Trial Outcomes & Findings for Panitumumab, Gemcitabine and Carboplatin in Triple-Negative Metastatic Breast Cancer (NCT NCT00894504)

NCT ID: NCT00894504

Last Updated: 2015-05-15

Results Overview

Measured from Day 1 of study drug administration to disease progression - defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as a 20% increase in the sum of the longest diameter of target lesions and/or appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 71 participants
• Primary outcome timeframe: every 6 weeks until treatment discontinuation
• Results posted on: 2015-05-15

Participant Flow

Participant milestones

Measure	Panitumumab/Gemcitabine/Carboplatin Treatment cycles are repeated every 14 days (2 weeks) Panitumumab: 6mg/kg intravenous (IV), Day 1 of each 2-week treatment cycle. Gemcitabine: 1500mg/m2 IV, Day 1 of each 2-week treatment cycle Carboplatin: Area Under the Curve (AUC) = 2.5 IV, Day 1 of each 2-week treatment cycle
Overall Study STARTED	71
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	71

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Panitumumab, Gemcitabine and Carboplatin in Triple-Negative Metastatic Breast Cancer

Baseline characteristics by cohort

Measure	Panitumumab/Gemcitabine/Carboplatin n=71 Participants Panitumumab - 6 mg/kg IV on Day 1 of each 2-week treatment cycle for 3 cycles (6 weeks) Carboplatin - AUC=2.5 IV, Day 1 of each 2-week treatment cycle for 3 cycles (6 weeks) Gemcitabine - 1500 mg/m2 IV, Day 1 of each 2-week treatment cycle for 3 cycles (6 weeks)
Age, Continuous	54 Years n=5 Participants
Sex: Female, Male Female	71 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Region of Enrollment United States	71 participants n=5 Participants

PRIMARY outcome

Timeframe: every 6 weeks until treatment discontinuation

Measured from Day 1 of study drug administration to disease progression - defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as a 20% increase in the sum of the longest diameter of target lesions and/or appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions

Outcome measures

Measure	Panitumumab/Gemcitabine/Carboplatin n=71 Participants Panitumumab - 6 mg/kg IV on Day 1 of each 2-week treatment cycle for 3 cycles (6 weeks) Carboplatin - AUC=2.5 IV, Day 1 of each 2-week treatment cycle for 3 cycles (6 weeks) Gemcitabine - 1500 mg/m2 IV, Day 1 of each 2-week treatment cycle for 3 cycles (6 weeks)	EGFR Amplified	p53 Normal	p53 Loss	PTEN Normal	PTEN Loss	PIK3CA No Mutation	PIK3CA Mutation(s)
Progression-free Survival (PFS)	4.4 Months Interval 3.2 to 5.5	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: every 6 weeks until treatment discontinuation

Population: All evaluable patients per RECIST v 1.1

Estimated as the proportion of subjects who meet the criteria for complete or partial response (CR or PR) per Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 - for target lesions assessed by MRI: Complete Response (CR) is defined as disappearance of all target lesions; Partial Response (PR) is defined as >=30% decrease in the sum of the longest diameter of target lesions.

Outcome measures

Measure	Panitumumab/Gemcitabine/Carboplatin n=69 Participants Panitumumab - 6 mg/kg IV on Day 1 of each 2-week treatment cycle for 3 cycles (6 weeks) Carboplatin - AUC=2.5 IV, Day 1 of each 2-week treatment cycle for 3 cycles (6 weeks) Gemcitabine - 1500 mg/m2 IV, Day 1 of each 2-week treatment cycle for 3 cycles (6 weeks)	EGFR Amplified	p53 Normal	p53 Loss	PTEN Normal	PTEN Loss	PIK3CA No Mutation	PIK3CA Mutation(s)
Objective Response Rate and Clinical Benefit Rate Clinical benefit rate (CR + PR + SD>6 months)	32 Participants	—	—	—	—	—	—	—
Objective Response Rate and Clinical Benefit Rate Objective response rate (CR + PR)	30 Participants	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: every 6 weeks until discontinuation of treatment, expected average of 18 months

Assessments made through analysis of treatment-related adverse events and serious adverse events

Outcome measures

Measure	Panitumumab/Gemcitabine/Carboplatin n=71 Participants Panitumumab - 6 mg/kg IV on Day 1 of each 2-week treatment cycle for 3 cycles (6 weeks) Carboplatin - AUC=2.5 IV, Day 1 of each 2-week treatment cycle for 3 cycles (6 weeks) Gemcitabine - 1500 mg/m2 IV, Day 1 of each 2-week treatment cycle for 3 cycles (6 weeks)	EGFR Amplified	p53 Normal	p53 Loss	PTEN Normal	PTEN Loss	PIK3CA No Mutation	PIK3CA Mutation(s)
Number of Treatment-related Toxicities Occurring in ≥10% of Patients as a Measure of Tolerability and Toxicity Mucositis/stomatitis	16 participants	—	—	—	—	—	—	—
Number of Treatment-related Toxicities Occurring in ≥10% of Patients as a Measure of Tolerability and Toxicity Neutropenia	32 participants	—	—	—	—	—	—	—
Number of Treatment-related Toxicities Occurring in ≥10% of Patients as a Measure of Tolerability and Toxicity Thrombocytopenia	32 participants	—	—	—	—	—	—	—
Number of Treatment-related Toxicities Occurring in ≥10% of Patients as a Measure of Tolerability and Toxicity Leukopenia	25 participants	—	—	—	—	—	—	—
Number of Treatment-related Toxicities Occurring in ≥10% of Patients as a Measure of Tolerability and Toxicity Anemia	20 participants	—	—	—	—	—	—	—
Number of Treatment-related Toxicities Occurring in ≥10% of Patients as a Measure of Tolerability and Toxicity Rash	50 participants	—	—	—	—	—	—	—
Number of Treatment-related Toxicities Occurring in ≥10% of Patients as a Measure of Tolerability and Toxicity Fatigue	37 participants	—	—	—	—	—	—	—
Number of Treatment-related Toxicities Occurring in ≥10% of Patients as a Measure of Tolerability and Toxicity Nausea/vomiting	36 participants	—	—	—	—	—	—	—
Number of Treatment-related Toxicities Occurring in ≥10% of Patients as a Measure of Tolerability and Toxicity Dry skin	21 participants	—	—	—	—	—	—	—
Number of Treatment-related Toxicities Occurring in ≥10% of Patients as a Measure of Tolerability and Toxicity Hypomagnesemia	18 participants	—	—	—	—	—	—	—
Number of Treatment-related Toxicities Occurring in ≥10% of Patients as a Measure of Tolerability and Toxicity Constipation	15 participants	—	—	—	—	—	—	—
Number of Treatment-related Toxicities Occurring in ≥10% of Patients as a Measure of Tolerability and Toxicity Dyspnea	12 participants	—	—	—	—	—	—	—
Number of Treatment-related Toxicities Occurring in ≥10% of Patients as a Measure of Tolerability and Toxicity Pruritis	12 participants	—	—	—	—	—	—	—
Number of Treatment-related Toxicities Occurring in ≥10% of Patients as a Measure of Tolerability and Toxicity Anorexia	10 participants	—	—	—	—	—	—	—
Number of Treatment-related Toxicities Occurring in ≥10% of Patients as a Measure of Tolerability and Toxicity Diarrhea	9 participants	—	—	—	—	—	—	—
Number of Treatment-related Toxicities Occurring in ≥10% of Patients as a Measure of Tolerability and Toxicity AST/ALT increased	9 participants	—	—	—	—	—	—	—
Number of Treatment-related Toxicities Occurring in ≥10% of Patients as a Measure of Tolerability and Toxicity Alopecia	7 participants	—	—	—	—	—	—	—
Number of Treatment-related Toxicities Occurring in ≥10% of Patients as a Measure of Tolerability and Toxicity Dyspepsia	7 participants	—	—	—	—	—	—	—
Number of Treatment-related Toxicities Occurring in ≥10% of Patients as a Measure of Tolerability and Toxicity Myalgia	7 participants	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: 18 months

Population: Excludes patients in the following categories due to insufficient data: PTEN status unknown, PIK3CA Status unknown and KRAS no mutation

Median PFS (95% CI), months, reported by biomarker expression/mutation status for: EGFR, p53, PTEN, PIK3CA, KRAS

Outcome measures

Measure	Panitumumab/Gemcitabine/Carboplatin n=56 Participants Panitumumab - 6 mg/kg IV on Day 1 of each 2-week treatment cycle for 3 cycles (6 weeks) Carboplatin - AUC=2.5 IV, Day 1 of each 2-week treatment cycle for 3 cycles (6 weeks) Gemcitabine - 1500 mg/m2 IV, Day 1 of each 2-week treatment cycle for 3 cycles (6 weeks)	EGFR Amplified n=12 Participants	p53 Normal n=34 Participants	p53 Loss n=34 Participants	PTEN Normal n=62 Participants	PTEN Loss n=5 Participants	PIK3CA No Mutation n=55 Participants	PIK3CA Mutation(s) n=12 Participants
Correlation of Biomarker Expressions of EGFR, K-ras, p53, PTEN Expression, and PI3K in Triple-negative Breast Cancer With Response to Treatment With the Combination of Gemcitabine, Carboplatin, and Panitumumab	4.57 months Interval 3.88 to 6.44	3.42 months Interval 1.51 to Upper limit of 95% Confidence Interval not available - too few patients in this category	4.16 months Interval 2.69 to 5.49	5.32 months Interval 3.19 to 9.03	4.4 months Interval 3.88 to 5.59	2.91 months Interval 0.82 to Upper limit of 95% Confidence Interval not available - too few patients in this category	4.37 months Interval 3.19 to 6.05	4.73 months Interval 2.56 to Upper limit of 95% Confidence Interval not available - too few patients in this category

Adverse Events

Panitumumab/Gemcitabine/Carboplatin

Serious events: 10 serious events

Other events: 70 other events

Deaths: 0 deaths

Serious adverse events

Measure	Panitumumab/Gemcitabine/Carboplatin n=71 participants at risk
Cardiac disorders ATRIAL FIBRILLATION	1.4% 1/71 • Number of events 1
Cardiac disorders CARDIAC TAMPONADE	1.4% 1/71 • Number of events 1
Cardiac disorders PERICARDIAL EFFUSION	1.4% 1/71 • Number of events 2
Cardiac disorders SUPRAVENTRICULAR TACHYCARDIA	1.4% 1/71 • Number of events 1
Gastrointestinal disorders DIARRHOEA	1.4% 1/71 • Number of events 1
Gastrointestinal disorders NAUSEA	1.4% 1/71 • Number of events 1
Gastrointestinal disorders VOMITING	1.4% 1/71 • Number of events 1
General disorders CHEST PAIN	1.4% 1/71 • Number of events 1
Infections and infestations PNEUMONIA	1.4% 1/71 • Number of events 1
Neoplasms benign, malignant and unspecified (incl cysts and polyps) MALIGNANT PLEURAL EFFUSION	1.4% 1/71 • Number of events 1
Nervous system disorders HEPATIC ENCEPHALOPATHY	1.4% 1/71 • Number of events 1
Renal and urinary disorders HAEMORRHAGE URINARY TRACT	1.4% 1/71 • Number of events 1
Renal and urinary disorders HYDRONEPHROSIS	1.4% 1/71 • Number of events 1
Respiratory, thoracic and mediastinal disorders DYSPNOEA	2.8% 2/71 • Number of events 2
Respiratory, thoracic and mediastinal disorders CHRONIC OBSTRUCTIVE PULMONARY DISEASE	1.4% 1/71 • Number of events 3
Vascular disorders EMBOLISM	1.4% 1/71 • Number of events 1

Other adverse events

Measure	Panitumumab/Gemcitabine/Carboplatin n=71 participants at risk
Blood and lymphatic system disorders ANAEMIA	22.5% 16/71 • Number of events 46
Blood and lymphatic system disorders LEUKOPENIA	25.4% 18/71 • Number of events 114
Blood and lymphatic system disorders NEUTROPENIA	33.8% 24/71 • Number of events 121
Blood and lymphatic system disorders THROMBOCYTOPENIA	35.2% 25/71 • Number of events 54
Cardiac disorders TACHYCARDIA	8.5% 6/71 • Number of events 8
Eye disorders DRY EYE	5.6% 4/71 • Number of events 4
Gastrointestinal disorders CONSTIPATION	39.4% 28/71 • Number of events 41
Gastrointestinal disorders DIARRHOEA	18.3% 13/71 • Number of events 26
Gastrointestinal disorders DYSPEPSIA	9.9% 7/71 • Number of events 9
Gastrointestinal disorders GASTROOESOPHAGEAL REFLUX DISEASE	7.0% 5/71 • Number of events 6
Gastrointestinal disorders NAUSEA	53.5% 38/71 • Number of events 56
Gastrointestinal disorders STOMATITIS	9.9% 7/71 • Number of events 8
Gastrointestinal disorders VOMITING	23.9% 17/71 • Number of events 28
General disorders FATIGUE	63.4% 45/71 • Number of events 109
General disorders MUCOSAL INFLAMMATION	12.7% 9/71 • Number of events 22
General disorders OEDEMA PERIPHERAL	7.0% 5/71 • Number of events 5
General disorders PYREXIA	9.9% 7/71 • Number of events 8
Investigations ALANINE AMINOTRANSFERASE INCREASED	9.9% 7/71 • Number of events 40
Investigations ASPARTATE AMINOTRANSFERASE INCREASED	14.1% 10/71 • Number of events 32
Investigations BLOOD ALKALINE PHOSPHATASE INCREASED	8.5% 6/71 • Number of events 20
Investigations WHITE BLOOD CELL COUNT DECREASED	5.6% 4/71 • Number of events 19
Metabolism and nutrition disorders DECREASED APPETITE	18.3% 13/71 • Number of events 26
Metabolism and nutrition disorders DEHYDRATION	9.9% 7/71 • Number of events 8
Metabolism and nutrition disorders HYPERGLYCAEMIA	5.6% 4/71 • Number of events 17
Metabolism and nutrition disorders HYPOCALCAEMIA	5.6% 4/71 • Number of events 6
Metabolism and nutrition disorders HYPOKALAEMIA	11.3% 8/71 • Number of events 14
Metabolism and nutrition disorders HYPOMAGNESAEMIA	22.5% 16/71 • Number of events 29
Musculoskeletal and connective tissue disorders ARTHRALGIA	5.6% 4/71 • Number of events 5
Musculoskeletal and connective tissue disorders BACK PAIN	7.0% 5/71 • Number of events 6
Musculoskeletal and connective tissue disorders BONE PAIN	8.5% 6/71 • Number of events 8
Musculoskeletal and connective tissue disorders MUSCULOSKELETAL PAIN	5.6% 4/71 • Number of events 21
Musculoskeletal and connective tissue disorders MYALGIA	9.9% 7/71 • Number of events 8
Musculoskeletal and connective tissue disorders PAIN IN EXTREMITY	7.0% 5/71 • Number of events 6
Nervous system disorders DIZZINESS	7.0% 5/71 • Number of events 6
Nervous system disorders DYSGEUSIA	8.5% 6/71 • Number of events 6
Nervous system disorders HEADACHE	8.5% 6/71 • Number of events 8
Nervous system disorders PERIPHERAL SENSORY NEUROPATHY	11.3% 8/71 • Number of events 10
Psychiatric disorders ANXIETY	9.9% 7/71 • Number of events 8
Psychiatric disorders DEPRESSION	5.6% 4/71 • Number of events 4
Psychiatric disorders INSOMNIA	16.9% 12/71 • Number of events 12
Renal and urinary disorders DYSURIA	7.0% 5/71 • Number of events 5
Respiratory, thoracic and mediastinal disorders COUGH	14.1% 10/71 • Number of events 13
Respiratory, thoracic and mediastinal disorders DYSPNOEA	19.7% 14/71 • Number of events 21
Skin and subcutaneous tissue disorders ACNE	8.5% 6/71 • Number of events 11
Skin and subcutaneous tissue disorders ALOPECIA	9.9% 7/71 • Number of events 7
Skin and subcutaneous tissue disorders DERMATITIS ACNEIFORM	11.3% 8/71 • Number of events 17
Skin and subcutaneous tissue disorders DRY SKIN	33.8% 24/71 • Number of events 28
Skin and subcutaneous tissue disorders EXFOLIATIVE RASH	8.5% 6/71 • Number of events 13
Skin and subcutaneous tissue disorders PRURITUS	15.5% 11/71 • Number of events 13
Skin and subcutaneous tissue disorders RASH	43.7% 31/71 • Number of events 55

Additional Information

John D. Hainsworth, MD

Sarah Cannon Research Institute

Phone: 1-877-691-7274

Email: asksarah@scresearch.net

Results disclosure agreements

• Principal investigator is a sponsor employee The sponsor can review/embargo results communications prior to public release for a period that is \>60 days but ≤180 days from date submitted to sponsor, who may require changes to the communication in order to remove specifically identified confidential information (other than study data) and/or delay the proposed publication to enable the sponsor to seek patent protection for inventions. The PI may not publish its results until 18 mos. after the trial has been completed at all sites
• Publication restrictions are in place

Restriction type: OTHER