Lapatinib and Bortezomib in Patients With Advanced Malignancies

NCT01497626 | Terminated Phase 1 DMC

• 3 other identifiers: 2010-533XO53718LAP114999
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

This study is for patients with an advanced type of cancer for which no curative treatment exists. The purpose of this study is to test the safety and efficacy of the combination of the study drugs, lapatinib and bortezomib. Lapatinib is a drug that targets two proteins important for the growth of cancer cells known as HER1 (EGFR) and HER2. By inhibiting these proteins, lapatinib can inhibit cancer cell growth and even lead to their death. Lapatinib is an oral pill given by mouth once every day. Lapatinib is approved by the FDA for patients with breast cancer. Bortezomib is a drug that targets a part of cancer cells known as the proteosome. By inhibiting the proteosome, bortezomib can inhibit cancer cell growth and even lead to their death. Bortezomib is given intravenously, once a week, 2 out of every 3 weeks. Bortezomib is approved by the FDA for patients with multiple myeloma and mantle cell lymphoma. This research is being done because it is not known if the combination of lapatinib and bortezomib will work better than lapatinib or bortezomib alone, although in the lab and in animal studies the combination of the two drugs was much more effective than either drug alone. As part of this study biopsies will be taken of patients' tumors before any treatment, after starting lapatinib alone, and after receiving both lapatinib and bortezomib. Investigators want to study what markers inside tumors may relate to how well these two medications work. These biopsies are required as part of the study.

Conditions

Advanced Solid Tumors

Keywords

Advanced cancer; Solid tumor

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose

  The highest dose at which \</= 1 out of 6 subjects has a dose-limiting toxicity

  18 months

Secondary Outcomes (4)

• toxicity

  18 months

• Response rate

  18 months

• Disease control rate

  2 months

• Pharmacodynamics

  pre-treatment, after 1 week of therapy and adter 3 weeks of therapy

Study Arms (1)

Bortezomib plus lapatinib

EXPERIMENTAL

Combination treatment with lapatinib and bortezomib

Drug: Lapatinib and bortezomib

Interventions

Lapatinib and bortezomib DRUG

Lapatinib will be taken orally continuously for 28 days of each 28-day cycle, including a run-in of lapatinib alone day -7 to day 1 of cycle 1. Bortezomib will be administered IV on days 1, 8, and 15 of each cycle. The exact doses of both drugs will be dependent on which cohort the subject is in and adverse events observed in previous cohorts.

Also known as: Velcade

Bortezomib plus lapatinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically proven malignant solid tumor with measurable disease
• Progression on, or intolerance of, or ineligibility for all standard therapies
• Biopsy accessible tumor deposits
• LVEF \>/= institutional normal
• Corrected QT interval less than 500 milliseconds by EKG
• ECOG performance status 0-2
• Subjects with no brain metastases or a history of previously treated brain metastases who have been treated by surgery or stereotactic radiosurgery at least 4 weeks prior to enrollment and have a baseline MRI that shows no evidence of active intercranial disease and have not had treatment with steroids within 1 week of enrollment.
• Adequate hepatic, bone marrow, and renal function
• Partial thromboplastin time must be \</= 1.5 x upper limit of institution's normal range and INR \< 1.5. Subjects on anticoagulants will be permitted to enroll as long as the INR is in the acceptable therapeutic range.
• Life expectancy \> 12 weeks
• Women of childbearing potential must have a negative serum pregnancy test within 14 days prior to initiation of treatment and/or postmenopausal women must be amenorrheic for at least 12 months.
• Subject is capable of understanding and complying with parameters as outlines in the protocol and able to sign and date the informed consent form.

You may not qualify if:

• Patients with lymphomas
• Peripheral neuropathy \>/= Grade 2 at baseline or peripheral neuropathy \>/= Grade 1 with neuropathic pain
• Active severe infection or known chronic infection with HIV or hepatitis B virus
• Cardiovascular disease problems including unstable angina, therapy for life-threatening ventricular arrhythmia, or myocardial infarction, stroke, or congestive heart failure within the last 6 months
• Life-threatening visceral disease or other severe concurrent disease
• Women who are pregnant or breastfeeding
• Anticipated patient survival under 3 months
• Concurrent use of known CYP 3A4 inhibiting or activating medications

Sponsors & Collaborators

• Georgetown University: lead
• GlaxoSmithKline: collaborator
• Millennium Pharmaceuticals, Inc.: collaborator

Study Sites (1)

Georgetown Lombardi Comprehensive Cancer Center

Washington D.C., District of Columbia, 20007, United States

Location

Related Publications (1)

• Lynce F, Wang H, Petricoin EF, Pohlmann PR, Smaglo B, Hwang J, He AR, Subramaniam DS, Deeken J, Marshall J, Pishvaian MJ. A phase I study of HER1, HER2 dual kinase inhibitor lapatinib plus the proteasome inhibitor bortezomib in patients with advanced malignancies. Cancer Chemother Pharmacol. 2019 Nov;84(5):1145-1151. doi: 10.1007/s00280-019-03947-7. Epub 2019 Sep 19.

  PMID: 31538230 DERIVED

MeSH Terms

Interventions

Lapatinib; Bortezomib

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring

Study Officials

• Michael Pishvaian, MD PhD

  Georgetown University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2011
• First Posted: December 22, 2011
• Study Start: September 1, 2011
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: February 17, 2016

Record last verified: 2015-09

Locations

US (1)