Patients were followed for at least 28 days after the last dose of TRC105 study drug for adverse events, up to approximately 2 years.
|
|
Gastrointestinal disorders
Diarrhoea
|
33.3%
1/3 • Number of events 1 • Patients were followed for at least 28 days after the last dose of TRC105 study drug for adverse events, up to approximately 2 years.
|
|
Gastrointestinal disorders
Dry Mouth
|
33.3%
1/3 • Number of events 1 • Patients were followed for at least 28 days after the last dose of TRC105 study drug for adverse events, up to approximately 2 years.
|
|
Gastrointestinal disorders
Dyspepsia
|
33.3%
1/3 • Number of events 1 • Patients were followed for at least 28 days after the last dose of TRC105 study drug for adverse events, up to approximately 2 years.
|
|
Gastrointestinal disorders
Faecal Incontinence
|
33.3%
1/3 • Number of events 2 • Patients were followed for at least 28 days after the last dose of TRC105 study drug for adverse events, up to approximately 2 years.
|
|
General disorders
Fatigue
|
33.3%
1/3 • Number of events 2 • Patients were followed for at least 28 days after the last dose of TRC105 study drug for adverse events, up to approximately 2 years.
|
|
Investigations
Fungal Test Positive
|
33.3%
1/3 • Number of events 1 • Patients were followed for at least 28 days after the last dose of TRC105 study drug for adverse events, up to approximately 2 years.
|
|
Gastrointestinal disorders
Gingival Bleeding
|
33.3%
1/3 • Number of events 1 • Patients were followed for at least 28 days after the last dose of TRC105 study drug for adverse events, up to approximately 2 years.
|
|
Nervous system disorders
Headache
|
100.0%
3/3 • Number of events 6 • Patients were followed for at least 28 days after the last dose of TRC105 study drug for adverse events, up to approximately 2 years.
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
33.3%
1/3 • Number of events 1 • Patients were followed for at least 28 days after the last dose of TRC105 study drug for adverse events, up to approximately 2 years.
|
|
Gastrointestinal disorders
Intestinal Obstruction
|
33.3%
1/3 • Number of events 1 • Patients were followed for at least 28 days after the last dose of TRC105 study drug for adverse events, up to approximately 2 years.
|
|
Investigations
Lipase Increased
|
33.3%
1/3 • Number of events 2 • Patients were followed for at least 28 days after the last dose of TRC105 study drug for adverse events, up to approximately 2 years.
|
|
General disorders
Localised Oedema
|
33.3%
1/3 • Number of events 1 • Patients were followed for at least 28 days after the last dose of TRC105 study drug for adverse events, up to approximately 2 years.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
33.3%
1/3 • Number of events 1 • Patients were followed for at least 28 days after the last dose of TRC105 study drug for adverse events, up to approximately 2 years.
|
|
Gastrointestinal disorders
Nausea
|
66.7%
2/3 • Number of events 2 • Patients were followed for at least 28 days after the last dose of TRC105 study drug for adverse events, up to approximately 2 years.
|
|
Gastrointestinal disorders
Oesophagitis
|
33.3%
1/3 • Number of events 1 • Patients were followed for at least 28 days after the last dose of TRC105 study drug for adverse events, up to approximately 2 years.
|
|
Infections and infestations
Pelvic Abscess
|
33.3%
1/3 • Number of events 3 • Patients were followed for at least 28 days after the last dose of TRC105 study drug for adverse events, up to approximately 2 years.
|
|
General disorders
Pyrexia
|
33.3%
1/3 • Number of events 3 • Patients were followed for at least 28 days after the last dose of TRC105 study drug for adverse events, up to approximately 2 years.
|
|
Cardiac disorders
Sinus Tachycardia
|
33.3%
1/3 • Number of events 1 • Patients were followed for at least 28 days after the last dose of TRC105 study drug for adverse events, up to approximately 2 years.
|
|
Gastrointestinal disorders
Small Intestinal Obstruction
|
33.3%
1/3 • Number of events 2 • Patients were followed for at least 28 days after the last dose of TRC105 study drug for adverse events, up to approximately 2 years.
|
|
Nervous system disorders
Spinal Cord Compression
|
33.3%
1/3 • Number of events 1 • Patients were followed for at least 28 days after the last dose of TRC105 study drug for adverse events, up to approximately 2 years.
|
|
Infections and infestations
Urinary Tract Infection
|
33.3%
1/3 • Number of events 2 • Patients were followed for at least 28 days after the last dose of TRC105 study drug for adverse events, up to approximately 2 years.
|
|
Reproductive system and breast disorders
Vaginal Haemorrhage
|
33.3%
1/3 • Number of events 1 • Patients were followed for at least 28 days after the last dose of TRC105 study drug for adverse events, up to approximately 2 years.
|
|
Eye disorders
Visual Impairment
|
33.3%
1/3 • Number of events 1 • Patients were followed for at least 28 days after the last dose of TRC105 study drug for adverse events, up to approximately 2 years.
|
|
Gastrointestinal disorders
Vomiting
|
100.0%
3/3 • Number of events 4 • Patients were followed for at least 28 days after the last dose of TRC105 study drug for adverse events, up to approximately 2 years.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60