Trial Outcomes & Findings for A Phase 2 Study of Amrubicin in Relapsed or Refractory Thymic Malignancies (NCT NCT01364727)
NCT ID: NCT01364727
Last Updated: 2019-04-16
Results Overview
Participants received amrubicin 35 mg/m2 IV days 1 to 3, every 3 weeks, until progression or toxicity. Tumor response rate was assessed radiographically by the Response Evaluation Criteria In Solid Tumors (RECIST), and the overall response rate (ORR) was expressed as the sum of the Complete Response (CR) rate and the Partial Response (PR) rate. RECIST criteria define when cancer patients improve ("respond"); stay the same ("stable"); or worsen ("progression") during treatments. The criteria presume that linear measures are an adequate substitute for 2-dimensional (2D) methods and includes 4 response categories: * CR = Disappearance of all target lesions * PR = 30% decrease in the sum of the longest diameter of target lesions * Progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions * Stable disease (SD) = Small changes that do not meet above criteria
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
33 participants
Primary outcome timeframe
2 years
Results posted on
2019-04-16
Participant Flow
35 participants were fully screened for this study,and all 35 are included in Baseline Characteristics. However, 2 were ineligible and did not receive treatment, and so are not included in Outcomes nor Adverse Events.
Participant milestones
| Measure |
Amrubicin
Amrubicin 35mg/m2 IV days 1-3 every 3 weeks until progression or toxicity
|
|---|---|
|
Overall Study
STARTED
|
35
|
|
Overall Study
COMPLETED
|
33
|
|
Overall Study
NOT COMPLETED
|
2
|
Reasons for withdrawal
| Measure |
Amrubicin
Amrubicin 35mg/m2 IV days 1-3 every 3 weeks until progression or toxicity
|
|---|---|
|
Overall Study
Not Eligible
|
2
|
Baseline Characteristics
A Phase 2 Study of Amrubicin in Relapsed or Refractory Thymic Malignancies
Baseline characteristics by cohort
| Measure |
Amrubicin
n=35 Participants
Amrubicin 35mg/m2 IV days 1-3 every 3 weeks until progression or toxicity
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
24 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
11 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
14 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
21 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
34 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
10 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
23 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Histology
Thymic Carcinoma
|
20 Participants
n=5 Participants
|
|
Histology
Thymoma
|
14 Participants
n=5 Participants
|
|
Histology
Unknown
|
1 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 2 yearsPopulation: Includes those participants with Complete Response (CR) plus those with Partial Response (PR).
Participants received amrubicin 35 mg/m2 IV days 1 to 3, every 3 weeks, until progression or toxicity. Tumor response rate was assessed radiographically by the Response Evaluation Criteria In Solid Tumors (RECIST), and the overall response rate (ORR) was expressed as the sum of the Complete Response (CR) rate and the Partial Response (PR) rate. RECIST criteria define when cancer patients improve ("respond"); stay the same ("stable"); or worsen ("progression") during treatments. The criteria presume that linear measures are an adequate substitute for 2-dimensional (2D) methods and includes 4 response categories: * CR = Disappearance of all target lesions * PR = 30% decrease in the sum of the longest diameter of target lesions * Progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions * Stable disease (SD) = Small changes that do not meet above criteria
Outcome measures
| Measure |
Amrubicin
n=33 Participants
|
|---|---|
|
Overall Response Rate (ORR)
Complete Response (CR)
|
0 Participants
|
|
Overall Response Rate (ORR)
Overall response rate (ORR)
|
6 Participants
|
|
Overall Response Rate (ORR)
Partial Response (PR)
|
6 Participants
|
SECONDARY outcome
Timeframe: 2 yearsPopulation: Some participants (2) continue to survive without progression, although a median and the 95% confidence interval (95% CI) for the 33 participants have been defined.
Median Progression-free survival in patients with thymic malignancies treated with amrubicin
Outcome measures
| Measure |
Amrubicin
n=33 Participants
|
|---|---|
|
Median Progression-free Survival (PFS)
|
8.5 Months
Interval 6.7 to 38.0
|
SECONDARY outcome
Timeframe: 2 yearsPopulation: Includes those participants with Complete Response (CR) plus those with Partial Response (PR), plus those with Stable Disease).
Disease control rate (DCR) is the sum of Complete Response (CR) rate + Partial Response (PR) rate + Stable Disease (SD) rate , and is expressed here as the sum of the Overall Response Rate (ORR = CR + PR) plus the Stable Disease (SD) rate, ORR + SD. Response was assessed by the RECIST criteria, elaborated above.
Outcome measures
| Measure |
Amrubicin
n=33 Participants
|
|---|---|
|
Disease Control Rate (DCR)
Overall Response Rate (ORR)
|
6 Participants
|
|
Disease Control Rate (DCR)
Stable Disease (SD)
|
23 Participants
|
|
Disease Control Rate (DCR)
Disease control rate (DCR)
|
29 Participants
|
Adverse Events
Amrubicin
Serious events: 16 serious events
Other events: 33 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Amrubicin
n=33 participants at risk
Amrubicin 35mg/m2 IV days 1-3 every 3 weeks until progression or toxicity
|
|---|---|
|
Blood and lymphatic system disorders
Anemia
|
3.0%
1/33 • Number of events 1 • 2 Years
|
|
Psychiatric disorders
Confusion
|
3.0%
1/33 • Number of events 1 • 2 Years
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
3.0%
1/33 • Number of events 5 • 2 Years
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
3.0%
1/33 • Number of events 1 • 2 Years
|
|
Infections and infestations
Infections and infestations
|
3.0%
1/33 • Number of events 1 • 2 Years
|
|
Nervous system disorders
Lethargy
|
3.0%
1/33 • Number of events 1 • 2 Years
|
|
Investigations
Neutrophil count decreased
|
9.1%
3/33 • Number of events 3 • 2 Years
|
|
Respiratory, thoracic and mediastinal disorders
Lung Infection
|
6.1%
2/33 • Number of events 2 • 2 Years
|
|
Infections and infestations
Sepsis
|
6.1%
2/33 • Number of events 2 • 2 Years
|
|
Renal and urinary disorders
Urinary tract infection
|
3.0%
1/33 • Number of events 1 • 2 Years
|
|
Cardiac disorders
Atrial fibrillation
|
3.0%
1/33 • Number of events 1 • 2 Years
|
|
Blood and lymphatic system disorders
Thromboembolic event
|
3.0%
1/33 • Number of events 1 • 2 Years
|
|
Investigations
White blood cell decreased
|
3.0%
1/33 • Number of events 1 • 2 Years
|
Other adverse events
| Measure |
Amrubicin
n=33 participants at risk
Amrubicin 35mg/m2 IV days 1-3 every 3 weeks until progression or toxicity
|
|---|---|
|
Psychiatric disorders
Insomnia
|
15.2%
5/33 • Number of events 5 • 2 Years
|
|
Investigations
Investigations
|
15.2%
5/33 • Number of events 5 • 2 Years
|
|
General disorders
Lethargy
|
3.0%
1/33 • Number of events 1 • 2 Years
|
|
General disorders
Malaise
|
6.1%
2/33 • Number of events 2 • 2 Years
|
|
Infections and infestations
Mucosal infection
|
3.0%
1/33 • Number of events 1 • 2 Years
|
|
Gastrointestinal disorders
Mucositis oral
|
87.9%
29/33 • Number of events 29 • 2 Years
|
|
Metabolism and nutrition disorders
Hyponatremia
|
6.1%
2/33 • Number of events 2 • 2 Years
|
|
Infections and infestations
Infections and infestations
|
42.4%
14/33 • Number of events 14 • 2 Years
|
|
General disorders
Abdominal pain
|
15.2%
5/33 • Number of events 6 • 2 Years
|
|
Investigations
Alanine aminotransferase increased
|
15.2%
5/33 • Number of events 5 • 2 Years
|
|
Investigations
Alkaline phosphatase increased
|
15.2%
5/33 • Number of events 5 • 2 Years
|
|
Immune system disorders
Allergic reaction
|
12.1%
4/33 • Number of events 4 • 2 Years
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
45.5%
15/33 • Number of events 15 • 2 Years
|
|
Blood and lymphatic system disorders
Anemia
|
97.0%
32/33 • Number of events 32 • 2 Years
|
|
Infections and infestations
Anorectal infection
|
9.1%
3/33 • Number of events 3 • 2 Years
|
|
Gastrointestinal disorders
Anorexia
|
48.5%
16/33 • Number of events 16 • 2 Years
|
|
Psychiatric disorders
Anxiety
|
9.1%
3/33 • Number of events 3 • 2 Years
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
3.0%
1/33 • Number of events 1 • 2 Years
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
3.0%
1/33 • Number of events 1 • 2 Years
|
|
Investigations
Aspartate aminotransferase increased
|
6.1%
2/33 • Number of events 2 • 2 Years
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
21.2%
7/33 • Number of events 7 • 2 Years
|
|
Infections and infestations
Bladder infection
|
3.0%
1/33 • Number of events 1 • 2 Years
|
|
Blood and lymphatic system disorders
lymph nodes palpable
|
3.0%
1/33 • Number of events 1 • 2 Years
|
|
Blood and lymphatic system disorders
Blood bilirubin increased
|
3.0%
1/33 • Number of events 2 • 2 Years
|
|
Eye disorders
Blurred vision
|
6.1%
2/33 • Number of events 2 • 2 Years
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
9.1%
3/33 • Number of events 3 • 2 Years
|
|
General disorders
Breast pain
|
3.0%
1/33 • Number of events 1 • 2 Years
|
|
Skin and subcutaneous tissue disorders
Bruising
|
3.0%
1/33 • Number of events 1 • 2 Years
|
|
General disorders
Buttock pain
|
6.1%
2/33 • Number of events 2 • 2 Years
|
|
Cardiac disorders
Cardiac disorders
|
21.2%
7/33 • Number of events 7 • 2 Years
|
|
Musculoskeletal and connective tissue disorders
Chest wall pain
|
3.0%
1/33 • Number of events 1 • 2 Years
|
|
Investigations
Chills
|
3.0%
1/33 • Number of events 1 • 2 Years
|
|
Gastrointestinal disorders
Conjunctivitis
|
9.1%
3/33 • Number of events 3 • 2 Years
|
|
Gastrointestinal disorders
Constipation
|
54.5%
18/33 • Number of events 18 • 2 Years
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
81.8%
27/33 • Number of events 27 • 2 Years
|
|
Metabolism and nutrition disorders
Creatinine increased
|
6.1%
2/33 • Number of events 2 • 2 Years
|
|
Psychiatric disorders
Depression
|
3.0%
1/33 • Number of events 1 • 2 Years
|
|
Gastrointestinal disorders
Diarrhea
|
39.4%
13/33 • Number of events 13 • 2 Years
|
|
General disorders
Dizziness
|
3.0%
1/33 • Number of events 1 • 2 Years
|
|
Eye disorders
Dry eye
|
3.0%
1/33 • Number of events 1 • 2 Years
|
|
Skin and subcutaneous tissue disorders
Dry mouth
|
3.0%
1/33 • Number of events 1 • 2 Years
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
3.0%
1/33 • Number of events 1 • 2 Years
|
|
Gastrointestinal disorders
Dysgeusia
|
12.1%
4/33 • Number of events 4 • 2 Years
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
57.6%
19/33 • Number of events 19 • 2 Years
|
|
Blood and lymphatic system disorders
Edema
|
27.3%
9/33 • Number of events 9 • 2 Years
|
|
Investigations
Ejection fraction decreased
|
12.1%
4/33 • Number of events 4 • 2 Years
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
3.0%
1/33 • Number of events 1 • 2 Years
|
|
Reproductive system and breast disorders
Erectile dysfunction
|
3.0%
1/33 • Number of events 1 • 2 Years
|
|
Ear and labyrinth disorders
External ear pain
|
3.0%
1/33 • Number of events 1 • 2 Years
|
|
Eye disorders
eye lacrimation
|
3.0%
1/33 • Number of events 1 • 2 Years
|
|
General disorders
Fatigue
|
100.0%
33/33 • Number of events 33 • 2 Years
|
|
General disorders
Fever
|
27.3%
9/33 • Number of events 9 • 2 Years
|
|
Gastrointestinal disorders
Gastroesophageal reflux disease
|
18.2%
6/33 • Number of events 6 • 2 Years
|
|
Gastrointestinal disorders
Gastrointestinal disorder and pain
|
30.3%
10/33 • Number of events 10 • 2 Years
|
|
General disorders
Night sweats
|
6.1%
2/33 • Number of events 2 • 2 Years
|
|
Musculoskeletal and connective tissue disorders
Generalized muscle weakness
|
3.0%
1/33 • Number of events 1 • 2 Years
|
|
Nervous system disorders
Headache
|
18.2%
6/33 • Number of events 6 • 2 Years
|
|
Respiratory, thoracic and mediastinal disorders
Hiccups
|
6.1%
2/33 • Number of events 2 • 2 Years
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
6.1%
2/33 • Number of events 2 • 2 Years
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
6.1%
2/33 • Number of events 2 • 2 Years
|
|
Endocrine disorders
Hypocalcemia
|
3.0%
1/33 • Number of events 1 • 2 Years
|
|
Metabolism and nutrition disorders
Hypokalemia
|
9.1%
3/33 • Number of events 3 • 2 Years
|
|
Metabolism and nutrition disorders
Hypomagnesemia
|
6.1%
2/33 • Number of events 2 • 2 Years
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness lower limb
|
3.0%
1/33 • Number of events 1 • 2 Years
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorder - Other, left chest pain
|
15.2%
5/33 • Number of events 5 • 2 Years
|
|
Skin and subcutaneous tissue disorders
Nail discoloration
|
3.0%
1/33 • Number of events 1 • 2 Years
|
|
Gastrointestinal disorders
Nausea
|
60.6%
20/33 • Number of events 20 • 2 Years
|
|
General disorders
Pain
|
75.8%
25/33 • Number of events 25 • 2 Years
|
|
Investigations
Neutrophil count decreased
|
24.2%
8/33 • Number of events 8 • 2 Years
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysesthesia syndrome
|
15.2%
5/33 • Number of events 5 • 2 Years
|
|
Cardiac disorders
Palpitations
|
9.1%
3/33 • Number of events 3 • 2 Years
|
|
Cardiac disorders
Pericardial effusion
|
3.0%
1/33 • Number of events 1 • 2 Years
|
|
Nervous system disorders
Peripheral motor neuropathy
|
9.1%
3/33 • Number of events 3 • 2 Years
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
3.0%
1/33 • Number of events 1 • 2 Years
|
|
Blood and lymphatic system disorders
Platelet count decreased
|
36.4%
12/33 • Number of events 12 • 2 Years
|
|
Vascular disorders
Portal vein thrombosis
|
3.0%
1/33 • Number of events 1 • 2 Years
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
3.0%
1/33 • Number of events 1 • 2 Years
|
|
Skin and subcutaneous tissue disorders
Rash acneiform
|
18.2%
6/33 • Number of events 6 • 2 Years
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
12.1%
4/33 • Number of events 4 • 2 Years
|
|
Skin and subcutaneous tissue disorders
Rash pustular
|
3.0%
1/33 • Number of events 1 • 2 Years
|
|
Gastrointestinal disorders
Rectal hemorrhage
|
6.1%
2/33 • Number of events 2 • 2 Years
|
|
Renal and urinary disorders
bladder calcifications
|
3.0%
1/33 • Number of events 1 • 2 Years
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders
|
27.3%
9/33 • Number of events 9 • 2 Years
|
|
Reproductive system and breast disorders
right breast gynocomastia
|
3.0%
1/33 • Number of events 1 • 2 Years
|
|
Psychiatric disorders
Restlessness
|
3.0%
1/33 • Number of events 1 • 2 Years
|
|
Cardiac disorders
Sinus tachycardia
|
12.1%
4/33 • Number of events 4 • 2 Years
|
|
Respiratory, thoracic and mediastinal disorders
Sinusitis
|
9.1%
3/33 • Number of events 3 • 2 Years
|
|
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders
|
18.2%
6/33 • Number of events 6 • 2 Years
|
|
Skin and subcutaneous tissue disorders
Skin infection
|
6.1%
2/33 • Number of events 2 • 2 Years
|
|
Skin and subcutaneous tissue disorders
Skin ulceration
|
3.0%
1/33 • Number of events 1 • 2 Years
|
|
Respiratory, thoracic and mediastinal disorders
Sleep apnea
|
3.0%
1/33 • Number of events 1 • 2 Years
|
|
Respiratory, thoracic and mediastinal disorders
Sore throat
|
12.1%
4/33 • Number of events 4 • 2 Years
|
|
Surgical and medical procedures
anal exam
|
3.0%
1/33 • Number of events 1 • 2 Years
|
|
Surgical and medical procedures
colonoscopy
|
3.0%
1/33 • Number of events 1 • 2 Years
|
|
Nervous system disorders
Syncope
|
9.1%
3/33 • Number of events 3 • 2 Years
|
|
Blood and lymphatic system disorders
Thromboembolic event
|
6.1%
2/33 • Number of events 2 • 2 Years
|
|
Gastrointestinal disorders
Tooth infection
|
9.1%
3/33 • Number of events 3 • 2 Years
|
|
Gastrointestinal disorders
Toothache
|
3.0%
1/33 • Number of events 1 • 2 Years
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory infection
|
36.4%
12/33 • Number of events 12 • 2 Years
|
|
Renal and urinary disorders
Urinary frequency
|
6.1%
2/33 • Number of events 2 • 2 Years
|
|
Psychiatric disorders
Urinary tract infection and pain
|
15.2%
5/33 • Number of events 5 • 2 Years
|
|
Blood and lymphatic system disorders
White blood cell decreased
|
12.1%
4/33 • Number of events 4 • 2 Years
|
|
Gastrointestinal disorders
Vomiting
|
21.2%
7/33 • Number of events 7 • 2 Years
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
9.1%
3/33 • Number of events 3 • 2 Years
|
|
General disorders
Vertigo
|
6.1%
2/33 • Number of events 2 • 2 Years
|
|
General disorders
Weight loss
|
3.0%
1/33 • Number of events 1 • 2 Years
|
|
General disorders
Voice alteration
|
3.0%
1/33 • Number of events 1 • 2 Years
|
|
Cardiac disorders
Vascular disorders
|
6.1%
2/33 • Number of events 2 • 2 Years
|
Additional Information
Heather A Wakelee, MD
Stanford University Medical Center
Phone: 650-736-7221
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place