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

Conditions

• Pituitary Adenomas
• Prolactinomas

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Lapatinib — DRUG
  All participants will be asked to take Lapatinib daily for six months during the research study.

Study Details

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.

Key Dates

Start date

Jul 31, 2009

Status verified

Jan 2020

Primary completion

Dec 31, 2018

Completion

Dec 31, 2018

Study Design

Enrollment

9 participants (actual)

Allocation

NA

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Arms

• Experimental: Lapatinib
  All participants will be asked to take Lapatinib daily for a total of six months during the research study.

Primary Outcome Measure

Change in Tumor Volume [ Time Frame: baseline and at 6 months ]

Locations (3)

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