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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Virginia Commonwealth University
Sponsor:
Information provided by (Responsible Party):
Virginia Commonwealth University
ClinicalTrials.gov Identifier:
NCT01427322
First received: August 30, 2011
Last updated: July 7, 2014
Last verified: July 2014
  Purpose

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


Condition Intervention Phase
Epithelial Cancer
Drug: Lapatinib
Radiation: Radiation therapy
Phase 0

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Virginia Commonwealth University:

Primary Outcome Measures:
  • TGFalpha [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 34
Study Start Date: September 2011
Estimated Study Completion Date: August 2016
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

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

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.
  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: NCT01427322

Contacts
Contact: Andrew S. Poklepovic, MD 804-628-2321 apoklepovic@vcu.edu
Contact: Diane Holdford, RN 804-828-0296 djholdfo@vcu.edu

Locations
United States, Virginia
Hunter Holmes McGuire VA Medical Center Recruiting
Richmond, Virginia, United States, 23249
Contact: Vicki L Skinner, RN    804-675-5646    vicki.skinner@va.gov   
Principal Investigator: Drew Moghanaki, MD         
Massey Cancer Center, Virginia Commonwealth University Recruiting
Richmond, Virginia, United States, 23298-0037
Contact: Andrew S. Poklepovic, MD    804-628-2321    apoklepovic@vcu.edu   
Contact: Diane Holdford, RN    804-828-0296    djholdfo@vcu.edu   
Principal Investigator: Andrew S. Poklepovic, MD         
Sponsors and Collaborators
Virginia Commonwealth University
Investigators
Principal Investigator: Andrew S. Poklepovic, MD Massey Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Virginia Commonwealth University
ClinicalTrials.gov Identifier: NCT01427322     History of Changes
Other Study ID Numbers: MCC-13711, NCI-2011-02734
Study First Received: August 30, 2011
Last Updated: July 7, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Virginia Commonwealth University:
lapatinib
radiation therapy
metastases

Additional relevant MeSH terms:
Neoplasm Metastasis
Neoplasms
Neoplastic Processes
Pathologic Processes
Lapatinib
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014