This Is The First Study Using Escalating Doses Of PF-03758309, An Oral Compound, In Patients With Advanced Solid Tumors

NCT00932126 | Terminated Phase 1 Results

• 1 other identifier: B1301001
• Study Type: interventional
• Target: 35
• Locations: 2 countries
• Sites: 3

Brief Summary

This is the first study using PF-03758309, an oral compound, in patients with advanced solid tumors. In this study different doses of PF-03758309 will be administered to different groups of patients. The study will assess the compound's safety, the blood levels of PF-03758309 during the treatment and the effect of the compound on the tumor cells.

Conditions

Advanced Solid Tumors

Keywords

Phase 1 dose escalation dose finding pharmacokinetic and pharmacodynamic study

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Cycle 1 Dose-limiting Toxicities (DLT)

  DLT includes: Grade (GR) 4 neutropenia (NP) that persisted for \>7 consecutive days; Febrile NP; GR3 NP infection; GR4 thrombocytopenia (TP); GR3 TP with bleeding; Any other GR\>=3 toxicity not classified under Common Terminology Criteria for Adverse Events (CTCAE) blood or bone marrow (exception of nausea, vomiting, or diarrhea in subjects who received optimal treatment with antiemetics or anti-diarrheals); Failure to recover to an adequate condition to recommence study treatment after a 2-week delay; Failure to receive \>= 80% of planned PF-03758309 dose due to study drug related toxicity

  Baseline (up to 30 days prior to first study drug administration) till 28 days after the last treatment administration (end of Cycle 1 [28 days])

Secondary Outcomes (11)

• Number of Participants With Objective Response

  Baseline until the date of first documented progression or discontinuation from the study due to any cause, assessed every 2 months until when the last participant was discontinued due to disease progression in Month 27 of the study

• Time to Tumor Progression (TTP)

  Baseline until the date of first documented progression or discontinuation from the study due to any cause, assessed every 2 months until when the last participant was discontinued due to disease progression in Month 27 of the study

• Duration of Response

  Baseline until the date of first documented progression or discontinuation from the study due to any cause, assessed every 2 months until when the last participant was discontinued due to disease progression in Month 27 of the study

• Maximum Observed Plasma Concentration (Cmax)

  predose, 0.5, 1, 2, 3, 5, 8, 10, 24 and 48 hours post dose, on Cycle 1 Day 8 and Cycle 2-4 Day 1 at pre-dose and 2 hours post morning dose, and on Cycle 1 Day 15 at predose, 0.5, 1, 2, 3, 5, 8 and 10 hours post morning dose

• Time to Reach Maximum Observed Plasma Concentration (Tmax)

  predose, 0.5, 1, 2, 3, 5, 8, 10, 24 and 48 hours post dose, on Cycle 1 Day 8 and Cycle 2-4 Day 1 at pre-dose and 2 hours post morning dose, and on Cycle 1 Day 15 at predose, 0.5, 1, 2, 3, 5, 8 and 10 hours post morning dose

Study Arms (1)

1

EXPERIMENTAL

Drug: PF-03758309

Interventions

PF-03758309 DRUG

Oral PF-03758309 will be administered in capsules (once or twice daily) until toxicity, progressive disease, or patient refusal to continue on therapy. The starting dose is 1 mg once daily.

1

Eligibility Criteria

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

You may qualify if:

• Advanced/metastatic solid tumor that is resistant to standard therapy or for which no standard therapy is available.
• ECOG (Eastern Cooperative Oncology Group) Performance Status (PS) must be 0 or 1.
• Adequate bone marrow, liver and kidney function.

You may not qualify if:

• Patients with known brain metastases.
• Previous high dose chemotherapy requiring stem cell rescue.
• Prior irradiation to \>25% of the bone marrow.
• Active bacterial, fungal or viral infection including hepatitis B (HBV), hepatitis C (HCV).
• Current active treatment in another clinical study.
• Pregnancy or breast feeding.
• Active inflammatory gastrointestinal disease, chronic diarrhea (unless related to underlying malignancy or prior related treatment) or history of abdominal fistula, gastrointestinal perforation, peptic ulcer disease, or intra-abdominal abscess within 6 months prior to study enrollment.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (3)

Pfizer Investigational Site

Santa Monica, California, 90404, United States

Location

Pfizer Investigational Site

Aurora, Colorado, 80045, United States

Location

Pfizer Investigational Site

East Melbourne, Victoria, 3002, Australia

Location

Related Publications (1)

• Mpilla GB, Uddin MH, Al-Hallak MN, Aboukameel A, Li Y, Kim SH, Beydoun R, Dyson G, Baloglu E, Senapedis WT, Landesman Y, Wagner KU, Viola NT, El-Rayes BF, Philip PA, Mohammad RM, Azmi AS. PAK4-NAMPT Dual Inhibition Sensitizes Pancreatic Neuroendocrine Tumors to Everolimus. Mol Cancer Ther. 2021 Oct;20(10):1836-1845. doi: 10.1158/1535-7163.MCT-20-1105. Epub 2021 Jul 12.

  PMID: 34253597 DERIVED

Related Links

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

Limitations and Caveats

The study was closed due to pharmacokinetic (PK) issues observed from initial PK data. Individual plasma concentration versus time were listed but final PK analysis and pharmacodynamic analyses were not conducted.

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: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 30, 2009
• First Posted: July 3, 2009
• Study Start: September 1, 2009
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2011
• Last Updated: October 28, 2015
• Results First Posted: March 6, 2013

Record last verified: 2015-10

Locations

US (2); AU (1)