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Study of Dalantercept and Axitinib in Patients With Advanced Renal Cell Carcinoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01727336
Recruitment Status : Terminated (The study was terminated by the sponsor following unblinding of the Progression Free Survival endpoint.)
First Posted : November 16, 2012
Results First Posted : May 24, 2021
Last Update Posted : September 23, 2021
Sponsor:
Information provided by (Responsible Party):
Acceleron Pharma Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Sequential Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Advanced Renal Cell Carcinoma
Interventions Drug: Dalantercept and axitinib
Drug: Placebo and axitinib
Enrollment 160
Recruitment Details  
Pre-assignment Details In the Part 1 dose escalation portion of the study, 4 dose levels of dalantercept plus an expansion cohort were planned. However, dose escalation was suspended following the 1.2 mg/kg dose level and additional subjects were added to the 1.2 mg/kg dose cohort, which represented the expansion; no subjects were enrolled in the 1.5 mg/kg dose level.
Arm/Group Title Part 1 Dalantercept 0.6 mg/kg Part 1 Dalantercept 0.9 mg/kg Part 1: Dalantercept 1.2 mg/kg Part 1: Dalantercept 1.5 mg/kg Part 2: Dalantercept 0.9 mg/kg Plus Axitinib Part 2: Placebo Plus Axitinib
Hide Arm/Group Description Dose escalation cohort 1: dalantercept 0.6 mg/kg plus axitinib 5 mg PO BID Dose escalation cohort 2: dalantercept 0.9 mg/kg plus axitinib 5 mg PO BID Part 1 cohort 3: dalantercept 1.2 mg/kg plus axitinib 5 mg PO BID Dose escalation cohort 4: dalantercept 1.5 mg/kg Subcutaneous (SC) injection of Dalantercept once every 3 weeks and oral axitinib 5 mg PO BID for continuous dosing. Subcutaneous injection of normal saline once every 3 weeks and oral axitinib 5 mg PO BID for continuous dosing
Period Title: Part 1 Dalantercept Dose Escalation
Started 6 9 14 0 0 0
Completed 3 7 6 0 0 0
Not Completed 3 2 8 0 0 0
Reason Not Completed
Adverse Event             0             1             5             0             0             0
Lack of Efficacy             3             1             3             0             0             0
Period Title: Part 2 Blinded
Started 0 0 0 0 63 68
Completed 0 0 0 0 0 0
Not Completed 0 0 0 0 63 68
Reason Not Completed
Death             0             0             0             0             20             16
Lack of Efficacy             0             0             0             0             42             44
Lost to Follow-up             0             0             0             0             0             1
Withdrawal by Subject             0             0             0             0             0             4
use of prohibited medications             0             0             0             0             1             3
Arm/Group Title Part 1 Dalantercept 0.6 mg/kg Part 1 Dalantercept 0.9 mg/kg Part 1 Dalantercept 1.2 mg/kg Part 1 Dalantercept 1.5 mg/kg Part 2 Dalantercept 0.9 mg/kg Plus Axitinib Placebo Plus Axitinib Total
Hide Arm/Group Description Dose escalation cohort 1: dalantercept 0.6 mg/kg Dose escalation cohort 2: dalantercept 0.9 mg/kg Dose escalation cohort 3: dalantercept 1.2 mg/kg Dose escalation cohort 4: dalantercept 1.5 mg/kg Subcutaneous (SC) injection of Dalantercept once every 3 weeks and oral axitinib 5 mg BID for continuous dosing. Subcutaneous injection of normal saline once every 3 weeks and oral axitinib 5 mg BID for continuous dosing Total of all reporting groups
Overall Number of Baseline Participants 6 9 14 0 63 68 160
Hide Baseline Analysis Population Description
No subjects were enrolled into the 1.5 mg/kg dose escalation cohort
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 6 participants 9 participants 14 participants 0 participants 63 participants 68 participants 160 participants
64.3  (7.2) 56.2  (9.2) 61.5  (10.9) 62.8  (8.1) 58.9  (10.1) 60.7  (9.4)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 9 participants 14 participants 0 participants 63 participants 68 participants 160 participants
Female
1
  16.7%
2
  22.2%
3
  21.4%
22
  34.9%
28
  41.2%
56
  35.0%
Male
5
  83.3%
7
  77.8%
11
  78.6%
41
  65.1%
40
  58.8%
104
  65.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 9 participants 14 participants 0 participants 63 participants 68 participants 160 participants
Hispanic or Latino
0
   0.0%
1
  11.1%
1
   7.1%
1
   1.6%
6
   8.8%
9
   5.6%
Not Hispanic or Latino
6
 100.0%
8
  88.9%
13
  92.9%
58
  92.1%
58
  85.3%
143
  89.4%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
4
   6.3%
4
   5.9%
8
   5.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 6 participants 9 participants 14 participants 0 participants 63 participants 68 participants 160 participants
6 9 14 63 68 160
1.Primary Outcome
Title Part 1: Number of Participants With Adverse Events as a Measure of Safety and Tolerability.
Hide Description Outcome measure is intended for Part 1 of the study in order to determine recommended dose level for Part 2.
Time Frame Assessed from time of first dose to approximately 30 days after last dose. Participants were allowed to remain on treatment until documented disease progression. The time frame for Part 1 of the study was up to 21.6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set (SAF) consisted of all patients who received at least 1 dose of study drug
Arm/Group Title Part 1 Dalantercept 0.6 mg/kg Part 1 Dalantercept 0.9 mg/kg Part 1 Dalantercept 1.2 mg/kg Part 1 Dalantercept 1.5 mg/kg
Hide Arm/Group Description:
Part 1 cohort 1; dalantercept 0.6 mg/kg plus axitinib 5 mg PO BID
Part 1 cohort 2; dalantercept 0.9 mg/kg plus axitinib 5 mg PO BID
Part 1 cohort 3; dalantercept 1.2 mg/kg plus axitinib 5 mg PO BID
Part 1 cohort 1; dalantercept 1.5 mg/kg plus axitinib 5 mg PO BID
Overall Number of Participants Analyzed 6 9 14 0
Measure Type: Count of Participants
Unit of Measure: Participants
6
 100.0%
9
 100.0%
14
 100.0%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1 Dalantercept 0.6 mg/kg, Part 1 Dalantercept 0.9 mg/kg, Part 1 Dalantercept 1.2 mg/kg, Part 1 Dalantercept 1.5 mg/kg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter recommended dose for Part 2
Estimated Value 0.9
Estimation Comments The recommended dose level for Part 2 was determined to be 0.9 mg/kg
2.Primary Outcome
Title Part 2: Progression Free Survival (PFS).
Hide Description

PFS was defined as the time from randomization to the date of first documentation of disease progression based on RECIST (version 1.1) or to death due to any cause, whichever occurred first. Disease progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study.

RECIST 1.1 defines disease progression as an increase of at least a 20% in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression)

Time Frame Progression free survival is defined as the time from the date of the randomization to the first documented disease progression (according to RECIST v1.1) or death due to any cause. The Time frame for Part 2 was up to 29.0 months
Hide Outcome Measure Data
Hide Analysis Population Description
The All Treated Set (ATS) included all randomized patients who received any study drug
Arm/Group Title Part 2: Dalantercept 0.9 mg/kg Plus Axitinib Part 2: Placebo Plus Axitinib
Hide Arm/Group Description:
Subcutaneous (SC) injection of Dalantercept 0.9 mg/kg once every 3 weeks and Oral axitinib 5 mg BID for continuous dosing.
Subcutaneous injection of normal saline once every 3 weeks and oral axitinib 5 mg BID for continuous dosing
Overall Number of Participants Analyzed 58 61
Median (95% Confidence Interval)
Unit of Measure: Months
6.8
(4.5 to 9.4)
5.6
(3.3 to 8.3)
3.Secondary Outcome
Title Part 1: Progression Free Survival (PFS).
Hide Description PFS was defined as the time from randomization to the date of first documentation of disease progression based on RECIST (version 1.1) or to death due to any cause, whichever occurred first. Disease progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study.
Time Frame The time frame for Part 1 of the study was up to 21.6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set; all subjects randomized in Part 1 of the study
Arm/Group Title Part 1 Dalantercept 0.6 mg/kg Part 1 Dalantercept 0.9 mg/kg Part 1: Dalantercept 1.2 mg/kg
Hide Arm/Group Description:
Dose escalation cohort 1: dalantercept 0.6 mg/kg plus axitinib 5 mg PO BID
Dose escalation cohort 2: dalantercept 0.9 mg/kg plus axitinib 5 mg PO BID
Part 1 cohort 3: dalantercept 1.2 mg/kg plus axitinib 5 mg PO BID
Overall Number of Participants Analyzed 6 9 14
Median (95% Confidence Interval)
Unit of Measure: Months
5.5
(1.3 to 20.6)
21.6
(2.8 to 21.6)
6.9
(2.7 to 20.7)
4.Secondary Outcome
Title Part 1: Overall Survival (OS). [The Time Frame for Part 1 of the Study Was up to 21.6 Months]
Hide Description Percentage of Part 1 subjects alive at the end of Part 1 of the study. [The time frame for Part 1 of the study was up to 21.6 months]
Time Frame Up to 21.6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set; all subjects randomized in Part 1 of the study
Arm/Group Title Part 1 Dalantercept 0.6 mg/kg Part 1 Dalantercept 0.9 mg/kg Part 1: Dalantercept 1.2 mg/kg
Hide Arm/Group Description:
Dose escalation cohort 1: dalantercept 0.6 mg/kg plus axitinib 5 mg PO BID
Dose escalation cohort 2: dalantercept 0.9 mg/kg plus axitinib 5 mg PO BID
Part 1 cohort 3: dalantercept 1.2 mg/kg plus axitinib 5 mg PO BID
Overall Number of Participants Analyzed 6 9 14
Measure Type: Count of Participants
Unit of Measure: Participants
4
  66.7%
7
  77.8%
9
  64.3%
5.Secondary Outcome
Title Part 1: Objective Response Rate (ORR)
Hide Description Objective response rate (ORR) is defined as the number and percentage of patients who have a partial response (PR) or complete response (CR) to therapy. A CR is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. A PR is defined as a decrease of at least a 30% in the sum of diameters of target lesions, taking as reference the baseline sum diameters. As no subjects in Part 1 experienced a CR, the ORR in Part 1 is defined by the PR
Time Frame Up to 21.6 months from randomization in Part 1 of the study
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set; all subjects randomized in Part 1 of the study
Arm/Group Title Part 1 Dalantercept 0.6 mg/kg Part 1 Dalantercept 0.9 mg/kg Part 1: Dalantercept 1.2 mg/kg
Hide Arm/Group Description:
Dose escalation cohort 1: dalantercept 0.6 mg/kg plus axitinib 5 mg PO BID
Dose escalation cohort 2: dalantercept 0.9 mg/kg plus axitinib 5 mg PO BID
Part 1 cohort 3: dalantercept 1.2 mg/kg plus axitinib 5 mg PO BID
Overall Number of Participants Analyzed 6 9 14
Measure Type: Count of Participants
Unit of Measure: Participants
2
  33.3%
3
  33.3%
2
  14.3%
6.Secondary Outcome
Title Part 1: Disease Control Rate (DCR)
Hide Description The number and percentage of patients whose disease shrinks or remains stable. DCR is the sum of the complete, partial and stable disease rates.
Time Frame From randomization up to 21.6 months in Part 1 of the study
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Part 1 Dalantercept 0.6 mg/kg Part 1 Dalantercept 0.9 mg/kg Part 1: Dalantercept 1.2 mg/kg
Hide Arm/Group Description:
Dose escalation cohort 1: dalantercept 0.6 mg/kg plus axitinib 5 mg PO BID
Dose escalation cohort 2: dalantercept 0.9 mg/kg plus axitinib 5 mg PO BID
Part 1 cohort 3: dalantercept 1.2 mg/kg plus axitinib 5 mg PO BID
Overall Number of Participants Analyzed 6 9 14
Measure Type: Count of Participants
Unit of Measure: Participants
3
  50.0%
5
  55.6%
6
  42.9%
7.Secondary Outcome
Title Part 1: Duration of Response (DoR)
Hide Description Response duration is measured from the time measurement criteria are first met for objective response until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded on study.
Time Frame From randomization up to 21.6 months in Part 1 of the study.
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set; all subjects randomized in Part 1 of the study
Arm/Group Title Part 1 Dalantercept 0.6 mg/kg Part 1 Dalantercept 0.9 mg/kg Part 1: Dalantercept 1.2 mg/kg
Hide Arm/Group Description:
Dose escalation cohort 1: dalantercept 0.6 mg/kg plus axitinib 5 mg PO BID
Dose escalation cohort 2: dalantercept 0.9 mg/kg plus axitinib 5 mg PO BID
Part 1 cohort 3: dalantercept 1.2 mg/kg plus axitinib 5 mg PO BID
Overall Number of Participants Analyzed 6 9 14
Median (95% Confidence Interval)
Unit of Measure: months
3
(2.8 to 21.6)
6.9
(6.9 to 21.6)
10
(8.8 to 11.1)
8.Secondary Outcome
Title Part 2: Progression Free Survival (PFS) for the Subset of Participants With 2 or More Lines of Prior Systemic Chemotherapy
Hide Description Progression Free Survival (PFS) for the subset of participants with 2 or more lines of prior systemic chemotherapy. PFS was based upon RECIST 1.1 assessment, as described in outcome measure 2.
Time Frame Progression free survival is defined as the time from the date of the randomization to the first documented disease progression (according to RECIST v1.1) or death due to any cause. The Time frame for Part 2 was up to 29.0 months
Hide Outcome Measure Data
Hide Analysis Population Description

Subgroup of Part 2 participants:

24 of 63 participants in the dalantercept arm and 22 of 68 participants in the placebo arm had at least 2 lines of prior systemic chemotherapy

Arm/Group Title Part 2: Dalantercept 0.9 mg/kg Plus Axitinib Part 2: Placebo Plus Axitinib
Hide Arm/Group Description:
Subcutaneous (SC) injection of Dalantercept 0.9 mg/kg once every 3 weeks and Oral axitinib 5 mg BID for continuous dosing.
Subcutaneous injection of normal saline once every 3 weeks and oral axitinib 5 mg BID for continuous dosing
Overall Number of Participants Analyzed 24 22
Median (95% Confidence Interval)
Unit of Measure: Months
8.1
(3.6 to 10.5)
7.0
(2.8 to 9.5)
9.Secondary Outcome
Title Part 2: Overall Survival.
Hide Description The number of months from the date of randomization to the date of death.
Time Frame Patients to be contacted every 3 months for up to 12 months (anticipated) for survival follow-up, as well as tumor assessment scans if progression of disease has not previously been documented. The time frame for Part 2 was up to 29.0 months
Hide Outcome Measure Data
Hide Analysis Population Description
The All Treated Set (ATS) included all randomized patients who received any study drug
Arm/Group Title Part 2: Dalantercept 0.9 mg/kg Plus Axitinib Part 2: Placebo Plus Axitinib
Hide Arm/Group Description:
Subcutaneous (SC) injection of Dalantercept 0.9 mg/kg once every 3 weeks and Oral axitinib 5 mg BID for continuous dosing.
Subcutaneous injection of normal saline once every 3 weeks and oral axitinib 5 mg BID for continuous dosing
Overall Number of Participants Analyzed 58 61
Median (Inter-Quartile Range)
Unit of Measure: Months
13.0
(9.3 to 14.5)
14.7
(7.3 to 20.0)
10.Secondary Outcome
Title Part 2: Objective Response Rate.
Hide Description Objective response rate (ORR) is defined as the number and percentage of patients who have a partial response (PR) or complete response (CR) to therapy. A CR is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. A PR is defined as a decrease of at least a 30% in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time Frame Assessed at 30 days after last dose of study drug; up to 29.0 months for Part 2 of the study
Hide Outcome Measure Data
Hide Analysis Population Description
The All Treated Set (ATS) included all randomized patients who received any study drug
Arm/Group Title Part 2: Dalantercept 0.9 mg/kg Plus Axitinib Part 2: Placebo Plus Axitinib
Hide Arm/Group Description:
Subcutaneous (SC) injection of Dalantercept 0.9 mg/kg once every 3 weeks and oral axitinib 5 mg BID for continuous dosing.
Subcutaneous injection of normal saline once every 3 weeks and oral axitinib 5 mg BID for continuous dosing
Overall Number of Participants Analyzed 58 61
Measure Type: Count of Participants
Unit of Measure: Participants
11
  19.0%
15
  24.6%
11.Secondary Outcome
Title Part 2: Duration of Response
Hide Description Response duration is measured from the time measurement criteria are first met for objective response until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded on study.
Time Frame Assessed at 30 days after the last dose of study drug; up to 29.0 months for Part 2 of the study.
Hide Outcome Measure Data
Hide Analysis Population Description
The All Treatment Set (ATS) included all randomized patients who received any study drug. Please see Outcome Measure 5 for Objective Response Rate data. Since there were too few participants with events, an estimation of response duration was not able to be calculated due to the early termination of the study.
Arm/Group Title Dalantercept 0.9 mg/kg Plus Axitinib Part 2: Placebo Plus Axitinib
Hide Arm/Group Description:
Subcutaneous (SC) injection of Dalantercept 0.9 mg/kg once every 3 weeks and oral axitinib 5 mg BID for continuous dosing.
Subcutaneous injection of normal saline once every 3 weeks and oral axitinib 5 mg BID for continuous dosing
Overall Number of Participants Analyzed 58 61
Median (95% Confidence Interval)
Unit of Measure: Months
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
too few participants with events were available for an estimation of response duration due to the early termination of the study
12.Secondary Outcome
Title Part 2: Disease Control Rate.
Hide Description The number and percentage of patients whose disease shrinks or remains stable. DCR is the sum of the complete, partial and stable disease rates.
Time Frame Assessed at 30 days after last dose of study drug. The time frame for Part 2 was up to 29.0 months
Hide Outcome Measure Data
Hide Analysis Population Description
The All Treated Set (ATS) included all randomized patients who received any study drug
Arm/Group Title Part 2: Dalantercept 0.9 mg/kg Plus Axitinib Part 2: Placebo Plus Axitinib
Hide Arm/Group Description:
Subcutaneous (SC) injection of Dalantercept 0.9 mg/kg once every 3 weeks and oral axitinib 5 mg BID for continuous dosing.
Subcutaneous injection of normal saline once every 3 weeks and oral axitinib 5 mg BID for continuous dosing
Overall Number of Participants Analyzed 58 61
Measure Type: Count of Participants
Unit of Measure: Participants
48
  82.8%
50
  82.0%
13.Other Pre-specified Outcome
Title Part 1: Exploratory PD - Serum BMP9
Hide Description Exploratory analysis. Absolute change from baseline in serum Bone Morphogenetic Protein 9 (BMP9)
Time Frame From randomization up to 21.6 months in Part 1 of the study
Hide Outcome Measure Data
Hide Analysis Population Description
All subjects randomized to Part 1 of the study and treated with at least 1 dose of dalantercept. Given the high degree of variability in serum BMP9 levels in study subjects [Baseline value 23.55 ng/mL (SD 20.54 ng/mL)] and the relative small numbers of subjects in each treatment arm, it was decided that the best way to understand a treatment effect was to conduct a pooled analysis of all 29 Part 1 subjects for the comparison of change from Baseline.
Arm/Group Title Part 1 Participants
Hide Arm/Group Description:
Pooled number of Part 1 participants across the dose escalation groups 0.6 mg/kg (N=6), 0.9 mg/kg (N=9) and 1.2 mg/kg (N=14); total N=29 subjects
Overall Number of Participants Analyzed 29
Mean (Standard Deviation)
Unit of Measure: ng/mL
-11.5  (2.58)
14.Other Pre-specified Outcome
Title Part 2: PD Biomarker Activities.
Hide Description Exploratory analysis. Absolute change from baseline in serum Bone Morphogenetic Protein 9 (BMP9)
Time Frame Assessed at 30 days after the last dose of dalantercept ± 10 days. The time frame for Part 2 was up to 29.0 months.
Hide Outcome Measure Data
Hide Analysis Population Description
The All Treated Set (ATS) included all randomized patients who received any study drug, and for whom sufficient blood sample was available to assess the exploratory biomarker.
Arm/Group Title Part 2: Dalantercept 0.9 mg/kg Plus Axitinib Part 2: Placebo Plus Axitinib
Hide Arm/Group Description:
Subcutaneous (SC) injection of Dalantercept 0.9 mg/kg once every 3 weeks and oral axitinib 5 mg BID for continuous dosing.
Subcutaneous injection of normal saline once every 3 weeks and oral axitinib 5 mg BID for continuous dosing
Overall Number of Participants Analyzed 45 46
Mean (Standard Deviation)
Unit of Measure: pg/mL
-53.34  (37.87) 8.55  (86.32)
Time Frame Adverse events were collected from the initial study drug administration on Cycle 1, Day 1 (C1D1) until 30 days after the last study drug administration for each subject on study, up to a total of 29.0 months of study drug exposure
Adverse Event Reporting Description

Analyses of adverse events were carried out on the Safety Analysis Set, defined as all participants who received at least one dose of study drug.

There were no subjects enrolled in Part 1 cohort 4 (1.5 mg/kg dalantercept), thus no subjects were at risk for adverse events

 
Arm/Group Title Part 1: Dalantercept 0.6 mg/kg Part 1: Dalantercept 0.9 mg/kg Part 1: Dalantercept 1.2 mg/kg Part 1: Dalantercept 1.5 mg/kg Part 2: Dalantercept 0.9 mg/kg Plus Axitinib Part 2: Placebo Plus Axitinib
Hide Arm/Group Description Part 1 cohort 1: dalantercept 0.6 mg/kg plus axitinib 5 mg PO BID Part 1 cohort 1: dalantercept 0.9 mg/kg plus axitinib 5 mg PO BID Part 1 cohort 1: dalantercept 1.2 mg/kg plus axitinib 5 mg PO BID Part 1 cohort 1: dalantercept 1.5 mg/kg plus axitinib 5 mg PO BID Subcutaneous (SC) injection of Dalantercept 0.9 mg/kg once every 3 weeks and oral axitinib 5 mg BID for continuous dosing. Subcutaneous injection of normal saline once every 3 weeks and oral axitinib 5 mg BID for continuous dosing
All-Cause Mortality
Part 1: Dalantercept 0.6 mg/kg Part 1: Dalantercept 0.9 mg/kg Part 1: Dalantercept 1.2 mg/kg Part 1: Dalantercept 1.5 mg/kg Part 2: Dalantercept 0.9 mg/kg Plus Axitinib Part 2: Placebo Plus Axitinib
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/6 (33.33%)      2/9 (22.22%)      5/14 (35.71%)      0/0      20/63 (31.75%)      16/68 (23.53%)    
Hide Serious Adverse Events
Part 1: Dalantercept 0.6 mg/kg Part 1: Dalantercept 0.9 mg/kg Part 1: Dalantercept 1.2 mg/kg Part 1: Dalantercept 1.5 mg/kg Part 2: Dalantercept 0.9 mg/kg Plus Axitinib Part 2: Placebo Plus Axitinib
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/6 (33.33%)      1/9 (11.11%)      6/14 (42.86%)      0/0      19/62 (30.65%)      16/64 (25.00%)    
Cardiac disorders             
Acute myocardial infarction  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  0/62 (0.00%)  1/64 (1.56%) 
Sinus bradycardia  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  0/62 (0.00%)  1/64 (1.56%) 
Gastrointestinal disorders             
Abdominal pain  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  0/62 (0.00%)  0 1/64 (1.56%)  1
Anal ulcer  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  0/62 (0.00%)  1/64 (1.56%) 
Obstruction gastric  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  0/62 (0.00%)  1/64 (1.56%) 
Mouth haemorrhage  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  1/62 (1.61%)  0/64 (0.00%) 
Pancreatitus  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  0/62 (0.00%)  1/64 (1.56%) 
Bile duct stenosis  1  0/6 (0.00%)  0/9 (0.00%)  1/14 (7.14%)  0/0  0/62 (0.00%)  0/64 (0.00%) 
Transaminase increase  1  0/6 (0.00%)  0/9 (0.00%)  1/14 (7.14%)  1 0/0  0/62 (0.00%)  0/64 (0.00%) 
General disorders             
Disease progression  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  1/62 (1.61%)  1/64 (1.56%) 
Non-cardiac chest pain  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  2/62 (3.23%)  0/64 (0.00%) 
Oedema peripheral  1  0/6 (0.00%)  0/9 (0.00%)  1/14 (7.14%)  0/0  0/62 (0.00%)  1/64 (1.56%) 
Pain  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  0/62 (0.00%)  1/64 (1.56%) 
Gate disturbance  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  0/62 (0.00%)  0/64 (0.00%) 
Hepatobiliary disorders             
Periportal oedema  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  0/62 (0.00%)  1/64 (1.56%) 
Infections and infestations             
pneumonia  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  2/62 (3.23%)  0/64 (0.00%) 
Anorectal infection  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  1/62 (1.61%)  0/64 (0.00%) 
Diverticulitis  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  1/62 (1.61%)  0/64 (0.00%) 
Gastroenteritis  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  1/62 (1.61%)  0/64 (0.00%) 
Skin infection  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  0/62 (0.00%)  1/64 (1.56%) 
Upper respiratory tract infection  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  0/62 (0.00%)  1/64 (1.56%) 
Injury, poisoning and procedural complications             
Soft tissue injury  1  0/6 (0.00%)  0/9 (0.00%)  1/14 (7.14%)  0/0  0/62 (0.00%)  0/64 (0.00%) 
Metabolism and nutrition disorders             
Dehydration  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  0/62 (0.00%)  1/64 (1.56%) 
Diabetes mellitus  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  1/62 (1.61%)  0/64 (0.00%) 
Hypoglycaemia  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  1/62 (1.61%)  0/64 (0.00%) 
Hyponatraemia  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  0/62 (0.00%)  1/64 (1.56%) 
Musculoskeletal and connective tissue disorders             
Back pain  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  0/62 (0.00%)  2/64 (3.13%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)             
Hodgkin's disease  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  1/62 (1.61%)  0/64 (0.00%) 
Tumour thrombosis  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  0/62 (0.00%)  1/64 (1.56%) 
Nervous system disorders             
Peripheral motor neuropathy  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  1/62 (1.61%)  0/64 (0.00%) 
Spinal cord compression  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  0/62 (0.00%)  1/64 (1.56%) 
Transient ischaemic attack  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  0/62 (0.00%)  1/64 (1.56%) 
Convulsion  1  0/6 (0.00%)  1/9 (11.11%)  0/14 (0.00%)  0/0  0/62 (0.00%)  0/64 (0.00%) 
Renal and urinary disorders             
Renal failure acute  1  0/6 (0.00%)  0/9 (0.00%)  2/14 (14.29%)  0/0  2/62 (3.23%)  1/64 (1.56%) 
Respiratory, thoracic and mediastinal disorders             
PLeural effusion  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  3/62 (4.84%)  0/64 (0.00%) 
Pulmonary embolism  1  1/6 (16.67%)  1 0/9 (0.00%)  0/14 (0.00%)  0/0  1/62 (1.61%)  1/64 (1.56%) 
Epistaxis  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  1/62 (1.61%)  0/64 (0.00%) 
Hypoxia  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  1/62 (1.61%)  0/64 (0.00%) 
Pneumothorax  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  1/62 (1.61%)  0/64 (0.00%) 
Dyspnea  1  1/6 (16.67%)  0/9 (0.00%)  1/14 (7.14%)  0/0  0/58 (0.00%)  0/61 (0.00%) 
Vascular disorders             
Hypertension  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  1/62 (1.61%)  0/64 (0.00%) 
1
Term from vocabulary, NCI CTCAE
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Part 1: Dalantercept 0.6 mg/kg Part 1: Dalantercept 0.9 mg/kg Part 1: Dalantercept 1.2 mg/kg Part 1: Dalantercept 1.5 mg/kg Part 2: Dalantercept 0.9 mg/kg Plus Axitinib Part 2: Placebo Plus Axitinib
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   6/6 (100.00%)      9/9 (100.00%)      14/14 (100.00%)      0/0      61/62 (98.39%)      64/64 (100.00%)    
Blood and lymphatic system disorders             
Anaemia  1  0/6 (0.00%)  1/9 (11.11%)  1 3/14 (21.43%)  3 0/0  13/62 (20.97%)  13 4/64 (6.25%)  4
Thrombocytopenia  1  0/6 (0.00%)  1/9 (11.11%)  1 3/14 (21.43%)  3 0/0  4/62 (6.45%)  4 4/64 (6.25%)  4
Endocrine disorders             
Hypothyroidism  1  0/6 (0.00%)  2/9 (22.22%)  2 3/14 (21.43%)  3 0/0  8/62 (12.90%)  8 12/64 (18.75%)  12
Eye disorders             
Vision blurred  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  2/62 (3.23%)  2 7/64 (10.94%)  7
Gastrointestinal disorders             
Diarrhoea  1  2/6 (33.33%)  2 4/9 (44.44%)  4 6/14 (42.86%)  6 0/0  0 54/62 (87.10%)  54 55/64 (85.94%)  55
Nausea  1  2/6 (33.33%)  2 3/9 (33.33%)  3 3/14 (21.43%)  3 0/0  38/62 (61.29%)  38 40/64 (62.50%)  40
Constipation  1  1/6 (16.67%)  1 3/9 (33.33%)  3 0/14 (0.00%)  0/0  24/62 (38.71%)  24 28/64 (43.75%)  28
Vomiting  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  18/62 (29.03%)  18 18/64 (28.13%)  18
Abdominal pain  1  0/6 (0.00%)  1/9 (11.11%)  1 3/14 (21.43%)  3 0/0  13/62 (20.97%)  13 16/64 (25.00%)  16
Stomatitis  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  8/62 (12.90%)  8 15/64 (23.44%)  15
Dyspepsia  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  6/62 (9.68%)  6 8/64 (12.50%)  8
Abdominal pain upper  1  0/6 (0.00%)  1/9 (11.11%)  1 3/14 (21.43%)  3 0/0  4/62 (6.45%)  4 5/64 (7.81%)  5
Oral pain  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  6/62 (9.68%)  6 3/64 (4.69%)  3
Dry mouth  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  7/62 (11.29%)  7 1/64 (1.56%)  1
Dysphagia  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  2/62 (3.23%)  2 5/64 (7.81%)  5
Flatulence  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  3/62 (4.84%)  3 4/64 (6.25%)  4
General disorders             
Fatigue  1  4/6 (66.67%)  4 5/9 (55.56%)  5 10/14 (71.43%)  10 /0  35/62 (56.45%)  35 47/64 (73.44%)  47
Chills  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  8/62 (12.90%)  8 5/64 (7.81%)  5
Oedema peripheral  1  0/6 (0.00%)  3/9 (33.33%)  3 6/14 (42.86%)  6 0/0  24/62 (38.71%)  24 14/64 (21.88%)  14
Non-cardiac chest pain  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  6/62 (9.68%)  6 6/64 (9.38%)  6
Pyrexia  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  7/62 (11.29%)  7 5/64 (7.81%)  5
Mucosal inflammation  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  7/62 (11.29%)  7 3/64 (4.69%)  3
Infections and infestations             
Upper respiratory tract infection  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  2/62 (3.23%)  2 6/64 (9.38%)  6
Sinusitis  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  4/62 (6.45%)  4 3/64 (4.69%)  3
Urinary tract infection  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  3/62 (4.84%)  3 4/64 (6.25%)  4
Investigations             
Weight decreased  1  1/6 (16.67%)  1 1/9 (11.11%)  1 3/14 (21.43%)  3 0/0  13/62 (20.97%)  13 20/64 (31.25%)  20
Blood creatinine increased  1  0/6 (0.00%)  0/9 (0.00%)  6/14 (42.86%)  6 0/0  21/62 (33.87%)  21 11/64 (17.19%)  11
Aspartate aminotransferase increased  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  5/62 (8.06%)  5 7/64 (10.94%)  7
Lipase increased  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  7/62 (11.29%)  7 5/64 (7.81%)  5
Ejection fraction decreased  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  2/62 (3.23%)  2 9/64 (14.06%)  9
Amylase increased  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  5/62 (8.06%)  5 5/64 (7.81%)  5
Alanine aminotransferase increased  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  2/62 (3.23%)  2 5/64 (7.81%)  5
Weight increased  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  6/62 (9.68%)  6 1/64 (1.56%)  1
Metabolism and nutrition disorders             
Decreased appetite  1  0/6 (0.00%)  0/9 (0.00%)  5/14 (35.71%)  5 0/0  23/62 (37.10%)  23 20/64 (31.25%)  20
Hyponatraemia  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  5/62 (8.06%)  5 13/64 (20.31%)  13
Hyperkalaemia  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  7/62 (11.29%)  7 8/64 (12.50%)  8
Dehydration  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  6/62 (9.68%)  6 8/64 (12.50%)  8
Hypophosphataemia  1  1/6 (16.67%)  1 0/9 (0.00%)  2/14 (14.29%)  2 0/0  7/62 (11.29%)  7 6/64 (9.38%)  6
Musculoskeletal and connective tissue disorders             
Arthralgia  1  0/6 (0.00%)  2/9 (22.22%)  2 3/14 (21.43%)  3 /0  17/62 (27.42%)  17 19/64 (29.69%)  19
Back pain  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  10/62 (16.13%)  10 14/64 (21.88%)  14
Myalgia  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  14/62 (22.58%)  14 9/64 (14.06%)  9
Muscle spasms  1  2/6 (33.33%)  2 0/9 (0.00%)  0 2/14 (14.29%)  2 0/0  7/62 (11.29%)  7 10/64 (15.63%)  10
Pain in extremity  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  9/62 (14.52%)  9 4/64 (6.25%)  4
Muscular weakness  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  4/62 (6.45%)  4 6/64 (9.38%)  6
Musculoskeletal chest pain  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  3/62 (4.84%)  3 7/64 (10.94%)  7
Musculoskeletal pain  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  3/62 (4.84%)  3 7/64 (10.94%)  7
Flank pain  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  2/62 (3.23%)  2 5/64 (7.81%)  5
Neck pain  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  4/62 (6.45%)  4 3/64 (4.69%)  3
Nervous system disorders             
Headache  1  0/6 (0.00%)  1/9 (11.11%)  1 2/14 (14.29%)  2 0/0  14/62 (22.58%)  14 21/64 (32.81%)  21
Dizziness  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  7/62 (11.29%)  7 6/64 (9.38%)  6
Dysgeusia  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  4/62 (6.45%)  4 6/64 (9.38%)  6
Psychiatric disorders             
Insomnia  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  4/62 (6.45%)  4 9/64 (14.06%)  9
Depression  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  6/62 (9.68%)  6 5/64 (7.81%)  5
Anxiety  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  2/62 (3.23%)  2 5/64 (7.81%)  5
Renal and urinary disorders             
Proteinuria  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  4/62 (6.45%)  4 11/64 (17.19%)  11
Pollakiuria  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  9/62 (14.52%)  9 2/64 (3.13%)  2
Respiratory, thoracic and mediastinal disorders             
Dysphonia  1  1/6 (16.67%)  1 1/9 (11.11%)  1 3/14 (21.43%)  3 0/0  11/62 (17.74%)  11 25/64 (39.06%)  25
Epistaxis  1  1/6 (16.67%)  1 1/9 (11.11%)  1 4/14 (28.57%)  4 0/0  24/62 (38.71%)  24 8/64 (12.50%)  8
Cough  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  16/62 (25.81%)  16 13/64 (20.31%)  13
Oropharyngeal pain  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  7/62 (11.29%)  7 8/64 (12.50%)  8
Nasal congestion  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  6/62 (9.68%)  6 7/64 (10.94%)  7
Pleural effusion  1  0/6 (0.00%)  1/9 (11.11%)  1 3/14 (21.43%)  3 0/0  6/62 (9.68%)  6 3/64 (4.69%)  3
Dyspnoea exertional  1  1/6 (16.67%)  1 1/9 (11.11%)  1 3/14 (21.43%)  3 0/0  4/62 (6.45%)  4 3/64 (4.69%)  3
Skin and subcutaneous tissue disorders             
Palmar-plantar erythrodysaesthesia syndrome  1  0/6 (0.00%)  1/9 (11.11%)  1 3/14 (21.43%)  3 0/0  15/62 (24.19%)  15 15/64 (23.44%)  15
Pruritus  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  4/62 (6.45%)  4 12/64 (18.75%)  12
Rash  1  0/6 (0.00%)  2/9 (22.22%)  2 1/14 (7.14%)  1 0/0  6/62 (9.68%)  6 8/64 (12.50%)  8
Rash maculo-papular  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  6/62 (9.68%)  6 6/64 (9.38%)  6
Night sweats  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  5/62 (8.06%)  5 6/64 (9.38%)  6
Telangiectasia  1  0/6 (0.00%)  5/9 (55.56%)  5 1/14 (7.14%)  1 0/0  6/62 (9.68%)  6 5/64 (7.81%)  5
Dry skin  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  2/62 (3.23%)  2 7/64 (10.94%)  7
Alopecia  1  0/6 (0.00%)  0/9 (0.00%)  0/14 (0.00%)  0/0  1/62 (1.61%)  1 6/64 (9.38%)  6
Vascular disorders             
Hypertension  1  0/6 (0.00%)  2/9 (22.22%)  2 1/14 (7.14%)  1 0/0  13/62 (20.97%)  13 30/64 (46.88%)  30
1
Term from vocabulary, NCI CTCAE
Indicates events were collected by systematic assessment
All 131 patients in Part 2 discontinued from the study; the most frequent reasons were (i) study terminated at the discretion of the sponsor [86 patients (65.6%)] and (ii) death [36 patients (27.5%)]. The discontinuations prior to planned sample collections, as outlined in the protocol schedule of events, precluded the ability to carry out all planned analyses, including but not limited to PK analyses. Dalantercept PK in patients with advanced cancer has been reported previously.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Sr. Vice President, Regulatory Affairs
Organization: Acceleron Pharma
Phone: 617-649-9200
EMail: jdesiderio@acceleronpharma.com
Layout table for additonal information
Responsible Party: Acceleron Pharma Inc.
ClinicalTrials.gov Identifier: NCT01727336    
Other Study ID Numbers: A041-04
ACE-041 ( Other Identifier: Acceleron Pharma Inc. )
First Submitted: November 8, 2012
First Posted: November 16, 2012
Results First Submitted: April 28, 2021
Results First Posted: May 24, 2021
Last Update Posted: September 23, 2021