Study of Oral CNF2024 (BIIB021) in Advanced Solid Tumors

Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00345189
• Other study ID #: CNF2024-ST-05003
• Secondary ID: 120ST101
• Status: Completed
• Phase: Phase 1
• First received: June 23, 2006
• Last updated: July 10, 2009
• Start date: February 2006
• Est. completion date: April 2009

Study information

• Verified date: July 2009
• Source: Biogen
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 70
• Est. completion date: April 2009
• Est. primary completion date: July 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

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

Related Conditions & MeSH terms

• Lymphoma
• Tumors

Intervention

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.

Locations

Country	Name	City	State
United Kingdom	Research site	Sutton	Surrey
United States	Research site	New Haven	Connecticut
United States	Research site	San Antonio	Texas
United States	Research site	Scottsdale	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Biogen

Countries where clinical trial is conducted

United States,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Yes
Primary	To determine the safety profile		Study duration	Yes
Primary	pharmacokinetic profile		Dosing period	No
Primary	effect on pharmacodynamic biomarkers		Dosing period	No
Primary	antitumor activity		At screening and after every 2 courses	No