A Phase 1 interventional study of PF-00337210 and PF-00337210 in Neoplasm, sponsored by Pfizer. Completed at 3 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2013-03-19.
Sponsored by Pfizer · Phase 1, Interventional, and Treatment
This study will test a new cancer medication to determine if this medication will block blood supply to a tumor and decrease growth of a tumor. This study will also define the safety profile and define the safest dose of this new medication for people who have cancer.
9,616 studies on the registry are indexed under Neoplasms; 2,508 are open to participants now.
This study's enrollment of 46 is close to the median of 50 across 7,432 interventional studies indexed under Neoplasms.
Browse Neoplasms studies →Pfizer is the lead sponsor of 3,326 studies on the registry; 147 are open to participants now.
Of its 598 completed or terminated interventional studies of FDA-regulated products, 391 (65%) have results posted.
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During dose expansion - patient's whose hypertension is controlled by antihypertensive therapy.
Exclusion Criteria:
Drug: PF-00337210
Drug: PF-00337210
Drug: PF-00337210
Drug: PF-00337210
Drug: PF-00337210
Drug: PF-00337210
Drug: PF-00337210
Drug: PF-00337210
Drug: PF-00337210
Drug: PF-00337210
0.67mg Capsule Once Daily (Accelerated Dose Escalation) Continuous
1mg Capsule Once Daily (Dose Escalation) Continuous
2mg Capsule Once Daily (Dose Escalation) Continuous
4mg Capsule Once Daily (Dose Escalation) Continuous
6mg Capsule Once Daily (Dose Escalation) Continuous
9mg Capsule Once Daily (Dose Escalation) Continuous
8mg Capsule Once Daily (Dose Escalation) Continuous
4mg Capsule Twice Daily (Dose Escalation) Continuous
6mg Capsule Twice Daily (Dose Escalation) Continuous
6mg Capsule Twice Daily (Dose Expansion) Continuous
Number of Participants With Dose-limiting Toxicities (DLTs)
DLTs included events occurring in Cycle 1: blood pressure of 180/110 millimeters of mercury (mmHg) or higher for 3 readings over 3 hours regardless of use of anti-hypertensive drugs or greater than (\>) 160/100 mmHg for 3 readings over 3 days on maximum anti-hypertensive drugs; afebrile Grade 4 neutropenia for greater than or equal to (\>=) 7 days or \>=Grade 3 neutropenia associated with fever (1 reading of oral temperature \>38.5 degree Celsius \[degree C\] or 3 readings of oral temperature \>38.0 degree C in 24-hour period); Grade 4 thrombocytopenia; hemoptysis of \>1/2 teaspoon of bright red blood per day; proteinuria of \>=2 grams/24 hours; inability to resume PF-00337210 dosing at current dose level within 14 days of stopping due to treatment-related toxicity; \>=Grade 3 nonhematological toxicities (except alopecia and blood pressure/hypertension); Grade 3 nonhematological toxicities that could be controlled to Grade 2 or less with appropriate treatment were not considered dose limiting.
Time frame: Baseline up to Day 28
Maximum Tolerated Dose (MTD)
MTD: dose level at which no more than 1 of 6 participants experienced DLT during Cycle 1. DLTs: blood pressure of 180/110 mmHg or higher for 3 readings over 3 hours regardless of use of anti-hypertensive drugs or \>160/100 mmHg for 3 readings over 3 days on maximum anti-hypertensive drugs; afebrile Grade 4 neutropenia \>=7 days or \>= Grade 3 neutropenia associated with fever (1 reading of oral temperature \>38.5 degree C or 3 readings of oral temperature \>38.0 degree C in 24-hour period); Grade 4 thrombocytopenia; hemoptysis of \>1/2 teaspoon of bright red blood per day; proteinuria of \>=2 grams/24 hours; inability to resume PF-00337210 dosing at current dose level within 14 days of stopping due to treatment-related toxicity; \>=Grade 3 nonhematological toxicities (except alopecia and blood pressure/hypertension); Grade 3 nonhematological toxicities that could be controlled to Grade 2 or less with appropriate treatment were not considered dose limiting.
Time frame: Day 28
Maximum Administered Dose (MAD)
MAD: dose level at which 2 or more out of 6 participants experienced DLT during Cycle 1. DLTs: blood pressure of 180/110 mmHg or higher for 3 readings over 3 hours regardless of use of anti-hypertensive drugs or \>160/100 mmHg for 3 readings over 3 days on maximum anti-hypertensive drugs; afebrile Grade 4 neutropenia \>=7 days or \>= Grade 3 neutropenia associated with fever (1 reading of oral temperature \>38.5 degree C or 3 readings of oral temperature \>38.0 degree C in 24-hour period); Grade 4 thrombocytopenia; hemoptysis of \>1/2 teaspoon of bright red blood per day; proteinuria of \>=2 grams/24 hours; inability to resume PF-00337210 dosing at current dose level within 14 days of stopping due to treatment-related toxicity; \>=Grade 3 nonhematological toxicities (except alopecia and blood pressure/hypertension); Grade 3 nonhematological toxicities that could be controlled to Grade 2 or less with appropriate treatment were not considered dose limiting.
Time frame: Day 28
Recommended Phase-2 Dose (RP2D)
RP2D was determined based on the safety profile and pharmacodynamic findings. The twice daily dosing was preferred over once daily dosing for RP2D, as per investigator's discretion, due to more consistent changes in pharmacodynamic markers and greater clinical benefit observed in twice daily dosing.
Time frame: Day 28
Maximum Observed Plasma Concentration (Cmax)
Time frame: Pre-dose,0.5,1,2,4,6,8,10,16,20,24 hours(hrs) post-dose on Day 1(0.67 mg group);pre-dose,0.5,1,2,4,6,8,18,20,24 hrs post-dose on Day 1,15,29(once daily groups);pre-dose,0.5,1,2,4,6,8 hrs post-dose on Day 1,15,29 (twice daily groups);pre-dose on Day 43, 57
Plasma Decay Half-Life (t1/2)
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Time frame: Pre-dose,0.5,1,2,4,6,8,10,16,20,24 hrs post-dose on Day 1(0.67 mg group);pre-dose,0.5,1,2,4,6,8,18,20,24 hrs post-dose on Day 1,15,29(once daily groups);pre-dose,0.5,1,2,4,6,8 hrs post-dose on Day 1,15,29 (twice daily groups);pre-dose on Day 43, 57
Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-24)]
AUC (0-24)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-24).
Time frame: Pre-dose,0.5,1,2,4,6,8,10,16,20,24 hrs post-dose on Day 1(0.67 mg group);pre-dose,0.5,1,2,4,6,8,18,20,24 hrs post-dose on Day 1,15,29(once daily groups);pre-dose,0.5,1,2,4,6,8 hrs post-dose on Day 1,15,29 (twice daily groups);pre-dose on Day 43, 57
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)]
AUC (0 - ∞)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞).
Time frame: Pre-dose,0.5,1,2,4,6,8,10,16,20,24 hrs post-dose on Day 1(0.67 mg group);pre-dose,0.5,1,2,4,6,8,18,20,24 hrs post-dose on Day 1,15,29(once daily groups);pre-dose,0.5,1,2,4,6,8 hrs post-dose on Day 1,15,29 (twice daily groups);pre-dose on Day 43, 57
Apparent Volume of Distribution (Vss)
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose is influenced by the fraction absorbed.
Time frame: Pre-dose,0.5,1,2,4,6,8,10,16,20,24 hrs post-dose on Day 1(0.67 mg group);pre-dose,0.5,1,2,4,6,8,18,20,24 hrs post-dose on Day 1,15,29(once daily groups);pre-dose,0.5,1,2,4,6,8 hrs post-dose on Day 1,15,29 (twice daily groups);pre-dose on Day 43, 57
Systemic Clearance (CL)
CL is a quantitative measure of the rate at which a drug substance is removed from the body.
Time frame: Pre-dose,0.5,1,2,4,6,8,10,16,20,24 hrs post-dose on Day 1(0.67 mg group);pre-dose,0.5,1,2,4,6,8,18,20,24 hrs post-dose on Day 1,15,29(once daily groups);pre-dose,0.5,1,2,4,6,8 hrs post-dose on Day 1,15,29 (twice daily groups);pre-dose on Day 43, 57
Number of Participants With Objective Response of Complete Response or Partial Response
Number of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed CR defined as disappearance of all target and non-target lesions and no appearance of new lesions. Confirmed PR defined as at least 30 percent decrease in sum of the longest dimensions (LD) of the target lesions, taking as a reference the baseline sum LD, without progression of non-target lesions and no appearance of new lesions. Confirmed responses are those that persist on repeat imaging study \>=4 weeks after initial documentation of response.
Time frame: Baseline, every 8 weeks up to Cycle 25 (Week 100)
Change From Baseline in Biomarkers at Day 1 of Each Cycle up to Cycle 25
Biomarkers included soluble plasma proteins associated with angiogenesis (vascular endothelial growth factor \[VEGF\], soluble vascular endothelial growth factor-2 receptor \[sVEGFR2\], soluble vascular endothelial growth factor-3 receptor \[sVEGFR3\], soluble beta type platelet-derived growth factor \[sPDGFR beta\]) and tumor proliferation (soluble stem-cell factor receptor \[sKIT\])
Time frame: Baseline, Day 1 of Cycle 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25
Effect of Food on Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-24)]
AUC (0-24)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-24).
Time frame: Pre-dose,0.5,1,2,4,6,8,18,20,24 hrs post-dose on Day 29 (fasted state), Day 30 (fed state) for once daily groups, pre-dose,0.5,1,2,4,6,8 hrs post-dose on Day 29 Day 29 (fasted state), Day 30 (fed state) for twice daily groups
| Milestone | PF-00337210 0.67 mg Once Daily | PF-00337210 1 mg Once Daily | PF-00337210 2 mg Once Daily | PF-00337210 4 mg Once Daily | PF-00337210 6 mg Once Daily | PF-00337210 8 mg Once Daily | PF-00337210 9 mg Once Daily | PF-00337210 4 mg Twice Daily | PF-00337210 6 mg Twice Daily |
|---|---|---|---|---|---|---|---|---|---|
| Started | 1 | 1 | 3 | 3 | 7 | 7 | 8 | 4 | 12 |
| Completed | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Not completed | 1 | 1 | 3 | 3 | 7 | 7 | 8 | 4 | 12 |
| Withdrew: Death | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Withdrew: Lack of efficacy | 1 | 1 | 3 | 3 | 4 | 5 | 3 | 2 | 9 |
| Withdrew: Adverse event | 0 | 0 | 0 | 0 | 1 | 2 | 2 | 0 | 1 |
| Withdrew: Other | 0 | 0 | 0 | 0 | 1 | 0 | 3 | 1 | 2 |
| Withdrew: Physician decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
DLTs included events occurring in Cycle 1: blood pressure of 180/110 millimeters of mercury (mmHg) or higher for 3 readings over 3 hours regardless of use of anti-hypertensive drugs or greater than (\>) 160/100 mmHg for 3 readings over 3 days on maximum anti-hypertensive drugs; afebrile Grade 4 neutropenia for greater than or equal to (\>=) 7 days or \>=Grade 3 neutropenia associated with fever (1 reading of oral temperature \>38.5 degree Celsius \[degree C\] or 3 readings of oral temperature \>38.0 degree C in 24-hour period); Grade 4 thrombocytopenia; hemoptysis of \>1/2 teaspoon of bright red blood per day; proteinuria of \>=2 grams/24 hours; inability to resume PF-00337210 dosing at current dose level within 14 days of stopping due to treatment-related toxicity; \>=Grade 3 nonhematological toxicities (except alopecia and blood pressure/hypertension); Grade 3 nonhematological toxicities that could be controlled to Grade 2 or less with appropriate treatment were not considered dose limiting.
| participants | PF-00337210 0.67 mg Once Daily | PF-00337210 1 mg Once Daily | PF-00337210 2 mg Once Daily | PF-00337210 4 mg Once Daily | PF-00337210 6 mg Once Daily | PF-00337210 8 mg Once Daily | PF-00337210 9 mg Once Daily | PF-00337210 4 mg Twice Daily | PF-00337210 6 mg Twice Daily |
|---|---|---|---|---|---|---|---|---|---|
| Number of Participants With Dose-limiting Toxicities (DLTs) | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 1 |
MTD: dose level at which no more than 1 of 6 participants experienced DLT during Cycle 1. DLTs: blood pressure of 180/110 mmHg or higher for 3 readings over 3 hours regardless of use of anti-hypertensive drugs or \>160/100 mmHg for 3 readings over 3 days on maximum anti-hypertensive drugs; afebrile Grade 4 neutropenia \>=7 days or \>= Grade 3 neutropenia associated with fever (1 reading of oral temperature \>38.5 degree C or 3 readings of oral temperature \>38.0 degree C in 24-hour period); Grade 4 thrombocytopenia; hemoptysis of \>1/2 teaspoon of bright red blood per day; proteinuria of \>=2 grams/24 hours; inability to resume PF-00337210 dosing at current dose level within 14 days of stopping due to treatment-related toxicity; \>=Grade 3 nonhematological toxicities (except alopecia and blood pressure/hypertension); Grade 3 nonhematological toxicities that could be controlled to Grade 2 or less with appropriate treatment were not considered dose limiting.
| mg once daily | PF-00337210 |
|---|---|
| Maximum Tolerated Dose (MTD) | 8 |
MAD: dose level at which 2 or more out of 6 participants experienced DLT during Cycle 1. DLTs: blood pressure of 180/110 mmHg or higher for 3 readings over 3 hours regardless of use of anti-hypertensive drugs or \>160/100 mmHg for 3 readings over 3 days on maximum anti-hypertensive drugs; afebrile Grade 4 neutropenia \>=7 days or \>= Grade 3 neutropenia associated with fever (1 reading of oral temperature \>38.5 degree C or 3 readings of oral temperature \>38.0 degree C in 24-hour period); Grade 4 thrombocytopenia; hemoptysis of \>1/2 teaspoon of bright red blood per day; proteinuria of \>=2 grams/24 hours; inability to resume PF-00337210 dosing at current dose level within 14 days of stopping due to treatment-related toxicity; \>=Grade 3 nonhematological toxicities (except alopecia and blood pressure/hypertension); Grade 3 nonhematological toxicities that could be controlled to Grade 2 or less with appropriate treatment were not considered dose limiting.
| mg once daily | PF-00337210 |
|---|---|
| Maximum Administered Dose (MAD) | 9 |
RP2D was determined based on the safety profile and pharmacodynamic findings. The twice daily dosing was preferred over once daily dosing for RP2D, as per investigator's discretion, due to more consistent changes in pharmacodynamic markers and greater clinical benefit observed in twice daily dosing.
| mg twice daily | PF-00337210 |
|---|---|
| Recommended Phase-2 Dose (RP2D) | 6 |
No measurements were reported for this outcome.
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
No measurements were reported for this outcome.
AUC (0-24)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-24).
No measurements were reported for this outcome.
AUC (0 - ∞)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞).
No measurements were reported for this outcome.
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose is influenced by the fraction absorbed.
No measurements were reported for this outcome.
CL is a quantitative measure of the rate at which a drug substance is removed from the body.
No measurements were reported for this outcome.
Number of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed CR defined as disappearance of all target and non-target lesions and no appearance of new lesions. Confirmed PR defined as at least 30 percent decrease in sum of the longest dimensions (LD) of the target lesions, taking as a reference the baseline sum LD, without progression of non-target lesions and no appearance of new lesions. Confirmed responses are those that persist on repeat imaging study \>=4 weeks after initial documentation of response.
| participants | PF-00337210 |
|---|---|
| Number of Participants With Objective Response of Complete Response or Partial Response | 2 |
Biomarkers included soluble plasma proteins associated with angiogenesis (vascular endothelial growth factor \[VEGF\], soluble vascular endothelial growth factor-2 receptor \[sVEGFR2\], soluble vascular endothelial growth factor-3 receptor \[sVEGFR3\], soluble beta type platelet-derived growth factor \[sPDGFR beta\]) and tumor proliferation (soluble stem-cell factor receptor \[sKIT\])
No measurements were reported for this outcome.
AUC (0-24)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-24).
No measurements were reported for this outcome.
Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| PF-00337210 | — | 19/46 (41.3%) | 46/46 (100%) |
| Event | PF-00337210 |
|---|---|
| Disease progressionGeneral disorders | 4/46 |
| DehydrationMetabolism and nutrition disorders | 4/46 |
| VomitingGastrointestinal disorders | 2/46 |
| FatigueGeneral disorders | 2/46 |
| PneumoniaInfections and infestations | 2/46 |
| Alanine aminotransferase increasedInvestigations | 2/46 |
| Aspartate aminotransferase increasedInvestigations | 2/46 |
| Blood bilirubin increasedInvestigations | 2/46 |
| Palmar-plantar erythrodysaesthesia syndromeSkin and subcutaneous tissue disorders | 2/46 |
| LeukocytosisBlood and lymphatic system disorders | 1/46 |
| Event | PF-00337210 |
|---|---|
| HypertensionVascular disorders | 24/46 |
| FatigueGeneral disorders | 23/46 |
| DiarrhoeaGastrointestinal disorders | 18/46 |
| NauseaGastrointestinal disorders | 18/46 |
| Decreased appetiteMetabolism and nutrition disorders | 11/46 |
| ProteinuriaRenal and urinary disorders | 11/46 |
| Abdominal painGastrointestinal disorders | 10/46 |
| Back painMusculoskeletal and connective tissue disorders | 10/46 |
| DizzinessNervous system disorders | 9/46 |
| HeadacheNervous system disorders | 9/46 |
| Age Continuous(years) | PF-00337210 |
|---|---|
| Mean | 53.9 ± 13.1 |
| Sex: Female, Male(Participants) | PF-00337210 |
|---|---|
| Female | 21 |
| Male | 25 |
The record gives a start of May 2006, a primary completion of Oct 2010 and a completion of Sep 2011. It does not say whether these dates are actual or estimated.
Results were first posted in Mar 2013, 2 years 5 months after primary completion.
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This study is completed, as verified in Feb 2013. You cannot join it, but the record below documents what was studied.
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