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Targeted Therapy With Lapatinib in Patients With Recurrent Pituitary Tumors Resistant to Standard Therapy

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.
ClinicalTrials.gov Identifier: NCT00939523
Recruitment Status : Completed
First Posted : July 15, 2009
Results First Posted : January 13, 2020
Last Update Posted : January 22, 2020
Information provided by (Responsible Party):
Odelia Cooper, Cedars-Sinai Medical Center

Brief Summary:
This study focuses on new therapies for a challenging disease in pituitary medicine, that of aggressive pituitary tumors which have limited therapeutic options beyond standard surgical, radiotherapy, and select medical therapies, each incurring significant morbidity and mortality, and each not optimally effective. To improve this gap in knowledge, we seek to translate findings from the laboratory into clinical practice and hone in on therapies directed at pituitary molecular targets, namely ErbB receptors. We have shown that human prolactinomas express nuclear EGFR and membranous ErbB2, ErbB3 and ErbB4, and expression correlates with tumor invasion. Pituitary tumor cell lines transfected with EGFR and ErbB2 translated to downstream effects on prolactin (PRL) gene expression and secretion,as well as cell proliferation. Animal models implanted with these cell lines developed larger tumors and PRL elevations. Treatment with ErbB tyrosine kinase inhibitors (TKIs) led to regression of tumors xenografted into these animals and attenuated PRL secretion. Primary culture of human prolactinomas confirmed expression of ErbB receptors and inhibitory effects of TKIs on PRL secretion and cell proliferation. Based on these exciting preliminary data, the objective of this new proposal is to conduct a Phase IIa clinical trial as a trenchant test of our translational hypothesis that tyrosine kinase inhibition constitutes highly effective targeted biologic therapy for these hitherto refractory pituitary adenomas. Specifically, our aims are to test the: 1) efficacy of TKI therapy with a clinical trial; 2) threshold level of tumor receptor expression to achieve TKI clinical response. Nineteen subjects will be treated with lapatinib for 6 months in combination with their current dopamine agonist therapy, with monthly measurements of PRL levels and MRI imaging every 3 months to evaluate the primary endpoints of achieving 40% reduction in tumor size and 50% reduction in PRL and secondary endpoints of radiologic stabilization and/or reduction and PRL normalization. Mean ErbB receptor protein expression will be compared between responders to lapatinib and non-responders by immunohistochemistry in pituitary tumor samples of these subjects collected from prior surgeries.

Condition or disease Intervention/treatment Phase
Pituitary Adenomas Prolactinomas Drug: Lapatinib Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 9 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Targeted Therapy With Lapatinib in Patients With Recurrent Pituitary Tumors Resistant to Standard Therapy
Study Start Date : July 2009
Actual Primary Completion Date : December 2018
Actual Study Completion Date : December 2018

Arm Intervention/treatment
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.
Other Name: Tykerb

Primary Outcome Measures :
  1. Change in Tumor Volume [ Time Frame: baseline and at 6 months ]
    Tumor volume will be assessed on MRI at 6 months on therapy and compared to baseline MRI.

  2. Number of Participants With 50% Reduction in Prolactin Levels [ Time Frame: every month, up to 6 months ]
    50% reduction in prolactin level measured monthly on 6 months therapy compared to baseline level.

Secondary Outcome Measures :
  1. % Change in Prolactin From Baseline to Study End [ Time Frame: Baseline and at 6 months ]
    Percent prolactin change from start of lapatinib to end of study participant participation

  2. ErbB Receptor Expression [ Time Frame: at 6 months ]
    Mean percent positive expression of EGFR and ErbB2 will be tested on pathologic tumor specimens from subjects treated with lapatinib

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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 malignant pituitary tumors
  • 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

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 ClinicalTrials.gov identifier (NCT number): NCT00939523

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United States, California
Cedars-Sinai Medical Center
Los Angeles, California, United States, 90048
United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Cedars-Sinai Medical Center
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Principal Investigator: Odelia Cooper, MD Cedars-Sinai Medical Center
  Study Documents (Full-Text)

Documents provided by Odelia Cooper, Cedars-Sinai Medical Center:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Odelia Cooper, Principal investigator, Cedars-Sinai Medical Center
ClinicalTrials.gov Identifier: NCT00939523    
Other Study ID Numbers: 18129
First Posted: July 15, 2009    Key Record Dates
Results First Posted: January 13, 2020
Last Update Posted: January 22, 2020
Last Verified: January 2020
Keywords provided by Odelia Cooper, Cedars-Sinai Medical Center:
recurrent nonfunctioning adenoma
resistant pituitary tumors
aggressive pituitary tumors
malignant pituitary adenomas
Additional relevant MeSH terms:
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Pituitary Neoplasms
Pituitary Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Hypothalamic Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Endocrine System Diseases
Endocrine Gland Neoplasms
Neoplasms by Site
Hypothalamic Neoplasms
Supratentorial Neoplasms
Brain Neoplasms
Central Nervous System Neoplasms
Nervous System Neoplasms
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action