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A Study of PD 0332991 in Patients With Recurrent Rb Positive Glioblastoma (PD0332991)

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ClinicalTrials.gov Identifier: NCT01227434
Recruitment Status : Terminated
First Posted : October 25, 2010
Results First Posted : June 12, 2015
Last Update Posted : July 17, 2015
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
University of California, San Francisco

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Glioblastoma
Gliosarcoma
Anaplastic Astrocytoma
Interventions Drug: PD 0332991 (pre-surgery)
Drug: PD 0332991
Procedure: Resection as clinical care
Enrollment 23
Recruitment Details  
Pre-assignment Details Of 23 participants consented, 1 was found ineligible prior to randomization
Arm/Group Title Surgical Group Non-surgical Group
Hide Arm/Group Description PD 0332991 125 mg daily for 7 days prior to an indicated, surgical resection for progression, and resume drug at the same dose after recovery from surgery on a repeating schedule of 21 consecutive days of drug followed by a 7 day break off therapy (cycle length is 28 days). Treatment repeated every 28 days, and in the absence of disease progression patients may receive treatment for 12 cycles. At that time patients given the option to continue on study past 12 cycles, up to a maximum of 24 cycles. Patients not in need of surgery treated with PD 0332991 at a dose of 125 mg daily for 21 consecutive days followed by a 7 day break off therapy (cycle length is 28 days). Treatment repeated every 28 days, and in the absence of disease progression patients may receive treatment for 12 cycles. At that time patients given the option to continue on study past 12 cycles, up to a maximum of 24 cycles.
Period Title: Overall Study
Started 6 16
Completed 6 16
Not Completed 0 0
Arm/Group Title Surgical Group Non-surgical Group Total
Hide Arm/Group Description PD 0332991 125 mg daily for 7 days prior to an indicated, intended surgical resection for progression, and then resume drug at the same dose after recovery from surgery on a repeating schedule of 21 consecutive days of drug followed by a 7 day break off therapy (cycle length is 28 days). Treatment repeated every 28 days, and in the absence of disease progression patients may receive treatment for 12 cycles. At that time patients given the option to continue on study past 12 cycles, up to a maximum of 24 cycles. Patients not in need of surgery treated with PD 0332991 125 mg daily for 21 consecutive days followed by a 7 day break off therapy (cycle length is 28 days). Treatment repeated every 28 days, and in the absence of disease progression patients may receive treatment for 12 cycles. At that time patients given the option to continue on study past 12 cycles, up to a maximum of 24 cycles. Total of all reporting groups
Overall Number of Baseline Participants 6 16 22
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 16 participants 22 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
5
  83.3%
14
  87.5%
19
  86.4%
>=65 years
1
  16.7%
2
  12.5%
3
  13.6%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 16 participants 22 participants
Female
3
  50.0%
7
  43.8%
10
  45.5%
Male
3
  50.0%
9
  56.3%
12
  54.5%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 6 participants 16 participants 22 participants
6 16 22
1.Primary Outcome
Title Progression Free Survival
Hide Description Efficacy of the small molecule CDK4/6 inhibitor PD 0332991 in patients with recurrent glioblastoma multiforme or gliosarcoma who are Rb positive was measured by progression free survival. A total of 30 patients was intended to be treated; up to 15 patients were to undergo a planned, intended surgical resection and receive drug for 7 days prior to surgery, followed by drug after recovery from surgery; and up to 15 patients were to receive drug without a planned surgical procedure.
Time Frame up to 142 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Surgical Group Non-surgical Group
Hide Arm/Group Description:
PD 0332991 125 mg daily for 7 days prior to an indicated, intended surgical resection for progression, and then resume drug at the same dose after recovery from surgery on a repeating schedule of 21 consecutive days of drug followed by a 7 day break off therapy (cycle length is 28 days). Treatment repeated every 28 days, and in the absence of disease progression patients may receive treatment for 12 cycles. At that time patients given the option to continue on study past 12 cycles, up to a maximum of 24 cycles.
Patients not requiring surgery treated with PD 0332991 125 mg daily for 21 consecutive days followed by a 7 day break off therapy (cycle length is 28 days). Treatment repeated every 28 days, and in the absence of disease progression patients may receive treatment for 12 cycles. At that time patients given the option to continue on study past 12 cycles, up to a maximum of 24 cycles.
Overall Number of Participants Analyzed 6 16
Mean (Full Range)
Unit of Measure: weeks
4
(3 to 6)
14
(1 to 142)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Surgical Group, Non-surgical Group
Comments Compared to historical estimates of PFS-6 months. With 30 patients, there would be 90% power to detect an improvement in the PFS-6 months rate from 10% (historical estimate) to 30% based on a one-sided exact test with alpha=0.1.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.10
Comments [Not Specified]
Method Exact binomial distribution
Comments [Not Specified]
Method of Estimation Estimation Parameter Exact binomial distribution
Estimated Value 0.10
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Number of Participants With Adverse Events as a Measure of Safety and Tolerability
Hide Description The number of participants with protocol related toxicity described by CTCAE version 4.0
Time Frame 1-2 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Surgical Group Non-surgical Group
Hide Arm/Group Description:
PD 0332991 at a dose of 125 mg daily for 7 days prior to an indicated, intended surgical resection for progression, and then resume drug at the same dose after recovery from surgery on a repeating schedule of 21 consecutive days of drug followed by a 7 day break off therapy (cycle length is 28 days). Treatment repeated every 28 days, and in the absence of disease progression patients may receive treatment for 12 cycles. At that time patients given the option to continue on study past 12 cycles, up to a maximum of 24 cycles.
Patients not requiring surgery treated with PD 0332991 125 mg daily for 21 consecutive days followed by a 7 day break off therapy (cycle length is 28 days). Treatment repeated every 28 days, and in the absence of disease progression patients may receive treatment for 12 cycles. At that time patients given the option to continue on study past 12 cycles, up to a maximum of 24 cycles.
Overall Number of Participants Analyzed 6 16
Measure Type: Number
Unit of Measure: participants
6 16
Time Frame 3 years
Adverse Event Reporting Description Adverse events were collected from date of first drug, until 30 days following completion of study treatment
 
Arm/Group Title Surgical Group Non-surgical Group
Hide Arm/Group Description PD 0332991 125 mg daily for 7 days prior to an indicated, intended surgical resection for progression, and then resume drug at the same dose after recovery from surgery on a repeating schedule of 21 consecutive days of drug followed by a 7 day break off therapy (cycle length is 28 days). Treatment repeated every 28 days, and in the absence of disease progression patients may receive treatment for 12 cycles. At that time patients given the option to continue on study past 12 cycles, up to a maximum of 24 cycles. Patients not requiring surgery treated with PD 0332991 125 mg daily for 21 consecutive days followed by a 7 day break off therapy (cycle length is 28 days). Treatment repeated every 28 days, and in the absence of disease progression patients may receive treatment for 12 cycles. At that time patients given the option to continue on study past 12 cycles, up to a maximum of 24 cycles.
All-Cause Mortality
Surgical Group Non-surgical Group
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Surgical Group Non-surgical Group
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   5/6 (83.33%)      4/16 (25.00%)    
Gastrointestinal disorders     
Abdominal Pain  [1]  0/6 (0.00%)  0 1/16 (6.25%)  1
Mucositis  [2]  0/6 (0.00%)  0 1/16 (6.25%)  1
General disorders     
Death NOS  [1]  1/6 (16.67%)  1 2/16 (12.50%)  2
Infections and infestations     
Meningitis  [1]  1/6 (16.67%)  1 0/16 (0.00%)  0
Wound Infection  [1]  1/6 (16.67%)  2 0/16 (0.00%)  0
Lung Infection  [3]  0/6 (0.00%)  0 1/16 (6.25%)  1
Musculoskeletal and connective tissue disorders     
Muscle Weakness  [1]  1/6 (16.67%)  1 0/16 (0.00%)  0
Nervous system disorders     
Cerebral Spinal Fluid Leakage  [1]  1/6 (16.67%)  1 0/16 (0.00%)  0
Cognitive disturbance  [1]  1/6 (16.67%)  1 0/16 (0.00%)  0
Headache  [1]  2/6 (33.33%)  2 1/16 (6.25%)  1
Seizure  [1]  2/6 (33.33%)  2 0/16 (0.00%)  0
Peripheral Motor Neuropathy  [1]  0/6 (0.00%)  0 1/16 (6.25%)  1
Indicates events were collected by systematic assessment
[1]
Not related to study drug
[2]
Possibly related
[3]
Probably related
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Surgical Group Non-surgical Group
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/6 (66.67%)      15/16 (93.75%)    
Cardiac disorders     
Atrial fibrillation   0/6 (0.00%)  1/16 (6.25%) 
Sinus tachycardia   1/6 (16.67%)  2/16 (12.50%) 
Ear and labyrinth disorders     
Tinnitus   1/6 (16.67%)  0/16 (0.00%) 
Endocrine disorders     
Cushingoid   0/6 (0.00%)  1/16 (6.25%) 
Eye disorders     
Blurred vision   1/6 (16.67%)  0/16 (0.00%) 
Right upper quadrant defect   1/6 (16.67%)  0/16 (0.00%) 
Gastrointestinal disorders     
Abdominal pain   0/6 (0.00%)  1/16 (6.25%) 
Constipation   0/6 (0.00%)  3/16 (18.75%) 
Diarrhea   1/6 (16.67%)  0/16 (0.00%) 
Dyspepsia   0/6 (0.00%)  1/16 (6.25%) 
Stool urgency   0/6 (0.00%)  1/16 (6.25%) 
Food craving   0/6 (0.00%)  1/16 (6.25%) 
Stomach discomfort   1/6 (16.67%)  0/16 (0.00%) 
Hemorrhoidal hemorrhage   0/6 (0.00%)  1/16 (6.25%) 
Mucositis Oral   0/6 (0.00%)  4/16 (25.00%) 
Nausea   1/6 (16.67%)  3/16 (18.75%) 
Vomiting   0/6 (0.00%)  2/16 (12.50%) 
General disorders     
Death NOS   1/6 (16.67%)  2/16 (12.50%) 
Edema limbs   1/6 (16.67%)  1/16 (6.25%) 
Fatigue   2/6 (33.33%)  7/16 (43.75%) 
Flu like symptoms   0/6 (0.00%)  1/16 (6.25%) 
Gait disturbance   0/6 (0.00%)  2/16 (12.50%) 
Groin pain   0/6 (0.00%)  2/16 (12.50%) 
Infections and infestations     
Bronchial infection   0/6 (0.00%)  1/16 (6.25%) 
Eye infection   0/6 (0.00%)  1/16 (6.25%) 
Lung infection   0/6 (0.00%)  1/16 (6.25%) 
Meningitis   1/6 (16.67%)  0/16 (0.00%) 
Skin infection   0/6 (0.00%)  1/16 (6.25%) 
Upper respiratory infection   0/6 (0.00%)  1/16 (6.25%) 
Wound infection   0/6 (0.00%)  1/16 (6.25%) 
Injury, poisoning and procedural complications     
Bruising   0/6 (0.00%)  1/16 (6.25%) 
Investigations     
Alanine aminotransferase increased   2/6 (33.33%)  0/16 (0.00%) 
Aspartate aminotransferase increased   1/6 (16.67%)  0/16 (0.00%) 
Lymphocyte count decreased   2/6 (33.33%)  7/16 (43.75%) 
Neutrophil count decreased   0/6 (0.00%)  8/16 (50.00%) 
Platelet count decreased   1/6 (16.67%)  5/16 (31.25%) 
Weight gain   0/6 (0.00%)  2/16 (12.50%) 
White blood cell decreased   0/6 (0.00%)  5/16 (31.25%) 
Metabolism and nutrition disorders     
Anorexia   0/6 (0.00%)  1/16 (6.25%) 
Dehydration   0/6 (0.00%)  1/16 (6.25%) 
Hyperglycemia   0/6 (0.00%)  1/16 (6.25%) 
Hyponatremia   1/6 (16.67%)  0/16 (0.00%) 
Musculoskeletal and connective tissue disorders     
Back pain   0/6 (0.00%)  1/16 (6.25%) 
Generalized muscle weakness   1/6 (16.67%)  2/16 (12.50%) 
Muscle weakness-left sided   1/6 (16.67%)  2/16 (12.50%) 
Muscle weakness lower limb   0/6 (0.00%)  1/16 (6.25%) 
Muscle weakness right-sided   1/6 (16.67%)  0/16 (0.00%) 
Muscle weakness upper limb   1/6 (16.67%)  2/16 (12.50%) 
Hip and shoulder pain   0/6 (0.00%)  1/16 (6.25%) 
Pain in chest and shoulder-from fall   0/6 (0.00%)  1/16 (6.25%) 
Myalgia   1/6 (16.67%)  1/16 (6.25%) 
Pain in extremity   0/6 (0.00%)  1/16 (6.25%) 
Nervous system disorders     
Ataxia   0/6 (0.00%)  2/16 (12.50%) 
Cerebrospinal fluid leakage   1/6 (16.67%)  0/16 (0.00%) 
Cognitive disturbance   2/6 (33.33%)  1/16 (6.25%) 
Dysarthria   0/6 (0.00%)  1/16 (6.25%) 
Dysphasia   1/6 (16.67%)  3/16 (18.75%) 
Facial nerve disorder   0/6 (0.00%)  2/16 (12.50%) 
Headache   2/6 (33.33%)  8/16 (50.00%) 
Hydrocephalus   1/6 (16.67%)  0/16 (0.00%) 
Intracranial hemorrhage   1/6 (16.67%)  0/16 (0.00%) 
Memory impairment   0/6 (0.00%)  3/16 (18.75%) 
Trouble reading   0/6 (0.00%)  1/16 (6.25%) 
Neglect   0/6 (0.00%)  1/16 (6.25%) 
Decreased coordination   0/6 (0.00%)  1/16 (6.25%) 
L UQ VF neglect   0/6 (0.00%)  1/16 (6.25%) 
Intraventricular hemorrhage   1/6 (16.67%)  0/16 (0.00%) 
Peripheral motor neuropathy   1/6 (16.67%)  0/16 (0.00%) 
Peripheral sensory neuropathy   0/6 (0.00%)  1/16 (6.25%) 
Seizure   2/6 (33.33%)  0/16 (0.00%) 
Spasticity   0/6 (0.00%)  1/16 (6.25%) 
Tremor   0/6 (0.00%)  1/16 (6.25%) 
Psychiatric disorders     
Agitation   1/6 (16.67%)  0/16 (0.00%) 
Anxiety   1/6 (16.67%)  3/16 (18.75%) 
Confusion   0/6 (0.00%)  1/16 (6.25%) 
Depression   0/6 (0.00%)  2/16 (12.50%) 
Insomnia   1/6 (16.67%)  3/16 (18.75%) 
Renal and urinary disorders     
Urinary frequency   0/6 (0.00%)  1/16 (6.25%) 
Urinary incontinence   0/6 (0.00%)  3/16 (18.75%) 
Urinary urgency   0/6 (0.00%)  1/16 (6.25%) 
Reproductive system and breast disorders     
Painful lump   0/6 (0.00%)  1/16 (6.25%) 
Respiratory, thoracic and mediastinal disorders     
Allergic rhinitis   1/6 (16.67%)  1/16 (6.25%) 
Atelectasis   0/6 (0.00%)  1/16 (6.25%) 
Cough   0/6 (0.00%)  2/16 (12.50%) 
Dyspnea   0/6 (0.00%)  1/16 (6.25%) 
Epistaxis   0/6 (0.00%)  3/16 (18.75%) 
Hoarseness   0/6 (0.00%)  1/16 (6.25%) 
Nasal congestion   0/6 (0.00%)  1/16 (6.25%) 
Productive cough   0/6 (0.00%)  1/16 (6.25%) 
Sore throat   0/6 (0.00%)  1/16 (6.25%) 
Skin and subcutaneous tissue disorders     
Alopecia   0/6 (0.00%)  1/16 (6.25%) 
Dry skin   0/6 (0.00%)  1/16 (6.25%) 
Erythema multiforme   0/6 (0.00%)  1/16 (6.25%) 
Pain of skin   1/6 (16.67%)  0/16 (0.00%) 
Rash maculo-papular   0/6 (0.00%)  1/16 (6.25%) 
Strial rash   0/6 (0.00%)  1/16 (6.25%) 
Minor skin changes   0/6 (0.00%)  1/16 (6.25%) 
Skin hyperpigmentation   0/6 (0.00%)  1/16 (6.25%) 
Vascular disorders     
Hematoma   0/6 (0.00%)  1/16 (6.25%) 
Thromboembolic event   1/6 (16.67%)  0/16 (0.00%) 
Deep vein thrombosis (DVT)   0/6 (0.00%)  1/16 (6.25%) 
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Michael Prados, MD
Organization: University of California San Francisco
Phone: 4154767217
Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT01227434     History of Changes
Other Study ID Numbers: 10105
First Submitted: October 15, 2010
First Posted: October 25, 2010
Results First Submitted: May 18, 2015
Results First Posted: June 12, 2015
Last Update Posted: July 17, 2015