Study of Oral CNF2024 (BIIB021) in Advanced Solid Tumors - Full Text View

Sponsored by:	Biogen Idec
Information provided by:	Biogen Idec
ClinicalTrials.gov Identifier:	NCT00345189

Purpose

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

Condition	Intervention	Phase
Tumors Lymphoma	Drug: CNF2024	Phase I

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Dose Comparison, Parallel Assignment, Safety/Efficacy Study
Official Title:	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

Resource links provided by NLM:

MedlinePlus related topics: Cancer Lymphoma

U.S. FDA Resources

Further study details as provided by Biogen Idec:

Primary Outcome Measures:

To determine the maximum tolerated dose (MTD) [ Time Frame: 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. ] [ Designated as safety issue: Yes ]
To determine the safety profile [ Time Frame: Study duration ] [ Designated as safety issue: Yes ]
pharmacokinetic profile [ Time Frame: Dosing period ] [ Designated as safety issue: No ]
effect on pharmacodynamic biomarkers [ Time Frame: Dosing period ] [ Designated as safety issue: No ]
antitumor activity [ Time Frame: At screening and after every 2 courses ] [ Designated as safety issue: No ]

Enrollment:	70
Study Start Date:	February 2006
Study Completion Date:	April 2009
Primary Completion Date:	July 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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.
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.

Arms

Assigned Interventions

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.

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.

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00345189

Locations

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

Sponsors and Collaborators

Biogen Idec

Investigators

Study Director:

Biogen Idec Medical Monitor, MD

Biogen Idec

More Information

No publications provided

Responsible Party:	Biogen Idec ( Biogen Idec MD )
Study ID Numbers:	CNF2024-ST-05003, 120ST101
Study First Received:	June 23, 2006
Last Updated:	July 10, 2009
ClinicalTrials.gov Identifier:	NCT00345189 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by Biogen Idec:

Hsp90 inhibitor
CNF2024
Advanced Solid Tumors

Study placed in the following topic categories:

Lymphatic Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Lymphoma

Additional relevant MeSH terms:

Lymphatic Diseases
Neoplasms
Immunoproliferative Disorders
Neoplasms by Histologic Type

Immune System Diseases
Lymphoproliferative Disorders
Lymphoma

ClinicalTrials.gov processed this record on September 11, 2009