Trial Outcomes & Findings for Therapeutic Angiotensin-(1-7) in Treating Patients With Metastatic Sarcoma That Cannot Be Removed By Surgery (NCT NCT01553539)

Last Updated: 2018-07-05

Results Overview

'Activity' will be operationalized using objective tumor response, which will be estimated as the proportion of partial and complete responders (according to Response Evaluation Criteria in Solid Tumors \[RECIST\] criteria) among all evaluable patients. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

20 participants

Primary outcome timeframe

Approximately 1 year

Results posted on

2018-07-05

Participant Flow

Participant milestones

Participant milestones
Measure	Treatment (Antiangiogenesis Therapy) Patients receive therapeutic angiotensin-(1-7) subcutaneous (SC) once daily in the absence of disease progression or unacceptable toxicity.
Overall Study STARTED	20
Overall Study COMPLETED	20
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Therapeutic Angiotensin-(1-7) in Treating Patients With Metastatic Sarcoma That Cannot Be Removed By Surgery

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment (Antiangiogenesis Therapy) n=20 Participants Patients receive therapeutic angiotensin-(1-7) SC once daily in the absence of disease progression or unacceptable toxicity.
Age, Categorical <=18 years	0 Participants n=113 Participants
Age, Categorical Between 18 and 65 years	18 Participants n=113 Participants
Age, Categorical >=65 years	2 Participants n=113 Participants
Age, Continuous	51.4 years STANDARD_DEVIATION 14.9 • n=113 Participants
Sex: Female, Male Female	9 Participants n=113 Participants
Sex: Female, Male Male	11 Participants n=113 Participants
Region of Enrollment United States	20 participants n=113 Participants

PRIMARY outcome

Timeframe: Approximately 1 year

Outcome measures

Outcome measures
Measure	Treatment (Antiangiogenesis Therapy) n=20 Participants Patients receive therapeutic angiotensin-(1-7) SC once daily in the absence of disease progression or unacceptable toxicity.
Antitumor Activity as Assessed by Number of Patients Showing an Objective Tumor Response	0 participants

PRIMARY outcome

Timeframe: Approximately 1 year

See the adverse event tables for specifics.

Outcome measures

Outcome measures
Measure	Treatment (Antiangiogenesis Therapy) n=20 Participants Patients receive therapeutic angiotensin-(1-7) SC once daily in the absence of disease progression or unacceptable toxicity.
Number of Participants Who Experienced Adverse Events as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0	20 Participants experiencing adverse events

SECONDARY outcome

Timeframe: Approximately 5 years

Outcome measures

Outcome measures
Measure	Treatment (Antiangiogenesis Therapy) n=20 Participants Patients receive therapeutic angiotensin-(1-7) SC once daily in the absence of disease progression or unacceptable toxicity.
Time to Disease Progression	2.7 months Interval 1.4 to 4.1

SECONDARY outcome

Timeframe: Approximately 5 years

Outcome measures

Outcome measures
Measure	Treatment (Antiangiogenesis Therapy) n=20 Participants Patients receive therapeutic angiotensin-(1-7) SC once daily in the absence of disease progression or unacceptable toxicity.
Overall Survival	10.2 months Interval 5.3 to 18.3

SECONDARY outcome

Timeframe: Baseline and Day 22

Outcome measures

Outcome measures
Measure	Treatment (Antiangiogenesis Therapy) n=20 Participants Patients receive therapeutic angiotensin-(1-7) SC once daily in the absence of disease progression or unacceptable toxicity.
Plasma Levels of Angiogenic Peptides Including Placental Growth Factor (PlGF) Ang-(1-7) Baseline	18.4 pg/mL Standard Deviation 385.0
Plasma Levels of Angiogenic Peptides Including Placental Growth Factor (PlGF) Ang-(1-7) Day 22	41.2 pg/mL Standard Deviation 2840.0
Plasma Levels of Angiogenic Peptides Including Placental Growth Factor (PlGF) Ang II Baseline	21.3 pg/mL Standard Deviation 11.5
Plasma Levels of Angiogenic Peptides Including Placental Growth Factor (PlGF) Ang II Day 22	31.5 pg/mL Standard Deviation 26.5
Plasma Levels of Angiogenic Peptides Including Placental Growth Factor (PlGF) Ang I Baseline	22.5 pg/mL Standard Deviation 127
Plasma Levels of Angiogenic Peptides Including Placental Growth Factor (PlGF) Ang I Day 22	17.5 pg/mL Standard Deviation 52.7
Plasma Levels of Angiogenic Peptides Including Placental Growth Factor (PlGF) VEGF Baseline	65.6 pg/mL Standard Deviation 66.4
Plasma Levels of Angiogenic Peptides Including Placental Growth Factor (PlGF) VEGF Day 22	49.6 pg/mL Standard Deviation 43.0
Plasma Levels of Angiogenic Peptides Including Placental Growth Factor (PlGF) PIGF Baseline	4.3 pg/mL Standard Deviation 2.1
Plasma Levels of Angiogenic Peptides Including Placental Growth Factor (PlGF) PIGF Day 22	3.0 pg/mL Standard Deviation 1.7

Adverse Events

Treatment (Antiangiogenesis Therapy)

Serious events: 11 serious events

Other events: 20 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Treatment (Antiangiogenesis Therapy) n=20 participants at risk Patients receive therapeutic angiotensin-(1-7) SC once daily in the absence of disease progression or unacceptable toxicity.
Investigations Low Hemoglobin	10.0% 2/20 • Number of events 2 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
Gastrointestinal disorders Vomiting	5.0% 1/20 • Number of events 1 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
Investigations Alkaline phosphatase	5.0% 1/20 • Number of events 1 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
Respiratory, thoracic and mediastinal disorders Dyspnea	10.0% 2/20 • Number of events 2 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
Respiratory, thoracic and mediastinal disorders Pleural effusion (non-malignant)	10.0% 2/20 • Number of events 2 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
Investigations hyperglycemia	10.0% 2/20 • Number of events 2 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
Investigations hypomagnesemia	5.0% 1/20 • Number of events 1 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
Investigations hyponatremia	10.0% 2/20 • Number of events 2 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
Investigations hypokalemia	5.0% 1/20 • Number of events 1 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
Investigations hypoalbuminemia	10.0% 2/20 • Number of events 2 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
Investigations hyperbilirubinemia	5.0% 1/20 • Number of events 1 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
Investigations serum glutamic pyruvic transaminase	5.0% 1/20 • Number of events 1 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
Investigations hypophosphatemia	5.0% 1/20 • Number of events 1 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
Gastrointestinal disorders Constipation	5.0% 1/20 • Number of events 1 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
Vascular disorders Thrombosis/thrombus/embolism	10.0% 2/20 • Number of events 2 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
Investigations serum glutamic oxaloacetic transaminase	5.0% 1/20 • Number of events 1 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
Investigations hyperkalemia	5.0% 1/20 • Number of events 1 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
Investigations Hypoxia	10.0% 2/20 • Number of events 2 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
Investigations hyperuricemia	5.0% 1/20 • Number of events 1 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
General disorders Pain: Abdomen	10.0% 2/20 • Number of events 2 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
Investigations Acidosis	10.0% 2/20 • Number of events 2 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
Investigations Alkalosis	5.0% 1/20 • Number of events 1 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
General disorders Pain: Chest wall	5.0% 1/20 • Number of events 1 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
Gastrointestinal disorders Obstruction, GI: Colon	5.0% 1/20 • Number of events 1 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
Investigations Lymphopenia	20.0% 4/20 • Number of events 4 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
General disorders Muscle weakness	10.0% 2/20 • Number of events 2 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
General disorders Pain: Extremity-limb	5.0% 1/20 • Number of events 1 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
General disorders Pain	5.0% 1/20 • Number of events 1 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
Cardiac disorders Pericardial effusion (non-malignant)	5.0% 1/20 • Number of events 1 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
General disorders Pain: Pleura	5.0% 1/20 • Number of events 1 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
Infections and infestations Lung infection	10.0% 2/20 • Number of events 2 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
General disorders Pain: Stomach	5.0% 1/20 • Number of events 1 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
Cardiac disorders Supraventricular and nodal arrhythmia: Supraventricular tachycardia	5.0% 1/20 • Number of events 1 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
General disorders Obstruction, GU: Ureter	15.0% 3/20 • Number of events 3 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
General disorders Pain: Urethra	5.0% 1/20 • Number of events 1 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
Infections and infestations Urinary with low grade neutropenia	5.0% 1/20 • Number of events 1 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils: Oral cavity-gums	5.0% 1/20 • Number of events 1 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
Gastrointestinal disorders Prolapse of stoma, GI	5.0% 1/20 • Number of events 1 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
Infections and infestations Infection Biliary tree	5.0% 1/20 • Number of events 1 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
Respiratory, thoracic and mediastinal disorders Infection with unknown ANC Lung (pneumonia)	5.0% 1/20 • Number of events 1 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
Musculoskeletal and connective tissue disorders Muscle weakness, generalized or specific area (not due to neuropathy): Extremity-lower	5.0% 1/20 • Number of events 1 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
General disorders Intra-operative injury: Spinal cord	5.0% 1/20 • Number of events 2 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
Infections and infestations Blood Infection with high grade neutropenia	5.0% 1/20 • Number of events 1 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient

Other adverse events

Other adverse events
Measure	Treatment (Antiangiogenesis Therapy) n=20 participants at risk Patients receive therapeutic angiotensin-(1-7) SC once daily in the absence of disease progression or unacceptable toxicity.
Investigations Creatinine	10.0% 2/20 • Number of events 2 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
General disorders Dizziness	10.0% 2/20 • Number of events 2 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
General disorders Taste alteration	10.0% 2/20 • Number of events 2 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
Investigations Bicarbonate serum-low	10.0% 2/20 • Number of events 2 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
Investigations hyperbilirubinemia	10.0% 2/20 • Number of events 2 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
Investigations serum glutamic pyruvic transaminase	10.0% 2/20 • Number of events 2 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
General disorders Pain: Head/headache	10.0% 2/20 • Number of events 2 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
Investigations hypermagnesemia	10.0% 2/20 • Number of events 2 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
General disorders Heartburn/dyspepsia	10.0% 2/20 • Number of events 2 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
General disorders Depression	10.0% 2/20 • Number of events 2 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
General disorders Muscle weakness	10.0% 2/20 • Number of events 2 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
General disorders Pain: Muscle	10.0% 2/20 • Number of events 2 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
General disorders Pain: Dental/teeth/peridontal	10.0% 2/20 • Number of events 2 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
General disorders Urinary retention (including neurogenic bladder)	15.0% 3/20 • Number of events 3 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
Respiratory, thoracic and mediastinal disorders Pleural effusion (non-malignant)	15.0% 3/20 • Number of events 3 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
Cardiac disorders Hypotension	15.0% 3/20 • Number of events 3 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
General disorders Pain	15.0% 3/20 • Number of events 3 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
General disorders Sweating	15.0% 3/20 • Number of events 3 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
Investigations hypocalcemia	15.0% 3/20 • Number of events 3 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
Investigations serum glutamic oxaloacetic transaminase	15.0% 3/20 • Number of events 3 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
General disorders Dehydration	15.0% 3/20 • Number of events 3 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
General disorders Anxiety	15.0% 3/20 • Number of events 3 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
Investigations Partial Thromboplastin Time	15.0% 3/20 • Number of events 3 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
Respiratory, thoracic and mediastinal disorders Atelectasis	15.0% 3/20 • Number of events 3 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
General disorders Pain: Chest/thorax	15.0% 3/20 • Number of events 3 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
General disorders Pain: Neck	15.0% 3/20 • Number of events 3 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
Skin and subcutaneous tissue disorders Allergic rhinitis	15.0% 3/20 • Number of events 3 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
Vascular disorders Hemorrhage pulmonary/upper respiratory	15.0% 3/20 • Number of events 3 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
General disorders Insomnia	20.0% 4/20 • Number of events 4 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
General disorders Weight loss	20.0% 4/20 • Number of events 4 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
General disorders Pruritus/itching	20.0% 4/20 • Number of events 5 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
General disorders Pain: Abdomen	20.0% 4/20 • Number of events 4 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
Respiratory, thoracic and mediastinal disorders Bronchospasm wheezing	20.0% 4/20 • Number of events 4 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
Cardiac disorders Sinus tachycardia	20.0% 4/20 • Number of events 4 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
Gastrointestinal disorders Vomiting	25.0% 5/20 • Number of events 5 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
Investigations Proteinuria	25.0% 5/20 • Number of events 5 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
Cardiac disorders Neuropathy: sensory	25.0% 5/20 • Number of events 5 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
Investigations hyponatremia	25.0% 5/20 • Number of events 5 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
Investigations hypoalbuminemia	25.0% 5/20 • Number of events 5 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
General disorders Pain: Back	25.0% 5/20 • Number of events 5 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
Gastrointestinal disorders Diarrhea	30.0% 6/20 • Number of events 6 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
Immune system disorders Injection site reaction	30.0% 6/20 • Number of events 6 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
Investigations low Platelets	35.0% 7/20 • Number of events 7 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
General disorders Anorexia	35.0% 7/20 • Number of events 7 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
Investigations Alkaline phosphatase	35.0% 7/20 • Number of events 7 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
Gastrointestinal disorders Constipation	35.0% 7/20 • Number of events 7 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
General disorders Pain: Joint	35.0% 7/20 • Number of events 8 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
Gastrointestinal disorders Nausea	40.0% 8/20 • Number of events 8 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
General disorders Fatigue	40.0% 8/20 • Number of events 8 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
Respiratory, thoracic and mediastinal disorders Cough	40.0% 8/20 • Number of events 8 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
Investigations Low WBC	45.0% 9/20 • Number of events 9 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
Respiratory, thoracic and mediastinal disorders Dyspnea	45.0% 9/20 • Number of events 9 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
Investigations hypokalemia	45.0% 9/20 • Number of events 9 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
Vascular disorders Edema: limb	45.0% 9/20 • Number of events 9 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
Investigations Lymphopenia	60.0% 12/20 • Number of events 12 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
Investigations Low Hemoglobin	70.0% 14/20 • Number of events 14 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient
Investigations hyperglycemia	70.0% 14/20 • Number of events 14 • Duration of treatment, up to one year worst of each type of adverse event was recorded for each patient

Additional Information

Dr. William J. Petty

Wake Forest University Health Sciences

Phone: 336-716-3313

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place