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
Overview
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Biogen
- Enrollment
- 70
- Locations
- 1
- Primary Endpoint
- effect on pharmacodynamic biomarkers
Overview
Brief Summary
This is an open-label, multicenter, dose-escalation, safety, pharmacokinetics, and pharmacodynamics study.
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 Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
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
Arms & 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.
Intervention: CNF2024 (Drug)
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).
Intervention: CNF2024 (Drug)
Outcomes
Primary Outcomes
effect on pharmacodynamic biomarkers
Time Frame: Dosing period
antitumor activity
Time Frame: At screening and after every 2 courses
pharmacokinetic profile
Time Frame: Dosing period
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.
To determine the safety profile
Time Frame: Study duration
Secondary Outcomes
No secondary outcomes reported