CNF2024 (BIIB021) HER2- (QD) HER2+ (BIW w/Herceptin) PK/PD Study

A Ph1 Open-Label,Dose-Escalation,Safety,PK & PD Study of CNF2024 as a Single-Agent Treatment in Subjects w/HER2- Adv Breast Cancer or in Combo w/Trastuzumab in Subjects w/HER2+ Advanced Breast Cancer

The goal of this clinical research study is to study the drug CNF2024 as a single agent or in combination with trastuzumab in patients with advanced breast cancer and to:

• find the highest dose of the drug CNF2024 as a single agent or in combination with trastuzumab that can be given safely
• measure levels of CNF2024 as a single agent or in combination with trastuzumab in blood
• determine if CNF2024 as a single agent or in combination with trastuzumab can stop breast cancer cells from growing

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: CNF2024; Drug: CNF2024 + trastuzumab

Detailed Description

A Phase 1 Open-Label, Dose-Escalation, Safety, Pharmacokinetic, and Pharmacodynamic Study of CNF2024 as a Single-Agent Treatment in Subjects with HER2- Advanced Breast Cancer or in Combination with Trastuzumab in Subjects with HER2+ Advanced Breast Cancer

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Tampa, Florida, United States, 33612
      • Research Site
  • New York
    • New York, New York, United States, 10021
      • Research Site
  • Texas
    • Houston, Texas, United States, 77030
      • 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 (Group A):

• Age ≥18 years at the time of informed consent.
• Male and female subjects with confirmed HER2 adenocarcinoma of the breast with advanced disease (advanced disease will be defined as metastatic disease or locally advanced disease that is surgically unresectable and considered unmanageable with standard therapies such as radiation or systemic therapies) who have had disease progression on at least one standard hormonal or chemotherapy regimen for advanced breast cancer or who have refused standard therapies.
• Evaluable disease either by measurable disease (RECIST) or nonmeasurable disease.
• ECOG ≤2.
• Required Laboratory Values:ANC ≥1500 cells/mm3,platelet count ≥100,000 cells/mm3,hemoglobin ≥9 gm/L; Glucose >3.3 mmol/L, sodium >130 mmol/L, calcium >2.0 mmol/L.
• Plasma cortisol and ACTH levels that are not suggestive of adrenal insufficiency.
• Normal electrocardiogram (ECG) with QTc ≤450 msec for men and ≤470 msec for women.
• Female subjects of childbearing potential must have a negative pregnancy test within 7 days prior to first study drug administration.

Inclusion Criteria (Group B):

• Age ≥18 years at the time of informed consent.
• Male and female subjects with confirmed HER2+ (IHC 3+ or IHC 2+/FISH+) adenocarcinoma of the breast with advanced disease that have had disease progression on at least 1 standard hormonal or chemotherapy regimen for advanced metastatic breast cancer. Advanced disease will be defined as metastatic disease or locally advanced disease that is surgically unresectable and considered unmanageable with standard therapies such as radiation or systemic therapies.
• Subjects must have progressed either within 3 months following last dose of adjuvant trastuzumab treatment or progressed following trastuzumab based therapies for metastatic disease.
• Measurable disease by RECIST or evaluable nonmeasurable disease
• ECOG ≤2.
• Required Laboratory Values: ANC ≥1500 cells/mm3,platelet count ≥100,000 cells/mm3,hemoglobin ≥9 gm/L; Glucose >3.3 mmol/L, sodium >130 mmol/L, calcium >2.0 mmol/L.
• Plasma cortisol and ACTH levels that are not suggestive of adrenal insufficiency.
• Normal ECG with QTc ≤450 msec for men and ≤470 msec for women.
• Female subjects of childbearing potential must have a negative pregnancy test within 7 days prior to first study drug administration.

Exclusion Criteria (Group A):

• Prior antitumor therapies including prior experimental agents or approved antitumor therapies, within 1 month.
• Active infection requiring intravenous (IV) antibiotic treatment.
• History of prior malignancies within the past 5 years with the exception of curatively treated basal or squamous cell carcinomas of the skin or carcinoma in situ of the cervix.
• Concurrent severe or uncontrolled diabetes and/or other medical disease
• Problems with swallowing or malabsorption.
• History of major surgery to small intestine.
• Prior treatment with Hsp90 inhibitors.
• History of central nervous system (CNS) metastasis.

Exclusion Criteria (Group B):

• Prior antitumor therapies, including prior experimental agents or approved antitumor therapies, within 1 month.
• Active infection requiring intravenous (IV) antibiotic treatment.
• History of prior malignancies within the past 5 years with the exception of curatively treated basal or squamous cell carcinomas of the skin or carcinoma in situ of the cervix.
• Concurrent severe or uncontrolled diabetes and/or other medical disease
• Problems with swallowing or malabsorption.
• History of major surgery to small intestine.
• Cardiac left ventricular function with resting ejection fraction <50%, assessed by either ECHO or MUGA.
• Prior treatment with Hsp90 inhibitors.
• Diabetes treated with insulin.
• History of CNS metastasis.

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
Experimental: A; Patients with HER2- Breast Cancer	Drug: CNF2024; Oral doses of CNF2024 as specified in the protocol.; Other Names: BIIB021
Experimental: B; Patients with HER2+ Breast Cancer	Drug: CNF2024 + trastuzumab; Oral doses of CNF2024 as specified in the protocol Intravenous doses of trastuzumab as specified in the package insert.; Other Names: BIIB021 (CNF2024); Herceptin (trastuzumab)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Clinical and laboratory safety assessments	30 days after discontinuation of CNF2024 or until drug-related toxicites have returned to less than Grade 1

Collaborators and Investigators

• Sponsor: Biogen

Study record dates

Study Major Dates

• Study Start: December 1, 2007
• Primary Completion (Actual): April 1, 2011
• Study Completion (Actual): April 1, 2011

Study Registration Dates

• First Submitted: December 15, 2006
• First Submitted That Met QC Criteria: December 15, 2006
• First Posted (Estimate): December 18, 2006

Study Record Updates

• Last Update Posted (Estimate): June 8, 2012
• Last Update Submitted That Met QC Criteria: June 7, 2012
• Last Verified: December 1, 2011

More Information

Terms related to this study

• Keywords: Cancer of the Breast; Cancer of Breast
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Trastuzumab
• Other Study ID Numbers: 120BC101