Lapatinib and Bortezomib in Patients With Advanced Malignancies

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Georgetown University
Sponsor:
Collaborators:
GlaxoSmithKline
Millennium Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Georgetown University
ClinicalTrials.gov Identifier:
NCT01497626
First received: December 20, 2011
Last updated: August 13, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
Advanced Solid Tumors
Drug: Lapatinib and bortezomib
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of the HER1, HER2 Dual Kinase Inhibitor, Lapatinib Plus the Proteosomal Inhibitor Bortezomib in Patients With Advanced Malignancies

Resource links provided by NLM:


Further study details as provided by Georgetown University:

Primary Outcome Measures:
  • Maximum tolerated dose [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
    The highest dose at which </= 1 out of 6 subjects has a dose-limiting toxicity


Secondary Outcome Measures:
  • toxicity [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
    Adverse events seen during the trial graded using CTCAE version 4

  • Response rate [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    complete response and partial response measured by RECIST 1.1

  • Disease control rate [ Time Frame: 2 months ] [ Designated as safety issue: No ]
    stable disease after two cycles+ partial response + complete response as determined by RECIST 1.1 criteria

  • Pharmacodynamics [ Time Frame: pre-treatment, after 1 week of therapy and adter 3 weeks of therapy ] [ Designated as safety issue: No ]
    To assess changes in the following in serial tumor samples: EGFR, HER2, HER3, AKT, Actin, ERK, GSK3a-beta, IGF-1R, MEK 1/2, mTOR, p70S6, P13K, PTEN, SHC Y317, NFKB, IKB, CFK4, CDK2, cyclin D1, cyclin A, Cyclin E, p15, p16, p21, p27, beta-catenin, and ras gene mutation


Estimated Enrollment: 40
Study Start Date: September 2011
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Bortezomib plus lapatinib
Combination treatment with lapatinib and bortezomib
Drug: Lapatinib and bortezomib

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.

Other Name: Velcade

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • Patients with lymphomas
  • CNS metastases which do not meet the criteria outlines in the inclusion criteria
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01497626

Contacts
Contact: Ion Cotarla 202-687-4510 ic34@georgetown.edu
Contact: Christine Fasano 202-687-2007 ccf42@georgetown.edu

Locations
United States, District of Columbia
Georgetown Lombardi Comprehensive Cancer Center Recruiting
Washington, District of Columbia, United States, 20007
Contact: Ion Cotarla    202-687-4510    ic34@georgetown.edu   
Contact: Christine Fasano, RN    202-687-2007    ccf42@georgetown.edu   
Principal Investigator: Michael Pishvaian, MD PhD         
Sponsors and Collaborators
Georgetown University
GlaxoSmithKline
Millennium Pharmaceuticals, Inc.
Investigators
Principal Investigator: Michael Pishvaian, MD PhD Georgetown University
  More Information

No publications provided

Responsible Party: Georgetown University
ClinicalTrials.gov Identifier: NCT01497626     History of Changes
Other Study ID Numbers: 2010-533, XO5371, 8LAP114999
Study First Received: December 20, 2011
Last Updated: August 13, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Georgetown University:
Advanced cancer
Solid tumor

Additional relevant MeSH terms:
Bortezomib
Lapatinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 18, 2014