Trial Outcomes & Findings for Cyclin Dependent Kinase (CDK)4/6 Inhibitor, PD0332991 in Advanced Non-small Cell Lung Cancer NSCLC. (NCT NCT01291017)

NCT ID: NCT01291017

Last Updated: 2016-05-13

Results Overview

Response is a decrease in the sum of the longest diameters of the target lesions by more than 30% compared to the baseline.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 19 participants
• Primary outcome timeframe: 6 months
• Results posted on: 2016-05-13

Participant Flow

Participant milestones

Measure	PD0332991 PD0332991 125 mg PO days 1 - 21 PD0332991: PD0332991 125 mg PO days 1 - 21
Overall Study STARTED	19
Overall Study COMPLETED	14
Overall Study NOT COMPLETED	5

Reasons for withdrawal

Measure	PD0332991 PD0332991 125 mg PO days 1 - 21 PD0332991: PD0332991 125 mg PO days 1 - 21
Overall Study Lost to Follow-up	2
Overall Study Withdrawal by Subject	3

Baseline Characteristics

Cyclin Dependent Kinase (CDK)4/6 Inhibitor, PD0332991 in Advanced Non-small Cell Lung Cancer NSCLC.

Baseline characteristics by cohort

Measure	PD0332991 n=19 Participants PD0332991 125 mg PO days 1 - 21 PD0332991: PD0332991 125 mg PO days 1 - 21
Age, Categorical <=18 years	0 Participants n=93 Participants
Age, Categorical Between 18 and 65 years	7 Participants n=93 Participants
Age, Categorical >=65 years	12 Participants n=93 Participants
Sex: Female, Male Female	9 Participants n=93 Participants
Sex: Female, Male Male	10 Participants n=93 Participants
Region of Enrollment United States	19 participants n=93 Participants

PRIMARY outcome

Timeframe: 6 months

Response is a decrease in the sum of the longest diameters of the target lesions by more than 30% compared to the baseline.

Outcome measures

Measure	PD0332991 n=16 Participants PD0332991 125 mg PO days 1 - 21 PD0332991: PD0332991 125 mg PO days 1 - 21
Tumor Response by Direct RECIST Measurement	0 participants

SECONDARY outcome

Timeframe: 14 months

Median overall survival

Outcome measures

Measure	PD0332991 n=14 Participants PD0332991 125 mg PO days 1 - 21 PD0332991: PD0332991 125 mg PO days 1 - 21
Overall Survival	20.3 weeks Standard Error 1.7

SECONDARY outcome

Timeframe: 12 months

Median progression-free survival.

Outcome measures

Measure	PD0332991 n=16 Participants PD0332991 125 mg PO days 1 - 21 PD0332991: PD0332991 125 mg PO days 1 - 21
Progression-free Survival	8 Weeks Standard Error 0.7

SECONDARY outcome

Timeframe: 6 months

Population: 4 of the 16 samples were tested by protein immunoblot (Western blot), and due to the test not being sensitive enough to detect p16, phosphorylated RB or cyclin D1 protein bands in any of the samples, the decision was made not to purse this testing any further.

Plasma levels of p16, phosphorylated RB and cyclin d1 in blood.

Outcome measures

Measure	PD0332991 n=4 Participants PD0332991 125 mg PO days 1 - 21 PD0332991: PD0332991 125 mg PO days 1 - 21
Plasma Levels	NA Arbitrary Units 4 of the 16 samples were tested by Western blot, and due to the test not being sensitive enough to detect p16, phosphorylated RB or cyclin D1 protein bands in any of the samples, the decision was made not to pursue this testing any further.

SECONDARY outcome

Timeframe: 24 months

The number of all toxicities and grades 3 and 4 (per CTCAE v3.0) toxicities that occured during the administration of the drug and during the follow up period.

Outcome measures

Measure	PD0332991 n=16 Participants PD0332991 125 mg PO days 1 - 21 PD0332991: PD0332991 125 mg PO days 1 - 21
Grade of Study Drug Toxicity Grade 3 and 4 Toxicities	9 Events
Grade of Study Drug Toxicity All Toxicities (Grades 1 - 5)	86 Events

Adverse Events

PD0332991

Serious events: 2 serious events

Other events: 16 other events

Deaths: 0 deaths

Serious adverse events

Measure	PD0332991 n=19 participants at risk PD0332991 125 mg PO days 1 - 21 PD0332991: PD0332991 125 mg PO days 1 - 21
Musculoskeletal and connective tissue disorders Arthralgia	5.3% 1/19 • Number of events 1 • Adverse events were collected from the signing of the Informed Consent Form through 30 days after the last dose of study drug (approximately 20 weeks). All adverse events were assessed using the results of routine bloodwork, imaging or by a qualified healthcare provider.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	5.3% 1/19 • Number of events 1 • Adverse events were collected from the signing of the Informed Consent Form through 30 days after the last dose of study drug (approximately 20 weeks). All adverse events were assessed using the results of routine bloodwork, imaging or by a qualified healthcare provider.
Investigations Aspartate aminotransferase	5.3% 1/19 • Number of events 1 • Adverse events were collected from the signing of the Informed Consent Form through 30 days after the last dose of study drug (approximately 20 weeks). All adverse events were assessed using the results of routine bloodwork, imaging or by a qualified healthcare provider.
Investigations Alanine aminotransferase	5.3% 1/19 • Number of events 1 • Adverse events were collected from the signing of the Informed Consent Form through 30 days after the last dose of study drug (approximately 20 weeks). All adverse events were assessed using the results of routine bloodwork, imaging or by a qualified healthcare provider.
Renal and urinary disorders Acute kidney injury	5.3% 1/19 • Number of events 1 • Adverse events were collected from the signing of the Informed Consent Form through 30 days after the last dose of study drug (approximately 20 weeks). All adverse events were assessed using the results of routine bloodwork, imaging or by a qualified healthcare provider.
Investigations Creatinine increased	5.3% 1/19 • Number of events 1 • Adverse events were collected from the signing of the Informed Consent Form through 30 days after the last dose of study drug (approximately 20 weeks). All adverse events were assessed using the results of routine bloodwork, imaging or by a qualified healthcare provider.
Blood and lymphatic system disorders Neutrophil count decreased	5.3% 1/19 • Number of events 1 • Adverse events were collected from the signing of the Informed Consent Form through 30 days after the last dose of study drug (approximately 20 weeks). All adverse events were assessed using the results of routine bloodwork, imaging or by a qualified healthcare provider.
Investigations CPK increased	5.3% 1/19 • Number of events 1 • Adverse events were collected from the signing of the Informed Consent Form through 30 days after the last dose of study drug (approximately 20 weeks). All adverse events were assessed using the results of routine bloodwork, imaging or by a qualified healthcare provider.

Other adverse events

Measure	PD0332991 n=19 participants at risk PD0332991 125 mg PO days 1 - 21 PD0332991: PD0332991 125 mg PO days 1 - 21
Gastrointestinal disorders Abdominal pain	15.8% 3/19 • Number of events 3 • Adverse events were collected from the signing of the Informed Consent Form through 30 days after the last dose of study drug (approximately 20 weeks). All adverse events were assessed using the results of routine bloodwork, imaging or by a qualified healthcare provider.
Investigations Alkaline phosphatase increased	5.3% 1/19 • Number of events 1 • Adverse events were collected from the signing of the Informed Consent Form through 30 days after the last dose of study drug (approximately 20 weeks). All adverse events were assessed using the results of routine bloodwork, imaging or by a qualified healthcare provider.
Blood and lymphatic system disorders Anemia	21.1% 4/19 • Number of events 4 • Adverse events were collected from the signing of the Informed Consent Form through 30 days after the last dose of study drug (approximately 20 weeks). All adverse events were assessed using the results of routine bloodwork, imaging or by a qualified healthcare provider.
Metabolism and nutrition disorders Anorexia	21.1% 4/19 • Number of events 4 • Adverse events were collected from the signing of the Informed Consent Form through 30 days after the last dose of study drug (approximately 20 weeks). All adverse events were assessed using the results of routine bloodwork, imaging or by a qualified healthcare provider.
Psychiatric disorders Anxiety	10.5% 2/19 • Number of events 2 • Adverse events were collected from the signing of the Informed Consent Form through 30 days after the last dose of study drug (approximately 20 weeks). All adverse events were assessed using the results of routine bloodwork, imaging or by a qualified healthcare provider.
Musculoskeletal and connective tissue disorders Back pain	5.3% 1/19 • Number of events 1 • Adverse events were collected from the signing of the Informed Consent Form through 30 days after the last dose of study drug (approximately 20 weeks). All adverse events were assessed using the results of routine bloodwork, imaging or by a qualified healthcare provider.
Gastrointestinal disorders Bloating	5.3% 1/19 • Number of events 1 • Adverse events were collected from the signing of the Informed Consent Form through 30 days after the last dose of study drug (approximately 20 weeks). All adverse events were assessed using the results of routine bloodwork, imaging or by a qualified healthcare provider.
Eye disorders Blurred vision	10.5% 2/19 • Number of events 2 • Adverse events were collected from the signing of the Informed Consent Form through 30 days after the last dose of study drug (approximately 20 weeks). All adverse events were assessed using the results of routine bloodwork, imaging or by a qualified healthcare provider.
Musculoskeletal and connective tissue disorders Bone pain	5.3% 1/19 • Number of events 1 • Adverse events were collected from the signing of the Informed Consent Form through 30 days after the last dose of study drug (approximately 20 weeks). All adverse events were assessed using the results of routine bloodwork, imaging or by a qualified healthcare provider.
Psychiatric disorders Confusion	5.3% 1/19 • Number of events 1 • Adverse events were collected from the signing of the Informed Consent Form through 30 days after the last dose of study drug (approximately 20 weeks). All adverse events were assessed using the results of routine bloodwork, imaging or by a qualified healthcare provider.
Gastrointestinal disorders Constipation	26.3% 5/19 • Number of events 5 • Adverse events were collected from the signing of the Informed Consent Form through 30 days after the last dose of study drug (approximately 20 weeks). All adverse events were assessed using the results of routine bloodwork, imaging or by a qualified healthcare provider.
Respiratory, thoracic and mediastinal disorders Cough	15.8% 3/19 • Number of events 3 • Adverse events were collected from the signing of the Informed Consent Form through 30 days after the last dose of study drug (approximately 20 weeks). All adverse events were assessed using the results of routine bloodwork, imaging or by a qualified healthcare provider.
Metabolism and nutrition disorders Dehydration	5.3% 1/19 • Number of events 1 • Adverse events were collected from the signing of the Informed Consent Form through 30 days after the last dose of study drug (approximately 20 weeks). All adverse events were assessed using the results of routine bloodwork, imaging or by a qualified healthcare provider.
Psychiatric disorders Depression	5.3% 1/19 • Number of events 1 • Adverse events were collected from the signing of the Informed Consent Form through 30 days after the last dose of study drug (approximately 20 weeks). All adverse events were assessed using the results of routine bloodwork, imaging or by a qualified healthcare provider.
Gastrointestinal disorders Diarrhea	10.5% 2/19 • Number of events 2 • Adverse events were collected from the signing of the Informed Consent Form through 30 days after the last dose of study drug (approximately 20 weeks). All adverse events were assessed using the results of routine bloodwork, imaging or by a qualified healthcare provider.
Nervous system disorders Dizziness	15.8% 3/19 • Number of events 3 • Adverse events were collected from the signing of the Informed Consent Form through 30 days after the last dose of study drug (approximately 20 weeks). All adverse events were assessed using the results of routine bloodwork, imaging or by a qualified healthcare provider.
Nervous system disorders Dysgeusia	10.5% 2/19 • Number of events 2 • Adverse events were collected from the signing of the Informed Consent Form through 30 days after the last dose of study drug (approximately 20 weeks). All adverse events were assessed using the results of routine bloodwork, imaging or by a qualified healthcare provider.
Respiratory, thoracic and mediastinal disorders Dyspnea	10.5% 2/19 • Number of events 2 • Adverse events were collected from the signing of the Informed Consent Form through 30 days after the last dose of study drug (approximately 20 weeks). All adverse events were assessed using the results of routine bloodwork, imaging or by a qualified healthcare provider.
General disorders Edema limbs	5.3% 1/19 • Number of events 1 • Adverse events were collected from the signing of the Informed Consent Form through 30 days after the last dose of study drug (approximately 20 weeks). All adverse events were assessed using the results of routine bloodwork, imaging or by a qualified healthcare provider.
Respiratory, thoracic and mediastinal disorders Epistaxis	10.5% 2/19 • Number of events 2 • Adverse events were collected from the signing of the Informed Consent Form through 30 days after the last dose of study drug (approximately 20 weeks). All adverse events were assessed using the results of routine bloodwork, imaging or by a qualified healthcare provider.
Injury, poisoning and procedural complications Fall	5.3% 1/19 • Number of events 1 • Adverse events were collected from the signing of the Informed Consent Form through 30 days after the last dose of study drug (approximately 20 weeks). All adverse events were assessed using the results of routine bloodwork, imaging or by a qualified healthcare provider.
General disorders Fatigue	47.4% 9/19 • Number of events 13 • Adverse events were collected from the signing of the Informed Consent Form through 30 days after the last dose of study drug (approximately 20 weeks). All adverse events were assessed using the results of routine bloodwork, imaging or by a qualified healthcare provider.
Gastrointestinal disorders Gastroesophageal reflux disease	5.3% 1/19 • Number of events 1 • Adverse events were collected from the signing of the Informed Consent Form through 30 days after the last dose of study drug (approximately 20 weeks). All adverse events were assessed using the results of routine bloodwork, imaging or by a qualified healthcare provider.
General disorders General disorders and administration site conditions - Other, specify: Chills	5.3% 1/19 • Number of events 1 • Adverse events were collected from the signing of the Informed Consent Form through 30 days after the last dose of study drug (approximately 20 weeks). All adverse events were assessed using the results of routine bloodwork, imaging or by a qualified healthcare provider.
Nervous system disorders Headache	10.5% 2/19 • Number of events 2 • Adverse events were collected from the signing of the Informed Consent Form through 30 days after the last dose of study drug (approximately 20 weeks). All adverse events were assessed using the results of routine bloodwork, imaging or by a qualified healthcare provider.
Respiratory, thoracic and mediastinal disorders Hoarseness	5.3% 1/19 • Number of events 2 • Adverse events were collected from the signing of the Informed Consent Form through 30 days after the last dose of study drug (approximately 20 weeks). All adverse events were assessed using the results of routine bloodwork, imaging or by a qualified healthcare provider.
Vascular disorders Hot flashes	5.3% 1/19 • Number of events 1 • Adverse events were collected from the signing of the Informed Consent Form through 30 days after the last dose of study drug (approximately 20 weeks). All adverse events were assessed using the results of routine bloodwork, imaging or by a qualified healthcare provider.
Respiratory, thoracic and mediastinal disorders Laryngeal hemorrhage	10.5% 2/19 • Number of events 2 • Adverse events were collected from the signing of the Informed Consent Form through 30 days after the last dose of study drug (approximately 20 weeks). All adverse events were assessed using the results of routine bloodwork, imaging or by a qualified healthcare provider.
Respiratory, thoracic and mediastinal disorders Laryngeal inflammation	5.3% 1/19 • Number of events 1 • Adverse events were collected from the signing of the Informed Consent Form through 30 days after the last dose of study drug (approximately 20 weeks). All adverse events were assessed using the results of routine bloodwork, imaging or by a qualified healthcare provider.
Gastrointestinal disorders Mucositis oral	31.6% 6/19 • Number of events 8 • Adverse events were collected from the signing of the Informed Consent Form through 30 days after the last dose of study drug (approximately 20 weeks). All adverse events were assessed using the results of routine bloodwork, imaging or by a qualified healthcare provider.
Musculoskeletal and connective tissue disorders Muscle weakness lower limb	5.3% 1/19 • Number of events 1 • Adverse events were collected from the signing of the Informed Consent Form through 30 days after the last dose of study drug (approximately 20 weeks). All adverse events were assessed using the results of routine bloodwork, imaging or by a qualified healthcare provider.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other, specify: Body aches	5.3% 1/19 • Number of events 1 • Adverse events were collected from the signing of the Informed Consent Form through 30 days after the last dose of study drug (approximately 20 weeks). All adverse events were assessed using the results of routine bloodwork, imaging or by a qualified healthcare provider.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other, specify: Muscle cramps	10.5% 2/19 • Number of events 2 • Adverse events were collected from the signing of the Informed Consent Form through 30 days after the last dose of study drug (approximately 20 weeks). All adverse events were assessed using the results of routine bloodwork, imaging or by a qualified healthcare provider.
Respiratory, thoracic and mediastinal disorders Nasal congestion	5.3% 1/19 • Number of events 1 • Adverse events were collected from the signing of the Informed Consent Form through 30 days after the last dose of study drug (approximately 20 weeks). All adverse events were assessed using the results of routine bloodwork, imaging or by a qualified healthcare provider.
Gastrointestinal disorders Nausea	36.8% 7/19 • Number of events 10 • Adverse events were collected from the signing of the Informed Consent Form through 30 days after the last dose of study drug (approximately 20 weeks). All adverse events were assessed using the results of routine bloodwork, imaging or by a qualified healthcare provider.
Blood and lymphatic system disorders Neutrophil count decreased	26.3% 5/19 • Number of events 7 • Adverse events were collected from the signing of the Informed Consent Form through 30 days after the last dose of study drug (approximately 20 weeks). All adverse events were assessed using the results of routine bloodwork, imaging or by a qualified healthcare provider.
General disorders Non-cardiac chest pain	5.3% 1/19 • Number of events 1 • Adverse events were collected from the signing of the Informed Consent Form through 30 days after the last dose of study drug (approximately 20 weeks). All adverse events were assessed using the results of routine bloodwork, imaging or by a qualified healthcare provider.
General disorders Pain	10.5% 2/19 • Number of events 5 • Adverse events were collected from the signing of the Informed Consent Form through 30 days after the last dose of study drug (approximately 20 weeks). All adverse events were assessed using the results of routine bloodwork, imaging or by a qualified healthcare provider.
Skin and subcutaneous tissue disorders Photosensitivity	5.3% 1/19 • Number of events 1 • Adverse events were collected from the signing of the Informed Consent Form through 30 days after the last dose of study drug (approximately 20 weeks). All adverse events were assessed using the results of routine bloodwork, imaging or by a qualified healthcare provider.
Blood and lymphatic system disorders Platelet count decreased	21.1% 4/19 • Number of events 4 • Adverse events were collected from the signing of the Informed Consent Form through 30 days after the last dose of study drug (approximately 20 weeks). All adverse events were assessed using the results of routine bloodwork, imaging or by a qualified healthcare provider.
Respiratory, thoracic and mediastinal disorders Productive cough	5.3% 1/19 • Number of events 2 • Adverse events were collected from the signing of the Informed Consent Form through 30 days after the last dose of study drug (approximately 20 weeks). All adverse events were assessed using the results of routine bloodwork, imaging or by a qualified healthcare provider.
General disorders Pruritus	5.3% 1/19 • Number of events 2 • Adverse events were collected from the signing of the Informed Consent Form through 30 days after the last dose of study drug (approximately 20 weeks). All adverse events were assessed using the results of routine bloodwork, imaging or by a qualified healthcare provider.
Psychiatric disorders Psychiatric disorders - Other, specify: Mood changes	10.5% 2/19 • Number of events 2 • Adverse events were collected from the signing of the Informed Consent Form through 30 days after the last dose of study drug (approximately 20 weeks). All adverse events were assessed using the results of routine bloodwork, imaging or by a qualified healthcare provider.
Skin and subcutaneous tissue disorders Rash maculo-papular	10.5% 2/19 • Number of events 2 • Adverse events were collected from the signing of the Informed Consent Form through 30 days after the last dose of study drug (approximately 20 weeks). All adverse events were assessed using the results of routine bloodwork, imaging or by a qualified healthcare provider.
Respiratory, thoracic and mediastinal disorders Sore throat	10.5% 2/19 • Number of events 2 • Adverse events were collected from the signing of the Informed Consent Form through 30 days after the last dose of study drug (approximately 20 weeks). All adverse events were assessed using the results of routine bloodwork, imaging or by a qualified healthcare provider.
Nervous system disorders Tremor	5.3% 1/19 • Number of events 1 • Adverse events were collected from the signing of the Informed Consent Form through 30 days after the last dose of study drug (approximately 20 weeks). All adverse events were assessed using the results of routine bloodwork, imaging or by a qualified healthcare provider.
Respiratory, thoracic and mediastinal disorders Upper respiratory infection	5.3% 1/19 • Number of events 1 • Adverse events were collected from the signing of the Informed Consent Form through 30 days after the last dose of study drug (approximately 20 weeks). All adverse events were assessed using the results of routine bloodwork, imaging or by a qualified healthcare provider.
Ear and labyrinth disorders Vertigo	5.3% 1/19 • Number of events 1 • Adverse events were collected from the signing of the Informed Consent Form through 30 days after the last dose of study drug (approximately 20 weeks). All adverse events were assessed using the results of routine bloodwork, imaging or by a qualified healthcare provider.
Gastrointestinal disorders Vomiting	31.6% 6/19 • Number of events 8 • Adverse events were collected from the signing of the Informed Consent Form through 30 days after the last dose of study drug (approximately 20 weeks). All adverse events were assessed using the results of routine bloodwork, imaging or by a qualified healthcare provider.
Eye disorders Watering eyes	5.3% 1/19 • Number of events 1 • Adverse events were collected from the signing of the Informed Consent Form through 30 days after the last dose of study drug (approximately 20 weeks). All adverse events were assessed using the results of routine bloodwork, imaging or by a qualified healthcare provider.
Respiratory, thoracic and mediastinal disorders Wheezing	5.3% 1/19 • Number of events 1 • Adverse events were collected from the signing of the Informed Consent Form through 30 days after the last dose of study drug (approximately 20 weeks). All adverse events were assessed using the results of routine bloodwork, imaging or by a qualified healthcare provider.
Blood and lymphatic system disorders White blood cell decreased	10.5% 2/19 • Number of events 2 • Adverse events were collected from the signing of the Informed Consent Form through 30 days after the last dose of study drug (approximately 20 weeks). All adverse events were assessed using the results of routine bloodwork, imaging or by a qualified healthcare provider.

Additional Information

Priya K Gopalan, MD

University of Florida

Phone: 352-273-8699

Email: gopalpk@ufl.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place