Randomized RT +/- Lapatinib for Advanced Solid Tumor Cancer Patients Receiving Radiation Therapy for Metastatic Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01427322
Recruitment Status : Terminated (Slow accrual)
First Posted : September 1, 2011
Last Update Posted : July 8, 2015
Information provided by (Responsible Party):
Virginia Commonwealth University

Brief Summary:
Lapatinib will prevent radiation-induced increase in Transforming Growth Factor alpha (TGFα), an important growth factor in cancer cell recovery after ionizing irradiation.

Condition or disease Intervention/treatment Phase
Epithelial Cancer Drug: Lapatinib Radiation: Radiation therapy Early Phase 1

Detailed Description:
Lapatinib is an orally bioavailable small molecule inhibitor of ERBB1 and ERBB2 (HER2). It is currently indicated for use in patients with HER2 over-expressing metastatic breast cancer. Serum increases in TGFα can have growth potentiating effects on distant sites of metastatic disease. Palliative irradiation paradoxically may promote distant tumor growth; blocking shedding of TGFα from irradiated tumors may prevent this effect and improve the therapeutic index of radiation therapy.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 6 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized Study of Lapatinib With Radiation Versus Radiation Alone in Advanced Solid Tumor Cancer Patients Receiving Radiation Therapy for Metastatic Disease
Study Start Date : September 2011
Primary Completion Date : December 2014
Study Completion Date : July 2015

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: lapatinib + radiation therapy
lapatinib given orally 2-4 hours prior to first fraction of radiation
Drug: Lapatinib
given orally 2-4 hours before first fraction of radiation therapy
Other Names:
  • GW572016
  • Tykerb
Radiation: Radiation therapy
Standard radiation therapy
Active Comparator: No therapy prior to radiation
Radiation therapy alone
Radiation: Radiation therapy
Standard radiation therapy

Primary Outcome Measures :
  1. TGFalpha [ Time Frame: 3 years ]
    Blockade of the ERBB1 receptor will abrogate increases in TGFalpha in response to radiation therapy. We will compare serum changes in TGFalpha between the lapatinib and control groups for patients receiving radiotherapy for stage IV epithelial-derived cancer.

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • History of stage IV epithelial-derived cancer requiring palliative radiation. Patients with sarcoma, lymphoma, myeloma or neuroendocrin cancers are not eligible.
  • Evidence of metastatic disease
  • Recommendation by patient's radiation oncologist to receive palliative external beam radiation for metastases -- minimum fraction size of 3 Gy.
  • Age 18 years or older
  • Patients may be undergoing concurrent therapy with GNRH agonists or combined androgen blockade or anti-estrogen hormonal therapy for breast cancer, as these are standard care for advanced prostate and some breast cancers respectively.
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  • Any contraindication to lapatinib treatment.
  • Prior radiation therapy within 30 days of the start of the planned course of treatment.
  • Prior cytotoxic chemotherapy within 4-2 weeks of planned first dose of radiation. Persistent grade 2 or greater non-hematologic toxicity (other than neuropathy) from cytotoxic chemotherapy regardless of interval since last dose. Persistent grade 3 or greater hematologic toxicity (other than lymphopenia) reglardless of interval since last dose.
  • Prior administration of an ERBB1 or ERK1/2 inhibitor within 30 days of the start of the planned course of treatment.
  • Patients with a medical necessity to continue active therapy with CYP3A4 strong inhibitors or inducers. The concomitant use of strong CYP3A4 inhibitors should be avoided (e.g., ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole, aprepitant). Grapefruit may also increase plasma concentrations of lapatinib and should be avoided. Once the strong inhibitor or inducer is discontinued, a washout period of approximately 1 week should be allowed before the lapatinib administration. If a patient is unable to discontinue these medications, they are not eligible for enrollment.
  • Concurrent administration of any other investigational agents.
  • Uncontrolled concurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, active hepatic or biliary disease with a Child-Pugh class of B or C, or psychiatric illness/social situations that would limit compliance with study requirements or that would interfere with accomplishing the study objectives.
  • Pregnant or nursing. Women of childbearing potential must have a negative pregnancy test performed within 7 days prior to the start of treatment. Women of childbearing potential and men must agree to use a medically accepted form of birth control for the duration of study participation. Men must agree to use a medically accepted form of birth control for 4 months following completion of study treatment.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01427322

United States, Virginia
Hunter Holmes McGuire VA Medical Center
Richmond, Virginia, United States, 23249
Massey Cancer Center, Virginia Commonwealth University
Richmond, Virginia, United States, 23298-0037
Sponsors and Collaborators
Virginia Commonwealth University
Principal Investigator: Andrew S. Poklepovic, MD Massey Cancer Center

Additional Information:
Responsible Party: Virginia Commonwealth University Identifier: NCT01427322     History of Changes
Other Study ID Numbers: MCC-13711
NCI-2011-02734 ( Registry Identifier: CTRP )
First Posted: September 1, 2011    Key Record Dates
Last Update Posted: July 8, 2015
Last Verified: July 2015

Keywords provided by Virginia Commonwealth University:
radiation therapy

Additional relevant MeSH terms:
Neoplasm Metastasis
Neoplastic Processes
Pathologic Processes
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action