NCT01499160

GCC 0901- A Phase II Study of Letrozole in Combination With Lapatinib Followed by an Addition of Everolimus in Postmenopausal Women With Advanced Endocrine Resistant Breast Cancer

Terminated Phase 2 Results posted Last updated 9 February 2022

What this trial tests

Phase 2 trial testing letrozole in Breast Neoplasms in 7 participants. Terminated before completion.

Timeline

1 May 2012

Primary endpoint
1 November 2014

1 December 2016

Quick facts

Lead sponsor	University of Maryland, Baltimore
Phase	Phase 2
Status	Terminated
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	7
Start date	1 May 2012
Primary completion	1 November 2014
Estimated completion	1 December 2016
Sites	1 location across United States

Drugs / interventions tested

• letrozole — full drug profile →
• lapatinib (LAPATINIB) — full drug profile →
• everolimus (everolimus) — full drug profile →

Conditions studied

• Breast Neoplasms — all drugs for Breast Neoplasms →
• Endocrine Breast Diseases — all drugs for Endocrine Breast Diseases →
• Neoplasm Metastasis — all drugs for Neoplasm Metastasis →

Sponsor

University of Maryland, Baltimore

Who can join

18 and older, female only, with Breast Neoplasms or Endocrine Breast Diseases. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Clinical Benefit Rate of Patients Treated With the Combination of Letrozole and Lapatinib and Then After Progression, Treated With Everolimus, Letrozole and Lapatinib.
  Time frame: From date of study entry until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
  Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progression, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion,

Sponsor's own description

About a third of patients with breast cancer are usually treated by hormone pills called tamoxifen and aromatase inhibitors. Aromatase inhibitors are drugs that stop female hormone production. Female hormone or estrogen is an important hormone for the growth of breast cancer cells. Letrozole is one of the aromatase inhibitors that is approved by the FDA and has been used to treat breast cancer since 1997. However, hormone pills usually work for about 6-10 months in most patients. Later on, breast cancer will start to grow again. This condition when hormone pills or endocrine therapy no longer work is called "endocrine resistant" breast cancer. The scientists here at University of Maryland have discovered how these cancer cells can become resistant to hormone pills. In our laboratory tests, the investigators found that lapatinib and everolimus can reverse this resistance and make letrozole work again. However, it is not known if the drugs can reverse the resistance in humans.

The purpose of this study is to find out whether the combination of letrozole, lapatinib, and everolimus is effective in women with breast cancer when hormone pills no longer work.

Lapatinib is an anti-cancer drug that is already approved by the Food and Drug Administration (FDA). It is the standard of care for the treatment of a particular type of breast cancer called human epithelial growth factor receptor 2 (HER2)-positive breast cancer. HER2 is a protein involved in the growth of some cancer cells. This study will also include patients with HER2-negative breast cancer. This means that the cancer cells in these patients do not depend on the HER2 protein. The use of lapatinib in these patients is considered experimental.

Everolimus is also an anti-cancer drug that is approved by the FDA for kidney cancer. Initial studies in mice and later studies in women with breast cancer have shown that everolimus may also slow the growth of breast cancer. The use of everolimus is experimental in this study.

Publications & conference data

7 peer-reviewed publications reference this trial (live from Europe PMC):

1. The therapeutic potential of mTOR inhibitors in breast cancer.
   Steelman LS, Martelli AM, Cocco L, Libra M, et al · · 2016 · cited 88× · PMID 27059645 · DOI 10.1111/bcp.12958
2. Aromatase inhibition 2013: clinical state of the art and questions that remain to be solved.
   Lønning PE, Eikesdal HP. · · 2013 · cited 76× · PMID 23625614 · DOI 10.1530/erc-13-0099
3. Role of lapatinib alone or in combination in the treatment of HER2-positive breast cancer.
   Hurvitz SA, Kakkar R. · · 2012 · cited 18× · PMID 24367193 · DOI 10.2147/bctt.s29996
4. Phase I study evaluating the combination of lapatinib (a Her2/Neu and EGFR inhibitor) and everolimus (an mTOR inhibitor) in patients with advanced cancers: South West Oncology Group (SWOG) Study S0528.
   Gadgeel SM, Lew DL, Synold TW, LoRusso P, et al · · 2013 · cited 17× · PMID 24057042 · DOI 10.1007/s00280-013-2297-4
5. Treating Elderly Patients With Hormone Receptor-Positive Advanced Breast Cancer.
   Riseberg D. · · 2015 · cited 11× · PMID 26339192 · DOI 10.4137/cmo.s26067
6. Targeted Therapies in Breast Cancer: Implications for Advanced Oncology Practice.
   Bourdeanu L, Luu T. · · 2014 · cited 10× · PMID 26110069 · DOI 10.6004/jadpro.2014.5.4.2
7. Invadopodia in cancer metastasis: dynamics, regulation, and targeted therapies.
   Hao Z, Zhang M, Du Y, Liu J, et al · · 2025 · cited 3× · PMID 40380267 · DOI 10.1186/s12967-025-06526-y