Trial Outcomes & Findings for Sunitinib, Cyclophosphamide, and Methotrexate in Treating Patients With Metastatic Breast Cancer (NCT NCT00616122)
NCT ID: NCT00616122
Last Updated: 2020-01-13
Results Overview
Patients in each cohort were followed for DLT for at least 8 weeks (2 week lead-in with sunitinib and 6 weeks of treatment with sunitinib and metronomic cyclophosphamide and methotrexate) before opening accrual to the next dose level. Dose limiting toxicity (DLT) defined as: 1) ≥ grade 3 anemia that does not resolve with appropriate growth factors afebrile grade 4 neutropenia that does not resolve with growth factor support after ≥ 7 days 2) grade 4 neutropenia associated with fever (1 reading of oral temperature \> 38.5 degrees Celsius or 3 readings of oral temperature \> 38.0 degrees Celsius in a 24 hour period) 3) ≥ grade 3 thrombocytopenia 4) ≥ grade 3 non-hematologic toxicities, except those that can be controlled to grade 2 or less with appropriate treatment. 5\) Inability to resume treatment with any of the study medications within 14 days of stopping due to treatment related toxicity.
Recruitment status
TERMINATED
Study phase
PHASE1/PHASE2
Target enrollment
32 participants
Primary outcome timeframe
8 weeks
Results posted on
2020-01-13
Participant Flow
Phase I patients received escalating doses of sunitinib in a 3x3 design. None of the patients in the phase I study was included in phase II. Phase I patients receiving treatment at the phase II dose were included in the overall efficacy analysis of the phase II study but were not counted toward the enrollment accrual of the phase II study.
Participant milestones
| Measure |
Phase I, Dose 1
One cycle = 21 days
Sunitinib only (12.5 mg) for 2 weeks, followed by the addition of metronomic cyclophosphamide (50mg/day) and methotrexate (2.5mg twice a day (BID) 2 days/week).
Patients in each cohort will be followed for at least 8 weeks (2 week lead in with sunitinib and 6 weeks of treatment with sunitinib and metronomic cyclophosphamide and methotrexate) before opening accrual to the next dose level.
|
Phase I, Dose 2
One cycle = 21 days
Sunitinib only (25 mg) for 2 weeks, followed by the addition of metronomic cyclophosphamide (50mg/day) and methotrexate (2.5mg BID 2 days/week).
Patients in each cohort will be followed for at least 8 weeks (2 week lead in with sunitinib and 6 weeks of treatment with sunitinib and metronomic cyclophosphamide and methotrexate) before opening accrual to the next dose level.
|
Phase I, Dose 3
One cycle = 21 days
Sunitinib only (37.5 mg) for 2 weeks, followed by the addition of metronomic cyclophosphamide (50mg/day) and methotrexate (2.5mg BID 2 days/week).
Patients in each cohort will be followed for at least 8 weeks (2 week lead in with sunitinib and 6 weeks of treatment with sunitinib and metronomic cyclophosphamide and methotrexate) before opening accrual to the next dose level.
|
Phase II
* 37.5mg sunitinib during the 2-week lead-in period followed by either:
* 37.5mg sunitinib
* metronomic cyclophosphamide (50mg/day) and methotrexate (2.5mg BID 2 days/week)(CM)
* 25mg sunitinib
* metronomic CM (50mg/day)
* methotrexate (2.5mg BID 2 days/week)
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
4
|
7
|
10
|
11
|
|
Overall Study
COMPLETED
|
4
|
7
|
10
|
0
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
11
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Sunitinib, Cyclophosphamide, and Methotrexate in Treating Patients With Metastatic Breast Cancer
Baseline characteristics by cohort
| Measure |
Sunitinib, Cyclophosphamide, and Methotrexate
n=32 Participants
Phase I patients received escalating doses of sunitinib in a 3x3 design (12.5, 25, 37.5 mg). Phase I and II patients received sunitinib for 2 weeks, followed by the addition of metronomic cyclophosphamide (50mg/day) and methotrexate (2.5mg BID 2 days/week). Phase II patients received 37.5mg sunitinib during the 2-week lead-in period followed by either 37.5mg sunitinib and metronomic CM or 25mg sunitinib and metronomic CM (dose reduction due to a protocol amendment).
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=93 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
23 Participants
n=93 Participants
|
|
Age, Categorical
>=65 years
|
9 Participants
n=93 Participants
|
|
Age, Continuous
|
58 years
STANDARD_DEVIATION 15 • n=93 Participants
|
|
Sex: Female, Male
Female
|
31 Participants
n=93 Participants
|
|
Sex: Female, Male
Male
|
1 Participants
n=93 Participants
|
|
Region of Enrollment
United States
|
32 participants
n=93 Participants
|
PRIMARY outcome
Timeframe: 8 weeksPatients in each cohort were followed for DLT for at least 8 weeks (2 week lead-in with sunitinib and 6 weeks of treatment with sunitinib and metronomic cyclophosphamide and methotrexate) before opening accrual to the next dose level. Dose limiting toxicity (DLT) defined as: 1) ≥ grade 3 anemia that does not resolve with appropriate growth factors afebrile grade 4 neutropenia that does not resolve with growth factor support after ≥ 7 days 2) grade 4 neutropenia associated with fever (1 reading of oral temperature \> 38.5 degrees Celsius or 3 readings of oral temperature \> 38.0 degrees Celsius in a 24 hour period) 3) ≥ grade 3 thrombocytopenia 4) ≥ grade 3 non-hematologic toxicities, except those that can be controlled to grade 2 or less with appropriate treatment. 5\) Inability to resume treatment with any of the study medications within 14 days of stopping due to treatment related toxicity.
Outcome measures
| Measure |
Sunitinib, Cyclophosphamide, and Methotrexate
n=21 Participants
Phase I patients received escalating doses of sunitinib in a 3x3 design (12.5, 25, 37.5 mg). Phase I and II patients received sunitinib for 2 weeks, followed by the addition of metronomic cyclophosphamide (50mg/day) and methotrexate (2.5mg BID 2 days/week). Phase II patients received 37.5mg sunitinib during the 2-week lead-in period followed by either 37.5mg sunitinib and metronomic CM or 25mg sunitinib and metronomic CM (dose reduction due to a protocol amendment).
|
|---|---|
|
Maximum Tolerated Dose of Sunitinib (Phase I)
|
37.5 mg
|
PRIMARY outcome
Timeframe: up to 12 weeks after treatment start datePopulation: Patients who received either 25mg or 37.5mg of sunitinib and were not removed from study due to voluntary withdrawal or PD prior to receiving combination sunitinib and metronomic CM chemotherapy.
Progression defined as: 25% increase or an increase of 10 sq. cm (whichever is smaller) in the sum of products of measurable lesions over smallest sum observed (over baseline if no decrease), or appearance of any lesion which had disappeared, or clear worsening of any evaluable disease, or appearance of any new lesion/site, or failure to return for evaluation due to deteriorating condition (unless deterioration is clearly unrelated to this cancer).
Outcome measures
| Measure |
Sunitinib, Cyclophosphamide, and Methotrexate
n=23 Participants
Phase I patients received escalating doses of sunitinib in a 3x3 design (12.5, 25, 37.5 mg). Phase I and II patients received sunitinib for 2 weeks, followed by the addition of metronomic cyclophosphamide (50mg/day) and methotrexate (2.5mg BID 2 days/week). Phase II patients received 37.5mg sunitinib during the 2-week lead-in period followed by either 37.5mg sunitinib and metronomic CM or 25mg sunitinib and metronomic CM (dose reduction due to a protocol amendment).
|
|---|---|
|
Patients With Progression-free Survival (PFS) Greater Than or Equal to 12 Weeks (Phase II)
|
7 participants
|
SECONDARY outcome
Timeframe: until disease progression, up to 13 months post treatmentPer Response Evaluation Criteria in Solid Tumors (RECIST): Complete Response (CR): Complete disappearance of all measurable and evaluable disease. No new lesions. Partial Response (PR): greater than or equal to 50% decrease under baseline in the sum of the products of perpendicular diameters of all measurable lesions. No progression of evaluable disease. No new lesions. Stable: Does not qualify for complete response, partial response or progression.
Outcome measures
| Measure |
Sunitinib, Cyclophosphamide, and Methotrexate
n=23 Participants
Phase I patients received escalating doses of sunitinib in a 3x3 design (12.5, 25, 37.5 mg). Phase I and II patients received sunitinib for 2 weeks, followed by the addition of metronomic cyclophosphamide (50mg/day) and methotrexate (2.5mg BID 2 days/week). Phase II patients received 37.5mg sunitinib during the 2-week lead-in period followed by either 37.5mg sunitinib and metronomic CM or 25mg sunitinib and metronomic CM (dose reduction due to a protocol amendment).
|
|---|---|
|
Overall Response Rate
|
1 participants
|
SECONDARY outcome
Timeframe: until disease progression up to 13 months post treatmentPopulation: A partial response was only reported for one patient, while a complete response was not recorded for any patients.
Duration of response refers to duration of single partial response observed per Response Evaluation Criteria in Solid Tumors (RECIST): Complete Response (CR): Complete disappearance of all measurable and evaluable disease. No new lesions. Partial Response (PR): greater than or equal to 50% decrease under baseline in the sum of the products of perpendicular diameters of all measurable lesions. No progression of evaluable disease. No new lesions. Stable: Does not qualify for complete response, partial response or progression. Progression: 25% increase or an increase of 10 sq. cm (whichever is smaller) in the sum of products of measurable lesions over smallest sum observed (over baseline if no decrease), OR appearance of any lesion which had disappeared, or clear worsening of any evaluable disease, or appearance of any new lesion/site, or failure to return for evaluation due to deteriorating condition (unless deterioration is clearly unrelated to this cancer).
Outcome measures
| Measure |
Sunitinib, Cyclophosphamide, and Methotrexate
n=1 Participants
Phase I patients received escalating doses of sunitinib in a 3x3 design (12.5, 25, 37.5 mg). Phase I and II patients received sunitinib for 2 weeks, followed by the addition of metronomic cyclophosphamide (50mg/day) and methotrexate (2.5mg BID 2 days/week). Phase II patients received 37.5mg sunitinib during the 2-week lead-in period followed by either 37.5mg sunitinib and metronomic CM or 25mg sunitinib and metronomic CM (dose reduction due to a protocol amendment).
|
|---|---|
|
Duration of Response
|
10.6 weeks
|
Adverse Events
Phase I, Dose 1
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Phase I, Dose 2
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Phase I, Dose 3
Serious events: 1 serious events
Other events: 8 other events
Deaths: 0 deaths
Phase II
Serious events: 0 serious events
Other events: 11 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Phase I, Dose 1
n=4 participants at risk
One cycle = 21 days
Sunitinib only (12.5 mg) for 2 weeks, followed by the addition of metronomic cyclophosphamide (50mg/day) and methotrexate (2.5mg BID 2 days/week).
Patients in each cohort will be followed for at least 8 weeks (2 week lead in with sunitinib and 6 weeks of treatment with sunitinib and metronomic cyclophosphamide and methotrexate) before opening accrual to the next dose level.
|
Phase I, Dose 2
n=7 participants at risk
One cycle = 21 days
Sunitinib only (25 mg) for 2 weeks, followed by the addition of metronomic cyclophosphamide (50mg/day) and methotrexate (2.5mg BID 2 days/week).
Patients in each cohort will be followed for at least 8 weeks (2 week lead in with sunitinib and 6 weeks of treatment with sunitinib and metronomic cyclophosphamide and methotrexate) before opening accrual to the next dose level.
|
Phase I, Dose 3
n=10 participants at risk
One cycle = 21 days
Sunitinib only (37.5 mg) for 2 weeks, followed by the addition of metronomic cyclophosphamide (50mg/day) and methotrexate (2.5mg BID 2 days/week).
Patients in each cohort will be followed for at least 8 weeks (2 week lead in with sunitinib and 6 weeks of treatment with sunitinib and metronomic cyclophosphamide and methotrexate) before opening accrual to the next dose level.
|
Phase II
n=11 participants at risk
* 37.5mg sunitinib during the 2-week lead-in period followed by either:
* 37.5mg sunitinib
* metronomic CM (50mg/day)
* methotrexate (2.5mg BID 2 days/week)
or
* 25mg sunitinib
* metronomic CM (50mg/day)
* methotrexate (2.5mg BID 2 days/week)
(dose reduction due to a protocol amendment)
|
|---|---|---|---|---|
|
Musculoskeletal and connective tissue disorders
fracture
|
0.00%
0/4
|
0.00%
0/7
|
10.0%
1/10
|
0.00%
0/11
|
Other adverse events
| Measure |
Phase I, Dose 1
n=4 participants at risk
One cycle = 21 days
Sunitinib only (12.5 mg) for 2 weeks, followed by the addition of metronomic cyclophosphamide (50mg/day) and methotrexate (2.5mg BID 2 days/week).
Patients in each cohort will be followed for at least 8 weeks (2 week lead in with sunitinib and 6 weeks of treatment with sunitinib and metronomic cyclophosphamide and methotrexate) before opening accrual to the next dose level.
|
Phase I, Dose 2
n=7 participants at risk
One cycle = 21 days
Sunitinib only (25 mg) for 2 weeks, followed by the addition of metronomic cyclophosphamide (50mg/day) and methotrexate (2.5mg BID 2 days/week).
Patients in each cohort will be followed for at least 8 weeks (2 week lead in with sunitinib and 6 weeks of treatment with sunitinib and metronomic cyclophosphamide and methotrexate) before opening accrual to the next dose level.
|
Phase I, Dose 3
n=10 participants at risk
One cycle = 21 days
Sunitinib only (37.5 mg) for 2 weeks, followed by the addition of metronomic cyclophosphamide (50mg/day) and methotrexate (2.5mg BID 2 days/week).
Patients in each cohort will be followed for at least 8 weeks (2 week lead in with sunitinib and 6 weeks of treatment with sunitinib and metronomic cyclophosphamide and methotrexate) before opening accrual to the next dose level.
|
Phase II
n=11 participants at risk
* 37.5mg sunitinib during the 2-week lead-in period followed by either:
* 37.5mg sunitinib
* metronomic CM (50mg/day)
* methotrexate (2.5mg BID 2 days/week)
or
* 25mg sunitinib
* metronomic CM (50mg/day)
* methotrexate (2.5mg BID 2 days/week)
(dose reduction due to a protocol amendment)
|
|---|---|---|---|---|
|
Gastrointestinal disorders
abdominal distention
|
0.00%
0/4
|
0.00%
0/7
|
10.0%
1/10
|
0.00%
0/11
|
|
Gastrointestinal disorders
abdominal pain
|
0.00%
0/4
|
0.00%
0/7
|
10.0%
1/10
|
18.2%
2/11
|
|
Investigations
activated partial thromboplastin time prolonged
|
0.00%
0/4
|
0.00%
0/7
|
10.0%
1/10
|
0.00%
0/11
|
|
Investigations
alanine aminotransferase increased
|
50.0%
2/4
|
0.00%
0/7
|
20.0%
2/10
|
36.4%
4/11
|
|
Investigations
alkaline phosphatase increased
|
50.0%
2/4
|
0.00%
0/7
|
20.0%
2/10
|
36.4%
4/11
|
|
Immune system disorders
allergic reaction
|
0.00%
0/4
|
0.00%
0/7
|
10.0%
1/10
|
0.00%
0/11
|
|
Skin and subcutaneous tissue disorders
alopecia
|
0.00%
0/4
|
0.00%
0/7
|
10.0%
1/10
|
0.00%
0/11
|
|
Gastrointestinal disorders
anal pain
|
0.00%
0/4
|
14.3%
1/7
|
0.00%
0/10
|
0.00%
0/11
|
|
Blood and lymphatic system disorders
anemia
|
0.00%
0/4
|
28.6%
2/7
|
50.0%
5/10
|
63.6%
7/11
|
|
Metabolism and nutrition disorders
anorexia
|
25.0%
1/4
|
57.1%
4/7
|
30.0%
3/10
|
9.1%
1/11
|
|
Psychiatric disorders
anxiety
|
0.00%
0/4
|
28.6%
2/7
|
0.00%
0/10
|
18.2%
2/11
|
|
Musculoskeletal and connective tissue disorders
arthralgia
|
0.00%
0/4
|
14.3%
1/7
|
10.0%
1/10
|
0.00%
0/11
|
|
Gastrointestinal disorders
ascites
|
0.00%
0/4
|
0.00%
0/7
|
10.0%
1/10
|
0.00%
0/11
|
|
Investigations
aspartate aminotransferase increased
|
50.0%
2/4
|
0.00%
0/7
|
40.0%
4/10
|
54.5%
6/11
|
|
Musculoskeletal and connective tissue disorders
back pain
|
0.00%
0/4
|
28.6%
2/7
|
10.0%
1/10
|
27.3%
3/11
|
|
Infections and infestations
bacterial vaginosis
|
0.00%
0/4
|
14.3%
1/7
|
0.00%
0/10
|
0.00%
0/11
|
|
Investigations
blood blirubin increased
|
0.00%
0/4
|
0.00%
0/7
|
20.0%
2/10
|
18.2%
2/11
|
|
Investigations
blood urea nitrogen increased
|
0.00%
0/4
|
0.00%
0/7
|
0.00%
0/10
|
9.1%
1/11
|
|
Infections and infestations
breast infection
|
25.0%
1/4
|
0.00%
0/7
|
0.00%
0/10
|
0.00%
0/11
|
|
Injury, poisoning and procedural complications
bruising
|
0.00%
0/4
|
0.00%
0/7
|
10.0%
1/10
|
0.00%
0/11
|
|
General disorders
chills
|
0.00%
0/4
|
14.3%
1/7
|
10.0%
1/10
|
18.2%
2/11
|
|
Nervous system disorders
cognitive disturbance
|
0.00%
0/4
|
14.3%
1/7
|
0.00%
0/10
|
0.00%
0/11
|
|
Gastrointestinal disorders
cold sore
|
0.00%
0/4
|
14.3%
1/7
|
0.00%
0/10
|
0.00%
0/11
|
|
Gastrointestinal disorders
constipation
|
0.00%
0/4
|
0.00%
0/7
|
30.0%
3/10
|
18.2%
2/11
|
|
Respiratory, thoracic and mediastinal disorders
cough
|
0.00%
0/4
|
14.3%
1/7
|
30.0%
3/10
|
27.3%
3/11
|
|
Investigations
creatinine increased
|
0.00%
0/4
|
0.00%
0/7
|
0.00%
0/10
|
27.3%
3/11
|
|
Psychiatric disorders
depression
|
0.00%
0/4
|
0.00%
0/7
|
10.0%
1/10
|
9.1%
1/11
|
|
Skin and subcutaneous tissue disorders
desquamation, blistering
|
0.00%
0/4
|
14.3%
1/7
|
0.00%
0/10
|
0.00%
0/11
|
|
Gastrointestinal disorders
diarrhea
|
0.00%
0/4
|
28.6%
2/7
|
70.0%
7/10
|
45.5%
5/11
|
|
Nervous system disorders
dizziness
|
0.00%
0/4
|
14.3%
1/7
|
0.00%
0/10
|
9.1%
1/11
|
|
Eye disorders
dry eyes
|
0.00%
0/4
|
0.00%
0/7
|
10.0%
1/10
|
0.00%
0/11
|
|
Gastrointestinal disorders
dry mouth
|
0.00%
0/4
|
0.00%
0/7
|
0.00%
0/10
|
9.1%
1/11
|
|
Gastrointestinal disorders
dry mucous membrane
|
0.00%
0/4
|
0.00%
0/7
|
0.00%
0/10
|
9.1%
1/11
|
|
Skin and subcutaneous tissue disorders
dry skin
|
25.0%
1/4
|
28.6%
2/7
|
0.00%
0/10
|
9.1%
1/11
|
|
Respiratory, thoracic and mediastinal disorders
dullness in lungs
|
0.00%
0/4
|
0.00%
0/7
|
0.00%
0/10
|
9.1%
1/11
|
|
Gastrointestinal disorders
dysgeusia
|
0.00%
0/4
|
14.3%
1/7
|
20.0%
2/10
|
27.3%
3/11
|
|
Gastrointestinal disorders
dyspepsia
|
0.00%
0/4
|
14.3%
1/7
|
10.0%
1/10
|
0.00%
0/11
|
|
Respiratory, thoracic and mediastinal disorders
dyspnea
|
0.00%
0/4
|
0.00%
0/7
|
20.0%
2/10
|
9.1%
1/11
|
|
Ear and labyrinth disorders
ear pain
|
0.00%
0/4
|
14.3%
1/7
|
0.00%
0/10
|
9.1%
1/11
|
|
General disorders
edema limbs
|
0.00%
0/4
|
14.3%
1/7
|
0.00%
0/10
|
18.2%
2/11
|
|
Respiratory, thoracic and mediastinal disorders
epistaxis
|
0.00%
0/4
|
0.00%
0/7
|
10.0%
1/10
|
0.00%
0/11
|
|
Skin and subcutaneous tissue disorders
erythema
|
0.00%
0/4
|
0.00%
0/7
|
0.00%
0/10
|
9.1%
1/11
|
|
Respiratory, thoracic and mediastinal disorders
esophagoscopy abnormal
|
0.00%
0/4
|
0.00%
0/7
|
10.0%
1/10
|
0.00%
0/11
|
|
Injury, poisoning and procedural complications
fall
|
25.0%
1/4
|
0.00%
0/7
|
0.00%
0/10
|
0.00%
0/11
|
|
General disorders
fatigue
|
0.00%
0/4
|
71.4%
5/7
|
70.0%
7/10
|
63.6%
7/11
|
|
General disorders
fever
|
0.00%
0/4
|
14.3%
1/7
|
0.00%
0/10
|
36.4%
4/11
|
|
Eye disorders
floaters
|
0.00%
0/4
|
0.00%
0/7
|
10.0%
1/10
|
0.00%
0/11
|
|
Gastrointestinal disorders
gastroesophageal reflux disorder
|
0.00%
0/4
|
14.3%
1/7
|
0.00%
0/10
|
9.1%
1/11
|
|
Gastrointestinal disorders
gastrotitis
|
0.00%
0/4
|
0.00%
0/7
|
10.0%
1/10
|
0.00%
0/11
|
|
Musculoskeletal and connective tissue disorders
generalized muscle weakness
|
0.00%
0/4
|
0.00%
0/7
|
10.0%
1/10
|
9.1%
1/11
|
|
Musculoskeletal and connective tissue disorders
groin pain
|
0.00%
0/4
|
14.3%
1/7
|
0.00%
0/10
|
0.00%
0/11
|
|
Nervous system disorders
hand stiffness
|
0.00%
0/4
|
14.3%
1/7
|
0.00%
0/10
|
0.00%
0/11
|
|
Nervous system disorders
headache
|
0.00%
0/4
|
0.00%
0/7
|
30.0%
3/10
|
27.3%
3/11
|
|
Eye disorders
heavy eyelid
|
0.00%
0/4
|
14.3%
1/7
|
0.00%
0/10
|
0.00%
0/11
|
|
Musculoskeletal and connective tissue disorders
hip pain
|
0.00%
0/4
|
14.3%
1/7
|
0.00%
0/10
|
0.00%
0/11
|
|
Respiratory, thoracic and mediastinal disorders
hoarseness
|
0.00%
0/4
|
14.3%
1/7
|
0.00%
0/10
|
9.1%
1/11
|
|
Vascular disorders
hot flashes
|
25.0%
1/4
|
0.00%
0/7
|
0.00%
0/10
|
0.00%
0/11
|
|
Metabolism and nutrition disorders
hyperglycemia
|
0.00%
0/4
|
0.00%
0/7
|
0.00%
0/10
|
9.1%
1/11
|
|
Skin and subcutaneous tissue disorders
hyperpigmentation
|
0.00%
0/4
|
0.00%
0/7
|
0.00%
0/10
|
9.1%
1/11
|
|
Vascular disorders
hypertension
|
0.00%
0/4
|
0.00%
0/7
|
20.0%
2/10
|
27.3%
3/11
|
|
Metabolism and nutrition disorders
hypoalbuminemia
|
0.00%
0/4
|
0.00%
0/7
|
10.0%
1/10
|
9.1%
1/11
|
|
Metabolism and nutrition disorders
hypocalcemia
|
0.00%
0/4
|
0.00%
0/7
|
20.0%
2/10
|
9.1%
1/11
|
|
Metabolism and nutrition disorders
hypochloremia
|
0.00%
0/4
|
0.00%
0/7
|
0.00%
0/10
|
18.2%
2/11
|
|
Metabolism and nutrition disorders
hypokalemia
|
0.00%
0/4
|
14.3%
1/7
|
0.00%
0/10
|
0.00%
0/11
|
|
Metabolism and nutrition disorders
hyponatremia
|
0.00%
0/4
|
0.00%
0/7
|
10.0%
1/10
|
18.2%
2/11
|
|
Cardiac disorders
impaired LV
|
0.00%
0/4
|
0.00%
0/7
|
0.00%
0/10
|
9.1%
1/11
|
|
Psychiatric disorders
insomnia
|
0.00%
0/4
|
0.00%
0/7
|
10.0%
1/10
|
18.2%
2/11
|
|
Hepatobiliary disorders
jaundice
|
0.00%
0/4
|
0.00%
0/7
|
0.00%
0/10
|
9.1%
1/11
|
|
Nervous system disorders
lightheadedness
|
25.0%
1/4
|
0.00%
0/7
|
0.00%
0/10
|
9.1%
1/11
|
|
Nervous system disorders
loss of function in right hand
|
0.00%
0/4
|
14.3%
1/7
|
0.00%
0/10
|
0.00%
0/11
|
|
Investigations
lymphocyte count decreased
|
0.00%
0/4
|
0.00%
0/7
|
50.0%
5/10
|
27.3%
3/11
|
|
Gastrointestinal disorders
mucositis oral
|
0.00%
0/4
|
71.4%
5/7
|
10.0%
1/10
|
18.2%
2/11
|
|
Musculoskeletal and connective tissue disorders
myalgia
|
25.0%
1/4
|
57.1%
4/7
|
0.00%
0/10
|
27.3%
3/11
|
|
Musculoskeletal and connective tissue disorders
myositis
|
0.00%
0/4
|
0.00%
0/7
|
10.0%
1/10
|
0.00%
0/11
|
|
Gastrointestinal disorders
nausea
|
25.0%
1/4
|
28.6%
2/7
|
50.0%
5/10
|
36.4%
4/11
|
|
Musculoskeletal and connective tissue disorders
neck pain
|
0.00%
0/4
|
0.00%
0/7
|
0.00%
0/10
|
9.1%
1/11
|
|
Investigations
neutrophil count decreased
|
0.00%
0/4
|
85.7%
6/7
|
80.0%
8/10
|
81.8%
9/11
|
|
Vascular disorders
night sweats
|
0.00%
0/4
|
0.00%
0/7
|
0.00%
0/10
|
9.1%
1/11
|
|
General disorders
non-cardiac chest pain
|
0.00%
0/4
|
0.00%
0/7
|
0.00%
0/10
|
18.2%
2/11
|
|
Nervous system disorders
numbness to chin
|
0.00%
0/4
|
14.3%
1/7
|
0.00%
0/10
|
0.00%
0/11
|
|
Gastrointestinal disorders
oral pain
|
0.00%
0/4
|
0.00%
0/7
|
30.0%
3/10
|
9.1%
1/11
|
|
General disorders
pain
|
0.00%
0/4
|
0.00%
0/7
|
30.0%
3/10
|
0.00%
0/11
|
|
Musculoskeletal and connective tissue disorders
pain in extremity
|
0.00%
0/4
|
14.3%
1/7
|
10.0%
1/10
|
45.5%
5/11
|
|
Skin and subcutaneous tissue disorders
palmar-plantar erythrodysesthesia syndrome
|
0.00%
0/4
|
0.00%
0/7
|
10.0%
1/10
|
0.00%
0/11
|
|
Nervous system disorders
peripheral motor neuropathy
|
0.00%
0/4
|
0.00%
0/7
|
10.0%
1/10
|
0.00%
0/11
|
|
Nervous system disorders
peripheral sensory neuropathy
|
0.00%
0/4
|
28.6%
2/7
|
40.0%
4/10
|
27.3%
3/11
|
|
Skin and subcutaneous tissue disorders
petechia
|
0.00%
0/4
|
28.6%
2/7
|
0.00%
0/10
|
0.00%
0/11
|
|
Investigations
platelet count decreased
|
0.00%
0/4
|
42.9%
3/7
|
40.0%
4/10
|
81.8%
9/11
|
|
Skin and subcutaneous tissue disorders
pruritus
|
0.00%
0/4
|
0.00%
0/7
|
10.0%
1/10
|
0.00%
0/11
|
|
Skin and subcutaneous tissue disorders
psoriasis
|
0.00%
0/4
|
14.3%
1/7
|
0.00%
0/10
|
0.00%
0/11
|
|
Eye disorders
puffy eyelid
|
0.00%
0/4
|
14.3%
1/7
|
0.00%
0/10
|
0.00%
0/11
|
|
Ear and labyrinth disorders
pulsing in ear
|
0.00%
0/4
|
0.00%
0/7
|
0.00%
0/10
|
9.1%
1/11
|
|
Skin and subcutaneous tissue disorders
rash
|
0.00%
0/4
|
0.00%
0/7
|
10.0%
1/10
|
18.2%
2/11
|
|
Gastrointestinal disorders
rectal hemorrhage
|
0.00%
0/4
|
0.00%
0/7
|
10.0%
1/10
|
0.00%
0/11
|
|
Musculoskeletal and connective tissue disorders
rib pain
|
0.00%
0/4
|
14.3%
1/7
|
0.00%
0/10
|
9.1%
1/11
|
|
Cardiac disorders
sinus bradycardia
|
0.00%
0/4
|
0.00%
0/7
|
10.0%
1/10
|
0.00%
0/11
|
|
Cardiac disorders
sinus tachycardia
|
0.00%
0/4
|
14.3%
1/7
|
0.00%
0/10
|
0.00%
0/11
|
|
Infections and infestations
sinusitis
|
0.00%
0/4
|
14.3%
1/7
|
0.00%
0/10
|
0.00%
0/11
|
|
Skin and subcutaneous tissue disorders
skin peeling
|
0.00%
0/4
|
14.3%
1/7
|
0.00%
0/10
|
0.00%
0/11
|
|
Respiratory, thoracic and mediastinal disorders
sore throat
|
0.00%
0/4
|
42.9%
3/7
|
0.00%
0/10
|
0.00%
0/11
|
|
Injury, poisoning and procedural complications
spider bite
|
0.00%
0/4
|
14.3%
1/7
|
0.00%
0/10
|
0.00%
0/11
|
|
Vascular disorders
thromboembolic event
|
0.00%
0/4
|
14.3%
1/7
|
0.00%
0/10
|
0.00%
0/11
|
|
Infections and infestations
upper respiratory infection
|
0.00%
0/4
|
14.3%
1/7
|
0.00%
0/10
|
0.00%
0/11
|
|
Renal and urinary disorders
urinary incontinence
|
0.00%
0/4
|
0.00%
0/7
|
0.00%
0/10
|
9.1%
1/11
|
|
Infections and infestations
urinary tract infection
|
0.00%
0/4
|
14.3%
1/7
|
0.00%
0/10
|
0.00%
0/11
|
|
Ear and labyrinth disorders
vertigo
|
0.00%
0/4
|
14.3%
1/7
|
0.00%
0/10
|
0.00%
0/11
|
|
Respiratory, thoracic and mediastinal disorders
voice alteration
|
0.00%
0/4
|
0.00%
0/7
|
10.0%
1/10
|
0.00%
0/11
|
|
Gastrointestinal disorders
vomiting
|
0.00%
0/4
|
14.3%
1/7
|
30.0%
3/10
|
36.4%
4/11
|
|
Skin and subcutaneous tissue disorders
warmth to chest wall
|
0.00%
0/4
|
0.00%
0/7
|
10.0%
1/10
|
0.00%
0/11
|
|
Investigations
weight loss
|
0.00%
0/4
|
0.00%
0/7
|
10.0%
1/10
|
0.00%
0/11
|
|
Investigations
white blood cell decreased
|
0.00%
0/4
|
0.00%
0/7
|
60.0%
6/10
|
54.5%
6/11
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place