Dalantercept in Treating Patients With Recurrent or Persistent Endometrial Cancer

• Sponsor: Gynecologic Oncology Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT01642082
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 28
• Locations: 30
• Arm: 1
• Duration (Months): 40
• Patients Per Site: 0.9
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This phase II trial studies how well dalantercept works in treating patients with endometrial cancer that has come back or is persistent. Dalantercept may stop the growth of endometrial cancer by blocking blood flow to the tumor.

Condition or Disease	Intervention/Treatment	Phase
Endometrial Adenocarcinoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Mixed Adenocarcinoma; Endometrial Mucinous Adenocarcinoma; Endometrial Serous Adenocarcinoma; Endometrial Squamous Cell Carcinoma; Endometrial Transitional Cell Carcinoma; Endometrial Undifferentiated Carcinoma; Recurrent Uterine Corpus Carcinoma	Biological: Dalantercept; Other: Laboratory Biomarker Analysis	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To estimate the proportion of patients with persistent or recurrent endometrial cancer who survive progression-free for at least 6 months and the proportion of patients who have objective tumor response (complete or partial), treated with dalantercept (ACE-041).

2. To determine the nature and degree of toxicity of dalantercept in this cohort of patients.

SECONDARY OBJECTIVES:

1. To estimate progression-free survival (PFS) and overall survival (OS) of patients with persistent or recurrent endometrial cancer treated with dalantercept.

TERTIARY OBJECTIVES:

1. To measure the expression of vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), transforming growth factor-beta (TGF-β), activin receptor-like kinase 1 (ALK1), endoglin (CD105), and other markers via immunohistochemistry (IHC) and determine if there is correlation between expression and clinical response to treatment.

2. To determine the correlation between ALK1 gene expression, other markers, and clinical response to treatment.

3. To determine the correlation between concentration of VEGF, bone morphogenetic protein 9 (BMP9), bone morphogenetic protein 10 (BMP10), and ALK1 in pre-cycle 1 plasma using an enzyme-linked immunosorbent assay (ELISA), and clinical response to treatment.

4. To correlate somatic mutations in candidate genes with response to therapy.

OUTLINE:

Patients receive dalantercept subcutaneously (SC) on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 28 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Evaluation of Dalantercept, a Novel Soluble Recombinant Activin Receptor-Like Kinase 1 (ALK-1) Inhibitor Receptor-Fusion Protein, in the Treatment of Recurrent or Persistent Endometrial Carcinoma
• Study Start Date: Sep 1, 2012
• Actual Primary Completion Date: Jan 1, 2016
• Actual Study Completion Date: Jan 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (dalantercept) Patients receive dalantercept SC on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Biological: Dalantercept; Given SC; Other Names: ACE-041 Activin Receptor-like Kinase 1 Inhibitor ACE-041 ALK1-Fc Fusion Protein ACE-041 ; Other: Laboratory Biomarker Analysis; Correlative studies

Outcome Measures

Primary Outcome Measures

1. Response [Scans to assess response were done every other cycle for the first 6 months; every three months thereafter; and any time if clinically indicated based on symptoms or physical signs suggestive of progressive disease. Responses must be confirmed.]

   Response was defined by Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) and based on imaging done every other cycle. Responses can be either partial or complete. Per RECIST v1.1 target and non-target lesions are assessed by MRI or CT scan: Complete Response (CR), Disappearance of all target and non-target lesions and all lymph nodes must be < 10 mm in short axis; Partial Response (PR), >=30% decrease in the sum of the longest dimensions (LD) of all target measurable lesions taking as reference the baseline sum of LD.

2. Treatment and Progression-free Survival at 6 Months [CT scan or MRI were to assess progression every other cycle for the first 6 months; every three months thereafter; and any time if clinically indicated based on symptoms or physical signs suggestive of progressive disease]

   Treatment and Progression-free Survival is defined as the duration alive from study entry until progression is documented, death or non-protocol treatment is initiated; whichever comes sooner. Progressive disease is defined as at least a 5 mm absolute increase and a 20% relative increase in the sum of measurable target lesions' longest dimensions relative to the smallest sum at baseline or on study or the appearance of new lesions or unequivocal progression of existing non-target lesions. Non-protocol treatment initiation prior to disease progression and prior to 6 months from study entry was counted as an event for treatment and progression-free survival at 6 months. Disease progression within 6 months of study entry or death within 6 months of study entry and prior to disease progression counts as an event for treatment and progression-free survival at 6 months.

Secondary Outcome Measures

1. Progression-free Survival at 6 Months [: CT scan or MRI were to assess progression every other cycle for the first 6 months; every three months thereafter; and any time if clinically indicated based on symptoms or physical signs suggestive of progressive disease.]

   Progression-free survival is defined as the duration alive from study entry until progression is documented or death, whichever comes sooner. Progressive disease is defined as at least a 5 mm absolute increase and a 20% relative increase in the sum of measurable target lesions' longest dimensions relative to the smallest sum at baseline or on study or the appearance of new lesions or unequivocal progression of existing non-target lesions. Disease progression within 6 months of study entry or death within 6 months of study entry and prior to disease progression counts as an event for progression-free survival at 6 months.

2. Duration of Progression-free Survival [CT scan or MRI were to assess progression every other cycle for the first 6 months; every three months thereafter; and any time if clinically indicated based on symptoms or physical signs suggestive of progressive disease.]

   Progression-free survival is defined as the duration alive from study entry until progression is documented or death, whichever comes sooner. Progressive disease is defined as at least a 5 mm absolute increase and a 20% relative increase in the sum of measurable target lesions' longest dimensions relative to the smallest sum at baseline or on study or the appearance of new lesions or unequivocal progression of existing non-target lesions.

3. Duration of Survival [Patients are followed every three months for the first two years and then every six months for the next three years.]

   Duration of survival is defined as the duration alive from study entry until death or last contact.

4. Adverse Events (Primary Serious and All Other AEs) [Every cycle of study treatment and after treatment for a maximum of 5 years from study entry]

   The frequencies of the maximum grade of any acute adverse event, regardless of attribution are reported during treatment and up to 30 days after stopping the study treatment are reported.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients must have recurrent or persistent endometrial carcinoma; histologic confirmation of the original primary tumor is required

• Patients with the following histologic epithelial cell types are eligible: Endometrioid adenocarcinoma, serous adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, adenocarcinoma not otherwise specified (N.O.S.), mucinous adenocarcinoma, squamous cell carcinoma, and transitional cell carcinoma

• All patients must have measurable disease; measurable disease is defined by Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.1) as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded); each lesion must be >= 10 mm when measured by computed tomography (CT), magnetic resonance imaging (MRI), or caliper measurement by clinical exam; or >= 20 mm when measured by chest x-ray; lymph nodes must be > 15 mm in short axis when measured by CT or MRI

• Patients must have at least one "target lesion" to be used to assess response on this protocol as defined by RECIST version 1.1; tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy

• Patients must not be eligible for a higher priority Gynecologic Oncology Group (GOG) protocol, if one exists; in general, this would refer to any active GOG phase III protocol or rare tumor protocol for the same patient population

• Patients who have received one prior regimen must have a GOG performance status of 0, 1, or 2; patients who have received two prior regimens must have a GOG performance status of 0 or 1

• Recovery from effects of recent surgery, radiotherapy, or chemotherapy

• Patients should be free of active infection requiring antibiotics (with the exception of uncomplicated urinary tract infection [UTI])

• Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to registration

• Any other prior therapy directed at the malignant tumor, including chemotherapy and immunologic agents, must be discontinued at least three weeks prior to registration; any investigational drug must be discontinued at least 30 days prior to registration

• Any prior radiation therapy must be discontinued at least four weeks prior to registration

• At least 4 weeks must have elapsed since the patient underwent any major surgery (e.g., major: laparotomy, laparoscopy); there is no delay in treatment for minor procedures (e.g., central venous access catheter placement)

• Prior therapy

• Patients must have had one prior chemotherapeutic regimen for management of endometrial carcinoma. Initial treatment may include chemotherapy, chemotherapy and radiation therapy, and/or consolidation/maintenance therapy; chemotherapy administered in conjunction with primary radiation as a radio-sensitizer WILL be counted as a systemic chemotherapy regimen

• Patients are allowed to receive, but are not required to receive, one additional cytotoxic regimen for management of recurrent or persistent disease

• Patients must have NOT received any non-cytotoxic (biologic or targeted) agent(s) for management of recurrent or persistent disease; prior non-cytotoxic (biologic or targeted) agent(s) is allowed as part of initial treatment; prior hormonal therapy is allowed, but must be discontinued at least one week prior to registration

• Absolute neutrophil count (ANC) greater than or equal to 1,500/mcL

• Platelets greater than or equal to 100,000/mcL

• Hemoglobin greater than or equal to 9 g/dL

• Creatinine less than or equal to 1.5 times institutional upper limit normal (ULN)

• Sodium greater than or equal to 130 mEq/L (Common Terminology Criteria for Adverse Events [CTCAE] v. 4, grade 0 or 1)

• Urine protein should be screened by urinalysis; if protein is 2+ or higher, 24-hour urine protein should be obtained and the level should be < 1,000 mg (< 1.0 g/24 hrs) for patient enrollment

• Bilirubin less than or equal to 1.5 times ULN

• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to 3 times ULN

• Alkaline phosphatase less than or equal to 3 times ULN

• Albumin greater than or equal to 3 (CTCAE v. 4, grade 0 or 1)

• Prothrombin time (PT) such that international normalized ratio (INR) is less than or equal to 1.5 times ULN (or an in-range INR, usually between 2 and 3, if a patient is on a stable dose of therapeutic warfarin)

• Partial thromboplastin time (PTT) less than or equal to 1.5 times ULN

• Left ventricular ejection fraction (LVEF) greater than 50% (measured by echocardiogram or MUGA [multi-gated acquisition] scan)

• Patients must have signed an approved informed consent and authorization permitting release of personal health information

• Patients must meet pre-entry requirements

• Patients of childbearing potential must have a negative serum pregnancy test prior to the study entry and be practicing an effective form of contraception

Exclusion Criteria:

• Patients who have had prior therapy with dalantercept or other inhibitor of the ALK1 pathway

• Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancer and other specific malignancies, are excluded if there is any evidence of other malignancy being present within the last three years; patients are also excluded if their previous cancer treatment contraindicates this protocol therapy

• Patients who have received prior radiotherapy to any portion of the abdominal cavity or pelvis OTHER THAN for the treatment of endometrial cancer within the last three years are excluded; prior radiation for localized cancer of the breast, head and neck, or skin is permitted, provided that it was completed more than three years prior to registration, and the patient remains free of recurrent or metastatic disease

• Patients who have received prior chemotherapy for any abdominal or pelvic tumor OTHER THAN for the treatment of endometrial cancer within the last three years are excluded; patients may have received prior adjuvant chemotherapy for localized breast cancer, provided that it was completed more than three years prior to registration, and that the patient remains free of recurrent or metastatic disease

• Patients with history or evidence upon physical exam of central nervous system disease (CNS) disease, including primary brain tumor, seizures not controlled with standard medical therapy, or any brain metastases or leptomeningeal disease

• Serious or non-healing wound, ulcer, or bone fracture

• History of abdominal fistula or anastomotic leak, gastrointestinal perforation, or intra-abdominal abscess within 6 months of registration

• Patients requiring parenteral hydration or parenteral/total parenteral nutrition

• No patients with:

• Active bleeding (e.g., active hemoptysis, defined as bright red blood of greater than or equal to ½ teaspoon [2.5 ml] in any 24-hour period) within 2 weeks prior to registration or gastrointestinal bleeding within 3 months prior to registration

• Hereditary hemorrhagic telangiectasia (HHT)

• Platelet function abnormality

• Autoimmune or hereditary hemolysis

• Coagulopathy, or

• Tumor involving major vessels (defined as any lesion invading or abutting the wall [i.e., no fat plane evident] of major blood vessels as assessed by CT or MRI)

• Patients receiving treatment with full-dose aspirin (325 mg oral daily), clopidogrel (Plavix), or dabigatran (Pradaxa)

• Patients with peripheral edema greater than or equal to grade 1 within 4 weeks of registration

• No patients with clinically significant cardiovascular disease:

• Uncontrolled hypertension, defined as systolic > 150 mm Hg or diastolic > 90 mm Hg despite antihypertensive medications

• Evidence of hypertrophic cardiomyopathy

• New York Heart Association (NYHA) class II or greater congestive heart failure (CHF)

• Any of the following within 6 months prior to study registration:

• Bypass surgery

• Stent placement

• Myocardial infarction

• Acute coronary syndrome/unstable angina

• Hospitalization for congestive heart failure (CHF)

• Serious cardiac arrhythmia requiring medication; this does not include asymptomatic atrial fibrillation with controlled ventricular rate

• Prolonged QTc interval > 450 ms

• Prior anthracycline cumulative dose > 450 mg/m^2

• Patients who are pregnant or nursing

• History of syndrome of inappropriate antidiuretic hormone secretion (SIADH)

• Patients who have undergone a therapeutic paracentesis within 4 weeks of registration

• Known history of positive hepatitis C virus (HCV) antibody, hepatitis B virus (HBV) surface antigen (HBsAg), or HBV core antibody, or human immunodeficiency virus (HIV) antibody results

• History of severe (National Cancer Institute-Common Terminology Criteria for Adverse Events [NCI-CTCAE] v.4.0 >= grade 3) allergic or anaphylactic reaction or hypersensitivity to recombinant proteins or excipients (10 mM Tris buffered saline) in the investigational agent

• Clinically significant active pulmonary risk including pulmonary hypertension, pulmonary embolism, or history of pulmonary edema

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCSF Medical Center-Mount Zion	San Francisco	California	United States	94115
2	Beebe Medical Center	Lewes	Delaware	United States	19958
3	Christiana Care Health System-Christiana Hospital	Newark	Delaware	United States	19718
4	Florida Hospital Orlando	Orlando	Florida	United States	32803
5	Sarasota Memorial Hospital	Sarasota	Florida	United States	34239
6	University of Chicago Comprehensive Cancer Center	Chicago	Illinois	United States	60637
7	Decatur Memorial Hospital	Decatur	Illinois	United States	62526
8	Saint Vincent Hospital and Health Care Center	Indianapolis	Indiana	United States	46260
9	Maine Medical Center-Bramhall Campus	Portland	Maine	United States	04102
10	Union Hospital of Cecil County	Elkton	Maryland	United States	21921
11	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
12	Nebraska Methodist Hospital	Omaha	Nebraska	United States	68114
13	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10065
14	Carolinas Medical Center/Levine Cancer Institute	Charlotte	North Carolina	United States	28203
15	Novant Health Presbyterian Medical Center	Charlotte	North Carolina	United States	28204
16	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157
17	Case Western Reserve University	Cleveland	Ohio	United States	44106
18	Cleveland Clinic Cancer Center/Fairview Hospital	Cleveland	Ohio	United States	44111
19	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
20	Hillcrest Hospital Cancer Center	Mayfield Heights	Ohio	United States	44124
21	Lake University Ireland Cancer Center	Mentor	Ohio	United States	44060
22	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
23	Women and Infants Hospital	Providence	Rhode Island	United States	02905
24	Sanford Cancer Center-Oncology Clinic	Sioux Falls	South Dakota	United States	57104
25	Sanford NCI Community Oncology Research Program of the North Central Plains	Sioux Falls	South Dakota	United States	57104
26	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota	United States	57117-5134
27	Pacific Gynecology Specialists	Seattle	Washington	United States	98104
28	Seattle Cancer Care Alliance	Seattle	Washington	United States	98109
29	Northwest Hospital	Seattle	Washington	United States	98133
30	University of Washington Medical Center	Seattle	Washington	United States	98195

Sponsors and Collaborators

• Gynecologic Oncology Group
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Vicky Makker, NRG Oncology

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Gynecologic Oncology Group
• ClinicalTrials.gov Identifier: NCT01642082
• Other Study ID Numbers: GOG-0229N; NCI-2012-01986; GOG-0229N; CDR0000736764; GOG-0229N; GOG-0229N; U10CA180868; U10CA027469
• First Posted: Jul 17, 2012
• Last Update Posted: Mar 13, 2018
• Last Verified: May 1, 2017

• Additional relevant MeSH terms: Carcinoma; Adenocarcinoma; Carcinoma, Transitional Cell; Cystadenocarcinoma, Serous; Adenocarcinoma, Clear Cell; Adenocarcinoma, Mucinous; Cystadenocarcinoma; Recurrence; Immunoglobulin Fc Fragments

Study Results

Participant Flow

Recruitment Details	All patients underwent disease evaluation with baseline CT of the chest, abdomen and pelvis. After obtaining informed consent and verification of eligibility, patients were enrolled and treatment initiated.

Arm/Group Title	Dalantercept
Arm/Group Description	Dalantercept 1.2 mg/kg (maximum starting dose of 120 mg) subcutaneously once every three weeks. One cycle is defined as three weeks. Patients weighing more than 100 kg start treatment at 120 mg, and if dalantercept is tolerated for 2 cycles (i.e. toxicities are tolerable, less than grade 2 and resolved), the patient can be dose escalated to dosing based on actual body weight. A CT of the chest, abdomen and pelvis to assess response by RECIST 1.1 is required every two cycles. Treatment was to continue until disease progression or adverse effects prohibit further therapy.
Period Title: Overall Study
STARTED	28
COMPLETED	28
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Treatment (Dalantercept)
Arm/Group Description	Patients receive dalantercept SC on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Dalantercept: Given SC Laboratory Biomarker Analysis: Correlative studies
Overall Participants	28
Age, Customized (participants) [Number]
40-49	1 3.6%
50-59	9 32.1%
60-69	13 46.4%
70-79	5 17.9%
Sex: Female, Male (Count of Participants)
Female	28 100%
Male	0 0%
Region of Enrollment (participants) [Number]
United States	28 100%

Outcome Measures

1. Primary Outcome

Title	Response
Description	Response was defined by Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) and based on imaging done every other cycle. Responses can be either partial or complete. Per RECIST v1.1 target and non-target lesions are assessed by MRI or CT scan: Complete Response (CR), Disappearance of all target and non-target lesions and all lymph nodes must be < 10 mm in short axis; Partial Response (PR), >=30% decrease in the sum of the longest dimensions (LD) of all target measurable lesions taking as reference the baseline sum of LD.
Time Frame	Scans to assess response were done every other cycle for the first 6 months; every three months thereafter; and any time if clinically indicated based on symptoms or physical signs suggestive of progressive disease. Responses must be confirmed.

Outcome Measure Data

Analysis Population Description

All eligible and treated patients

Arm/Group Title	Dalantercept
Arm/Group Description	Dalantercept 1.2 mg/kg (maximum starting dose of 120 mg) subcutaneously once every three weeks. One cycle is defined as three weeks. Patients weighing more than 100 kg start treatment at 120 mg, and if dalantercept is tolerated for 2 cycles (i.e. toxicities are tolerable, less than grade 2 and resolved), the patient can be dose escalated to dosing based on actual body weight. A CT of the chest, abdomen and pelvis to assess response by RECIST 1.1 is required every two cycles. Treatment was to continue until disease progression or adverse effects prohibit further therapy.
Measure Participants	28
Number (90% Confidence Interval) [percentage of participants]	0 0%

2. Primary Outcome

Title	Treatment and Progression-free Survival at 6 Months
Description	Treatment and Progression-free Survival is defined as the duration alive from study entry until progression is documented, death or non-protocol treatment is initiated; whichever comes sooner. Progressive disease is defined as at least a 5 mm absolute increase and a 20% relative increase in the sum of measurable target lesions' longest dimensions relative to the smallest sum at baseline or on study or the appearance of new lesions or unequivocal progression of existing non-target lesions. Non-protocol treatment initiation prior to disease progression and prior to 6 months from study entry was counted as an event for treatment and progression-free survival at 6 months. Disease progression within 6 months of study entry or death within 6 months of study entry and prior to disease progression counts as an event for treatment and progression-free survival at 6 months.
Time Frame	CT scan or MRI were to assess progression every other cycle for the first 6 months; every three months thereafter; and any time if clinically indicated based on symptoms or physical signs suggestive of progressive disease

Outcome Measure Data

Analysis Population Description

All eligible and treated patients

Arm/Group Title	Dalantercept
Arm/Group Description	Dalantercept 1.2 mg/kg (maximum starting dose of 120 mg) subcutaneously once every three weeks. One cycle is defined as three weeks. Patients weighing more than 100 kg start treatment at 120 mg, and if dalantercept is tolerated for 2 cycles (i.e. toxicities are tolerable, less than grade 2 and resolved), the patient can be dose escalated to dosing based on actual body weight. A CT of the chest, abdomen and pelvis to assess response by RECIST 1.1 is required every two cycles. Treatment was to continue until disease progression or adverse effects prohibit further therapy.
Measure Participants	28
Number (90% Confidence Interval) [percentage of participants]	10.7 38.2%

3. Secondary Outcome

Title	Progression-free Survival at 6 Months
Description	Progression-free survival is defined as the duration alive from study entry until progression is documented or death, whichever comes sooner. Progressive disease is defined as at least a 5 mm absolute increase and a 20% relative increase in the sum of measurable target lesions' longest dimensions relative to the smallest sum at baseline or on study or the appearance of new lesions or unequivocal progression of existing non-target lesions. Disease progression within 6 months of study entry or death within 6 months of study entry and prior to disease progression counts as an event for progression-free survival at 6 months.
Time Frame	: CT scan or MRI were to assess progression every other cycle for the first 6 months; every three months thereafter; and any time if clinically indicated based on symptoms or physical signs suggestive of progressive disease.

Outcome Measure Data

Analysis Population Description

All eligible and treated patients

Arm/Group Title	Dalantercept
Arm/Group Description	Dalantercept 1.2 mg/kg (maximum starting dose of 120 mg) subcutaneously once every three weeks. One cycle is defined as three weeks. Patients weighing more than 100 kg start treatment at 120 mg, and if dalantercept is tolerated for 2 cycles (i.e. toxicities are tolerable, less than grade 2 and resolved), the patient can be dose escalated to dosing based on actual body weight. A CT of the chest, abdomen and pelvis to assess response by RECIST 1.1 is required every two cycles. Treatment was to continue until disease progression or adverse effects prohibit further therapy.
Measure Participants	28
Number (90% Confidence Interval) [percentage of participants]	17.9 63.9%

4. Secondary Outcome

Title	Duration of Progression-free Survival
Description	Progression-free survival is defined as the duration alive from study entry until progression is documented or death, whichever comes sooner. Progressive disease is defined as at least a 5 mm absolute increase and a 20% relative increase in the sum of measurable target lesions' longest dimensions relative to the smallest sum at baseline or on study or the appearance of new lesions or unequivocal progression of existing non-target lesions.
Time Frame	CT scan or MRI were to assess progression every other cycle for the first 6 months; every three months thereafter; and any time if clinically indicated based on symptoms or physical signs suggestive of progressive disease.

Outcome Measure Data

Analysis Population Description

All eligible and treated patients.

Arm/Group Title	Treatment (Dalantercept)
Arm/Group Description	Patients receive dalantercept SC on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Dalantercept: Given SC Laboratory Biomarker Analysis: Correlative studies
Measure Participants	28
Median (90% Confidence Interval) [months]	2.1

5. Secondary Outcome

Title	Duration of Survival
Description	Duration of survival is defined as the duration alive from study entry until death or last contact.
Time Frame	Patients are followed every three months for the first two years and then every six months for the next three years.

Outcome Measure Data

Analysis Population Description

All eligible and treated patients

Arm/Group Title	Dalantercept
Arm/Group Description	Dalantercept 1.2 mg/kg (maximum starting dose of 120 mg) subcutaneously once every three weeks. One cycle is defined as three weeks. Patients weighing more than 100 kg start treatment at 120 mg, and if dalantercept is tolerated for 2 cycles (i.e. toxicities are tolerable, less than grade 2 and resolved), the patient can be dose escalated to dosing based on actual body weight. A CT of the chest, abdomen and pelvis to assess response by RECIST 1.1 is required every two cycles. Treatment was to continue until disease progression or adverse effects prohibit further therapy.
Measure Participants	28
Median (90% Confidence Interval) [months]	14.5

6. Secondary Outcome

Title	Adverse Events (Primary Serious and All Other AEs)
Description	The frequencies of the maximum grade of any acute adverse event, regardless of attribution are reported during treatment and up to 30 days after stopping the study treatment are reported.
Time Frame	Every cycle of study treatment and after treatment for a maximum of 5 years from study entry

Outcome Measure Data

Analysis Population Description

Eligible and treated patients

Arm/Group Title	Grade 0	Grade 1 (CTCAE v4.0)	Grade 2 (CTCAE v4.0)	Grade 3 (CTCAE v 4.0)	Grade 4 (CTCAE v 4.0)	Grade 5 (CTCAE v 4.0)
Arm/Group Description	Number of patients who did not experience the specified AE.	Number of patients who experienced a grade 1 event using Common Terminology Criteria version 4.0	Number of patients who experienced a grade 2 event using Common Terminology Criteria version 4.0	Number of patients who experienced a grade 3 event using Common Terminology version 4.0	Number of patients who experienced a grade 4 event using Common Terminology Criteria version 4.0	Number of patients who experienced a grade 5 event using Common Terminology Criteria version 4.0
Measure Participants	28	28	28	28	28	28
Anemia	13 46.4%	5 NaN	8 NaN	1 NaN	1 NaN	0 NaN
Abdominal Distention	24 85.7%	2 NaN	2 NaN	0 NaN	0 NaN	0 NaN
Abdominal Pain	20 71.4%	6 NaN	2 NaN	0 NaN	0 NaN	0 NaN
Ascites	24 85.7%	0 NaN	2 NaN	2 NaN	0 NaN	0 NaN
Constipation	11 39.3%	12 NaN	5 NaN	0 NaN	0 NaN	0 NaN
Diarrhea	22 78.6%	5 NaN	1 NaN	0 NaN	0 NaN	0 NaN
Gastric Hemorrhage	27 96.4%	0 NaN	0 NaN	0 NaN	0 NaN	1 NaN
Nausea	16 57.1%	11 NaN	1 NaN	0 NaN	0 NaN	0 NaN
Rectal Fistula	27 96.4%	0 NaN	0 NaN	1 NaN	0 NaN	0 NaN
Rectal Hemorrhage	26 92.9%	2 NaN	0 NaN	0 NaN	0 NaN	0 NaN
Vomiting	19 67.9%	8 NaN	0 NaN	1 NaN	0 NaN	0 NaN
Edema Face	26 92.9%	1 NaN	1 NaN	0 NaN	0 NaN	0 NaN
Edema Limbs	11 39.3%	15 NaN	2 NaN	0 NaN	0 NaN	0 NaN
Fatigue	4 14.3%	17 NaN	6 NaN	1 NaN	0 NaN	0 NaN
Prolonged activated partial thromboplastin time	27 96.4%	0 NaN	0 NaN	1 NaN	0 NaN	0 NaN
Alkaline Phosphatase Increased	22 78.6%	4 NaN	2 NaN	0 NaN	0 NaN	0 NaN
Creatinine Increased	19 67.9%	5 NaN	4 NaN	0 NaN	0 NaN	0 NaN
Lymphocyte Count Decreased	25 89.3%	1 NaN	1 NaN	1 NaN	0 NaN	0 NaN
Weight Loss	24 85.7%	2 NaN	2 NaN	0 NaN	0 NaN	0 NaN
Anorexia	24 85.7%	2 NaN	2 NaN	0 NaN	0 NaN	0 NaN
Dehydration	26 92.9%	0 NaN	2 NaN	0 NaN	0 NaN	0 NaN
Hyperglycemia	22 78.6%	5 NaN	1 NaN	0 NaN	0 NaN	0 NaN
Hypoalbuminemia	19 67.9%	4 NaN	4 NaN	1 NaN	0 NaN	0 NaN
Hypoglycemia	27 96.4%	0 NaN	1 NaN	0 NaN	0 NaN	0 NaN
Hypokalemia	24 85.7%	1 NaN	2 NaN	1 NaN	0 NaN	0 NaN
Arthralgia	24 85.7%	4 NaN	0 NaN	0 NaN	0 NaN	0 NaN
Back Pain	19 67.9%	4 NaN	4 NaN	1 NaN	0 NaN	0 NaN
Myalgia	25 89.3%	3 NaN	0 NaN	0 NaN	0 NaN	0 NaN
Dizziness	26 92.9%	2 NaN	0 NaN	0 NaN	0 NaN	0 NaN
Headache	15 53.6%	13 NaN	0 NaN	0 NaN	0 NaN	0 NaN
Neuralgia	27 96.4%	0 NaN	1 NaN	0 NaN	0 NaN	0 NaN
Urinary Tract Obstruction	27 96.4%	0 NaN	0 NaN	1 NaN	0 NaN	0 NaN
Dyspnea	18 64.3%	8 NaN	1 NaN	1 NaN	0 NaN	0 NaN
Epistaxis	24 85.7%	4 NaN	0 NaN	0 NaN	0 NaN	0 NaN
Pleural Effusion	24 85.7%	1 NaN	2 NaN	1 NaN	0 NaN	0 NaN
Hypertension	25 89.3%	1 NaN	1 NaN	1 NaN	0 NaN	0 NaN
Thromboembolic Event	26 92.9%	0 NaN	1 NaN	1 NaN	0 NaN	0 NaN

Adverse Events

Time Frame	Every cycle of study treatment and after treatment for a maximum of 5 years from study entry
Adverse Event Reporting Description	The frequencies of the maximum grade of any serious adverse event or all other adverse events by category or specific term occurring during treatment and up to 30 days after stopping the study treatment are reported
Arm/Group Title	Dalantercept
Arm/Group Description	Dalantercept 1.2 mg/kg (maximum starting dose of 120 mg) subcutaneously once every three weeks. One cycle is defined as three weeks. Patients weighing more than 100 kg start treatment at 120 mg, and if dalantercept is tolerated for 2 cycles (i.e. toxicities are tolerable, less than grade 2 and resolved), the patient can be dose escalated to dosing based on actual body weight. A CT of the chest, abdomen and pelvis to assess response by RECIST 1.1 is required every two cycles. Treatment was to continue until disease progression or adverse effects prohibit further therapy.
All Cause Mortality
	Dalantercept
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Dalantercept
	Affected / at Risk (%)	# Events
Total	11/28 (39.3%)
Blood and lymphatic system disorders
Anemia	1/28 (3.6%)	1
Gastrointestinal disorders
Rectal Fistula	1/28 (3.6%)	1
Gastric Hemorrhage	1/28 (3.6%)	1
Ascites	1/28 (3.6%)	1
Metabolism and nutrition disorders
Hypokalemia	1/28 (3.6%)	1
Musculoskeletal and connective tissue disorders
Pain in Extremity	1/28 (3.6%)	1
Back Pain	1/28 (3.6%)	1
Renal and urinary disorders
Urinary Tract Obstruction	1/28 (3.6%)	1
Respiratory, thoracic and mediastinal disorders
Pleural Effusion	1/28 (3.6%)	1
Dyspnea	2/28 (7.1%)	2
Vascular disorders
Thromboembolic Event	1/28 (3.6%)	1
Other (Not Including Serious) Adverse Events
	Dalantercept
	Affected / at Risk (%)	# Events
Total	28/28 (100%)
Blood and lymphatic system disorders
Anemia	15/28 (53.6%)
Cardiac disorders
Ventricular Arrhythmia	1/28 (3.6%)
Ear and labyrinth disorders
Tinnitus	1/28 (3.6%)
Hearing Impaired	1/28 (3.6%)
Ear Pain	2/28 (7.1%)
Eye disorders
Flashing Lights	1/28 (3.6%)
Eye Pain	2/28 (7.1%)
Blurred Vision	3/28 (10.7%)
Floaters	1/28 (3.6%)
Gastrointestinal disorders
Dysphagia	1/28 (3.6%)
Constipation	17/28 (60.7%)
Diarrhea	6/28 (21.4%)
Vomiting	9/28 (32.1%)
Abdominal Pain	8/28 (28.6%)
Rectal Hemorrhage	2/28 (7.1%)
Mucositis Oral	2/28 (7.1%)
Abdominal Distension	4/28 (14.3%)
Nausea	12/28 (42.9%)
Gastroparesis	1/28 (3.6%)
Gastroesophageal Reflux Disease	1/28 (3.6%)
Hemorrhoids	1/28 (3.6%)
Ascites	4/28 (14.3%)
General disorders
Pain	3/28 (10.7%)
Localized Edema	1/28 (3.6%)
Injection Site Reaction	1/28 (3.6%)
Edema Trunk	1/28 (3.6%)
Non-Cardiac Chest Pain	2/28 (7.1%)
Edema Limbs	17/28 (60.7%)
Edema Face	2/28 (7.1%)
Fatigue	24/28 (85.7%)
Fever	1/28 (3.6%)
Infections and infestations
Wound Infection	1/28 (3.6%)
Upper Respiratory Infection	1/28 (3.6%)
Soft Tissue Infection	1/28 (3.6%)
Papulopustular Rash	1/28 (3.6%)
Urinary Tract Infection	2/28 (7.1%)
Investigations
Weight Loss	4/28 (14.3%)
Weight Gain	2/28 (7.1%)
Lymphocyte Count Decreased	3/28 (10.7%)
Creatinine Increased	9/28 (32.1%)
Aspartate Aminotransferase Increased	4/28 (14.3%)
Alkaline Phosphatase Increased	6/28 (21.4%)
Alanine Aminotransferase Increased	1/28 (3.6%)
Activated Partial Thromboplastin Time Prolonged	1/28 (3.6%)
Metabolism and nutrition disorders
Hyponatremia	6/28 (21.4%)
Hypomagnesemia	3/28 (10.7%)
Hypokalemia	4/28 (14.3%)
Hypoglycemia	1/28 (3.6%)
Hypocalcemia	2/28 (7.1%)
Hypoalbuminemia	9/28 (32.1%)
Hypernatremia	1/28 (3.6%)
Hypermagnesemia	1/28 (3.6%)
Hyperkalemia	3/28 (10.7%)
Hyperglycemia	6/28 (21.4%)
Hypercalcemia	1/28 (3.6%)
Dehydration	2/28 (7.1%)
Anorexia	4/28 (14.3%)
Musculoskeletal and connective tissue disorders
Pain In Extremity	4/28 (14.3%)
Myalgia	3/28 (10.7%)
Generalized Muscle Weakness	1/28 (3.6%)
Flank Pain	1/28 (3.6%)
Chest Wall Pain	1/28 (3.6%)
Back Pain	8/28 (28.6%)
Arthralgia	4/28 (14.3%)
Nervous system disorders
Peripheral Sensory Neuropathy	5/28 (17.9%)
Paresthesia	4/28 (14.3%)
Neuralgia	1/28 (3.6%)
Headache	13/28 (46.4%)
Facial Nerve Disorder	1/28 (3.6%)
Dysgeusia	1/28 (3.6%)
Dizziness	2/28 (7.1%)
Psychiatric disorders
Insomnia	1/28 (3.6%)
Depression	3/28 (10.7%)
Anxiety	2/28 (7.1%)
Renal and urinary disorders
Urinary Tract Pain	2/28 (7.1%)
Urinary Frequency	1/28 (3.6%)
Reproductive system and breast disorders
Vaginal Hemorrhage	1/28 (3.6%)
Vaginal Discharge	2/28 (7.1%)
Respiratory, thoracic and mediastinal disorders
Sore Throat	1/28 (3.6%)
Pleural Effusion	3/28 (10.7%)
Nasal Congestion	4/28 (14.3%)
Pleuritic Pain	1/28 (3.6%)
Epistaxis	4/28 (14.3%)
Dyspnea	8/28 (28.6%)
Cough	7/28 (25%)
Skin and subcutaneous tissue disorders
Urticaria	1/28 (3.6%)
Purpura	1/28 (3.6%)
Pruritus	1/28 (3.6%)
Periorbital Edema	1/28 (3.6%)
Rash Maculo-Papular	2/28 (7.1%)
Telangiectasia	6/28 (21.4%)
Alopecia	3/28 (10.7%)
Vascular disorders
Thromboembolic Event	1/28 (3.6%)
Hypotension	1/28 (3.6%)
Hypertension	3/28 (10.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.