Study of Oral CNF2024 (BIIB021) in Advanced Solid Tumors

A Phase 1, Multicenter, Open-Label, Dose-Escalation, Safety, PK, and PD Study of CNF2024 Administered Orally Twice Weekly for 3 Weeks of a 4 Week Course or Twice Weekly for 4 Weeks of a 4 Week Course to Patients With Advanced Solid Tumors

This is an open-label, multicenter, dose-escalation, safety, pharmacokinetics, and pharmacodynamics study.

Study Overview

• Status: Completed
• Conditions: Lymphoma; Tumors
• Intervention / Treatment: Drug: CNF2024

Detailed Description

Heat shock protein 90 (Hsp90) is an ubiquitous molecular chaperone protein that is involved in folding, activation, and assembly of many proteins, including key mediators of signal transduction, cell cycle control, and transcriptional regulation. In cancer cells that are dependent upon Hsp90 client proteins, the degree to which clients are inhibited correlates closely with induction of growth inhibition and apoptosis with Hsp90 inhibitory drugs. The active pharmaceutical ingredient of CNF2024, CF1983 mesylate, is a synthetic, new chemical entity designed to inhibit Hsp90. CF1983 hada strong affinity for tumor derived Hsp90 and weaker affinity for Hsp90 isolated from normal cells or recombinant Hsp90.

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Surrey
    • Sutton, Surrey, United Kingdom, SM2 5PT
      • Research Site
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • Research Site
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Research Site
  • Texas
    • San Antonio, Texas, United States, 78245
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically or cytologically confirmed solid tumor which has failed standard therapies (surgery, radiotherapy, endocrine therapy, chemotherapy) or for which effective therapy is not available
• At least 18 years of age
• Hematology: Absolute neutrophil count (ANC) > 1500 cells/mm3, platelet count > 100,000 cells/mm3 and hemoglobin >= 9 gm/L
• Hepatic: Bilirubin < 1.5 X upper limit of normal (ULN); alanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 2.5 X ULN. Patients with known liver metastases or liver neoplasms: alanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 5.0 X ULN.
• Renal: Serum creatinine levels < 2.0 mg/dL or creatinine clearance > 60 mL/min
• Coagulation: international normalized ratio (INR) < 1.5 times normal
• Adrenal: Normal plasma cortisol and adrenocorticotropic hormone (ACTH) levels
• Normal electrocardiogram (ECG) with QTc <= 450 msec for men and <= 470 msec for women
• Estimated life expectancy of at least 3 months as determined by the Investigator
• Eastern Cooperative Oncology Group (ECOG) performance status <= 2
• Male and female patients of childbearing potential must practice effective double-barrier contraception during the study and continue contraception for 3 months after their last dose of study drug. Male patients must agree to not have intercourse with pregnant or nursing women during the study and for 3 months after their last dose of study drug, unless using double-barrier contraception. The only exceptions to double-barrier contraception are: Patient or partner is surgically sterile,female patient is postmenopausal for at least 1 year before screening or patient abstains from sexual intercourse, at the discretion of the Investigator

Exclusion Criteria:

• Pregnant or nursing women, women of child-bearing age not using reliable means of contraception.
• Radiotherapy or chemotherapy within the previous 28 days. Recovery to Grade 1 or less from chemotherapy-induced toxic effect, except alopecia, is required.
• Participation in any investigational drug study within 28 days prior to CNF2024 administration
• Active infection requiring intravenous antibiotic treatment
• Patients with second malignancy requiring active treatment (except hormonal therapy)
• Concurrent severe or uncontrolled medical disease (i.e., systemic infection, diabetes, hypertension, coronary artery disease, congestive heart failure)
• Active symptomatic fungal, bacterial and/or viral infection including active HIV or viral (A, B or C) hepatitis
• Problems with swallowing or malabsorption
• Chronic diarrhea (excess of 2-3 stools/day above normal frequency)
• Gastrointestinal diseases including gastritis, ulcerative colitis, Crohn's disease, or hemorrhagic coloproctitis
• Major surgery of the stomach or small intestine
• Adrenal dysfunction > Grade 2
• Patients with diabetes (your doctor will discuss if you are eligible for this study)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Dosing Schedule 1; Starting dose of 25 mg, with dosing twice a week for 3 weeks out of a 4-week course (Schedule 1). Dosing for schedule 1 is currently closed.	Drug: CNF2024; CNF2024 capsules administered orally following 2 schedules: starting dose of 25 mg, twice a week for 3 weeks out of a 4-week course (Schedule 1) or; starting dose of 600 mg twice a week for 4 weeks out of a 4-week course (without drug holidays; Schedule 2). Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Dose escalation proceeds according to the predetermined scheme until the stopping dose is reached due to a dose limiting toxicity (DLT) occurring during the first 4-week course of treatment.; Other Names: Advanced Solid Tumors
Other: Dosing Schedule 2; Starting dose of 600 mg, with dosing twice a week for 4 weeks out of a 4-week course (without drug holidays; Schedule 2).	Drug: CNF2024; CNF2024 capsules administered orally following 2 schedules: starting dose of 25 mg, twice a week for 3 weeks out of a 4-week course (Schedule 1) or; starting dose of 600 mg twice a week for 4 weeks out of a 4-week course (without drug holidays; Schedule 2). Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Dose escalation proceeds according to the predetermined scheme until the stopping dose is reached due to a dose limiting toxicity (DLT) occurring during the first 4-week course of treatment.; Other Names: Advanced Solid Tumors

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To determine the maximum tolerated dose (MTD)	Dose escalation will proceed according to the predetermined scheme until the stopping dose (dose > MTD) is reached due to dose limiting toxicities (DLT) occurring during the first 4-week course of treatment.
To determine the safety profile	Study duration
pharmacokinetic profile	Dosing period
effect on pharmacodynamic biomarkers	Dosing period
antitumor activity	At screening and after every 2 courses

Collaborators and Investigators

• Sponsor: Biogen
• Investigators: Study Director: Biogen Idec Medical Monitor, MD, Biogen

Study record dates

Study Major Dates

• Study Start: February 1, 2006
• Primary Completion (Actual): July 1, 2008
• Study Completion (Actual): April 1, 2009

Study Registration Dates

• First Submitted: June 23, 2006
• First Submitted That Met QC Criteria: June 23, 2006
• First Posted (Estimate): June 27, 2006

Study Record Updates

• Last Update Posted (Estimate): July 14, 2009
• Last Update Submitted That Met QC Criteria: July 10, 2009
• Last Verified: July 1, 2009

More Information

Terms related to this study

• Keywords: Advanced Solid Tumors; Hsp90 inhibitor; CNF2024
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: CNF2024-ST-05003; 120ST101