Study of TRC105 and Bevacizumab in Patients With Refracto... | NCT02664961

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
TRC105 and/or bevacizumab	Experimental	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 Drug: Bevacizumab

Interventions

Name	Type	Description	Arm Group Labels	Other Names
TRC105	Drug	Subjects will begin by receiving TRC105 weekly. Subjects who achieve a complete response on single agent TRC105 may transition to every two week dosing.	TRC105 and/or bevacizumab

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Overall Response Rate on TRC105 Alone and on the Combination of TRC105 and Bevacizumab	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.	8 weeks

Secondary Outcomes

Measure	Description	Time Frame
Progression-Free Survival (PFS)	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.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Willingness and ability to consent for self to participate in study
Willingness and ability to comply with study procedures
Elevated serum hCG (in cases of choriocarcinoma); elevated hCG or measurable disease (in cases of PSTT or ETT)
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.
Age of 16 years or older
ECOG performance status ≤ 1
Resolution of all acute adverse events resulting from prior cancer therapies to NCI CTCAE grade ≤ 1 or baseline
Adequate organ function

Exclusion Criteria:

Male
Prior treatment with TRC105
. Current treatment on another therapeutic clinical trial
Uncontrolled chronic hypertension defined as systolic > 150 or diastolic > 90 despite optimal therapy
Significant pericardial effusion, pleural effusion, or ascites
Active bleeding or pathologic condition that carries a high risk of bleeding
Tumors located in the central chest or other location where bleeding is associated with high morbidity
Thrombolytic use (except to maintain i.v. catheters) within 10 days prior to first day of study therapy
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
Known active viral or nonviral hepatitis
Pregnant or actively breastfeeding without intention to discontinue prior to initiation of study
Open wounds or unhealed fractures within 28 days of starting study treatment
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
History of gastrointestinal perforation or fistula in the past 6 months, or while previously on antiangiogenic therapy, unless underlying risk has been resolved
Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness
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
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
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
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
Major surgical procedure or significant traumatic injury within 6 weeks prior to study registration or not fully recovered from any such procedure

Name	Affiliation	Role
Charles Theuer, MD, PhD	Tracon Pharmaceuticals Inc.	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Dana Farber Cancer Institute		Boston	Massachusetts	02215	United States
Ohio State University

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	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.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
SAP	No	Yes	No	Statistical Analysis Plan	Aug 7, 2018	Apr 3, 2019

Arm/Group Information

ID	Title	Description
BG000	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.

Units	Counts
Participants	BG0003

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Median

Full Range

years

Title

Denominators

Categories

Title	Measurements
	BG00048(46 to 52)

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0003
Male	BG0000

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0000
Not Hispanic or Latino	BG0003

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0001
Asian	BG0000

Region of Enrollment

Count of Participants

Participants

Title

Denominators

Categories

United States

Title	Measurements
	BG0003

Number of Prior Regimens

Median

Full Range

prior regimens

Title

Denominators

Categories

Title	Measurements
	BG0006(1 to 8)

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Overall Response Rate on TRC105 Alone and on the Combination of TRC105 and Bevacizumab

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.

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

Posted

Count of Participants

Participants

8 weeks

ID	Title	Description
OG000	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.

Units	Counts
Participants	OG0003

Title

Denominators

Categories

Number of patients with best response of PR

Title	Measurements
	OG0000

Number of patients with best response of SD

Title	Measurements
	OG0000

Number of patients with best response of PD

Secondary

Progression-Free Survival (PFS)

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.

Progression Free Survival

Posted

Median

Full Range

weeks

8 weeks

ID	Title	Description
OG000	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.

Secondary

Overall Response Rate on 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.

No patients received bevacizumab alone.

Posted

8 weeks

ID	Title	Description
OG000	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.

Secondary

Maximum Plasma Concentration (Cmax) of TRC105.

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

Posted

Mean

Full Range

ng/mL

cycle 2 day 1 (28 days after initiation of dosing)

ID	Title	Description
OG000	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.

Units	Counts
Participants

Secondary

TRC105 Immunogenicity as Assessed by Anti-Product Antibody (APA).

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.

Posted

Count of Participants

Participants

8 weeks

ID	Title	Description
OG000	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.

Units	Counts

Secondary

Frequency and Severity of Adverse Events

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

Posted

Count of Participants

Participants

20 months

ID	Title	Description
OG000	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.

Units	Counts
Participants	OG000

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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.	0	3	1	3	3	3

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA (14.1)	Systematic Assessment	EG0007 events2 affected3 at risk
Ascites	Gastrointestinal disorders	MedDRA (14.1)	Systematic Assessment	EG0001 events1 affected3 at risk
Blood Amylase Increased	Investigations	MedDRA (14.1)	Systematic Assessment	EG0002 events1 affected3 at risk
Candiduria	Infections and infestations	MedDRA (14.1)	Systematic Assessment	EG0001 events1 affected3 at risk
Constipation	Gastrointestinal disorders	MedDRA (14.1)	Systematic Assessment	EG0002 events1 affected3 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (14.1)	Systematic Assessment	EG0001 events1 affected3 at risk
Decreased Appetite	Metabolism and nutrition disorders	MedDRA (14.1)	Systematic Assessment	EG0001 events1 affected3 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA (14.1)	Systematic Assessment	EG0001 events1 affected3 at risk
Device Related Infection	Infections and infestations	MedDRA (14.1)	Systematic Assessment	EG0002 events1 affected3 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA (14.1)	Systematic Assessment	EG0001 events1 affected3 at risk
Dry Mouth	Gastrointestinal disorders	MedDRA (14.1)	Systematic Assessment	EG0001 events1 affected3 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA (14.1)	Systematic Assessment	EG0001 events1 affected3 at risk
Faecal Incontinence	Gastrointestinal disorders	MedDRA (14.1)	Systematic Assessment	EG0002 events1 affected3 at risk
Fatigue	General disorders	MedDRA (14.1)	Systematic Assessment	EG0002 events1 affected3 at risk
Fungal Test Positive	Investigations	MedDRA (14.1)	Systematic Assessment	EG0001 events1 affected3 at risk
Gingival Bleeding	Gastrointestinal disorders	MedDRA (14.1)	Systematic Assessment	EG0001 events1 affected3 at risk
Headache	Nervous system disorders	MedDRA (14.1)	Systematic Assessment	EG0006 events3 affected3 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA (14.1)	Systematic Assessment	EG0001 events1 affected3 at risk
Intestinal Obstruction	Gastrointestinal disorders	MedDRA (14.1)	Systematic Assessment	EG0001 events1 affected3 at risk
Lipase Increased	Investigations	MedDRA (14.1)	Systematic Assessment	EG0002 events1 affected3 at risk
Localised Oedema	General disorders	MedDRA (14.1)	Systematic Assessment	EG0001 events1 affected3 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA (14.1)	Systematic Assessment	EG0001 events1 affected3 at risk
Nausea	Gastrointestinal disorders	MedDRA (14.1)	Systematic Assessment	EG0002 events2 affected3 at risk
Oesophagitis	Gastrointestinal disorders	MedDRA (14.1)	Systematic Assessment	EG0001 events1 affected3 at risk
Pelvic Abscess	Infections and infestations	MedDRA (14.1)	Systematic Assessment	EG0003 events1 affected3 at risk
Pyrexia	General disorders	MedDRA (14.1)	Systematic Assessment	EG0003 events1 affected3 at risk
Sinus Tachycardia	Cardiac disorders	MedDRA (14.1)	Systematic Assessment	EG0001 events1 affected3 at risk
Small Intestinal Obstruction	Gastrointestinal disorders	MedDRA (14.1)	Systematic Assessment	EG0002 events1 affected3 at risk
Spinal Cord Compression	Nervous system disorders	MedDRA (14.1)	Systematic Assessment	EG0001 events1 affected3 at risk
Urinary Tract Infection	Infections and infestations	MedDRA (14.1)	Systematic Assessment	EG0002 events1 affected3 at risk
Vaginal Haemorrhage	Reproductive system and breast disorders	MedDRA (14.1)	Systematic Assessment	EG0001 events1 affected3 at risk
Visual Impairment	Eye disorders	MedDRA (14.1)	Systematic Assessment	EG0001 events1 affected3 at risk
Vomiting	Gastrointestinal disorders	MedDRA (14.1)	Systematic Assessment	EG0004 events3 affected3 at risk

ID	Term
D031901	Gestational Trophoblastic Disease
D002822	Choriocarcinoma
D018245	Trophoblastic Tumor, Placental Site

ID	Term
D014328	Trophoblastic Neoplasms
D009373	Neoplasms, Germ Cell and Embryonal
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D011252	Pregnancy Complications, Neoplastic
D011248	Pregnancy Complications
D005261	Female Urogenital Diseases and Pregnancy Complications
D000091642	Urogenital Diseases
D000230	Adenocarcinoma
D002277	Carcinoma
D009375	Neoplasms, Glandular and Epithelial

ID	Term
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins