Safety Study of XL647 and XL147 Administered in Combination Daily in Adults With Solid Tumors

NCT00704392 | Withdrawn Phase 1

• 1 other identifier: XL647-003
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to determine the safety, tolerability, and highest safe doses of XL647 in combination with XL147 in adults with solid tumors. XL647 is a small molecule that potently inhibits multiple receptor kinases, including EGFR, VEGFR2 (KDR), and ErbB2. XL147 is a new chemical entity that inhibits PI3 Kinase. Inactivation of PI3K has been shown to inhibit growth and induce apoptosis (programmed cell death) in tumor cells.

Conditions

Cancer; Non-small-cell Lung Cancer; Breast Cancer

Keywords

Solid tumors; NSCLC

Outcome Measures

Primary Outcomes (1)

• Safety, tolerability, and maximum tolerated dose (MTD) of XL647 administered in combination with XL147 orally daily

  Assessed at periodic visits

Secondary Outcomes (2)

• Characterize pharmacokinetic parameters of XL647 administered in combination with XL147 daily in subjects with solid tumors

  Assessed at periodic visits

• Assess pharmacodynamic effects of the XL647 and XL147 combination regimen at the highest safe dose of these agents in subjects with non-small-cell lung cancer or breast cancer

  Assessed at periodic visits

Study Arms (1)

1

EXPERIMENTAL

Drug: XL647; Drug: XL147

Interventions

XL647 DRUG

Tablets supplied at 50-mg strength administered orally daily

1

XL147 DRUG

Gelatin capsules supplied at 25-mg and 100-mg strengths administered orally daily

1

Eligibility Criteria

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

You may qualify if:

• The subject has a histologically confirmed solid tumor that is metastatic or unresectable and is no longer responding to therapies known to prolong survival or to other standard therapies, or has disease for which no standard therapy exists.
• The subject is ≥ 18 years old.
• The subject's weight is ≥ 50 kg.
• The subject has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
• The subject has a life expectancy of ≥ 3 months.
• The subject has adequate organ and marrow function.
• The subject has a fasting plasma glucose (FPG) \< 120 mg/dL at screening.
• The subject is capable of understanding and complying with the protocol and has signed the informed consent document.
• Sexually active subjects (male and female) must agree to use accepted methods of contraception during the course of the study and for 3 months after the last dose of protocol drug(s).
• Female subjects of childbearing potential must have a negative pregnancy test at screening.
• Subjects in the MTD Expansion Cohort:
• Must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST).
• Must have a histologically confirmed diagnosis of NSCLC (Stage IIIB or IV) OR a histologically confirmed diagnosis of metastatic breast cancer.

You may not qualify if:

• The subject has received cytotoxic chemotherapy (including investigational cytotoxic chemotherapy) within 3 weeks (or nitrosoureas or mitomycin C within 6 weeks) before the first dose of XL647.
• The subject has received prior treatment with a small molecule kinase inhibitor (including an investigational kinase inhibitor) within 14 days before the first dose of XL647.
• The subject has received any other type of investigational agent within 30 days before the first dose of study treatment.
• The subject has not recovered from toxicity due to prior therapy.
• The subject has had major surgery within 30 days before the first dose of study drug. Subjects must have recovered or stabilized from prior surgery.
• The subject is known to have diabetes.
• The subject is currently receiving anticoagulation with warfarin (low-dose warfarin ≤ 1mg/day, heparin, and low-molecular weight heparins are permitted).
• The subject has prothrombin time (PT)/International Normalized Ratio (INR) and /or partial thromboplastin time (PTT) test results at screening that are above 1.3 times the laboratory upper limit of normal.
• The subject has any of the following cardiac criteria:
• Corrected QT interval (QTc) of \> 0.46 seconds
• Has a finding of left bundle branch block
• Has important bradycardia defined as a heart rate of \< 50 bpm due to sinus node dysfunction
• Has an obligate pacemaker
• History of sustained ventricular arrhythmias (subjects with a history of atrial arrhythmias should be discussed with the sponsor before entry into the study)
• Family history of congenital long QT syndrome or unexplained sudden death

Sponsors & Collaborators

• Exelixis: lead

Study Sites (2)

Memorial Sloan Kettering Cancer Center

New York, New York, 10021, United States

Location

South Texas Accelerated Research Therapeutics

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Neoplasms; Carcinoma, Non-Small-Cell Lung; Breast Neoplasms

Interventions

XL647; XL147

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: June 20, 2008
• First Posted: June 24, 2008
• Study Start: June 1, 2008
• Primary Completion: December 1, 2009
• Study Completion: December 1, 2009
• Last Updated: August 20, 2015

Record last verified: 2015-08

Locations

US (2)