NCT03620643

Crizotinib in Lobular Breast, Diffuse Gastric and Triple Negative Lobular Breast Cancer or CDH1-mutated Solid Tumours

Phase II Study of ROS1 Targeting With Crizotinib in Advanced E-cadherin Negative, ER Positive Lobular Breast Cancer, Diffuse Gastric Cancer, Triple Negative Lobular Breast Cancer or CDH1-mutated Solid Tumours

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 33 (actual)
• Sponsor: Royal Marsden NHS Foundation Trust · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study was to find out how effective the combination of crizotinib and fulvestrant was in shrinking lobular breast cancer tumours. The investigators also assessed the side effects of the combination of crizotinib tablets and fulvestrant injections. The side effects and the doses of crizotinib and fulvestrant had already been evaluated in large clinical trials, but this was the first time these two drugs had been combined together.

Detailed description

This clinical study was looking at whether a drug called crizotinib, which is used in some patients with lung cancer, was effective in a sub-type of breast cancer, called lobular breast cancer. As the majority of lobular breast cancers are oestrogen receptor positive (ER+ve), crizotinib was combined with a second drug, fulvestrant, to try to block tumour growth that is driven by oestrogen. Crizotinib targets cancers with genetic changes in two genes called ALK and ROS1. Lung cancers with changes in these genes usually get smaller when treated with crizotinib. Laboratory work at the Institute of Cancer Research has shown that lobular breast cancer cells, due to a mutation in a different gene called CDH1, appear to be similarly affected by crizotinib. Fulvestrant is an oestrogen receptor down regulator and blocks the effects of oestrogen on oestrogen receptor positive (ER+ve) breast cancer cells. Fulvestrant is an established and approved anti-hormone therapy which patients with breast cancers are receiving in the clinic. It is possible that the combination of crizotinib and an anti-oestrogen agent will shrink the tumour(s) more effectively and prevent further growth. Because fulvestrant is only effective in post-menopausal women, if participants had not yet gone through the menopause, participants needed to start (or continue to receive) a monthly injection under the skin to temporarily stop the function of the participant's ovaries to be eligible to take part in the trial. This injection is called goserelin and had to be started at least 4 weeks before the first day of treatment on the trial. The overall aims of this clinical study were to find out: * The proportion of patients whose tumour(s) shrink when they are treated with crizotinib and fulvestrant * The safety and tolerability of fulvestrant in combination with crizotinib, to determine that they can be given together without unacceptable side effects * What the drugs do to the tumours, which will help us decide which patients may benefit from this combination in the future

Conditions

• Lobular Breast Carcinoma
• Gastric Cancer
• Triple Negative Breast Cancer
• CDH1 Gene Mutation

Interventions

Type	Name	Description
DRUG	Crizotinib Oral Capsule [Xalkori]	Crizotinib 250 mg Crizotinib 200mg
DRUG	Fulvestrant 50 MG/ML Prefilled Syringe [Faslodex or generic]	Fulvestrant (Faslodex or generic) is supplied as two 5-mL clear neutral glass (Type 1) barrels, each containing 250mg/5mL of fulvestrant solution for intramuscular injection and fitted with a tamper evident closure.

Timeline

• Start date: 2019-05-09
• Primary completion: 2024-08-30
• Completion: 2024-08-30
• First posted: 2018-08-08
• Last updated: 2025-10-30
• Results posted: 2025-10-30

Locations

5 sites across 1 country: United Kingdom

Regulatory

• FDA-regulated drug study