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

NCT01105533 | Completed Phase 1 Results

• 1 other identifier: A8051001
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Neoplasm

Keywords

VGEF inhibitor; Anti angiogenesis; Advanced Solid Tumors

Outcome Measures

Primary Outcomes (4)

• 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.

  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.

  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.

  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.

  Day 28

Secondary Outcomes (8)

• Maximum Observed Plasma Concentration (Cmax)

  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)

  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)]

  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 - ∞)]

  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)

  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

Other Outcomes (1)

• Effect of Food on Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-24)]

  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

Study Arms (10)

Cohort 1

EXPERIMENTAL

Drug: PF-00337210

Cohort 2

EXPERIMENTAL

Drug: PF-00337210

Cohort 3

EXPERIMENTAL

Drug: PF-00337210

Cohort 4

EXPERIMENTAL

Drug: PF-00337210

Cohort 5

EXPERIMENTAL

Drug: PF-00337210

Cohort 6

EXPERIMENTAL

Drug: PF-00337210

Cohort 7

EXPERIMENTAL

Drug: PF-00337210

Cohort 8

EXPERIMENTAL

Drug: PF-00337210

Cohort 9

EXPERIMENTAL

Drug: PF-00337210

Cohort 10

EXPERIMENTAL

Drug: PF-00337210

Interventions

PF-00337210 DRUG

0.67mg Capsule Once Daily (Accelerated Dose Escalation) Continuous

Cohort 1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pfizer: lead
• University of Wisconsin, Madison: collaborator

Study Sites (3)

Pfizer Investigational Site

Detroit, Michigan, 48201, United States

Location

Pfizer Investigational Site

Detroit, Michigan, 48202, United States

Location

Pfizer Investigational Site

Madison, Wisconsin, 53792, United States

Location

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Neoplasms

Interventions

PF 00337210

Limitations and Caveats

Designation of outcomes as primary and secondary was based on study team input as study did not specify primary or secondary outcome measures.

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 14, 2010
• First Posted: April 16, 2010
• Study Start: May 1, 2006
• Primary Completion: October 1, 2010
• Study Completion: September 1, 2011
• Last Updated: March 19, 2013
• Results First Posted: March 19, 2013

Record last verified: 2013-02

Locations

US (3)