Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Study of Oral CNF2024 (BIIB021) in Advanced Solid Tumors

This study has been completed.
Sponsor:
Information provided by:
Biogen Idec
ClinicalTrials.gov Identifier:
NCT00345189
First received: June 23, 2006
Last updated: July 10, 2009
Last verified: July 2009
  Purpose

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


Condition Intervention Phase
Tumors
Lymphoma
Drug: CNF2024
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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:


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.

Other Name: Advanced Solid Tumors
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 Name: Advanced Solid Tumors

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Keywords provided by Biogen Idec:
Hsp90 inhibitor
CNF2024
Advanced Solid Tumors

Additional relevant MeSH terms:
Neoplasms

ClinicalTrials.gov processed this record on November 20, 2014