Trial Outcomes & Findings for A Study Evaluating PF-03084014 In Patients With Advanced Breast Cancer With Or Without Notch Alterations (NCT NCT02299635)

Last Updated: 2019-01-08

Results Overview

OR status based on assessment of confirmed complete remission (CR) or confirmed partial remission (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1). CR: Complete disappearance of all target lesions with the exception of nodal disease and all target nodes decreased to normal size (short axis less than \[\<\]10 millimeter \[mm\]). PR: Greater than or equal to (\>=)30% decrease under baseline of the sum of diameters of all target measurable lesions. OR=CR+PR.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

19 participants

Primary outcome timeframe

Cycle 3 Day 1, Cycle 5 Day 1, and every 6 weeks for subsequent cycles ntil disease progression, patient refusal for further follow up, or start of another anti-cancer treatment, whichever occurred first.

Results posted on

2019-01-08

Participant Flow

Participant milestones

Participant milestones
Measure	PF-03084014 PF-03084014 at the starting dose of 150 mg twice daily (BID) (in the form of one 100-mg and one 50-mg tablet) was administered orally BID continuously in 21-day cycles until disease progression, patient refusal of further treatment, or unacceptable toxicity, whichever occurred first.
Overall Study STARTED	19
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	19

Reasons for withdrawal

Reasons for withdrawal
Measure	PF-03084014 PF-03084014 at the starting dose of 150 mg twice daily (BID) (in the form of one 100-mg and one 50-mg tablet) was administered orally BID continuously in 21-day cycles until disease progression, patient refusal of further treatment, or unacceptable toxicity, whichever occurred first.
Overall Study Adverse Event	2
Overall Study Death	1
Overall Study Global deterioration of health status	1
Overall Study Objective progression or relapse	10
Overall Study Withdrawal by Subject	2
Overall Study Other	3

Baseline Characteristics

A Study Evaluating PF-03084014 In Patients With Advanced Breast Cancer With Or Without Notch Alterations

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	PF-03084014 n=19 Participants PF-03084014 at the starting dose of 150 mg twice daily (BID) (in the form of one 100-mg and one 50-mg tablet) was administered orally BID continuously in 21-day cycles until disease progression, patient refusal of further treatment, or unacceptable toxicity, whichever occurred first.
Age, Continuous	57.4 years STANDARD_DEVIATION 12.1 • n=5 Participants
Sex: Female, Male Female	19 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Cycle 3 Day 1, Cycle 5 Day 1, and every 6 weeks for subsequent cycles ntil disease progression, patient refusal for further follow up, or start of another anti-cancer treatment, whichever occurred first.

Population: Data for this outcome measure was not collected due to early termination of this study.

Outcome measures

Outcome data not reported

SECONDARY outcome

Population: Data for this outcome measure was not collected due to early termination of this study.

OR status based on assessment of confirmed CR or confirmed PR according to RECIST 1.1. CR: Complete disappearance of all target lesions with the exception of nodal disease and all target nodes decreased to normal size (short axis \<10 mm). PR: \>=30% decrease under baseline of the sum of diameters of all target measurable lesions. OR=CR+PR.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 2 years

Population: Data for this outcome measure was not collected due to early termination of this study.

The period from study entry until disease progression, death, whichever occurred first as per RECIST version 1.1.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 2 years

Population: Data for this outcome measure was not collected due to early termination of this study.

Time from the first documentation of objective tumor response to objective tumor progression or death due to any cause. DR was calculated for the subgroup of patients with a confirmed objective tumor response. Objective Progression (PD): 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy), with a minimum absolute increase of 5 mm.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 1 year

Population: Data for this outcome measure was not collected due to early termination of this study.

Overall survival (OS) status (alive or not) at 1 year after study entry. The the survival probability at 1 year was summarized as a product limit estimator based on the Kaplan-Meier method to account for censored events.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 2 years

Population: Data for this outcome measure was not collected due to early termination of this study.

OS was the duration from enrollment to death. For participants who are alive, overall survival was censored at the last contact.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 2 years

Population: Data for this outcome measure was not collected due to early termination of this study.

Type of notch genomic alterations identified by NGS assay in patients with NA+ mTNBC

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Day 1 of Cycle 1, 2, 3, and 5

Population: Due to study termination, no PK analyses were performed for this study.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Day 1 of Cycle 1, 2, 3, and 5

Population: Due to study termination, no PD analyses were performed for this study.

Original diagnostic tumor tissue or the most recent metastatic tumor (archival or de novo biopsy), plasma, and peripheral blood samples were collected for biomarker assessments of circulating analytes, immunohistochemistry for notch receptors expression, expression of notch pathway components and modulators, mutational analysis of pathway and disease associated genes.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Day 1 of Cycle 1, 2, 3, and 5

Population: Due to study termination, no PD analyses were performed for this study.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 2 years

Population: The safety analysis set included all enrolled participants who received at least one dose of study medication.

An AE was any untoward medical occurrence without regard to causality in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs were defined as all deaths, regardless of cause, from treatment start until 28 days after the last dose and non-fatal events occurring after treatment start regardless of cause, up until 28 days after the last dose or until start of new anti-cancer treatment, whichever was first.

Outcome measures

Outcome measures
Measure	PF-03084014 n=19 Participants PF-03084014 at the starting dose of 150 mg twice daily (BID) (in the form of one 100-mg and one 50-mg tablet) was administered orally BID continuously in 21-day cycles until disease progression, patient refusal of further treatment, or unacceptable toxicity, whichever occurred first.
Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) Number of Participants with AEs	18 participants
Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) Number of Participants with SAEs	6 participants

SECONDARY outcome

Timeframe: 2 years

Population: The safety analysis set included all enrolled participants who received at least one dose of study medication.

An AE was any untoward medical occurrence without regard to causality in a participant who received study drug. AEs were defined according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.

Outcome measures

Outcome measures
Measure	PF-03084014 n=19 Participants PF-03084014 at the starting dose of 150 mg twice daily (BID) (in the form of one 100-mg and one 50-mg tablet) was administered orally BID continuously in 21-day cycles until disease progression, patient refusal of further treatment, or unacceptable toxicity, whichever occurred first.
Number of Participants With Treatment-Emergent AEs by CTCAE Grade Any AEs, Grade 1	1 participants
Number of Participants With Treatment-Emergent AEs by CTCAE Grade Any AEs, Grade 2	5 participants
Number of Participants With Treatment-Emergent AEs by CTCAE Grade Any AEs, Grade 3	9 participants
Number of Participants With Treatment-Emergent AEs by CTCAE Grade Any AEs, Grade 4	1 participants
Number of Participants With Treatment-Emergent AEs by CTCAE Grade Any AEs, Grade 5	2 participants

SECONDARY outcome

Timeframe: Day 1 of Cycles 1, 2, 3, 4, 5, and subsequent cycles.

Population: The safety analysis set included all enrolled participants who received at least one dose of study medication.

Number of participants with CTCAE version 4.03 grade 1 to 4 hematological test abnormalities.

Outcome measures

Outcome measures
Measure	PF-03084014 n=19 Participants PF-03084014 at the starting dose of 150 mg twice daily (BID) (in the form of one 100-mg and one 50-mg tablet) was administered orally BID continuously in 21-day cycles until disease progression, patient refusal of further treatment, or unacceptable toxicity, whichever occurred first.
Number of Participants With Laboratory Test (Hematology) Abnormalities Anemia	12 participants
Number of Participants With Laboratory Test (Hematology) Abnormalities Lymphocyte count increased	0 participants
Number of Participants With Laboratory Test (Hematology) Abnormalities Lymphopenia	11 participants
Number of Participants With Laboratory Test (Hematology) Abnormalities Neutrophils (absolute)	0 participants
Number of Participants With Laboratory Test (Hematology) Abnormalities Platelets	3 participants
Number of Participants With Laboratory Test (Hematology) Abnormalities White blood cells	4 participants

SECONDARY outcome

Timeframe: Day 1 and Day 15 of Cycles 1, 2, 3, 4, 5, and subsequent cycles up to Cycle 8 and Day 8 of Cycle 1

Population: The safety analysis set included all enrolled participants who received at least one dose of study medication.

Number of participants with CTCAE version 4.03 grade 1 to 4 chemistry test abnormalities

Outcome measures

Outcome measures
Measure	PF-03084014 n=19 Participants PF-03084014 at the starting dose of 150 mg twice daily (BID) (in the form of one 100-mg and one 50-mg tablet) was administered orally BID continuously in 21-day cycles until disease progression, patient refusal of further treatment, or unacceptable toxicity, whichever occurred first.
Number of Participants With Laboratory Test (Chemistry) Abnormalities Hyponatremia	6 participants
Number of Participants With Laboratory Test (Chemistry) Abnormalities Hypophosphatemia	14 participants
Number of Participants With Laboratory Test (Chemistry) Abnormalities Alanine aminotransferase	5 participants
Number of Participants With Laboratory Test (Chemistry) Abnormalities Alkaline phosphatase	6 participants
Number of Participants With Laboratory Test (Chemistry) Abnormalities Aspartate aminotransferase	9 participants
Number of Participants With Laboratory Test (Chemistry) Abnormalities Bilirubin (total)	1 participants
Number of Participants With Laboratory Test (Chemistry) Abnormalities Creatine kinase	1 participants
Number of Participants With Laboratory Test (Chemistry) Abnormalities Creatinine	13 participants
Number of Participants With Laboratory Test (Chemistry) Abnormalities Gamma glutamyl transferase	1 participants
Number of Participants With Laboratory Test (Chemistry) Abnormalities Hypercalcemia	3 participants
Number of Participants With Laboratory Test (Chemistry) Abnormalities Hyperglycemia	13 participants
Number of Participants With Laboratory Test (Chemistry) Abnormalities Hyperkalemia	3 participants
Number of Participants With Laboratory Test (Chemistry) Abnormalities Hypermagnesemia	1 participants
Number of Participants With Laboratory Test (Chemistry) Abnormalities Hypernatremia	0 participants
Number of Participants With Laboratory Test (Chemistry) Abnormalities Hypoalbuminemia	8 participants
Number of Participants With Laboratory Test (Chemistry) Abnormalities Hypocalcemia	4 participants
Number of Participants With Laboratory Test (Chemistry) Abnormalities Hypoglycemia	1 participants
Number of Participants With Laboratory Test (Chemistry) Abnormalities Hypokalemia	5 participants
Number of Participants With Laboratory Test (Chemistry) Abnormalities Hypomagnesemia	3 participants

SECONDARY outcome

Timeframe: Day 1 of Cycle 1

Population: The safety analysis set included all enrolled participants who received at least one dose of study medication.

Number of participants with CTCAE version 4.03 grade 1 to 4 urinalysis test abnormalities for urine protein.

Outcome measures

Outcome measures
Measure	PF-03084014 n=19 Participants PF-03084014 at the starting dose of 150 mg twice daily (BID) (in the form of one 100-mg and one 50-mg tablet) was administered orally BID continuously in 21-day cycles until disease progression, patient refusal of further treatment, or unacceptable toxicity, whichever occurred first.
Number of Participants With Laboratory Test (Urinalysis) Abnormalities	2 participants

SECONDARY outcome

Timeframe: 2 years

Population: Data for this outcome measure was not collected due to early termination of this study.

Number of notch genomic alterations identified by NGS assay in patients with NA+ mTNBC

Outcome measures

Outcome data not reported

Adverse Events

PF-03084014

Serious events: 6 serious events

Other events: 18 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	PF-03084014 n=19 participants at risk PF-03084014 at the starting dose of 150 mg twice daily (BID) (in the form of one 100-mg and one 50-mg tablet) was administered orally BID continuously in 21-day cycles until disease progression, patient refusal of further treatment, or unacceptable toxicity, whichever occurred first.
General disorders Disease progression	5.3% 1/19 • 2 years
General disorders Pyrexia	5.3% 1/19 • 2 years
Infections and infestations Lung infection	5.3% 1/19 • 2 years
Metabolism and nutrition disorders Hypophosphataemia	5.3% 1/19 • 2 years
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Transitional cell carcinoma	5.3% 1/19 • 2 years
Psychiatric disorders Confusional state	10.5% 2/19 • 2 years
Respiratory, thoracic and mediastinal disorders Dyspnoea	5.3% 1/19 • 2 years

Other adverse events

Other adverse events
Measure	PF-03084014 n=19 participants at risk PF-03084014 at the starting dose of 150 mg twice daily (BID) (in the form of one 100-mg and one 50-mg tablet) was administered orally BID continuously in 21-day cycles until disease progression, patient refusal of further treatment, or unacceptable toxicity, whichever occurred first.
Blood and lymphatic system disorders Anaemia	5.3% 1/19 • 2 years
Cardiac disorders Angina pectoris	5.3% 1/19 • 2 years
Ear and labyrinth disorders Vertigo	5.3% 1/19 • 2 years
Eye disorders Eye discharge	5.3% 1/19 • 2 years
Eye disorders Photopsia	5.3% 1/19 • 2 years
Eye disorders Vitreous floaters	5.3% 1/19 • 2 years
Gastrointestinal disorders Abdominal pain	5.3% 1/19 • 2 years
Gastrointestinal disorders Abdominal pain upper	5.3% 1/19 • 2 years
Gastrointestinal disorders Diarrhoea	57.9% 11/19 • 2 years
Gastrointestinal disorders Dry mouth	10.5% 2/19 • 2 years
Gastrointestinal disorders Dyspepsia	15.8% 3/19 • 2 years
Gastrointestinal disorders Nausea	42.1% 8/19 • 2 years
Gastrointestinal disorders Oral pain	5.3% 1/19 • 2 years
Gastrointestinal disorders Stomatitis	10.5% 2/19 • 2 years
Gastrointestinal disorders Vomiting	36.8% 7/19 • 2 years
General disorders Asthenia	5.3% 1/19 • 2 years
General disorders Chest pain	10.5% 2/19 • 2 years
General disorders Fatigue	42.1% 8/19 • 2 years
General disorders Mucosal inflammation	15.8% 3/19 • 2 years
General disorders Oedema peripheral	5.3% 1/19 • 2 years
General disorders Pyrexia	26.3% 5/19 • 2 years
Infections and infestations Conjunctivitis	15.8% 3/19 • 2 years
Infections and infestations Gastroenteritis viral	5.3% 1/19 • 2 years
Infections and infestations Nasopharyngitis	5.3% 1/19 • 2 years
Infections and infestations Pharyngitis	5.3% 1/19 • 2 years
Infections and infestations Respiratory tract infection	5.3% 1/19 • 2 years
Infections and infestations Urinary tract infection	10.5% 2/19 • 2 years
Investigations Alanine aminotransferase increased	5.3% 1/19 • 2 years
Investigations Aspartate aminotransferase increased	15.8% 3/19 • 2 years
Investigations Blood alkaline phosphatase increased	5.3% 1/19 • 2 years
Investigations Blood chloride decreased	5.3% 1/19 • 2 years
Investigations Blood creatinine increased	5.3% 1/19 • 2 years
Investigations Carbon dioxide increased	10.5% 2/19 • 2 years
Investigations Electrocardiogram QT prolonged	5.3% 1/19 • 2 years
Investigations Glomerular filtration rate decreased	5.3% 1/19 • 2 years
Investigations Protein total increased	5.3% 1/19 • 2 years
Investigations Transaminases increased	5.3% 1/19 • 2 years
Investigations Weight decreased	10.5% 2/19 • 2 years
Metabolism and nutrition disorders Decreased appetite	10.5% 2/19 • 2 years
Metabolism and nutrition disorders Hypercalcaemia	5.3% 1/19 • 2 years
Metabolism and nutrition disorders Hyperglycaemia	5.3% 1/19 • 2 years
Metabolism and nutrition disorders Hypoalbuminaemia	5.3% 1/19 • 2 years
Metabolism and nutrition disorders Hypocalcaemia	5.3% 1/19 • 2 years
Metabolism and nutrition disorders Hypokalaemia	15.8% 3/19 • 2 years
Metabolism and nutrition disorders Hypophosphataemia	36.8% 7/19 • 2 years
Metabolism and nutrition disorders Hypouricaemia	5.3% 1/19 • 2 years
Musculoskeletal and connective tissue disorders Bone pain	5.3% 1/19 • 2 years
Musculoskeletal and connective tissue disorders Flank pain	5.3% 1/19 • 2 years
Musculoskeletal and connective tissue disorders Muscular weakness	5.3% 1/19 • 2 years
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	5.3% 1/19 • 2 years
Musculoskeletal and connective tissue disorders Myalgia	10.5% 2/19 • 2 years
Musculoskeletal and connective tissue disorders Neck pain	5.3% 1/19 • 2 years
Musculoskeletal and connective tissue disorders Pain in extremity	5.3% 1/19 • 2 years
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour exudation	5.3% 1/19 • 2 years
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour haemorrhage	5.3% 1/19 • 2 years
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	5.3% 1/19 • 2 years
Nervous system disorders Balance disorder	5.3% 1/19 • 2 years
Nervous system disorders Dizziness	5.3% 1/19 • 2 years
Nervous system disorders Dysgeusia	10.5% 2/19 • 2 years
Nervous system disorders Headache	5.3% 1/19 • 2 years
Nervous system disorders Lethargy	10.5% 2/19 • 2 years
Nervous system disorders Peripheral motor neuropathy	5.3% 1/19 • 2 years
Psychiatric disorders Anxiety	5.3% 1/19 • 2 years
Psychiatric disorders Depression	5.3% 1/19 • 2 years
Renal and urinary disorders Haematuria	5.3% 1/19 • 2 years
Respiratory, thoracic and mediastinal disorders Cough	26.3% 5/19 • 2 years
Respiratory, thoracic and mediastinal disorders Nasal congestion	5.3% 1/19 • 2 years
Respiratory, thoracic and mediastinal disorders Productive cough	5.3% 1/19 • 2 years
Respiratory, thoracic and mediastinal disorders Upper respiratory tract inflammation	5.3% 1/19 • 2 years
Skin and subcutaneous tissue disorders Nail dystrophy	5.3% 1/19 • 2 years
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	5.3% 1/19 • 2 years
Skin and subcutaneous tissue disorders Rash	15.8% 3/19 • 2 years
Skin and subcutaneous tissue disorders Rash macular	5.3% 1/19 • 2 years
Skin and subcutaneous tissue disorders Urticaria	5.3% 1/19 • 2 years

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Publication restrictions are in place

Restriction type: OTHER