A Dose Finding Study Of A New Medication, PF-00337210 That Will Possibly Decrease Blood Supply To Tumors

This study has been completed.
Sponsor:
Collaborator:
University of Wisconsin, Madison
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01105533
First received: April 14, 2010
Last updated: February 13, 2013
Last verified: February 2013
  Purpose

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.


Condition Intervention Phase
Neoplasm
Drug: PF-00337210
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I, Open-Label, Multi-Center, Accelerated Dose Escalation Study Of The Anti-Angiogenesis Agent PF-00337210 In Patients With Advanced Solid Tumors

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Number of Participants With Dose-limiting Toxicities (DLTs) [ Time Frame: Baseline up to Day 28 ] [ Designated as safety issue: Yes ]
    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.

  • Maximum Tolerated Dose (MTD) [ Time Frame: Day 28 ] [ Designated as safety issue: Yes ]
    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.

  • Maximum Administered Dose (MAD) [ Time Frame: Day 28 ] [ Designated as safety issue: Yes ]
    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.

  • Recommended Phase-2 Dose (RP2D) [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • Plasma Decay Half-Life (t1/2) [ 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 ] [ Designated as safety issue: No ]
    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

  • Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (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 ] [ Designated as safety issue: No ]
    AUC (0-24)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-24).

  • Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] [ 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 ] [ Designated as safety issue: No ]
    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 - ∞).

  • Apparent Volume of Distribution (Vss) [ 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 ] [ Designated as safety issue: No ]
    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.

  • Systemic Clearance (CL) [ 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 ] [ Designated as safety issue: No ]
    CL is a quantitative measure of the rate at which a drug substance is removed from the body.

  • Number of Participants With Objective Response of Complete Response or Partial Response [ Time Frame: Baseline, every 8 weeks up to Cycle 25 (Week 100) ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Biomarkers at Day 1 of Each Cycle up to Cycle 25 [ 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 ] [ Designated as safety issue: No ]
    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])


Other Outcome Measures:
  • Effect of Food on Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (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 ] [ Designated as safety issue: No ]
    AUC (0-24)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-24).


Enrollment: 46
Study Start Date: May 2006
Study Completion Date: September 2011
Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1 Drug: PF-00337210
0.67mg Capsule Once Daily (Accelerated Dose Escalation) Continuous
Experimental: Cohort 2 Drug: PF-00337210
1mg Capsule Once Daily (Dose Escalation) Continuous
Experimental: Cohort 3 Drug: PF-00337210
2mg Capsule Once Daily (Dose Escalation) Continuous
Experimental: Cohort 4 Drug: PF-00337210
4mg Capsule Once Daily (Dose Escalation) Continuous
Experimental: Cohort 5 Drug: PF-00337210
6mg Capsule Once Daily (Dose Escalation) Continuous
Experimental: Cohort 6 Drug: PF-00337210
9mg Capsule Once Daily (Dose Escalation) Continuous
Experimental: Cohort 7 Drug: PF-00337210
8mg Capsule Once Daily (Dose Escalation) Continuous
Experimental: Cohort 8 Drug: PF-00337210
4mg Capsule Twice Daily (Dose Escalation) Continuous
Experimental: Cohort 9 Drug: PF-00337210
6mg Capsule Twice Daily (Dose Escalation) Continuous
Experimental: Cohort 10 Drug: PF-00337210
6mg Capsule Twice Daily (Dose Expansion) Continuous

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytologically confirmed advanced solid tumors un-responsive to currently available therapies or for which there is no standard therapy.
  • At least 1 measurable disease site as defined by Response Evaluation Criterion in Solid Tumors [RECIST].
  • Adequate bone marrow, liver function and renal function as defined by protocol.
  • Blood pressure Requirements During dose escalation - no evidence of pre-existing hypertension and no antihypertensive medications at baseline.

During dose expansion - patient's whose hypertension is controlled by antihypertensive therapy.

Exclusion Criteria:

  • Chemotherapy, radiotherapy or any investigational therapy within 4 weeks of study entry
  • Current use or anticipated need for drugs that are known CYP34 inhibitors or inducers.
  • Patients with carcinomatous meningitis or un-treated brain metastases.
  • Any acute cardiovascular incident within the past 12 months.
  • Patients with active gastrointestinal bleeding or significant gastrointestinal abnormalities as defined by protocol
  • Patients with no evidence of the following for 5 years: malignancy or metastatic disease of skin cancer (except melanoma), in situ cervical cancer or breast cancer or T1C prostate cancer.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01105533

Locations
United States, Michigan
Pfizer Investigational Site
Detroit, Michigan, United States, 48202
Pfizer Investigational Site
Detroit, Michigan, United States, 48201
United States, Wisconsin
Pfizer Investigational Site
Madison, Wisconsin, United States, 53792
Sponsors and Collaborators
Pfizer
University of Wisconsin, Madison
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01105533     History of Changes
Other Study ID Numbers: A8051001
Study First Received: April 14, 2010
Results First Received: December 20, 2012
Last Updated: February 13, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
VGEF inhibitor
Anti angiogenesis
Advanced Solid Tumors

Additional relevant MeSH terms:
Neoplasms
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 28, 2014