Trial Outcomes & Findings for Cisplatin, Paclitaxel, and Everolimus in Treating Patients With Metastatic Breast Cancer (NCT NCT01031446)
NCT ID: NCT01031446
Last Updated: 2018-08-31
Results Overview
The recommended dose for the Phase II trial will be the most prevalent dose delivered per week in Phase I that allows for safe and feasible administration of the medications.The maximum tolerated dose (MTD) is defined as the dose preceding that at which 2 or more of 3 patients experience dose-limiting toxicity (DLT) during the initial cycle of therapy. DLTs include Common Toxicity Criteria (CTC) Grade 4 neutropenia (absolute neutrophil count \[ANC\] \< 0.5 x 10 9/L for \> 5 days), febrile neutropenia (ANC \< 1.0 x 10 0/L with fever \> 38.5 degrees Centigrade) or documented infection associated with Grade 3-4 neutropenia, CTC Grade 4 thrombocytopenia \< 25 x 10 9/L or CTC Grade 3 \< 50-25 x 10 9/L thrombocytopenia with bleeding, and Grade 3-4 non-hematologic toxicity despite symptomatic therapy.
COMPLETED
PHASE1/PHASE2
55 participants
at 8 weeks
2018-08-31
Participant Flow
This study opened to accrual in October 2009 and ran to June 2011.
Fifty-seven patients consented for this study, two were determined ineligible to participate.
Participant milestones
| Measure |
RAD001 and Cisplatin and Pacletaxel
RAD001 (Everolimus) by mouth once a day. Cisplatin intravenously (IV) weekly for 3 weeks, then 1 week of rest; paclitaxel IV weekly for 3 weeks, then 1 week of rest. One cycle = 4 weeks. All patients began at the same dose level of the study drugs with no de-escalation of dose, thus results for Phase I and II were combined
|
|---|---|
|
Overall Study
STARTED
|
55
|
|
Overall Study
COMPLETED
|
0
|
|
Overall Study
NOT COMPLETED
|
55
|
Reasons for withdrawal
| Measure |
RAD001 and Cisplatin and Pacletaxel
RAD001 (Everolimus) by mouth once a day. Cisplatin intravenously (IV) weekly for 3 weeks, then 1 week of rest; paclitaxel IV weekly for 3 weeks, then 1 week of rest. One cycle = 4 weeks. All patients began at the same dose level of the study drugs with no de-escalation of dose, thus results for Phase I and II were combined
|
|---|---|
|
Overall Study
Disease Progression
|
38
|
|
Overall Study
Adverse Event
|
9
|
|
Overall Study
Physician Decision
|
4
|
|
Overall Study
Withdrawal by Subject
|
3
|
|
Overall Study
Still on treatment
|
1
|
Baseline Characteristics
Cisplatin, Paclitaxel, and Everolimus in Treating Patients With Metastatic Breast Cancer
Baseline characteristics by cohort
| Measure |
RAD001 Cisplatin Paclitaxel
n=55 Participants
RAD001 (Everolimus) by mouth once a day. Cisplatin intravenously (IV) weekly for 3 weeks, then 1 week of rest; paclitaxel IV weekly for 3 weeks, then 1 week of rest. One cycle = 4 weeks.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=93 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
47 Participants
n=93 Participants
|
|
Age, Categorical
>=65 years
|
8 Participants
n=93 Participants
|
|
Age, Continuous
|
52 years
STANDARD_DEVIATION 11 • n=93 Participants
|
|
Sex: Female, Male
Female
|
54 Participants
n=93 Participants
|
|
Sex: Female, Male
Male
|
1 Participants
n=93 Participants
|
|
Region of Enrollment
United States
|
55 participants
n=93 Participants
|
PRIMARY outcome
Timeframe: at 8 weeksPopulation: Patients enrolled to determine the safety profile and recommended doses of cisplatin + paclitaxel + everolimus (RAD001) in women with metastatic breast cancer
The recommended dose for the Phase II trial will be the most prevalent dose delivered per week in Phase I that allows for safe and feasible administration of the medications.The maximum tolerated dose (MTD) is defined as the dose preceding that at which 2 or more of 3 patients experience dose-limiting toxicity (DLT) during the initial cycle of therapy. DLTs include Common Toxicity Criteria (CTC) Grade 4 neutropenia (absolute neutrophil count \[ANC\] \< 0.5 x 10 9/L for \> 5 days), febrile neutropenia (ANC \< 1.0 x 10 0/L with fever \> 38.5 degrees Centigrade) or documented infection associated with Grade 3-4 neutropenia, CTC Grade 4 thrombocytopenia \< 25 x 10 9/L or CTC Grade 3 \< 50-25 x 10 9/L thrombocytopenia with bleeding, and Grade 3-4 non-hematologic toxicity despite symptomatic therapy.
Outcome measures
| Measure |
RAD001 and Cisplatin and Paclitazel
n=3 Participants
Cisplatin intravenously (IV) weekly for 3 weeks, then 1 week of rest; paclitaxel IV weekly for 3 weeks, then 1 week of rest. Everolimus (RAD001) po daily. One cycle = 4 weeks
|
|---|---|
|
Maximum Feasible Dose in Milligrams Per Meter Squared of Body Surface Area (mg/m2) of Cisplatin and Paclitaxel for Women With Metastatic Breast Cancer
Cisplatin
|
25 mg/m2
|
|
Maximum Feasible Dose in Milligrams Per Meter Squared of Body Surface Area (mg/m2) of Cisplatin and Paclitaxel for Women With Metastatic Breast Cancer
Paclitaxel
|
80 mg/m2
|
PRIMARY outcome
Timeframe: at 8 weeksPopulation: Patients enrolled to determine the safety profile and recommended dose of cisplatin + RAD001 + paclitaxel in women with metastatic breast cancer
The recommended dose for the Phase II trial will be the most prevalent dose delivered per day in Phase I that allows for safe and feasible administration the medication. The MTD is defined as the dose preceding that at which 2 or more of 3 patients experience dose-limiting toxicity (DLT) during the initial cycle of therapy. DLTs include Common Toxicity Criteria (CTC) Grade 4 neutropenia (absolute neutrophil count \[ANC\] \< 0.5 x 10 9/L for \> 5 days), febrile neutropenia (ANC \< 1.0 x 10 0/L with fever \> 38.5 degrees Centigrade) or documented infection associated with Grade 3-4 neutropenia, CTC Grade 4 thrombocytopenia \< 25 x 10 9/L or CTC Grade 3 \< 50-25 x 10 9/L thrombocytopenia with bleeding, and Grade 3-4 non-hematologic toxicity despite symptomatic therapy
Outcome measures
| Measure |
RAD001 and Cisplatin and Paclitazel
n=3 Participants
Cisplatin intravenously (IV) weekly for 3 weeks, then 1 week of rest; paclitaxel IV weekly for 3 weeks, then 1 week of rest. Everolimus (RAD001) po daily. One cycle = 4 weeks
|
|---|---|
|
Maximum Feasible Dose in mg of RAD001 (Everolimus)for Women With Metastatic Breast Cancer
|
5 mg
|
PRIMARY outcome
Timeframe: at 6 monthsPopulation: Patient who received the study drugs. Four patients were not available for measurement of progression at 6 months: toxicity (3), withdrew after beginning treatment (1)
Patients who had not experienced disease progression and who were alive at 6 months after study entry
Outcome measures
| Measure |
RAD001 and Cisplatin and Paclitazel
n=51 Participants
Cisplatin intravenously (IV) weekly for 3 weeks, then 1 week of rest; paclitaxel IV weekly for 3 weeks, then 1 week of rest. Everolimus (RAD001) po daily. One cycle = 4 weeks
|
|---|---|
|
Patients With Progression-free Survival
|
21 participants
Interval 0.0 to 23.0
|
SECONDARY outcome
Timeframe: every 12 weeksPopulation: Patients for whom an overall response could be measured. Four patients were not evaluable due to: withdrew after beginning treatment (1) and not evaluable due to only 1 cycle of treatment (3).
Per Response Evaluation Criteria in Solid Tumor (RECIST) criteria v. 1.0: measurable lesions: complete response (CR) disappearance of target lesions, partial response (PR) \> 30% decrease in the sum of the longest diameter (LD) of target lesions, progressive disease (PD) \> 20% increase in the sum of the LD of target lesions or appearance of new lesions, stable disease (SD) neither sufficient decrease nor increase of the sum of smallest sum of the LD of target lesions
Outcome measures
| Measure |
RAD001 and Cisplatin and Paclitazel
n=51 Participants
Cisplatin intravenously (IV) weekly for 3 weeks, then 1 week of rest; paclitaxel IV weekly for 3 weeks, then 1 week of rest. Everolimus (RAD001) po daily. One cycle = 4 weeks
|
|---|---|
|
Patients With Overall Response
Complete Response
|
1 participants
|
|
Patients With Overall Response
Partial Response
|
12 participants
|
|
Patients With Overall Response
Progressive Disease
|
11 participants
|
|
Patients With Overall Response
Stable Disease
|
27 participants
|
SECONDARY outcome
Timeframe: Up to 64 weeksPopulation: Patients who were available for determination of duration of time to progressive disease. Time to progression is unknown for 8 Phase II patients due to: on-treatment (1), toxicity (3), withdrew after beginning treatment (1), and no progression (3)
Duration in months from date on-study to date patient exhibited progressive disease
Outcome measures
| Measure |
RAD001 and Cisplatin and Paclitazel
n=47 Participants
Cisplatin intravenously (IV) weekly for 3 weeks, then 1 week of rest; paclitaxel IV weekly for 3 weeks, then 1 week of rest. Everolimus (RAD001) po daily. One cycle = 4 weeks
|
|---|---|
|
Time to Progression
|
4.0 months
Interval 0.4 to 23.0
|
SECONDARY outcome
Timeframe: Up to 64 weeksPopulation: Patients who are negative for estrogen, progesterone and HER2 receptors. Time to progression was not determined for 5 patients in this group: toxicity (2), withdrew after beginning treatment (1), no progression (1), and on-treatment (1).
Median duration in months from on-study to disease progression in patients with metastatic basal-like breast cancer. All patients with basal-like breast cancer are negative for estrogen, progesterone, and human epidermal growth factor (HER2) receptors.
Outcome measures
| Measure |
RAD001 and Cisplatin and Paclitazel
n=31 Participants
Cisplatin intravenously (IV) weekly for 3 weeks, then 1 week of rest; paclitaxel IV weekly for 3 weeks, then 1 week of rest. Everolimus (RAD001) po daily. One cycle = 4 weeks
|
|---|---|
|
Time to Progression in Patients With Metastatic Basal-like Breast Cancer.
|
4.0 months
Interval 0.4 to 23.0
|
Adverse Events
RAD001 and Cisplatin and Paclitaxel
Serious adverse events
| Measure |
RAD001 and Cisplatin and Paclitaxel
n=55 participants at risk
RAD001 (Everolimus) by mouth once a day. Cisplatin intravenously (IV) weekly for 3 weeks, then 1 week of rest; paclitaxel IV weekly for 3 weeks, then 1 week of rest. One cycle = 4 weeks.
|
|---|---|
|
Gastrointestinal disorders
pain-abdomen
|
5.5%
3/55 • Number of events 6
|
|
General disorders
death not associated with CTCAE term-disease progression NOS
|
5.5%
3/55 • Number of events 3
|
|
Infections and infestations
Left maxillary odontogenic abscess and cellulitis
|
1.8%
1/55 • Number of events 1
|
|
Metabolism and nutrition disorders
glucose, serum-low (hypoglycemia)
|
1.8%
1/55 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
pain-back
|
3.6%
2/55 • Number of events 3
|
|
Blood and lymphatic system disorders
neutrophils
|
3.6%
2/55 • Number of events 4
|
|
Blood and lymphatic system disorders
leukocytes
|
1.8%
1/55 • Number of events 2
|
|
Blood and lymphatic system disorders
platelets
|
1.8%
1/55 • Number of events 2
|
|
Hepatobiliary disorders
cholecystitis
|
1.8%
1/55 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
malignant pleural effusion
|
1.8%
1/55 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
dyspnea
|
9.1%
5/55 • Number of events 6
|
|
Infections and infestations
infection with unknown ANC-mucosititis
|
1.8%
1/55 • Number of events 1
|
|
Infections and infestations
infection with unknown ANC-wound, methicillin-resistant Staphylococcus aureus
|
1.8%
1/55 • Number of events 1
|
|
Blood and lymphatic system disorders
febrile neutropenia, ANC < 1.0 x 10e9L, fever ≥ 38.5 degrees Celsius
|
1.8%
1/55 • Number of events 1
|
|
General disorders
fever in absence of neutropenia w/ neutropenia defined as ANC < 1.0 x 10e9L
|
3.6%
2/55 • Number of events 4
|
|
Gastrointestinal disorders
diarrhea
|
1.8%
1/55 • Number of events 1
|
|
Gastrointestinal disorders
nausea
|
5.5%
3/55 • Number of events 3
|
|
Gastrointestinal disorders
vomiting
|
5.5%
3/55 • Number of events 3
|
|
Vascular disorders
thromboembolism (vascular access-related)
|
1.8%
1/55 • Number of events 1
|
|
Gastrointestinal disorders
enteritis, small bowel
|
1.8%
1/55 • Number of events 1
|
|
General disorders
edema, facial
|
1.8%
1/55 • Number of events 1
|
|
Renal and urinary disorders
infection with unknown ANC-urinary tract NOS
|
1.8%
1/55 • Number of events 1
|
|
Metabolism and nutrition disorders
calcium, serum-high (hypercalcemia)
|
1.8%
1/55 • Number of events 1
|
|
Nervous system disorders
hydrocephalus
|
1.8%
1/55 • Number of events 1
|
|
Nervous system disorders
pain-headache
|
1.8%
1/55 • Number of events 1
|
|
Cardiac disorders
ventricular tachycardia
|
1.8%
1/55 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
pain-right-sided thorax (non-cardiac)
|
1.8%
1/55 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
cough
|
1.8%
1/55 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
pneumonia
|
1.8%
1/55 • Number of events 1
|
|
Blood and lymphatic system disorders
anemia
|
3.6%
2/55 • Number of events 3
|
|
Blood and lymphatic system disorders
thrombocytopenia
|
3.6%
2/55 • Number of events 3
|
Other adverse events
| Measure |
RAD001 and Cisplatin and Paclitaxel
n=55 participants at risk
RAD001 (Everolimus) by mouth once a day. Cisplatin intravenously (IV) weekly for 3 weeks, then 1 week of rest; paclitaxel IV weekly for 3 weeks, then 1 week of rest. One cycle = 4 weeks.
|
|---|---|
|
Metabolism and nutrition disorders
albumin, serum-low
|
12.7%
7/55 • Number of events 8
|
|
Investigations
alkaline phosphatase
|
41.8%
23/55 • Number of events 51
|
|
Immune system disorders
allergic reaction\hypersensitivity (including drug fever)
|
5.5%
3/55 • Number of events 4
|
|
Immune system disorders
allergy/immunology-other
|
5.5%
3/55 • Number of events 3
|
|
Metabolism and nutrition disorders
ALT, SGPT (serum glutamic pyruvic transaminase)
|
40.0%
22/55 • Number of events 44
|
|
Metabolism and nutrition disorders
anorexia
|
21.8%
12/55 • Number of events 18
|
|
Metabolism and nutrition disorders
AST, SGOT (serum glutamic oxaloacetic transaminase)
|
25.5%
14/55 • Number of events 18
|
|
Metabolism and nutrition disorders
calcium, serum-high (hypercalcemia)
|
9.1%
5/55 • Number of events 7
|
|
Investigations
cholesterol, serum-high (hypercholesteremia
|
30.9%
17/55 • Number of events 26
|
|
Gastrointestinal disorders
constipation
|
32.7%
18/55 • Number of events 21
|
|
General disorders
constitutional symptoms-other
|
34.5%
19/55 • Number of events 162
|
|
Respiratory, thoracic and mediastinal disorders
cough
|
20.0%
11/55 • Number of events 12
|
|
Investigations
creatinine
|
7.3%
4/55 • Number of events 9
|
|
Skin and subcutaneous tissue disorders
dermatology/skin-other
|
23.6%
13/55 • Number of events 21
|
|
Gastrointestinal disorders
diarrhea
|
36.4%
20/55 • Number of events 28
|
|
Gastrointestinal disorders
dizziness
|
10.9%
6/55 • Number of events 6
|
|
Respiratory, thoracic and mediastinal disorders
dyspnea
|
18.2%
10/55 • Number of events 10
|
|
General disorders
edema limb
|
20.0%
11/55 • Number of events 17
|
|
General disorders
fatigue
|
58.2%
32/55 • Number of events 45
|
|
Gastrointestinal disorders
gastrointestinal-other
|
12.7%
7/55 • Number of events 9
|
|
Metabolism and nutrition disorders
glucose, serum-high (hyperglycemia)
|
60.0%
33/55 • Number of events 76
|
|
Skin and subcutaneous tissue disorders
hair loss/alopecia (scalp or body)
|
14.5%
8/55 • Number of events 9
|
|
Gastrointestinal disorders
heartburn/dyspepsia
|
5.5%
3/55 • Number of events 3
|
|
Blood and lymphatic system disorders
hemoglobin
|
94.5%
52/55 • Number of events 182
|
|
Respiratory, thoracic and mediastinal disorders
hemorrhage, pumonary/upper respiratory-nose
|
9.1%
5/55 • Number of events 5
|
|
Infections and infestations
infection-other
|
20.0%
11/55 • Number of events 11
|
|
Renal and urinary disorders
infection with normal ANC or grade 1 or 2 neutrophils-urinary tract NOS
|
5.5%
3/55 • Number of events 3
|
|
Psychiatric disorders
insomnia
|
16.4%
9/55 • Number of events 11
|
|
Blood and lymphatic system disorders
leukocytes (total WBC)
|
60.0%
33/55 • Number of events 141
|
|
Gastrointestinal disorders
nausea
|
61.8%
34/55 • Number of events 44
|
|
Nervous system disorders
neurology-other
|
21.8%
12/55 • Number of events 28
|
|
Nervous system disorders
neuropathy-sensory
|
29.1%
16/55 • Number of events 29
|
|
Blood and lymphatic system disorders
neutrophils/granulocytes (ANC/AGC)
|
50.9%
28/55 • Number of events 77
|
|
Musculoskeletal and connective tissue disorders
pain back
|
5.5%
3/55 • Number of events 4
|
|
Reproductive system and breast disorders
pain-breast
|
5.5%
3/55 • Number of events 4
|
|
Musculoskeletal and connective tissue disorders
pain-chest wall
|
5.5%
3/55 • Number of events 3
|
|
Musculoskeletal and connective tissue disorders
pain-extremity-limb
|
7.3%
4/55 • Number of events 6
|
|
Nervous system disorders
pain-head/headache
|
20.0%
11/55 • Number of events 12
|
|
General disorders
pain-other
|
40.0%
22/55 • Number of events 34
|
|
Blood and lymphatic system disorders
platelets
|
70.9%
39/55 • Number of events 85
|
|
Metabolism and nutrition disorders
potassium-serum-low (hypokalemia)
|
36.4%
20/55 • Number of events 33
|
|
Respiratory, thoracic and mediastinal disorders
pulmonary/upper respiratory-other
|
12.7%
7/55 • Number of events 9
|
|
Skin and subcutaneous tissue disorders
rash acne/acneiform
|
12.7%
7/55 • Number of events 8
|
|
Metabolism and nutrition disorders
sodium, serum-low (hyponatremia)
|
25.5%
14/55 • Number of events 25
|
|
Nervous system disorders
taste alteration (dysgeusia)
|
10.9%
6/55 • Number of events 7
|
|
Ear and labyrinth disorders
tinnitus
|
5.5%
3/55 • Number of events 3
|
|
Metabolism and nutrition disorders
triglyceride, serum-high (hypertriglyceridemia)
|
27.3%
15/55 • Number of events 17
|
|
Gastrointestinal disorders
vomiting
|
21.8%
12/55 • Number of events 18
|
|
Musculoskeletal and connective tissue disorders
pain-joint
|
5.5%
3/55 • Number of events 3
|
|
Metabolism and nutrition disorders
magnesium, serum-low (hypomagnesemia)
|
15.4%
8/52 • Number of events 11
|
|
Metabolism and nutrition disorders
metabolic/laboratory-other
|
34.5%
19/55 • Number of events 145
|
|
Blood and lymphatic system disorders
blood/bone marrow-other
|
7.3%
4/55 • Number of events 10
|
|
Metabolism and nutrition disorders
calcium, serum-low (hypocalcemia)
|
25.5%
14/55 • Number of events 30
|
|
Metabolism and nutrition disorders
potassium, serum-high (hyperkalemia)
|
5.5%
3/55 • Number of events 4
|
|
Gastrointestinal disorders
mucositis/stomatitis (clinical exam)-oral cavity
|
18.2%
10/55 • Number of events 12
|
|
Gastrointestinal disorders
mucositis/stomatitis (functional/symptomatic)-oral cavity
|
10.9%
6/55 • Number of events 6
|
|
Skin and subcutaneous tissue disorders
nail changes
|
7.3%
4/55 • Number of events 4
|
|
Skin and subcutaneous tissue disorders
pruritis/itching
|
5.5%
3/55 • Number of events 3
|
|
Skin and subcutaneous tissue disorders
rash/desquamation
|
5.5%
3/55 • Number of events 4
|
|
Psychiatric disorders
depression
|
5.5%
3/55 • Number of events 3
|
|
Infections and infestations
infection with normal ANC or Grade 1 or 2 neutrophils-nails
|
5.5%
3/55 • Number of events 4
|
|
Infections and infestations
infection with normal ANC or Grade 1 or 2 neutrophils-upper airway NOS
|
9.1%
5/55 • Number of events 6
|
|
Blood and lymphatic system disorders
lymphatics-other
|
5.5%
3/55 • Number of events 3
|
|
Musculoskeletal and connective tissue disorders
Pain-neck
|
5.5%
3/55 • Number of events 4
|
|
Gastrointestinal disorders
pain-abdomen NOS
|
7.3%
4/55 • Number of events 5
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place