Targeted Therapy With Lapatinib in Patients With Recurrent Pituitary Tumors Resistant to Standard Therapy
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Purpose
PURPOSE
The drug Lapatinib has been shown to inhibit both epidermal growth factor receptor (EGFR) and erbB2 tyrosine kinases resulting in an effective slowing of disease progression in breast cancer. It has also been demonstrated that erbB is overexpressed in human pituitary adenomas. The investigators are therefore assessing tumor size stabilization and pituitary tumor secretory profiles during the course of a six month therapy of lapatinib. The purpose of this trial will be to estimate the activity of lapatinib in slowing the growth rate of pituitary tumors. Lapatinib is an FDA approved drug used to treat breast cancer. However, in this study, the drug will be used to treat pituitary cancer.
STUDY POPULATION
This study will recruit patients from the Pituitary Center at CSMC who are over the age of 18 that have a recurrent nonfunctioning adenoma after at least one surgical resection as well as patients with prolactinomas who are resistant to dopamine agonist therapy and patients with recurrent Cushing's disease.
PARTICIPANT'S JOURNEY THROUGH THE RESEARCH
The principal investigator (PI) or co-investigator will determine patients' potential eligibility for the study based on inclusion and exclusion criteria.
The PI or the co-investigator will then approach subjects with recurrent nonfunctioning adenomas or prolactinomas resistant to dopamine agonist therapy or recurrent Cushing's disease during a visit in the clinic office and ask if these subjects would be interested in participating in this study. If the subjects express interest, they will be given the consent form to review. They will be encouraged to review it with family, friends, and/or other physicians. The PI, co-investigators, or research nurse will be available for any questions the subjects might have. If the subjects are still interested, they will be asked to sign and return the consent form to the office and a study visit will be scheduled.
The PI, co-investigator, or member of study staff may also attempt to contact current patients by phone to assess interest in participating in the study. The purpose and overall structure of the study will be discussed with the possible participant. They will be reminded that the study is strictly voluntary and that their involvement or disinterest in the study will not affect their ongoing care. If the patient is interested they will be mailed a consent to review and will be asked to call the center to schedule an appointment to further discuss the study if they decide they are interested.
Each participant will undergo 8 visits of the course of the study. Each participant will have a baseline visit where a medical history will be taken, a physical, visual field test, electrocardiogram (ECG), echocardiogram (ECHO), and blood draw will be performed. At this point lapatinib therapy will begin and the patients will be asked to take the drug daily for the next six months. Patients will take Lapatinib 1250 mg daily (orally), which is the standardized dose used to treat breast cancer patients. Visit 2 will be 1 month after the participant has started lapatinib. At visit 2 all participants will receive a physical exam, a history will be taken, an ECG will be performed, and a blood draw will occur. Visit 3 will be 2 months after starting lapatinib. A physical exam and history will be performed along with an ECG and echocardiogram and blood draw. Visit 4 will be 3 months after starting lapatinib. A physical, history, blood draw, ECG, visual field test, and a magnetic resonance imaging (MRI) of the pituitary will be performed. Visit 5 will occur 4 months after starting lapatinib. A physical exam and history along with a blood draw and ECG and echocardiogram will occur. Visit 6 will be 5 months after starting lapatinib. A physical exam, history, ECG, and a blood draw will occur. Visit 7 will occur 6 months after the start of lapatinib. A physical exam, history, blood draw, visual field test, ECG, echocardiogram and MRI of the pituitary will occur. At this point lapatinib will be discontinued. Visit 8 will occur 1 month after visit 7 and a physical exam, history, blood draw, and ECG and and echocardiogram will occur.
| Condition | Intervention | Phase |
|---|---|---|
|
Pituitary Adenomas Prolactinomas Cushing's Disease |
Drug: Lapatinib |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Targeted Therapy With Lapatinib in Patients With Recurrent Pituitary Tumors Resistant to Standard Therapy |
- Primary outcome in nonfunctioning adenomas: stabilization of tumor volume and mean tumor diameter on MRI. Stabilization is defined as < 2 mm change in any dimension. MRIs will be performed at baseline and at 3 and 6 months. [ Time Frame: baseline and every 3 months ] [ Designated as safety issue: No ]
- Primary outcome in prolactinomas: normalization of prolactin levels. Prolactin levels will be measured at baseline and monthly. [ Time Frame: every month ] [ Designated as safety issue: No ]
- Primary outcome in Cushing's disease is normalization of urinary free cortisol levels. [ Time Frame: monthly ] [ Designated as safety issue: No ]
- Secondary outcomes: measurement of pituitary hormones [ Time Frame: monthly ] [ Designated as safety issue: No ]In both nonfunctioning adenomas, Cushing's disease, and prolactinomas, patients will pituitary hormone lab testing.
- Secondary outcome: visual field testing [ Time Frame: every 1-3 months ] [ Designated as safety issue: Yes ]Patients with preexisting visual field compromise will undergo visual field tests at visits 1-4 and 7. Patients with normal baseline visual field test will undergo visual field testing on visit 1, 4, 7.
| Estimated Enrollment: | 21 |
| Study Start Date: | July 2009 |
| Estimated Study Completion Date: | July 2014 |
| Estimated Primary Completion Date: | December 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Lapatinib
All participants will be asked to take Lapatinib daily for a total of six months during the research study.
|
Drug: Lapatinib
All participants will be asked to take Lapatinib daily for six months during the research study.
|
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Patients with nonfunctioning adenomas who have undergone at least one prior surgical resection and have demonstrated recurrence on MRI
- Patients with prolactinomas who are resistant to dopamine agonist therapy
- Patients with recurrent Cushing's disease
- Patients with visual field deficits and/or compression of the optic chiasm must be stable for at least 6 months
Exclusion Criteria:
- Patients with compromised visual fields and/or compression of the optic chiasm on MRI that has not been stable for last 6 months.
- Patients that have reduced left ventricular ejection fraction less than 50%
- Patients with moderate to severe hepatic impairment
- Patients that are pregnant or lactating
- Patients under the age of 18
- Active hepatitis
- Known previous HIV Positive
- Concurrent cancers
- Life expectancy less than one year
Contacts and Locations| Contact: William Gellepis | 310-423-3395 | gellepisw@cshs.org |
| Contact: Lori Korsakoff, RN | 310-423-2411 | korsakoffl@cshs.org |
| United States, California | |
| Pituitary Center Cedars-Sinai Medical Center | Recruiting |
| Los Angeles, California, United States, 90048 | |
| Principal Investigator: | Shlomo Melmed, MD | Cedars-Sinai Medical Center |
More Information
No publications provided
| Responsible Party: | Odelia Cooper, Principal investigator, Cedars-Sinai Medical Center |
| ClinicalTrials.gov Identifier: | NCT00939523 History of Changes |
| Other Study ID Numbers: | 18129 |
| Study First Received: | July 14, 2009 |
| Last Updated: | November 16, 2011 |
| Health Authority: | United States: Institutional Review Board |
Keywords provided by Cedars-Sinai Medical Center:
|
recurrent nonfunctioning adenoma prolactinomas Cushing's disease resistant pituitary tumors aggressive pituitary tumors |
Additional relevant MeSH terms:
|
Pituitary ACTH Hypersecretion Pituitary Neoplasms Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Pituitary Diseases Endocrine Gland Neoplasms Neoplasms by Site Hypothalamic Neoplasms Supratentorial Neoplasms Brain Neoplasms Central Nervous System Neoplasms Nervous System Neoplasms Adenoma Cushing Syndrome |
Prolactinoma Adrenocortical Hyperfunction Adrenal Gland Diseases Endocrine System Diseases Hyperpituitarism Hypothalamic Diseases Brain Diseases Central Nervous System Diseases Nervous System Diseases Lapatinib Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Antineoplastic Agents |
ClinicalTrials.gov processed this record on May 23, 2013