Trial Outcomes & Findings for Phase I/II Study of MK-0752 Followed by Docetaxel in Advanced or Metastatic Breast Cancer (NCT NCT00645333)
NCT ID: NCT00645333
Last Updated: 2014-04-04
Results Overview
The number of DLTs experienced by participants within the first 21 days. DLTs were defined as toxicities possibly, probably, or definitely related to the study drug observed during the first 2 cycles (first 42 days) as follows: 1. Non-hematologic toxicity Grade ≥3 by the NCI CTCAE version 3.0. 2. ANC\<1000 for more than 7 days despite use of pegfilgrastim. 3. Platelet count \<25,000 for more than 7 days, or associated with bleeding, or less than 10,000 at any time.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
30 participants
Primary outcome timeframe
first 21 days
Results posted on
2014-04-04
Participant Flow
Eligible subjects included men or women with metastatic (Stage IV)breast cancer, or with locally advanced breast cancer (Stages IIIA\> 10cm, or stages IIIB and IIIC) that did not respond to first-line anthracycline-based chemotherapy.
There must b at least a 6 month interval since prior taxane therapy.
Participant milestones
| Measure |
MK-0752 and Docetaxel
MK-0752 in escalating doses, orally days 1-3, followed by docetaxel 80 mg/m2 IV on day 8, and pegfilgrastim 6mg SQ day 9. Cycle repeated every 21 days.
|
|---|---|
|
Overall Study
STARTED
|
30
|
|
Overall Study
COMPLETED
|
30
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Phase I/II Study of MK-0752 Followed by Docetaxel in Advanced or Metastatic Breast Cancer
Baseline characteristics by cohort
| Measure |
MK-0752 and Docetaxel
n=30 Participants
MK-0752 in escalating doses, orally days 1-3, followed by docetaxel 80 mg/m2 IV on day 8, and pegfilgrastim 6mg SQ day 9. Cycle repeated every 21 days.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=99 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
25 Participants
n=99 Participants
|
|
Age, Categorical
>=65 years
|
5 Participants
n=99 Participants
|
|
Sex: Female, Male
Female
|
30 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=99 Participants
|
|
Region of Enrollment
United States
|
30 participants
n=99 Participants
|
|
Metastatic sites (multiple sites possible)
Bone
|
12 Participants
n=99 Participants
|
|
Metastatic sites (multiple sites possible)
Lung/Pleura
|
16 Participants
n=99 Participants
|
|
Metastatic sites (multiple sites possible)
Liver
|
13 Participants
n=99 Participants
|
|
Metastatic sites (multiple sites possible)
Lymph Nodes
|
11 Participants
n=99 Participants
|
|
Metastatic sites (multiple sites possible)
Skin
|
5 Participants
n=99 Participants
|
|
Metastatic sites (multiple sites possible)
Other
|
7 Participants
n=99 Participants
|
|
Number of Metastatic Sites
0
|
4 participants
n=99 Participants
|
|
Number of Metastatic Sites
1
|
6 participants
n=99 Participants
|
|
Number of Metastatic Sites
2
|
6 participants
n=99 Participants
|
|
Number of Metastatic Sites
>=3
|
14 participants
n=99 Participants
|
|
Tumor Hormone Receptor Status
ER positive/or PgR positive
|
18 Participants
n=99 Participants
|
|
Tumor Hormone Receptor Status
ER negative and PgR negative
|
12 Participants
n=99 Participants
|
|
HER-2/neu status
Negative
|
28 Participants
n=99 Participants
|
|
HER-2/neu status
Positive
|
2 Participants
n=99 Participants
|
|
Prior Therapy For Metastatic Disease
None
|
7 Participants
n=99 Participants
|
|
Prior Therapy For Metastatic Disease
Chemotherapy
|
7 Participants
n=99 Participants
|
|
Prior Therapy For Metastatic Disease
Hormonal Therapy
|
0 Participants
n=99 Participants
|
|
Prior Therapy For Metastatic Disease
Chemotherapy and Hormonal Therapy
|
16 Participants
n=99 Participants
|
|
Number of Prior Metastatic Chemotherapy Regimens
0
|
7 Participants
n=99 Participants
|
|
Number of Prior Metastatic Chemotherapy Regimens
1
|
2 Participants
n=99 Participants
|
|
Number of Prior Metastatic Chemotherapy Regimens
2+
|
21 Participants
n=99 Participants
|
PRIMARY outcome
Timeframe: first 21 daysThe number of DLTs experienced by participants within the first 21 days. DLTs were defined as toxicities possibly, probably, or definitely related to the study drug observed during the first 2 cycles (first 42 days) as follows: 1. Non-hematologic toxicity Grade ≥3 by the NCI CTCAE version 3.0. 2. ANC\<1000 for more than 7 days despite use of pegfilgrastim. 3. Platelet count \<25,000 for more than 7 days, or associated with bleeding, or less than 10,000 at any time.
Outcome measures
| Measure |
MK-0752 and Docetaxel
n=30 Participants
MK-0752 in escalating doses, orally days 1-3, followed by docetaxel 80 mg/m2 IV on day 8, and pegfilgrastim 6mg SQ day 9. Cycle repeated every 21 days.
|
|---|---|
|
Dose Limiting Toxicity (DLT)
|
5 Dose Limiting Toxicities
|
PRIMARY outcome
Timeframe: Up to 3 yearsThe Maximum Tolerated Dose (MTD) for MK-0752 will be determined. Dose levels were: Level 1: 300 mg MK-0752 by mouth days 1-3; Level 2: 450 mg MK-0752 by mouth days 1-3; Level 3: 600 mg MK-0752 by mouth days 1-3; Level 4: 800 mg MK-0752 by mouth days 1-3.
Outcome measures
| Measure |
MK-0752 and Docetaxel
n=30 Participants
MK-0752 in escalating doses, orally days 1-3, followed by docetaxel 80 mg/m2 IV on day 8, and pegfilgrastim 6mg SQ day 9. Cycle repeated every 21 days.
|
|---|---|
|
Maximum Tolerated Dose (MTD)
|
600 mg
|
Adverse Events
MK-0752
Serious events: 16 serious events
Other events: 30 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
MK-0752
n=30 participants at risk
MK-0752 in escalating doses, orally days 1-3, followed by docetaxel 80 mg/m2 IV on day 8, and pegfilgrastim 6mg SQ day 9. Cycle repeated every 21 days.
|
|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
3.3%
1/30 • Number of events 1 • During therapy and for 30 days after therapy completion
|
|
Investigations
Alanine aminotransferase increased
|
3.3%
1/30 • Number of events 1 • During therapy and for 30 days after therapy completion
|
|
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis
|
3.3%
1/30 • Number of events 1 • During therapy and for 30 days after therapy completion
|
|
Immune system disorders
Autoimmune disorder
|
3.3%
1/30 • Number of events 1 • During therapy and for 30 days after therapy completion
|
|
Respiratory, thoracic and mediastinal disorders
Bronchospasm
|
3.3%
1/30 • Number of events 1 • During therapy and for 30 days after therapy completion
|
|
Cardiac disorders
Chest pain
|
3.3%
1/30 • Number of events 1 • During therapy and for 30 days after therapy completion
|
|
Skin and subcutaneous tissue disorders
Dermatology/Skin - Other (Specify)
|
3.3%
1/30 • Number of events 1 • During therapy and for 30 days after therapy completion
|
|
Infections and infestations
Device related infection
|
6.7%
2/30 • Number of events 3 • During therapy and for 30 days after therapy completion
|
|
Gastrointestinal disorders
Diarrhea
|
6.7%
2/30 • Number of events 2 • During therapy and for 30 days after therapy completion
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Disease progression
|
3.3%
1/30 • Number of events 1 • During therapy and for 30 days after therapy completion
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
6.7%
2/30 • Number of events 3 • During therapy and for 30 days after therapy completion
|
|
General disorders
Edema limbs
|
3.3%
1/30 • Number of events 1 • During therapy and for 30 days after therapy completion
|
|
Injury, poisoning and procedural complications
Fracture
|
3.3%
1/30 • Number of events 1 • During therapy and for 30 days after therapy completion
|
|
Nervous system disorders
Hand-and-foot syndrome
|
3.3%
1/30 • Number of events 1 • During therapy and for 30 days after therapy completion
|
|
General disorders
Hypersensitivity
|
6.7%
2/30 • Number of events 6 • During therapy and for 30 days after therapy completion
|
|
Immune system disorders
Immune system disorder
|
3.3%
1/30 • Number of events 1 • During therapy and for 30 days after therapy completion
|
|
Respiratory, thoracic and mediastinal disorders
Infection, Lung (pneumonia)
|
6.7%
2/30 • Number of events 2 • During therapy and for 30 days after therapy completion
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
3.3%
1/30 • Number of events 1 • During therapy and for 30 days after therapy completion
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
3.3%
1/30 • Number of events 2 • During therapy and for 30 days after therapy completion
|
|
Infections and infestations
Upper respiratory infection
|
3.3%
1/30 • Number of events 1 • During therapy and for 30 days after therapy completion
|
Other adverse events
| Measure |
MK-0752
n=30 participants at risk
MK-0752 in escalating doses, orally days 1-3, followed by docetaxel 80 mg/m2 IV on day 8, and pegfilgrastim 6mg SQ day 9. Cycle repeated every 21 days.
|
|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
10.0%
3/30 • Number of events 3 • During therapy and for 30 days after therapy completion
|
|
Investigations
Alanine aminotransferase increased
|
16.7%
5/30 • Number of events 9 • During therapy and for 30 days after therapy completion
|
|
Investigations
Alkaline phosphatase increased
|
26.7%
8/30 • Number of events 12 • During therapy and for 30 days after therapy completion
|
|
Immune system disorders
Allergic reaction
|
13.3%
4/30 • Number of events 6 • During therapy and for 30 days after therapy completion
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
23.3%
7/30 • Number of events 8 • During therapy and for 30 days after therapy completion
|
|
Metabolism and nutrition disorders
Anorexia
|
23.3%
7/30 • Number of events 7 • During therapy and for 30 days after therapy completion
|
|
Investigations
Aspartate aminotransferase increased
|
23.3%
7/30 • Number of events 13 • During therapy and for 30 days after therapy completion
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
16.7%
5/30 • Number of events 6 • During therapy and for 30 days after therapy completion
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
20.0%
6/30 • Number of events 7 • During therapy and for 30 days after therapy completion
|
|
Reproductive system and breast disorders
Breast pain
|
6.7%
2/30 • Number of events 2 • During therapy and for 30 days after therapy completion
|
|
Respiratory, thoracic and mediastinal disorders
Bronchitis
|
10.0%
3/30 • Number of events 3 • During therapy and for 30 days after therapy completion
|
|
Cardiac disorders
Cardiac Arrhythmia - Other (Specify)
|
6.7%
2/30 • Number of events 2 • During therapy and for 30 days after therapy completion
|
|
Gastrointestinal disorders
Constipation
|
20.0%
6/30 • Number of events 6 • During therapy and for 30 days after therapy completion
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
20.0%
6/30 • Number of events 7 • During therapy and for 30 days after therapy completion
|
|
Psychiatric disorders
Depression
|
6.7%
2/30 • Number of events 2 • During therapy and for 30 days after therapy completion
|
|
Skin and subcutaneous tissue disorders
Dermatology/Skin - Other (Specify)
|
16.7%
5/30 • Number of events 6 • During therapy and for 30 days after therapy completion
|
|
Gastrointestinal disorders
Diarrhea
|
33.3%
10/30 • Number of events 12 • During therapy and for 30 days after therapy completion
|
|
Eye disorders
Dry eye syndrome
|
6.7%
2/30 • Number of events 2 • During therapy and for 30 days after therapy completion
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
10.0%
3/30 • Number of events 3 • During therapy and for 30 days after therapy completion
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
13.3%
4/30 • Number of events 7 • During therapy and for 30 days after therapy completion
|
|
General disorders
Edema limbs
|
16.7%
5/30 • Number of events 6 • During therapy and for 30 days after therapy completion
|
|
General disorders
Fatigue
|
66.7%
20/30 • Number of events 26 • During therapy and for 30 days after therapy completion
|
|
General disorders
Fever
|
23.3%
7/30 • Number of events 10 • During therapy and for 30 days after therapy completion
|
|
Gastrointestinal disorders
GI - Other (Specify)
|
6.7%
2/30 • Number of events 2 • During therapy and for 30 days after therapy completion
|
|
Nervous system disorders
Hand-and-foot syndrome
|
23.3%
7/30 • Number of events 10 • During therapy and for 30 days after therapy completion
|
|
Nervous system disorders
Headache
|
13.3%
4/30 • Number of events 5 • During therapy and for 30 days after therapy completion
|
|
Blood and lymphatic system disorders
Hemoglobin
|
36.7%
11/30 • Number of events 16 • During therapy and for 30 days after therapy completion
|
|
Vascular disorders
Hot flashes
|
6.7%
2/30 • Number of events 2 • During therapy and for 30 days after therapy completion
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
33.3%
10/30 • Number of events 19 • During therapy and for 30 days after therapy completion
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
10.0%
3/30 • Number of events 3 • During therapy and for 30 days after therapy completion
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
30.0%
9/30 • Number of events 10 • During therapy and for 30 days after therapy completion
|
|
Metabolism and nutrition disorders
Hypokalemia
|
30.0%
9/30 • Number of events 12 • During therapy and for 30 days after therapy completion
|
|
Psychiatric disorders
Insomnia
|
16.7%
5/30 • Number of events 5 • During therapy and for 30 days after therapy completion
|
|
Musculoskeletal and connective tissue disorders
Joint pain
|
10.0%
3/30 • Number of events 3 • During therapy and for 30 days after therapy completion
|
|
Blood and lymphatic system disorders
Leukocytes
|
6.7%
2/30 • Number of events 2 • During therapy and for 30 days after therapy completion
|
|
Blood and lymphatic system disorders
Lymphopenia
|
13.3%
4/30 • Number of events 5 • During therapy and for 30 days after therapy completion
|
|
Skin and subcutaneous tissue disorders
Nail changes
|
33.3%
10/30 • Number of events 11 • During therapy and for 30 days after therapy completion
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
6.7%
2/30 • Number of events 2 • During therapy and for 30 days after therapy completion
|
|
Gastrointestinal disorders
Nausea
|
50.0%
15/30 • Number of events 17 • During therapy and for 30 days after therapy completion
|
|
General disorders
Pain - Other
|
10.0%
3/30 • Number of events 3 • During therapy and for 30 days after therapy completion
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
26.7%
8/30 • Number of events 13 • During therapy and for 30 days after therapy completion
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain
|
10.0%
3/30 • Number of events 3 • During therapy and for 30 days after therapy completion
|
|
Blood and lymphatic system disorders
Platelets
|
13.3%
4/30 • Number of events 5 • During therapy and for 30 days after therapy completion
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
6.7%
2/30 • Number of events 2 • During therapy and for 30 days after therapy completion
|
|
Skin and subcutaneous tissue disorders
Rash
|
16.7%
5/30 • Number of events 7 • During therapy and for 30 days after therapy completion
|
|
Infections and infestations
Skin infection
|
10.0%
3/30 • Number of events 3 • During therapy and for 30 days after therapy completion
|
|
General disorders
Sweating
|
6.7%
2/30 • Number of events 2 • During therapy and for 30 days after therapy completion
|
|
Nervous system disorders
Taste alteration
|
6.7%
2/30 • Number of events 2 • During therapy and for 30 days after therapy completion
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory infection
|
13.3%
4/30 • Number of events 5 • During therapy and for 30 days after therapy completion
|
|
Renal and urinary disorders
Urinary tract infection
|
10.0%
3/30 • Number of events 3 • During therapy and for 30 days after therapy completion
|
|
Gastrointestinal disorders
Vomiting
|
20.0%
6/30 • Number of events 6 • During therapy and for 30 days after therapy completion
|
|
Eye disorders
Watering eyes
|
20.0%
6/30 • Number of events 8 • During therapy and for 30 days after therapy completion
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place