Trial Outcomes & Findings for Doxil & Carboplatin Plus HER2+ in Metastatic Breast Cancer (NCT NCT00303108)

Last Updated: 2016-11-03

Results Overview

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; Objective response (OR) = CR + PR.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

136 participants

Primary outcome timeframe

From date of randomization until the date of first documented progression or date of intolerable toxicity, whichever came first, assessed up to 54 months.

Results posted on

2016-11-03

Participant Flow

Participant milestones

Participant milestones
Measure	D+C and Taxane Naive Doxil, Carboplatin and Taxane naive	D+C and Taxane Pretreated Doxil, Carboplatin and Taxane pretreated	D+C+H Doxil, Carboplatin, and Herceptin
Overall Study STARTED	43	46	47
Overall Study COMPLETED	31	37	31
Overall Study NOT COMPLETED	12	9	16

Reasons for withdrawal

Reasons for withdrawal
Measure	D+C and Taxane Naive Doxil, Carboplatin and Taxane naive	D+C and Taxane Pretreated Doxil, Carboplatin and Taxane pretreated	D+C+H Doxil, Carboplatin, and Herceptin
Overall Study Adverse Event	5	6	7
Overall Study Patient Request	4	2	8
Overall Study Failed Entry	1	0	1
Overall Study ineligible	2	1	0

Baseline Characteristics

Doxil & Carboplatin Plus HER2+ in Metastatic Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	D+C and Taxane Naive n=43 Participants Doxil, Carboplatin and Taxane naive	D+C and Taxane Pretreated n=46 Participants Doxil, Carboplatin and Taxane pretreated	D+C+H n=47 Participants Doxil, Carboplatin, and Herceptin	Total n=136 Participants Total of all reporting groups
Age, Continuous	61.0 years n=5 Participants	51.7 years n=7 Participants	54.1 years n=5 Participants	56.4 years n=4 Participants
Sex: Female, Male Female	42 Participants n=5 Participants	46 Participants n=7 Participants	47 Participants n=5 Participants	135 Participants n=4 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Caucasian	30 participants n=5 Participants	34 participants n=7 Participants	37 participants n=5 Participants	101 participants n=4 Participants
Race/Ethnicity, Customized Black	10 participants n=5 Participants	8 participants n=7 Participants	7 participants n=5 Participants	25 participants n=4 Participants
Race/Ethnicity, Customized Hispanic	3 participants n=5 Participants	4 participants n=7 Participants	2 participants n=5 Participants	9 participants n=4 Participants
Race/Ethnicity, Customized Hawaiian	0 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants	1 participants n=4 Participants
Region of Enrollment United States	43 participants n=5 Participants	46 participants n=7 Participants	47 participants n=5 Participants	136 participants n=4 Participants

PRIMARY outcome

Timeframe: From date of randomization until the date of first documented progression or date of intolerable toxicity, whichever came first, assessed up to 54 months.

Population: Evaluable population

Outcome measures

Outcome measures
Measure	D+C and Taxane Naive n=39 Participants Doxil, Carboplatin and Taxane naive	D+C and Taxane Pretreated n=42 Participants Doxil, Carboplatin and Taxane pretreated	D+C+H n=45 Participants Doxil, Carboplatin, and Herceptin
Objective Response Rate (ORR)	30.8 percentage of participants Interval 17.0 to 47.6	31.0 percentage of participants Interval 17.6 to 47.1	55.6 percentage of participants Interval 40.0 to 70.4

SECONDARY outcome

Timeframe: From date of randomization until the date of first documented progression or date of intolerable toxicity, whichever came first, assessed up to 54 months.

Population: Patients who achieved CR or PR.

Duration from date of stating treatment to the date of first CR or PR.

Outcome measures

Outcome measures
Measure	D+C and Taxane Naive n=12 Participants Doxil, Carboplatin and Taxane naive	D+C and Taxane Pretreated n=13 Participants Doxil, Carboplatin and Taxane pretreated	D+C+H n=25 Participants Doxil, Carboplatin, and Herceptin
Duration of Response	11.1 months Interval 0.9 to 15.2	7.0 months Interval 2.8 to 13.2	11.8 months Interval 2.3 to 16.8

SECONDARY outcome

Timeframe: 30 months

Population: ITT population

PFS is measured from the date of randomization to the date of first documented disease progression or date of death, whichever comes first. If a patient neither progresses nor dies, this patient will be censored at last contact date. Progression is defined as appearance of one or more new lesions. Unequivocal progression of existing non-target lesions. Although a clear progression of "non-target" lesions only is exceptional, in such circumstances, the opinion of the Treating Physician should prevail, and the progression status should be confirmed at a later time by the review panel.

Outcome measures

Outcome measures
Measure	D+C and Taxane Naive n=43 Participants Doxil, Carboplatin and Taxane naive	D+C and Taxane Pretreated n=46 Participants Doxil, Carboplatin and Taxane pretreated	D+C+H n=47 Participants Doxil, Carboplatin, and Herceptin
Progression-free Survival (PFS)	8.1 months Interval 0.3 to 28.5	5.4 months Interval 0.1 to 21.0	10.1 months Interval 0.2 to 18.5

SECONDARY outcome

Timeframe: 1 year

Population: ITT population

OS is measured from the date of randomization to the date of death for a dead patient. If a patient is still alive or is lost to follow up, the patient will be censored at the last contact date.

Outcome measures

Outcome measures
Measure	D+C and Taxane Naive n=43 Participants Doxil, Carboplatin and Taxane naive	D+C and Taxane Pretreated n=46 Participants Doxil, Carboplatin and Taxane pretreated	D+C+H n=47 Participants Doxil, Carboplatin, and Herceptin
1-year Overall Survival	0.83 probability of overall survival Interval 0.67 to 0.915	0.56 probability of overall survival Interval 0.4 to 0.69	0.90 probability of overall survival Interval 0.76 to 0.96

Adverse Events

D+C and Taxane Naive or Pretreated

Serious events: 8 serious events

Other events: 80 other events

Deaths: 0 deaths

D+C+H

Serious events: 3 serious events

Other events: 44 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	D+C and Taxane Naive or Pretreated n=83 participants at risk Doxil, Carboplatin and Taxane naive or pretreated.	D+C+H n=46 participants at risk Doxil, Carboplatin, and Herceptin
Blood and lymphatic system disorders ANEMIA	1.2% 1/83 • Number of events 1 • During the whole treatment period, up to 30 days following last dose.	0.00% 0/46 • During the whole treatment period, up to 30 days following last dose.
Gastrointestinal disorders ANOREXIA	1.2% 1/83 • Number of events 1 • During the whole treatment period, up to 30 days following last dose.	0.00% 0/46 • During the whole treatment period, up to 30 days following last dose.
Gastrointestinal disorders DEHYDRATION	2.4% 2/83 • Number of events 3 • During the whole treatment period, up to 30 days following last dose.	0.00% 0/46 • During the whole treatment period, up to 30 days following last dose.
Gastrointestinal disorders NAUSEA AND VOMITING	0.00% 0/83 • During the whole treatment period, up to 30 days following last dose.	4.3% 2/46 • Number of events 2 • During the whole treatment period, up to 30 days following last dose.
Blood and lymphatic system disorders PANCYTOPENIA	1.2% 1/83 • Number of events 2 • During the whole treatment period, up to 30 days following last dose.	0.00% 0/46 • During the whole treatment period, up to 30 days following last dose.
Respiratory, thoracic and mediastinal disorders PNEUMONIA	0.00% 0/83 • During the whole treatment period, up to 30 days following last dose.	2.2% 1/46 • Number of events 1 • During the whole treatment period, up to 30 days following last dose.
Renal and urinary disorders RENAL FAILURE ACUTE	1.2% 1/83 • Number of events 1 • During the whole treatment period, up to 30 days following last dose.	0.00% 0/46 • During the whole treatment period, up to 30 days following last dose.
Blood and lymphatic system disorders THROMBOCYTOPENIA	2.4% 2/83 • Number of events 2 • During the whole treatment period, up to 30 days following last dose.	0.00% 0/46 • During the whole treatment period, up to 30 days following last dose.
Renal and urinary disorders URINARY TRACT INFECTION	1.2% 1/83 • Number of events 1 • During the whole treatment period, up to 30 days following last dose.	0.00% 0/46 • During the whole treatment period, up to 30 days following last dose.
Gastrointestinal disorders VOMITING	1.2% 1/83 • Number of events 1 • During the whole treatment period, up to 30 days following last dose.	2.2% 1/46 • Number of events 1 • During the whole treatment period, up to 30 days following last dose.

Other adverse events

Additional Information

Dr. Rufus Collea

New York Oncology Hematology, Albany Medical Center

Phone: 518-262-6696

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	D+C and Taxane Naive or Pretreated n=83 participants at risk Doxil, Carboplatin and Taxane naive or pretreated.	D+C+H n=46 participants at risk Doxil, Carboplatin, and Herceptin
Immune system disorders ALLERGIC REACTION	6.0% 5/83 • Number of events 6 • During the whole treatment period, up to 30 days following last dose.	4.3% 2/46 • Number of events 2 • During the whole treatment period, up to 30 days following last dose.
Skin and subcutaneous tissue disorders ALOPECIA	13.3% 11/83 • Number of events 11 • During the whole treatment period, up to 30 days following last dose.	32.6% 15/46 • Number of events 17 • During the whole treatment period, up to 30 days following last dose.
Blood and lymphatic system disorders ANEMIA	57.8% 48/83 • Number of events 152 • During the whole treatment period, up to 30 days following last dose.	65.2% 30/46 • Number of events 90 • During the whole treatment period, up to 30 days following last dose.
Gastrointestinal disorders ANOREXIA	14.5% 12/83 • Number of events 14 • During the whole treatment period, up to 30 days following last dose.	23.9% 11/46 • Number of events 11 • During the whole treatment period, up to 30 days following last dose.
Gastrointestinal disorders CONSTIPATION	24.1% 20/83 • Number of events 24 • During the whole treatment period, up to 30 days following last dose.	17.4% 8/46 • Number of events 8 • During the whole treatment period, up to 30 days following last dose.
Gastrointestinal disorders DEHYDRATION	1.2% 1/83 • Number of events 1 • During the whole treatment period, up to 30 days following last dose.	6.5% 3/46 • Number of events 3 • During the whole treatment period, up to 30 days following last dose.
Gastrointestinal disorders DIARRHEA	14.5% 12/83 • Number of events 16 • During the whole treatment period, up to 30 days following last dose.	19.6% 9/46 • Number of events 15 • During the whole treatment period, up to 30 days following last dose.
Nervous system disorders DIZZINESS	6.0% 5/83 • Number of events 7 • During the whole treatment period, up to 30 days following last dose.	2.2% 1/46 • Number of events 1 • During the whole treatment period, up to 30 days following last dose.
Skin and subcutaneous tissue disorders DRY SKIN	3.6% 3/83 • Number of events 3 • During the whole treatment period, up to 30 days following last dose.	6.5% 3/46 • Number of events 4 • During the whole treatment period, up to 30 days following last dose.
Gastrointestinal disorders DYSPEPSIA	1.2% 1/83 • Number of events 1 • During the whole treatment period, up to 30 days following last dose.	6.5% 3/46 • Number of events 3 • During the whole treatment period, up to 30 days following last dose.
Blood and lymphatic system disorders EDEMA	8.4% 7/83 • Number of events 7 • During the whole treatment period, up to 30 days following last dose.	8.7% 4/46 • Number of events 11 • During the whole treatment period, up to 30 days following last dose.
General disorders FEVER	3.6% 3/83 • Number of events 3 • During the whole treatment period, up to 30 days following last dose.	8.7% 4/46 • Number of events 5 • During the whole treatment period, up to 30 days following last dose.
Skin and subcutaneous tissue disorders FLUSHING	1.2% 1/83 • Number of events 1 • During the whole treatment period, up to 30 days following last dose.	6.5% 3/46 • Number of events 3 • During the whole treatment period, up to 30 days following last dose.
Skin and subcutaneous tissue disorders HAND-FOOT SYNDROME	9.6% 8/83 • Number of events 15 • During the whole treatment period, up to 30 days following last dose.	15.2% 7/46 • Number of events 10 • During the whole treatment period, up to 30 days following last dose.
Metabolism and nutrition disorders HYPERGLYCEMIA	1.2% 1/83 • Number of events 2 • During the whole treatment period, up to 30 days following last dose.	8.7% 4/46 • Number of events 7 • During the whole treatment period, up to 30 days following last dose.
Metabolism and nutrition disorders HYPOKALEMIA	1.2% 1/83 • Number of events 4 • During the whole treatment period, up to 30 days following last dose.	6.5% 3/46 • Number of events 3 • During the whole treatment period, up to 30 days following last dose.
General disorders INSOMNIA	7.2% 6/83 • Number of events 6 • During the whole treatment period, up to 30 days following last dose.	6.5% 3/46 • Number of events 3 • During the whole treatment period, up to 30 days following last dose.
Blood and lymphatic system disorders LEUCOPENIA	25.3% 21/83 • Number of events 64 • During the whole treatment period, up to 30 days following last dose.	39.1% 18/46 • Number of events 75 • During the whole treatment period, up to 30 days following last dose.
Infections and infestations MUCOSITIS	7.2% 6/83 • Number of events 11 • During the whole treatment period, up to 30 days following last dose.	21.7% 10/46 • Number of events 20 • During the whole treatment period, up to 30 days following last dose.
Musculoskeletal and connective tissue disorders MUSCLE WEAKNESS	7.2% 6/83 • Number of events 8 • During the whole treatment period, up to 30 days following last dose.	6.5% 3/46 • Number of events 5 • During the whole treatment period, up to 30 days following last dose.
Musculoskeletal and connective tissue disorders MYALGIA	3.6% 3/83 • Number of events 4 • During the whole treatment period, up to 30 days following last dose.	13.0% 6/46 • Number of events 6 • During the whole treatment period, up to 30 days following last dose.
Skin and subcutaneous tissue disorders NAIL DISORDER	2.4% 2/83 • Number of events 2 • During the whole treatment period, up to 30 days following last dose.	8.7% 4/46 • Number of events 6 • During the whole treatment period, up to 30 days following last dose.
Gastrointestinal disorders NAUSEA	51.8% 43/83 • Number of events 88 • During the whole treatment period, up to 30 days following last dose.	63.0% 29/46 • Number of events 44 • During the whole treatment period, up to 30 days following last dose.
Nervous system disorders NEUROPATHY	4.8% 4/83 • Number of events 4 • During the whole treatment period, up to 30 days following last dose.	8.7% 4/46 • Number of events 5 • During the whole treatment period, up to 30 days following last dose.
Blood and lymphatic system disorders NEUTROPENIA	48.2% 40/83 • Number of events 177 • During the whole treatment period, up to 30 days following last dose.	56.5% 26/46 • Number of events 145 • During the whole treatment period, up to 30 days following last dose.
Musculoskeletal and connective tissue disorders PAIN BONE	1.2% 1/83 • Number of events 1 • During the whole treatment period, up to 30 days following last dose.	10.9% 5/46 • Number of events 5 • During the whole treatment period, up to 30 days following last dose.
Skin and subcutaneous tissue disorders RASH	9.6% 8/83 • Number of events 10 • During the whole treatment period, up to 30 days following last dose.	19.6% 9/46 • Number of events 15 • During the whole treatment period, up to 30 days following last dose.
Respiratory, thoracic and mediastinal disorders SHORTNESS OF BREATH	4.8% 4/83 • Number of events 5 • During the whole treatment period, up to 30 days following last dose.	8.7% 4/46 • Number of events 4 • During the whole treatment period, up to 30 days following last dose.
Gastrointestinal disorders STOMATITIS	6.0% 5/83 • Number of events 7 • During the whole treatment period, up to 30 days following last dose.	2.2% 1/46 • Number of events 1 • During the whole treatment period, up to 30 days following last dose.
Blood and lymphatic system disorders THROMBOCYTOPENIA	42.2% 35/83 • Number of events 139 • During the whole treatment period, up to 30 days following last dose.	30.4% 14/46 • Number of events 82 • During the whole treatment period, up to 30 days following last dose.
Gastrointestinal disorders VOMITING	19.3% 16/83 • Number of events 27 • During the whole treatment period, up to 30 days following last dose.	26.1% 12/46 • Number of events 14 • During the whole treatment period, up to 30 days following last dose.
General disorders WEAKNESS	48.2% 40/83 • Number of events 85 • During the whole treatment period, up to 30 days following last dose.	50.0% 23/46 • Number of events 41 • During the whole treatment period, up to 30 days following last dose.