CP-751871 In Treating Women With Early-Stage Breast Cancer That Can Be Removed By Surgery

A Phase 1 Pharmacodynamic Study Of CP-751,871 As Neoadjuvant Treatment For Early Breast Cancer

RATIONALE: Monoclonal antibodies, such as CP-751871, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them.

PURPOSE: This phase I trial is studying the side effects and best way to give CP-751871 in treating patients with early-stage breast cancer that can be removed by surgery.

Study Overview

• Status: Withdrawn
• Conditions: Breast Cancer
• Intervention / Treatment: Other: pharmacological study; Other: laboratory biomarker analysis; Procedure: neoadjuvant therapy; Procedure: conventional surgery; Other: imaging biomarker analysis; Procedure: magnetic resonance spectroscopic imaging; Biological: figitumumab

Detailed Description

Primary

• To evaluate the change in total tumor choline levels in women with operable early breast cancer in response to neoadjuvant CP-751871 treatment.

Secondary

• To assess changes in tumor glucose levels after CP-751871 treatment using magnetic resonance spectroscopy in these patients.
• To assess the safety, tolerability, and immunogenicity of CP-751871 in these patients.
• To assess the effect of CP-751871 on Insulin-like Growth Factor 1 receptor (IGF-1R) signaling markers in tumor tissues in these patients.
• To assess the clinical efficacy of CP-751871 in these patients (MRI and pathological responses).

OUTLINE: Patients receive CP-751871 IV over 5 hours on days 1 and 22 and undergo magnetic resonance spectroscopy on days 8 and 29. Patients may also undergo surgery between days 29-43 to obtain a tumor sample for analysis of markers related to the IGR-1R pathway.

After completion of study treatment, patients will be followed for 5 months.

• Study Type: Interventional
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed early operable adenocarcinoma of the breast
• No evidence of invasive lobular breast disease
• Measurable disease, defined as at least 1 lesion ≥ 2 cm by MRI
• Measurable levels of total choline according to institutional criteria by magnetic resonance spectroscopy
• Must have available or scheduled core breast biopsy procedure
• Hormone receptor status not specified

PATIENT CHARACTERISTICS:

• Menopausal status not specified
• ECOG performance status 0-1
• Platelet count ≥ 100,000/mm^³
• Neutrophil count ≥ 1,500/mm³
• Creatinine < 1.5 times upper limit of normal (ULN)
• Bilirubin < 1.5 times ULN
• ALT and AST < 2.5 times ULN
• Fertile patients must use adequate barrier method contraception during and for at least 150 days after completion of study treatment
• Ability to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures
• No known hypersensitivity to monoclonal antibodies
• No prior or active malignancies other than curatively treated in situ carcinoma of the cervix, uterus, or basal cell or squamous cell carcinoma of the skin
• No serious uncontrolled medical disorder or active infection that would impair the ability to receive study treatment

• No significant active cardiac disease including any of the following:

  • Uncontrolled high blood pressure (i.e., systolic blood pressure [BP] > 160 mm Hg and diastolic BP > 95 mm Hg)
  • Unstable angina
  • Deep venous thrombosis
  • Pulmonary embolism
  • Cerebrovascular attack
  • Valvular disease
  • Congestive heart failure
  • Myocardial infarction with the past 6 months
  • Serious cardiac arrhythmias
• No dementia or significantly altered mental status that would limit the understanding or rendering of informed consent and compliance with study requirements

PRIOR CONCURRENT THERAPY:

• More than 4 weeks since prior surgery and recovered
• More than 2 weeks since high-dose corticosteroid therapy (i.e., ≥ 100 mg prednisone per day or > 40 mg dexamethasone per day)
• No prior anti-IGF-1R based investigational therapy
• No prior systemic therapy for primary disease

• No concurrent chronic systemic high-dose immunosuppressive steroid therapy

  • Low-dose steroids for nausea and vomiting control allowed
  • Topical corticosteroid applications, inhaled sprays, eye drops or local injections (e.g., intraocular) allowed
• No concurrent other anticancer drugs or therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Tumor total choline (tCho) changes determined by magnetic resonance spectroscopy

Secondary Outcome Measures

Outcome Measure
Pathological response
Safety, tolerability and human anti-human antibodies (HAHA) response
Tissue markers
Measure of tumor glucose levels
Tumor size by MRI

Collaborators and Investigators

• Sponsor: Pfizer
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Douglas Yee, MD, Masonic Cancer Center, University of Minnesota

Study record dates

Study Registration Dates

• First Submitted: March 12, 2008
• First Submitted That Met QC Criteria: March 12, 2008
• First Posted (Estimate): March 13, 2008

Study Record Updates

• Last Update Posted (Estimate): March 11, 2015
• Last Update Submitted That Met QC Criteria: March 10, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: stage II breast cancer; stage IA breast cancer; stage IB breast cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: A4021012; P30CA077598 (U.S. NIH Grant/Contract); NCI-CDR0000589252