Randomized RT +/- Lapatinib for Advanced Solid Tumor Cancer Patients Receiving Radiation Therapy for Metastatic Disease
Primary Purpose
Epithelial Cancer
Status
Terminated
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Lapatinib
Radiation therapy
Sponsored by
About this trial
This is an interventional treatment trial for Epithelial Cancer focused on measuring lapatinib, radiation therapy, metastases
Eligibility 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.
Sites / Locations
- Hunter Holmes McGuire VA Medical Center
- Massey Cancer Center, Virginia Commonwealth University
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
lapatinib + radiation therapy
No therapy prior to radiation
Arm Description
lapatinib given orally 2-4 hours prior to first fraction of radiation
Radiation therapy alone
Outcomes
Primary Outcome Measures
TGFalpha
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.
Secondary Outcome Measures
Full Information
NCT ID
NCT01427322
First Posted
August 30, 2011
Last Updated
July 6, 2015
Sponsor
Virginia Commonwealth University
1. Study Identification
Unique Protocol Identification Number
NCT01427322
Brief Title
Randomized RT +/- Lapatinib for Advanced Solid Tumor Cancer Patients Receiving Radiation Therapy for Metastatic Disease
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 Type
Interventional
2. Study Status
Record Verification Date
July 2015
Overall Recruitment Status
Terminated
Why Stopped
Slow accrual
Study Start Date
September 2011 (undefined)
Primary Completion Date
December 2014 (Actual)
Study Completion Date
July 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Virginia Commonwealth University
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Epithelial Cancer
Keywords
lapatinib, radiation therapy, metastases
7. Study Design
Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
6 (Actual)
8. Arms, Groups, and Interventions
Arm Title
lapatinib + radiation therapy
Arm Type
Experimental
Arm Description
lapatinib given orally 2-4 hours prior to first fraction of radiation
Arm Title
No therapy prior to radiation
Arm Type
Active Comparator
Arm Description
Radiation therapy alone
Intervention Type
Drug
Intervention Name(s)
Lapatinib
Other Intervention Name(s)
GW572016, Tykerb
Intervention Description
given orally 2-4 hours before first fraction of radiation therapy
Intervention Type
Radiation
Intervention Name(s)
Radiation therapy
Intervention Description
Standard radiation therapy
Primary Outcome Measure Information:
Title
TGFalpha
Description
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.
Time Frame
3 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andrew S. Poklepovic, MD
Organizational Affiliation
Massey Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hunter Holmes McGuire VA Medical Center
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23249
Country
United States
Facility Name
Massey Cancer Center, Virginia Commonwealth University
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298-0037
Country
United States
12. IPD Sharing Statement
Links:
URL
http://www.massey.vcu.edu/
Description
Massey Cancer Center
Learn more about this trial
Randomized RT +/- Lapatinib for Advanced Solid Tumor Cancer Patients Receiving Radiation Therapy for Metastatic Disease
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