An Investigational Study Drug, Palbociclib (PD-0332991), Is Being Studied In Patients With Mantle Cell Lymphoma. Patients Must Have Received Prior Treatment(s) For Mantle Cell Lymphoma.
Study Details
Study Description
Brief Summary
This is a pilot study evaluating tumor activity using Positron Emission Tomography, which is also known as a "PET scan". This study will assess the safety of using PD-0332991 in patients with mantle cell lymphoma.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: PD-0332991
|
Drug: PD-0332991
125 mg, oral, Days 1-21 of a 28-day cycle
|
Outcome Measures
Primary Outcome Measures
- Correlation Coefficient Between Change From Baseline in Fluoro-L-thymidine Positron Emission Tomography (FLT-PET) Maximum Standard Uptake Value (SUVmax) and in Phosphorylated Retinoblastoma (Phospho-Rb) Percent Positive Cells at Cycle 1 Day 21 [Baseline, Cycle 1 Day 21]
Maximum standard uptake value (SUVmax) was defined as the maximum value attained for the ratio of tissue radioactivity concentration at any time and the injected radioactivity concentration divided by the body weight (in kilogram [kg]). Phosphorylation of retinoblastoma (Rb) protein in the tumor cells, expressed as phospho-Rb percent positive cells, was assessed using Immunohistochemical staining technique. Change from baseline in [(18)F]-FLT-PET SUVmax at Cycle 1 Day 21 and change from baseline in Phospho-Rb percent positive cells at Cycle 1 Day 21 were analyzed. The change values of FLT-PET SUVmax and Phospho-Rb percent positive cells were then correlated. Here, 'N' (number of participants analyzed) signifies participants evaluable for this measure.
- Correlation Coefficient Between Change From Baseline in Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) Maximum Standard Uptake Value (SUVmax) and in Phosphorylated Retinoblastoma (Phospho-Rb) Percent Positive Cells at Cycle 1 Day 21 [Baseline, Cycle 1 Day 21]
Maximum standard uptake value (SUVmax) was defined as the maximum value attained for the ratio of tissue radioactivity concentration at any time and the injected radioactivity concentration divided by the body weight (in kilogram [kg]). Phosphorylation of retinoblastoma (Rb) protein in the tumor cells, expressed as phospho-Rb percent positive cells, was assessed using Immunohistochemical staining technique. Change from baseline in [(18)F]-FDG-PET SUVmax at Cycle 1 Day 21 and change from baseline in Phospho-Rb percent positive cells at Cycle 1 Day 21 were analyzed. The change values of FLT-PET SUVmax and Phospho-Rb percent positive cells were then correlated. Here, 'N' (number of participants analyzed) signifies participants evaluable for this measure.
- Change From Baseline in Maximum Standard Uptake Value (SUVmax) at Cycle 1 Day 21 [Baseline, Cycle 1 Day 21]
Maximum standard uptake value (SUVmax) was defined as the maximum value attained for the ratio of tissue radioactivity concentration at any time and the injected radioactivity concentration divided by the body weight (in kilogram [kg]). Change from baseline in SUVmax was assessed using [(18)F]-FLT-PET and [(18)F]-FDG-PET techniques.
- Correlation Between Positron Emission Tomography (PET) Response and Progression-Free Survival (PFS) [Baseline, Cycle 1 Day 21 for PET response; Screening until tumor progression or death, assessed on Day 1 of every alternate cycle starting from Cycle 1 up to end of treatment (Day 609) or early withdrawal (if not completed during last 6 weeks) for PFS]
PET response was defined as complete response (CR) = mean SUVmax same as of background; partial response (PR) = mean SUVmax less than (<) 75 percent (%) of baseline; progressive disease (PD) = mean SUVmax greater than (>) 125% of baseline; stable disease (SD) = mean SUVmax greater than or equal to (>=) 75% of baseline and mean SUVmax less than or equal to (<=) 125% of baseline. PFS was defined as the time from first dose of study medication to the first documentation of objective tumor progression, or to death due to any cause, whichever occurred first. Tumor progression was defined as >50% increase in sum of products of diameters, of dominant nodes and documented non-nodal sites or appearance of new sites of disease.
- Correlation Between Positron Emission Tomography (PET) Response and Objective Response (OR) [Baseline, Cycle 1 Day 21 for PET response; Screening until tumor progression or death, assessed on Day 1 of every alternate cycle starting from Cycle 1 up to end of treatment (Day 609) or early withdrawal (if not completed during last 6 weeks) for OR]
OR: CR= disappearance of all clinical/radiographic evidence of disease, disease related symptoms and biochemical abnormalities, nodal masses regressed to normal size, if spleen and bone marrow were involved, spleen regressed to normal size and not palpable and clear infiltrate on repeat bone marrow aspiration; PR= dominant nodes decreased by >50% in sum of products of diameters (SPD), no increase in size of other nodes/liver/spleen, lesions regressed by >50% in SPD, no new sites of disease; SD= response <PR and no PD, documented >=1 time after start of therapy, no new sites of disease; PD= >50% increase in SPD of dominant nodes and other nodes or appearance of new sites of disease. PET response: CR= mean SUVmax same as background; PR= mean SUVmax <75% of baseline; PD= mean SUVmax >125% of baseline; SD= mean SUVmax >=75% of baseline but <=125% of baseline. Correlation was reported as conjoint number of participants with PET response at Cycle 1 Day 21 and OR at end of study.
- Phosphorylated Retinoblastoma (Phospho-Rb) Percent Positive Cells at Baseline [Baseline]
Phosphorylation of retinoblastoma (Rb) protein in the tumor cells, expressed as phospho-Rb percent positive cells, was assessed using Immunohistochemical staining technique.
- Phosphorylated Retinoblastoma (Phospho-Rb) Percent Positive Cells at Cycle 1 Day 21 [Cycle 1 Day 21]
Phosphorylation of retinoblastoma (Rb) protein in the tumor cells, expressed as phospho-Rb percent positive cells, was assessed using Immunohistochemical staining technique.
- Ki-67 Composite Score at Baseline [Baseline]
Percentage of Ki-67 positive cells was determined by Immunohistochemical staining technique. Composite score = (sum of each intensity category multiplied by percent of cells in that category). Intensity categories of staining (0 = no staining; 1 = weak staining; 2 = moderate staining; 3 = strong staining). Composite score ranges from 0 (no staining) to 300 (100% of cells with 3 staining intensity).
- Ki-67 Composite Score at Cycle 1 Day 21 [Cycle 1 Day 21]
Percentage of Ki-67 positive cells was determined by Immunohistochemical staining technique. Composite score = (sum of each intensity category multiplied by percent of cells in that category). Intensity categories of staining (0 = no staining; 1 = weak staining; 2 = moderate staining; 3 = strong staining). Composite score ranges from 0 (no staining) to 300 (100% of cells with 3 staining intensity).
- Cyclin D1 Composite Score at Baseline [Baseline]
Percentage of Cyclin D1 positive cells was determined by Immunohistochemical staining technique. Composite score = (sum of each intensity category multiplied by percent of cells in that category). Intensity categories of staining (0 = no staining; 1 = weak staining; 2 = moderate staining; 3 = strong staining). Composite score ranges from 0 (no staining) to 300 (100% of cells with 3 staining intensity).
- Cyclin D1 Composite Score at Cycle 1 Day 21 [Cycle 1 Day 21]
Percentage of Cyclin D1 positive cells was determined by Immunohistochemical staining technique. Composite score = (sum of each intensity category multiplied by percent of cells in that category). Intensity categories of staining (0 = no staining; 1 = weak staining; 2 = moderate staining; 3 = strong staining). Composite score ranges from 0 (no staining) to 300 (100% of cells with 3 staining intensity).
- Number of Participants With Laboratory Test Abnormalities [Baseline up to 28 days after last dose of study medication]
Criteria for laboratory test abnormality: Hematology (Hemoglobin [<0.8*lower limit of normal {LLN}], Platelets [<0.5*LLN/ >1.75*upper limit of normal {ULN}], White blood cells [<0.6*LLN/ >1.5*ULN], Lymphocytes, Neutrophils [<0.8*LLN/ >1.2*ULN], Basophils, Eosinophils, Monocytes [>1.2*ULN]); Liver Function (Total bilirubin [>1.5*ULN], Aspartate aminotransferase, Alanine aminotransferase, Lactate dehydrogenase, Alkaline phosphatase [>0.3*ULN], Total protein, Albumin [<0.8*LLN/ >1.2*ULN]); Renal Function (Blood urea nitrogen, Creatinine [>1.3*ULN], Uric acid [>1.2*ULN]); Electrolytes (sodium [<0.95*LLN/ >1.05*ULN], potassium, chloride, calcium, magnesium [<0.9*LLN/ >1.1*ULN], phosphate [<0.8*LLN/ >1.2*ULN]); Other (Glucose [<0.6*LLN/ >1.5*ULN]).
- Number of Participants With Treatment-Emergent Adverse Events by Severity [Day 1 up to 28 days after last dose of study medication]
AE = any untoward medical occurrence in participant who received study medication without regard to possibility of causal relationship. Severity was assessed as: Grade 1 (Mild); Grade 2 (Moderate); Grade 3 (Severe) = unacceptable or intolerable events, significantly interrupting usual daily activity, and requiring systemic medication therapy/other treatment; Grade 4 (Life-threatening) = events causing participant to be in imminent danger of death; Grade 5 (Death) = death related to an AE. Treatment-emergent events = between first dose of study medication and up to 28 days after last dose, that were absent before treatment or that worsened relative to pre-treatment state. A participant may be represented in more than 1 category.
- Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs) [Day 1 up to 28 days after last dose of study medication]
An AE was any untoward medical occurrence attributed to study drug 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. The events which were considered treatment-related by sponsor and/or investigator were reported.
Secondary Outcome Measures
- Progression-Free Survival (PFS) [Screening until tumor progression or death, assessed on Day 1 of every alternate cycle starting from Cycle 1 up to end of treatment (Day 609) or early withdrawal (if not completed during last 6 weeks)]
PFS was defined as the time from first dose of study medication to the first documentation of objective tumor progression, or to death due to any cause, whichever occurred first. Tumor progression was defined as >50% increase in sum of products of diameters, of dominant nodes and documented non-nodal sites or appearance of new sites of disease. PFS= (first event date minus the first dose date plus 1) divided by 30.44.
- Percentage of Participants With Objective Response [Screening until tumor progression or death, assessed on Day 1 of every alternate cycle starting from Cycle 1 up to end of treatment (Day 609) or early withdrawal (if not completed during last 6 weeks)]
OR is defined as the percentage of participants with confirmed complete response (CR) or confirmed partial response (PR). Confirmed responses are those that persist on repeat imaging study 4 weeks after initial documentation of response. Complete response (CR)= disappearance of all detectable clinical/radiographic evidence of disease, disease related symptoms present before therapy and biochemical abnormalities attributable to disease, nodal masses regressed to normal size, if spleen and bone marrow were involved, spleen regressed to normal size and not palpable and clear infiltrate on repeated bone marrow aspiration; Partial response (PR)= dominant nodes decreased by >50% in sum of products of diameters (SPD), no increase in size of other nodes/liver/spleen, lesions in organs (spleen/liver) regressed by >50% in SPD, no new sites of disease.
- Duration of Response (DR) [Screening until tumor progression or death, assessed on Day 1 of every alternate cycle starting from Cycle 1 up to end of treatment (Day 609) or early withdrawal (if not completed during last 6 weeks)]
Time in months from first documentation of objective tumor response (CR or PR) that was subsequently confirmed, to objective tumor progression (PD) or death due to any cause. DR= (date of first documentation of PD or death, minus the date of first CR or PR plus 1) divided by 30.44. CR= disappearance of all detectable clinical/radiographic evidence of disease, disease related symptoms present before start of therapy and biochemical abnormalities attributable to disease, nodal masses regressed to normal size, if spleen and bone marrow were involved, spleen regressed to normal size and not palpable and clear infiltrate on repeated bone marrow aspiration. PR= dominant nodes decreased by >50% in sum of products of diameters (SPD), no increase in size of other nodes/liver/spleen, lesions in organs (spleen/liver) regressed by >50% in SPD, no new sites of disease. PD= >50% increase in SPD of dominant nodes and other nodes or appearance of new sites of disease.
- Time to Tumor Progression (TTP) [Screening until tumor progression or death, assessed on Day 1 of every alternate cycle starting from Cycle 1 up to end of treatment (Day 609) or early withdrawal (if not completed during last 6 weeks)]
Time in months from date of first dose of study medication to first documentation of objective tumor progression (PD). TTP= (last known progression-free date minus date of first dose of study medication plus 1) divided by 30.44. PD was defined as greater than 50% increase in sum of products of diameters, of dominant nodes and documented non-nodal sites or appearance of new sites of disease.
- Correlation Coefficient Between Plasma PD 0332991 Concentration and Change From Baseline in Biomarkers and SUVmax at Cycle 1 Day 21 [Baseline, Cycle 1 Day 21]
Plasma PD 0332991 concentration at Cycle 1 Day 21 was analyzed. Change from baseline in biomarkers (Ki-67 composite score, Cyclin D1 composite score, phospho-Rb positive cells) and SUVmax (FLT-PET SUVmax, FDG-PET SUVmax) at Cycle 1 Day 21 were analyzed. Correlation between PD 0332991 concentration and change in biomarkers (concentration versus Ki-67, concentration versus Cyclin, and concentration versus phospho-Rb) and SUVmax (concentration versus FLT-PET SUVmax, concentration versus FDG-PET SUVmax) was then assessed. Composite score = (sum of each intensity category multiplied by percent of cells in that category). Intensity categories of staining (0 = no staining; 1 = weak staining; 2 = moderate staining; 3 = strong staining). Here, 'N' (number of participants analyzed) signifies participants evaluable for this measure.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Histologically documented MCL.
-
Must have received at least one prior therapy.
-
Eastern Cooperative Oncology Group (ECOG) performance status ≤1.
-
Adequate organ function as outlined in the protocol.
Exclusion Criteria:
-
Major surgery, radiation therapy, or systemic therapy within 4 weeks of study enrollment.
-
Prior radiation therapy to >25% of the bone marrow (whole pelvis is 25%).
-
Uncontrolled brain metastases, spinal cord compression, carcinomatous meningitis, or leptomeningeal disease.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Brigham & Women's Hospital | Boston | Massachusetts | United States | 02115 |
| 2 | Dana-Farber Cancer Institute | Boston | Massachusetts | United States | 02115 |
| 3 | Memorial Sloan-Kettering Cancer Center | New York | New York | United States | 10021 |
| 4 | New York Presbyterian Hospital | New York | New York | United States | 10021 |
| 5 | Weill Medical College of Cornell University - New York Presbyterian Hospital | New York | New York | United States | 10021 |
| 6 | Fox Chase Cancer Center | Philadelphia | Pennsylvania | United States | 19111 |
Sponsors and Collaborators
- Pfizer
Investigators
- Study Director: Pfizer CT.gov Call Center, Pfizer
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- A5481002
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | PD 0332991 |
|---|---|
| Arm/Group Description | PD 0332991 125 milligram (mg) capsule orally once daily in cycles of continuous dosing for 3 weeks followed by 1-week rest, with no dosing (schedule 3/1) until objective disease progression, withdrawal due to unacceptable toxicity or withdrawal of consent by the participant. Dose was reduced up to PD 0332991 75 mg once daily depending on the type and severity of toxicity encountered and as per investigator's discretion. |
| Period Title: Overall Study | |
| STARTED | 17 |
| COMPLETED | 0 |
| NOT COMPLETED | 17 |
Baseline Characteristics
| Arm/Group Title | PD 0332991 |
|---|---|
| Arm/Group Description | PD 0332991 125 milligram (mg) capsule orally once daily in cycles of continuous dosing for 3 weeks followed by 1-week rest, with no dosing (schedule 3/1) until objective disease progression, withdrawal due to unacceptable toxicity or withdrawal of consent by the participant. Dose was reduced up to PD 0332991 75 mg once daily depending on the type and severity of toxicity encountered and as per investigator's discretion. |
| Overall Participants | 17 |
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
66.1
(9.2)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
3
17.6%
|
| Male |
14
82.4%
|
Outcome Measures
| Title | Correlation Coefficient Between Change From Baseline in Fluoro-L-thymidine Positron Emission Tomography (FLT-PET) Maximum Standard Uptake Value (SUVmax) and in Phosphorylated Retinoblastoma (Phospho-Rb) Percent Positive Cells at Cycle 1 Day 21 |
|---|---|
| Description | Maximum standard uptake value (SUVmax) was defined as the maximum value attained for the ratio of tissue radioactivity concentration at any time and the injected radioactivity concentration divided by the body weight (in kilogram [kg]). Phosphorylation of retinoblastoma (Rb) protein in the tumor cells, expressed as phospho-Rb percent positive cells, was assessed using Immunohistochemical staining technique. Change from baseline in [(18)F]-FLT-PET SUVmax at Cycle 1 Day 21 and change from baseline in Phospho-Rb percent positive cells at Cycle 1 Day 21 were analyzed. The change values of FLT-PET SUVmax and Phospho-Rb percent positive cells were then correlated. Here, 'N' (number of participants analyzed) signifies participants evaluable for this measure. |
| Time Frame | Baseline, Cycle 1 Day 21 |
Outcome Measure Data
| Analysis Population Description |
|---|
| SUVmax was analyzed using imaging analysis set (participants in FAS who completed baseline [(18)F]-fluorodeoxyglucose PET [FDG-PET] and [(18)F]-FLT-PET, and at least 1 on-treatment [Day 21] PET) and phospho-Rb was analyzed using tumor analysis set (participants in FAS who completed tumor biomarker assessments at baseline and Day 21). |
| Arm/Group Title | PD 0332991 |
|---|---|
| Arm/Group Description | PD 0332991 125 milligram (mg) capsule orally once daily in cycles of continuous dosing for 3 weeks followed by 1-week rest, with no dosing (schedule 3/1) until objective disease progression, withdrawal due to unacceptable toxicity or withdrawal of consent by the participant. Dose was reduced up to PD 0332991 75 mg once daily depending on the type and severity of toxicity encountered and as per investigator's discretion. |
| Measure Participants | 10 |
| Number [correlation coefficient] |
-0.25034
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | PD 0332991 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4854 |
| Comments | ||
| Method | Regression, Linear | |
| Comments | ||
| Title | Correlation Coefficient Between Change From Baseline in Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) Maximum Standard Uptake Value (SUVmax) and in Phosphorylated Retinoblastoma (Phospho-Rb) Percent Positive Cells at Cycle 1 Day 21 |
|---|---|
| Description | Maximum standard uptake value (SUVmax) was defined as the maximum value attained for the ratio of tissue radioactivity concentration at any time and the injected radioactivity concentration divided by the body weight (in kilogram [kg]). Phosphorylation of retinoblastoma (Rb) protein in the tumor cells, expressed as phospho-Rb percent positive cells, was assessed using Immunohistochemical staining technique. Change from baseline in [(18)F]-FDG-PET SUVmax at Cycle 1 Day 21 and change from baseline in Phospho-Rb percent positive cells at Cycle 1 Day 21 were analyzed. The change values of FLT-PET SUVmax and Phospho-Rb percent positive cells were then correlated. Here, 'N' (number of participants analyzed) signifies participants evaluable for this measure. |
| Time Frame | Baseline, Cycle 1 Day 21 |
Outcome Measure Data
| Analysis Population Description |
|---|
| SUVmax was analyzed using imaging analysis set (participants in FAS who completed baseline [(18)F]-FDG-PET and [(18)F]-FLT-PET, and at least 1 on-treatment [Day 21] PET) and phospho-Rb was analyzed using tumor analysis set (participants in FAS who completed tumor biomarker assessments at baseline and Day 21). |
| Arm/Group Title | PD 0332991 |
|---|---|
| Arm/Group Description | PD 0332991 125 milligram (mg) capsule orally once daily in cycles of continuous dosing for 3 weeks followed by 1-week rest, with no dosing (schedule 3/1) until objective disease progression, withdrawal due to unacceptable toxicity or withdrawal of consent by the participant. Dose was reduced up to PD 0332991 75 mg once daily depending on the type and severity of toxicity encountered and as per investigator's discretion. |
| Measure Participants | 10 |
| Number [correlation coefficient] |
0.13551
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | PD 0332991 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7090 |
| Comments | ||
| Method | Regression, Linear | |
| Comments | ||
| Title | Change From Baseline in Maximum Standard Uptake Value (SUVmax) at Cycle 1 Day 21 |
|---|---|
| Description | Maximum standard uptake value (SUVmax) was defined as the maximum value attained for the ratio of tissue radioactivity concentration at any time and the injected radioactivity concentration divided by the body weight (in kilogram [kg]). Change from baseline in SUVmax was assessed using [(18)F]-FLT-PET and [(18)F]-FDG-PET techniques. |
| Time Frame | Baseline, Cycle 1 Day 21 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Imaging analysis set included participants in FAS who completed baseline [(18)F]-FDG-PET and [(18)F]-FLT-PET, and at least 1 on-treatment (Day 21) PET. |
| Arm/Group Title | PD 0332991 |
|---|---|
| Arm/Group Description | PD 0332991 125 milligram (mg) capsule orally once daily in cycles of continuous dosing for 3 weeks followed by 1-week rest, with no dosing (schedule 3/1) until objective disease progression, withdrawal due to unacceptable toxicity or withdrawal of consent by the participant. Dose was reduced up to PD 0332991 75 mg once daily depending on the type and severity of toxicity encountered and as per investigator's discretion. |
| Measure Participants | 17 |
| Baseline: FLT-PET |
9.964
(4.929)
|
| Baseline: FDG-PET |
9.049
(4.654)
|
| Change at Cycle 1 Day 21: FLT-PET |
-4.551
(2.968)
|
| Change at Cycle 1 Day 21: FDG-PET |
-2.271
(2.913)
|
| Title | Correlation Between Positron Emission Tomography (PET) Response and Progression-Free Survival (PFS) |
|---|---|
| Description | PET response was defined as complete response (CR) = mean SUVmax same as of background; partial response (PR) = mean SUVmax less than (<) 75 percent (%) of baseline; progressive disease (PD) = mean SUVmax greater than (>) 125% of baseline; stable disease (SD) = mean SUVmax greater than or equal to (>=) 75% of baseline and mean SUVmax less than or equal to (<=) 125% of baseline. PFS was defined as the time from first dose of study medication to the first documentation of objective tumor progression, or to death due to any cause, whichever occurred first. Tumor progression was defined as >50% increase in sum of products of diameters, of dominant nodes and documented non-nodal sites or appearance of new sites of disease. |
| Time Frame | Baseline, Cycle 1 Day 21 for PET response; Screening until tumor progression or death, assessed on Day 1 of every alternate cycle starting from Cycle 1 up to end of treatment (Day 609) or early withdrawal (if not completed during last 6 weeks) for PFS |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis for this outcome measure was not run as there were so few responders. |
| Arm/Group Title | PD 0332991 |
|---|---|
| Arm/Group Description | PD 0332991 125 milligram (mg) capsule orally once daily in cycles of continuous dosing for 3 weeks followed by 1-week rest, with no dosing (schedule 3/1) until objective disease progression, withdrawal due to unacceptable toxicity or withdrawal of consent by the participant. Dose was reduced up to PD 0332991 75 mg once daily depending on the type and severity of toxicity encountered and as per investigator's discretion. |
| Measure Participants | 0 |
| Title | Correlation Between Positron Emission Tomography (PET) Response and Objective Response (OR) |
|---|---|
| Description | OR: CR= disappearance of all clinical/radiographic evidence of disease, disease related symptoms and biochemical abnormalities, nodal masses regressed to normal size, if spleen and bone marrow were involved, spleen regressed to normal size and not palpable and clear infiltrate on repeat bone marrow aspiration; PR= dominant nodes decreased by >50% in sum of products of diameters (SPD), no increase in size of other nodes/liver/spleen, lesions regressed by >50% in SPD, no new sites of disease; SD= response <PR and no PD, documented >=1 time after start of therapy, no new sites of disease; PD= >50% increase in SPD of dominant nodes and other nodes or appearance of new sites of disease. PET response: CR= mean SUVmax same as background; PR= mean SUVmax <75% of baseline; PD= mean SUVmax >125% of baseline; SD= mean SUVmax >=75% of baseline but <=125% of baseline. Correlation was reported as conjoint number of participants with PET response at Cycle 1 Day 21 and OR at end of study. |
| Time Frame | Baseline, Cycle 1 Day 21 for PET response; Screening until tumor progression or death, assessed on Day 1 of every alternate cycle starting from Cycle 1 up to end of treatment (Day 609) or early withdrawal (if not completed during last 6 weeks) for OR |
Outcome Measure Data
| Analysis Population Description |
|---|
| PET response was analyzed using Imaging analysis set and OR was analyzed using response analysis set (all participants enrolled in the study who received at least 1 dose of study medication in cycle 1 and for whom a post-treatment response assessment was completed). |
| Arm/Group Title | PD 0332991 |
|---|---|
| Arm/Group Description | PD 0332991 125 milligram (mg) capsule orally once daily in cycles of continuous dosing for 3 weeks followed by 1-week rest, with no dosing (schedule 3/1) until objective disease progression, withdrawal due to unacceptable toxicity or withdrawal of consent by the participant. Dose was reduced up to PD 0332991 75 mg once daily depending on the type and severity of toxicity encountered and as per investigator's discretion. |
| Measure Participants | 17 |
| FLT-PET PR, Objective CR |
1
5.9%
|
| FLT-PET PR, Objective PR |
2
11.8%
|
| FLT-PET PR, Objective SD |
7
41.2%
|
| FLT-PET PR, Objective PD |
4
23.5%
|
| FLT-PET PR, Indetermined Objective Response |
1
5.9%
|
| FLT-PET SD, Objective PD |
2
11.8%
|
| FDG-PET PR, Objective PR |
2
11.8%
|
| FDG-PET PR, Objective SD |
3
17.6%
|
| FDG-PET PR, Objective PD |
2
11.8%
|
| FDG-PET SD, Objective CR |
1
5.9%
|
| FDG-PET SD, Objective SD |
4
23.5%
|
| FDG-PET SD, Objective PD |
4
23.5%
|
| FDG-PET SD, Objective Indetermined Response |
1
5.9%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | PD 0332991 |
|---|---|---|
| Comments | FLT-PET response versus Objective response | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Kappa |
| Estimated Value | 0.0638 | |
| Confidence Interval |
(2-Sided) 95% -0.0449 to 0.1726 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | PD 0332991 |
|---|---|---|
| Comments | FDG-PET response versus Objective response | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Kappa |
| Estimated Value | 0.1864 | |
| Confidence Interval |
(2-Sided) 95% -0.2316 to 0.6045 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Phosphorylated Retinoblastoma (Phospho-Rb) Percent Positive Cells at Baseline |
|---|---|
| Description | Phosphorylation of retinoblastoma (Rb) protein in the tumor cells, expressed as phospho-Rb percent positive cells, was assessed using Immunohistochemical staining technique. |
| Time Frame | Baseline |
Outcome Measure Data
| Analysis Population Description |
|---|
| Tumor analysis set include all participants in FAS who completed tumor biomarker assessments at baseline and Day 21. Here, 'N' (number of participants analyzed) signifies participants evaluable for this measure. |
| Arm/Group Title | PD 0332991 |
|---|---|
| Arm/Group Description | PD 0332991 125 milligram (mg) capsule orally once daily in cycles of continuous dosing for 3 weeks followed by 1-week rest, with no dosing (schedule 3/1) until objective disease progression, withdrawal due to unacceptable toxicity or withdrawal of consent by the participant. Dose was reduced up to PD 0332991 75 mg once daily depending on the type and severity of toxicity encountered and as per investigator's discretion. |
| Measure Participants | 10 |
| Mean (Standard Deviation) [percentage of tumor cells] |
47.9
(25.72)
|
| Title | Phosphorylated Retinoblastoma (Phospho-Rb) Percent Positive Cells at Cycle 1 Day 21 |
|---|---|
| Description | Phosphorylation of retinoblastoma (Rb) protein in the tumor cells, expressed as phospho-Rb percent positive cells, was assessed using Immunohistochemical staining technique. |
| Time Frame | Cycle 1 Day 21 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Tumor analysis set include all participants in FAS who completed tumor biomarker assessments at baseline and Day 21. Here, 'N' (number of participants analyzed) signifies participants evaluable for this measure. |
| Arm/Group Title | PD 0332991 |
|---|---|
| Arm/Group Description | PD 0332991 125 milligram (mg) capsule orally once daily in cycles of continuous dosing for 3 weeks followed by 1-week rest, with no dosing (schedule 3/1) until objective disease progression, withdrawal due to unacceptable toxicity or withdrawal of consent by the participant. Dose was reduced up to PD 0332991 75 mg once daily depending on the type and severity of toxicity encountered and as per investigator's discretion. |
| Measure Participants | 10 |
| Mean (Standard Deviation) [percentage of tumor cells] |
7.2
(14.4)
|
| Title | Ki-67 Composite Score at Baseline |
|---|---|
| Description | Percentage of Ki-67 positive cells was determined by Immunohistochemical staining technique. Composite score = (sum of each intensity category multiplied by percent of cells in that category). Intensity categories of staining (0 = no staining; 1 = weak staining; 2 = moderate staining; 3 = strong staining). Composite score ranges from 0 (no staining) to 300 (100% of cells with 3 staining intensity). |
| Time Frame | Baseline |
Outcome Measure Data
| Analysis Population Description |
|---|
| Tumor analysis set include all participants in FAS who completed tumor biomarker assessments at baseline and Day 21. Here, 'N' (number of participants analyzed) signifies participants evaluable for this measure. |
| Arm/Group Title | PD 0332991 |
|---|---|
| Arm/Group Description | PD 0332991 125 milligram (mg) capsule orally once daily in cycles of continuous dosing for 3 weeks followed by 1-week rest, with no dosing (schedule 3/1) until objective disease progression, withdrawal due to unacceptable toxicity or withdrawal of consent by the participant. Dose was reduced up to PD 0332991 75 mg once daily depending on the type and severity of toxicity encountered and as per investigator's discretion. |
| Measure Participants | 6 |
| Mean (Standard Deviation) [units on a scale] |
191.2
(64.56)
|
| Title | Ki-67 Composite Score at Cycle 1 Day 21 |
|---|---|
| Description | Percentage of Ki-67 positive cells was determined by Immunohistochemical staining technique. Composite score = (sum of each intensity category multiplied by percent of cells in that category). Intensity categories of staining (0 = no staining; 1 = weak staining; 2 = moderate staining; 3 = strong staining). Composite score ranges from 0 (no staining) to 300 (100% of cells with 3 staining intensity). |
| Time Frame | Cycle 1 Day 21 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Tumor analysis set include all participants in FAS who completed tumor biomarker assessments at baseline and Day 21. Here, 'N' (number of participants analyzed) signifies participants evaluable for this measure. |
| Arm/Group Title | PD 0332991 |
|---|---|
| Arm/Group Description | PD 0332991 125 milligram (mg) capsule orally once daily in cycles of continuous dosing for 3 weeks followed by 1-week rest, with no dosing (schedule 3/1) until objective disease progression, withdrawal due to unacceptable toxicity or withdrawal of consent by the participant. Dose was reduced up to PD 0332991 75 mg once daily depending on the type and severity of toxicity encountered and as per investigator's discretion. |
| Measure Participants | 6 |
| Mean (Standard Deviation) [units on a scale] |
78.5
(110.02)
|
| Title | Cyclin D1 Composite Score at Baseline |
|---|---|
| Description | Percentage of Cyclin D1 positive cells was determined by Immunohistochemical staining technique. Composite score = (sum of each intensity category multiplied by percent of cells in that category). Intensity categories of staining (0 = no staining; 1 = weak staining; 2 = moderate staining; 3 = strong staining). Composite score ranges from 0 (no staining) to 300 (100% of cells with 3 staining intensity). |
| Time Frame | Baseline |
Outcome Measure Data
| Analysis Population Description |
|---|
| Tumor analysis set include all participants in FAS who completed tumor biomarker assessments at baseline and Day 21. Here, 'N' (number of participants analyzed) signifies participants evaluable for this measure. |
| Arm/Group Title | PD 0332991 |
|---|---|
| Arm/Group Description | PD 0332991 125 milligram (mg) capsule orally once daily in cycles of continuous dosing for 3 weeks followed by 1-week rest, with no dosing (schedule 3/1) until objective disease progression, withdrawal due to unacceptable toxicity or withdrawal of consent by the participant. Dose was reduced up to PD 0332991 75 mg once daily depending on the type and severity of toxicity encountered and as per investigator's discretion. |
| Measure Participants | 6 |
| Mean (Standard Deviation) [units on a scale] |
165.0
(78.17)
|
| Title | Cyclin D1 Composite Score at Cycle 1 Day 21 |
|---|---|
| Description | Percentage of Cyclin D1 positive cells was determined by Immunohistochemical staining technique. Composite score = (sum of each intensity category multiplied by percent of cells in that category). Intensity categories of staining (0 = no staining; 1 = weak staining; 2 = moderate staining; 3 = strong staining). Composite score ranges from 0 (no staining) to 300 (100% of cells with 3 staining intensity). |
| Time Frame | Cycle 1 Day 21 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Tumor analysis set include all participants in FAS who completed tumor biomarker assessments at baseline and Day 21. Here, 'N' (number of participants analyzed) signifies participants evaluable for this measure. |
| Arm/Group Title | PD 0332991 |
|---|---|
| Arm/Group Description | PD 0332991 125 milligram (mg) capsule orally once daily in cycles of continuous dosing for 3 weeks followed by 1-week rest, with no dosing (schedule 3/1) until objective disease progression, withdrawal due to unacceptable toxicity or withdrawal of consent by the participant. Dose was reduced up to PD 0332991 75 mg once daily depending on the type and severity of toxicity encountered and as per investigator's discretion. |
| Measure Participants | 6 |
| Mean (Standard Deviation) [units on a scale] |
124.2
(47.58)
|
| Title | Number of Participants With Laboratory Test Abnormalities |
|---|---|
| Description | Criteria for laboratory test abnormality: Hematology (Hemoglobin [<0.8*lower limit of normal {LLN}], Platelets [<0.5*LLN/ >1.75*upper limit of normal {ULN}], White blood cells [<0.6*LLN/ >1.5*ULN], Lymphocytes, Neutrophils [<0.8*LLN/ >1.2*ULN], Basophils, Eosinophils, Monocytes [>1.2*ULN]); Liver Function (Total bilirubin [>1.5*ULN], Aspartate aminotransferase, Alanine aminotransferase, Lactate dehydrogenase, Alkaline phosphatase [>0.3*ULN], Total protein, Albumin [<0.8*LLN/ >1.2*ULN]); Renal Function (Blood urea nitrogen, Creatinine [>1.3*ULN], Uric acid [>1.2*ULN]); Electrolytes (sodium [<0.95*LLN/ >1.05*ULN], potassium, chloride, calcium, magnesium [<0.9*LLN/ >1.1*ULN], phosphate [<0.8*LLN/ >1.2*ULN]); Other (Glucose [<0.6*LLN/ >1.5*ULN]). |
| Time Frame | Baseline up to 28 days after last dose of study medication |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety analysis set included all participants enrolled in the study who received at least 1 dose of study medication. |
| Arm/Group Title | PD 0332991 |
|---|---|
| Arm/Group Description | PD 0332991 125 milligram (mg) capsule orally once daily in cycles of continuous dosing for 3 weeks followed by 1-week rest, with no dosing (schedule 3/1) until objective disease progression, withdrawal due to unacceptable toxicity or withdrawal of consent by the participant. Dose was reduced up to PD 0332991 75 mg once daily depending on the type and severity of toxicity encountered and as per investigator's discretion. |
| Measure Participants | 17 |
| Number [participants] |
16
94.1%
|
| Title | Number of Participants With Treatment-Emergent Adverse Events by Severity |
|---|---|
| Description | AE = any untoward medical occurrence in participant who received study medication without regard to possibility of causal relationship. Severity was assessed as: Grade 1 (Mild); Grade 2 (Moderate); Grade 3 (Severe) = unacceptable or intolerable events, significantly interrupting usual daily activity, and requiring systemic medication therapy/other treatment; Grade 4 (Life-threatening) = events causing participant to be in imminent danger of death; Grade 5 (Death) = death related to an AE. Treatment-emergent events = between first dose of study medication and up to 28 days after last dose, that were absent before treatment or that worsened relative to pre-treatment state. A participant may be represented in more than 1 category. |
| Time Frame | Day 1 up to 28 days after last dose of study medication |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety analysis set included all participants enrolled in the study who received at least 1 dose of study medication. |
| Arm/Group Title | PD 0332991 |
|---|---|
| Arm/Group Description | PD 0332991 125 milligram (mg) capsule orally once daily in cycles of continuous dosing for 3 weeks followed by 1-week rest, with no dosing (schedule 3/1) until objective disease progression, withdrawal due to unacceptable toxicity or withdrawal of consent by the participant. Dose was reduced up to PD 0332991 75 mg once daily depending on the type and severity of toxicity encountered and as per investigator's discretion. |
| Measure Participants | 17 |
| Grade 1 |
4
23.5%
|
| Grade 2 |
2
11.8%
|
| Grade 3 |
7
41.2%
|
| Grade 4 |
3
17.6%
|
| Grade 5 |
1
5.9%
|
| Title | Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs) |
|---|---|
| Description | An AE was any untoward medical occurrence attributed to study drug 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. The events which were considered treatment-related by sponsor and/or investigator were reported. |
| Time Frame | Day 1 up to 28 days after last dose of study medication |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety analysis set included all participants enrolled in the study who received at least 1 dose of study medication. |
| Arm/Group Title | PD 0332991 |
|---|---|
| Arm/Group Description | PD 0332991 125 milligram (mg) capsule orally once daily in cycles of continuous dosing for 3 weeks followed by 1-week rest, with no dosing (schedule 3/1) until objective disease progression, withdrawal due to unacceptable toxicity or withdrawal of consent by the participant. Dose was reduced up to PD 0332991 75 mg once daily depending on the type and severity of toxicity encountered and as per investigator's discretion. |
| Measure Participants | 17 |
| AEs |
16
94.1%
|
| SAEs |
2
11.8%
|
| Title | Progression-Free Survival (PFS) |
|---|---|
| Description | PFS was defined as the time from first dose of study medication to the first documentation of objective tumor progression, or to death due to any cause, whichever occurred first. Tumor progression was defined as >50% increase in sum of products of diameters, of dominant nodes and documented non-nodal sites or appearance of new sites of disease. PFS= (first event date minus the first dose date plus 1) divided by 30.44. |
| Time Frame | Screening until tumor progression or death, assessed on Day 1 of every alternate cycle starting from Cycle 1 up to end of treatment (Day 609) or early withdrawal (if not completed during last 6 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Response analysis set included all participants enrolled in the study who received at least 1 dose of study medication in cycle 1 and for whom a post-treatment response assessment was completed. |
| Arm/Group Title | PD 0332991 |
|---|---|
| Arm/Group Description | PD 0332991 125 milligram (mg) capsule orally once daily in cycles of continuous dosing for 3 weeks followed by 1-week rest, with no dosing (schedule 3/1) until objective disease progression, withdrawal due to unacceptable toxicity or withdrawal of consent by the participant. Dose was reduced up to PD 0332991 75 mg once daily depending on the type and severity of toxicity encountered and as per investigator's discretion. |
| Measure Participants | 16 |
| Median (95% Confidence Interval) [months] |
5.5
|
| Title | Percentage of Participants With Objective Response |
|---|---|
| Description | OR is defined as the percentage of participants with confirmed complete response (CR) or confirmed partial response (PR). Confirmed responses are those that persist on repeat imaging study 4 weeks after initial documentation of response. Complete response (CR)= disappearance of all detectable clinical/radiographic evidence of disease, disease related symptoms present before therapy and biochemical abnormalities attributable to disease, nodal masses regressed to normal size, if spleen and bone marrow were involved, spleen regressed to normal size and not palpable and clear infiltrate on repeated bone marrow aspiration; Partial response (PR)= dominant nodes decreased by >50% in sum of products of diameters (SPD), no increase in size of other nodes/liver/spleen, lesions in organs (spleen/liver) regressed by >50% in SPD, no new sites of disease. |
| Time Frame | Screening until tumor progression or death, assessed on Day 1 of every alternate cycle starting from Cycle 1 up to end of treatment (Day 609) or early withdrawal (if not completed during last 6 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Response analysis set included all participants enrolled in the study who received at least 1 dose of study medication in cycle 1 and for whom a post-treatment response assessment was completed. |
| Arm/Group Title | PD 0332991 |
|---|---|
| Arm/Group Description | PD 0332991 125 milligram (mg) capsule orally once daily in cycles of continuous dosing for 3 weeks followed by 1-week rest, with no dosing (schedule 3/1) until objective disease progression, withdrawal due to unacceptable toxicity or withdrawal of consent by the participant. Dose was reduced up to PD 0332991 75 mg once daily depending on the type and severity of toxicity encountered and as per investigator's discretion. |
| Measure Participants | 16 |
| Number (95% Confidence Interval) [percentage of participants] |
18.8
110.6%
|
| Title | Duration of Response (DR) |
|---|---|
| Description | Time in months from first documentation of objective tumor response (CR or PR) that was subsequently confirmed, to objective tumor progression (PD) or death due to any cause. DR= (date of first documentation of PD or death, minus the date of first CR or PR plus 1) divided by 30.44. CR= disappearance of all detectable clinical/radiographic evidence of disease, disease related symptoms present before start of therapy and biochemical abnormalities attributable to disease, nodal masses regressed to normal size, if spleen and bone marrow were involved, spleen regressed to normal size and not palpable and clear infiltrate on repeated bone marrow aspiration. PR= dominant nodes decreased by >50% in sum of products of diameters (SPD), no increase in size of other nodes/liver/spleen, lesions in organs (spleen/liver) regressed by >50% in SPD, no new sites of disease. PD= >50% increase in SPD of dominant nodes and other nodes or appearance of new sites of disease. |
| Time Frame | Screening until tumor progression or death, assessed on Day 1 of every alternate cycle starting from Cycle 1 up to end of treatment (Day 609) or early withdrawal (if not completed during last 6 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| For duration of response, the number of participants experiencing objective response was less than 50%, and therefore, it was not feasible to calculate duration of response using Kaplan-Meier method. Hence, no participant was analyzed for this outcome measure. |
| Arm/Group Title | PD 0332991 |
|---|---|
| Arm/Group Description | PD 0332991 125 milligram (mg) capsule orally once daily in cycles of continuous dosing for 3 weeks followed by 1-week rest, with no dosing (schedule 3/1) until objective disease progression, withdrawal due to unacceptable toxicity or withdrawal of consent by the participant. Dose was reduced up to PD 0332991 75 mg once daily depending on the type and severity of toxicity encountered and as per investigator's discretion. |
| Measure Participants | 0 |
| Title | Time to Tumor Progression (TTP) |
|---|---|
| Description | Time in months from date of first dose of study medication to first documentation of objective tumor progression (PD). TTP= (last known progression-free date minus date of first dose of study medication plus 1) divided by 30.44. PD was defined as greater than 50% increase in sum of products of diameters, of dominant nodes and documented non-nodal sites or appearance of new sites of disease. |
| Time Frame | Screening until tumor progression or death, assessed on Day 1 of every alternate cycle starting from Cycle 1 up to end of treatment (Day 609) or early withdrawal (if not completed during last 6 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Response analysis set included all participants enrolled in the study who received at least 1 dose of study medication in cycle 1 and for whom a post-treatment response assessment was completed. |
| Arm/Group Title | PD 0332991 |
|---|---|
| Arm/Group Description | PD 0332991 125 milligram (mg) capsule orally once daily in cycles of continuous dosing for 3 weeks followed by 1-week rest, with no dosing (schedule 3/1) until objective disease progression, withdrawal due to unacceptable toxicity or withdrawal of consent by the participant. Dose was reduced up to PD 0332991 75 mg once daily depending on the type and severity of toxicity encountered and as per investigator's discretion. |
| Measure Participants | 16 |
| Median (95% Confidence Interval) [months] |
5.5
|
| Title | Correlation Coefficient Between Plasma PD 0332991 Concentration and Change From Baseline in Biomarkers and SUVmax at Cycle 1 Day 21 |
|---|---|
| Description | Plasma PD 0332991 concentration at Cycle 1 Day 21 was analyzed. Change from baseline in biomarkers (Ki-67 composite score, Cyclin D1 composite score, phospho-Rb positive cells) and SUVmax (FLT-PET SUVmax, FDG-PET SUVmax) at Cycle 1 Day 21 were analyzed. Correlation between PD 0332991 concentration and change in biomarkers (concentration versus Ki-67, concentration versus Cyclin, and concentration versus phospho-Rb) and SUVmax (concentration versus FLT-PET SUVmax, concentration versus FDG-PET SUVmax) was then assessed. Composite score = (sum of each intensity category multiplied by percent of cells in that category). Intensity categories of staining (0 = no staining; 1 = weak staining; 2 = moderate staining; 3 = strong staining). Here, 'N' (number of participants analyzed) signifies participants evaluable for this measure. |
| Time Frame | Baseline, Cycle 1 Day 21 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PD 0332991 concentration was analyzed using pharmacokinetic analysis set (participants in FAS who had also completed pharmacokinetic blood sampling for at least 1 day); SUVmax and biomarkers were analyzed using imaging analysis set and tumor analysis set respectively. n= participants evaluable for this measure for specified comparisons. |
| Arm/Group Title | PD 0332991 |
|---|---|
| Arm/Group Description | PD 0332991 125 milligram (mg) capsule orally once daily in cycles of continuous dosing for 3 weeks followed by 1-week rest, with no dosing (schedule 3/1) until objective disease progression, withdrawal due to unacceptable toxicity or withdrawal of consent by the participant. Dose was reduced up to PD 0332991 75 mg once daily depending on the type and severity of toxicity encountered and as per investigator's discretion. |
| Measure Participants | 16 |
| Concentration versus Ki-67 (n=6) |
0.27677
|
| Concentration versus Cyclin D1 (n= 6) |
-0.69081
|
| Concentration versus phospho-Rb (n= 10) |
-0.55533
|
| Concentration versus FLT-PET SUVmax (n= 16) |
0.28767
|
| Concentration versus FDG-PET SUVmax (n= 16) |
-0.18526
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | PD 0332991 |
|---|---|---|
| Comments | Concentration versus Ki-67 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5954 |
| Comments | ||
| Method | Regression, Linear | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | PD 0332991 |
|---|---|---|
| Comments | Concentration versus Cyclin D1 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1286 |
| Comments | ||
| Method | Regression, Linear | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | PD 0332991 |
|---|---|---|
| Comments | Concentration versus phospho-Rb | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0956 |
| Comments | ||
| Method | Regression, Linear | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | PD 0332991 |
|---|---|---|
| Comments | Concentration versus FLT-PET SUVmax | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2800 |
| Comments | ||
| Method | Regression, Linear | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | PD 0332991 |
|---|---|---|
| Comments | Concentration versus FDG-PET SUVmax | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4921 |
| Comments | ||
| Method | Regression, Linear | |
| Comments | ||
Adverse Events
| Time Frame | ||
|---|---|---|
| Adverse Event Reporting Description | The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. | |
| Arm/Group Title | PD 0332991 | |
| Arm/Group Description | PD 0332991 125 milligram (mg) capsule orally once daily in cycles of continuous dosing for 3 weeks followed by 1-week rest, with no dosing (schedule 3/1) until objective disease progression, withdrawal due to unacceptable toxicity or withdrawal of consent by the participant. Dose was reduced up to PD 0332991 75 mg once daily depending on the type and severity of toxicity encountered and as per investigator's discretion. | |
All Cause Mortality |
||
| PD 0332991 | ||
| Affected / at Risk (%) | # Events | |
| Total | / (NaN) | |
Serious Adverse Events |
||
| PD 0332991 | ||
| Affected / at Risk (%) | # Events | |
| Total | 3/17 (17.6%) | |
| Cardiac disorders | ||
| Cardiac arrest | 1/17 (5.9%) | |
| Gastrointestinal disorders | ||
| Diarrhoea | 1/17 (5.9%) | |
| Infections and infestations | ||
| Pneumonia | 1/17 (5.9%) | |
| Metabolism and nutrition disorders | ||
| Dehydration | 1/17 (5.9%) | |
Other (Not Including Serious) Adverse Events |
||
| PD 0332991 | ||
| Affected / at Risk (%) | # Events | |
| Total | 17/17 (100%) | |
| Blood and lymphatic system disorders | ||
| Anaemia | 3/17 (17.6%) | |
| Febrile neutropenia | 1/17 (5.9%) | |
| Leukopenia | 3/17 (17.6%) | |
| Macrocytosis | 1/17 (5.9%) | |
| Neutropenia | 8/17 (47.1%) | |
| Thrombocytopenia | 6/17 (35.3%) | |
| Cardiac disorders | ||
| Palpitations | 2/17 (11.8%) | |
| Ear and labyrinth disorders | ||
| Ear pain | 1/17 (5.9%) | |
| Tympanic membrane perforation | 1/17 (5.9%) | |
| Eye disorders | ||
| Conjunctival haemorrhage | 1/17 (5.9%) | |
| Lacrimation increased | 1/17 (5.9%) | |
| Ocular hyperaemia | 1/17 (5.9%) | |
| Vision blurred | 2/17 (11.8%) | |
| Visual impairment | 1/17 (5.9%) | |
| Gastrointestinal disorders | ||
| Abdominal discomfort | 1/17 (5.9%) | |
| Abdominal pain | 2/17 (11.8%) | |
| Abdominal pain upper | 1/17 (5.9%) | |
| Constipation | 3/17 (17.6%) | |
| Diarrhoea | 4/17 (23.5%) | |
| Dry mouth | 1/17 (5.9%) | |
| Dyspepsia | 3/17 (17.6%) | |
| Haematochezia | 1/17 (5.9%) | |
| Nausea | 3/17 (17.6%) | |
| Oral pain | 1/17 (5.9%) | |
| Vomiting | 1/17 (5.9%) | |
| General disorders | ||
| Axillary pain | 1/17 (5.9%) | |
| Chest pain | 2/17 (11.8%) | |
| Chills | 1/17 (5.9%) | |
| Fatigue | 6/17 (35.3%) | |
| Influenza like illness | 1/17 (5.9%) | |
| Infusion site extravasation | 1/17 (5.9%) | |
| Oedema peripheral | 3/17 (17.6%) | |
| Pyrexia | 2/17 (11.8%) | |
| Thirst | 1/17 (5.9%) | |
| Oedema | 1/17 (5.9%) | |
| Hepatobiliary disorders | ||
| Hyperbilirubinaemia | 1/17 (5.9%) | |
| Infections and infestations | ||
| Balanitis candida | 1/17 (5.9%) | |
| Cellulitis | 1/17 (5.9%) | |
| Nasopharyngitis | 1/17 (5.9%) | |
| Proctitis monilial | 1/17 (5.9%) | |
| Tooth abscess | 1/17 (5.9%) | |
| Upper respiratory tract infection | 3/17 (17.6%) | |
| Urinary tract infection | 1/17 (5.9%) | |
| Eye infection | 1/17 (5.9%) | |
| Laryngitis | 1/17 (5.9%) | |
| Injury, poisoning and procedural complications | ||
| Ligament sprain | 1/17 (5.9%) | |
| Tendon injury | 1/17 (5.9%) | |
| Investigations | ||
| Blood creatinine increased | 1/17 (5.9%) | |
| Liver function test abnormal | 1/17 (5.9%) | |
| Blood phosphorus decreased | 1/17 (5.9%) | |
| Metabolism and nutrition disorders | ||
| Decreased appetite | 2/17 (11.8%) | |
| Dehydration | 1/17 (5.9%) | |
| Hyperuricaemia | 1/17 (5.9%) | |
| Hypoalbuminaemia | 1/17 (5.9%) | |
| Hypokalaemia | 1/17 (5.9%) | |
| Hypomagnesaemia | 1/17 (5.9%) | |
| Hypophosphataemia | 2/17 (11.8%) | |
| Musculoskeletal and connective tissue disorders | ||
| Arthralgia | 1/17 (5.9%) | |
| Back pain | 1/17 (5.9%) | |
| Muscle spasms | 2/17 (11.8%) | |
| Muscular weakness | 2/17 (11.8%) | |
| Musculoskeletal chest pain | 1/17 (5.9%) | |
| Myalgia | 2/17 (11.8%) | |
| Pain in extremity | 1/17 (5.9%) | |
| Nervous system disorders | ||
| Balance disorder | 1/17 (5.9%) | |
| Brachial plexopathy | 1/17 (5.9%) | |
| Dizziness | 3/17 (17.6%) | |
| Dysgeusia | 1/17 (5.9%) | |
| Headache | 3/17 (17.6%) | |
| Hypogeusia | 1/17 (5.9%) | |
| Neuropathy peripheral | 1/17 (5.9%) | |
| Peripheral sensory neuropathy | 1/17 (5.9%) | |
| Hypoaesthesia | 1/17 (5.9%) | |
| Psychiatric disorders | ||
| Anxiety | 1/17 (5.9%) | |
| Depression | 1/17 (5.9%) | |
| Insomnia | 1/17 (5.9%) | |
| Renal and urinary disorders | ||
| Nocturia | 1/17 (5.9%) | |
| Pollakiuria | 1/17 (5.9%) | |
| Reproductive system and breast disorders | ||
| Breast pain | 1/17 (5.9%) | |
| Scrotal pain | 1/17 (5.9%) | |
| Respiratory, thoracic and mediastinal disorders | ||
| Cough | 2/17 (11.8%) | |
| Dyspnoea | 2/17 (11.8%) | |
| Epistaxis | 2/17 (11.8%) | |
| Increased upper airway secretion | 1/17 (5.9%) | |
| Upper-airway cough syndrome | 1/17 (5.9%) | |
| Sleep apnoea syndrome | 1/17 (5.9%) | |
| Skin and subcutaneous tissue disorders | ||
| Alopecia | 1/17 (5.9%) | |
| Blister | 1/17 (5.9%) | |
| Decubitus ulcer | 1/17 (5.9%) | |
| Dry skin | 1/17 (5.9%) | |
| Skin lesion | 1/17 (5.9%) | |
| Night sweats | 3/17 (17.6%) | |
| Pain of skin | 1/17 (5.9%) | |
| Pruritus | 2/17 (11.8%) | |
| Rash | 6/17 (35.3%) | |
| Vascular disorders | ||
| Hot flush | 1/17 (5.9%) | |
| Hypotension | 3/17 (17.6%) | |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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.
Results Point of Contact
| Name/Title | Pfizer ClinicalTrials.gov Call Center |
|---|---|
| Organization | Pfizer, Inc. |
| Phone | 1-800-718-1021 |
| ClinicalTrials.gov_Inquiries@pfizer.com |
- A5481002