Study of the Safety and Pharmacokinetics of XL765 (SAR245409) in Adults With Solid Tumors

Cancer Clinical Trial

Official title:

A Phase 1 Dose-Escalation Study of the Safety and Pharmacokinetics of XL765 Administered Orally Daily to Subjects With Solid Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00485719
• Other study ID #: TED11440
• Secondary ID: 2007-002437-36XL
• Status: Completed
• Phase: Phase 1
• First received: June 11, 2007
• Last updated: May 29, 2013
• Start date: June 2007
• Est. completion date: September 2012

Study information

• Verified date: May 2013
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationSpain: Spanish Agency of Medicines
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine the safety and tolerability of XL765. XL765 is a new chemical entity that inhibits the kinases PI3K and mTOR. In preclinical studies, inactivation of PI3K has been shown to inhibit growth and induce apoptosis (programmed cell death) in tumor cells, whereas inactivation of mTOR has been shown to inhibit the growth of tumor cells.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 83
• Est. completion date: September 2012
• Est. primary completion date: September 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• The subject has a histologically confirmed metastatic or unresectable solid tumor for which standard curative or palliative measures do not exist or are no longer effective, and there are no therapies known to prolong survival.

• The subject has disease that is assessable by tumor marker, physical, or radiologic means.

• The subject is at least 18 years old.

• The subject's weight is at lease 40 kg.

• The subject has an Eastern Cooperative Oncology Group performance status of 0 - 2.

• The subject has adequate organ and bone marrow function.

• The subject has fasting plasma glucose < 120 mg/dL at screening.

• for subjects who are to be enrolled into the Expanded MTD Cohort and Lower-Dose Tumor Genetic Alteration Subjects:

1. tumor tissue amenable to serial biopsy;

2. additional informed consent

• The subject is capable of understanding the protocol and has signed the informed consent.

• Sexually active subjects (male and female) must use medically acceptable methods of contraception during the course of the study.

• Female subjects of childbearing potential must have a negative serum pregnancy test at screening.

• If the subject has received more than 3 prior regimens of cytotoxic chemotherapy, more than 2 biologic regimens, or more than 3000 cGy to >25% of his or her bone marrow, the sponsor must determine subject suitability before enrollment.

• The subject has had no other diagnosis of malignancy (unless non-melanoma skin cancer, in situ carcinoma of the cervix, or a malignancy diagnosed = 2 years ago, and has had no evidence of disease for 2 years prior to screening for this study.)

Exclusion Criteria:

• The subject has received anticancer treatment (chemotherapy, radiotherapy, cytokines, or hormones) within 30 days (6 weeks for nitrosoureas, mitomycin C, or bicalutamide) before the first dose of XL765.

• The subject has received radiation to > 25% of his or her bone marrow.

• The subject has not recovered from adverse events, except Grade 2 alopecia, due to other investigational or other agents administered prior to study enrollment.

• The subject has received another investigational agent within 30 days or the first dose of XL765 or a small-molecule kinase inhibitor within 14 days or 5 half-lives.

• The subject is known to have diabetes

• The subject has uncontrolled intercurrent illness including ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia.

• The subject has psychiatric illness/social situation that would limit compliance with study requirements.

• The subject is pregnant or breast feeding.

• The subject is known to be positive for HIV.

• The subject has a known allergy or hypersensitivity to components of the XL765 formulation.

• The subject has a baseline corrected QT interval > 450 ms.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cancer

Intervention

Drug:
• XL765 (SAR245409)
Gelatin capsules supplied in 5-mg, 10-mg, and 50-mg strengths administered orally

Locations

Country	Name	City	State
Spain	Investigational Site Number 3411	Barcelona
United States	Investigational Site Number 1302	Detroit	Michigan
United States	Investigational Site Number 1435	Omaha	Nebraska
United States	Investigational Site Number 1402	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety, tolerability, and maximum tolerated dose (MTD) of daily oral administration of XL765 in two treatment schedules		Assessed at each visit/periodic visits	Yes
Secondary	Plasma pharmacokinetics of daily oral administration of XL765 in two treatment schedules		Assessed at periodic visits	No
Secondary	Pharmacodynamic effects of XL765 on tumor tissue when administered at the MTD in two treatment schedules		Assessed during periodic vixits after MTD is determined	No