Lobular Breast CarcinomaPhase 2ROLoNCT03620643
Crizotinib in Lobular Breast, Diffuse Gastric and Triple Negative Lobular Breast Cancer or CDH1-mutated Solid Tumours
A Phase 2 study testing Crizotinib Oral Capsule [Xalkori] and Fulvestrant 50 MG/ML Prefilled Syringe [Faslodex or generic] in people with Lobular Breast Carcinoma and Gastric Cancer, run by Royal Marsden NHS Foundation Trust at 5 sites in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lobular Breast Carcinoma, Gastric Cancer, Triple Negative Breast Cancer
- What is being tested?
- Crizotinib Oral Capsule [Xalkori] and Fulvestrant 50 MG/ML Prefilled Syringe [Faslodex or generic]
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 5 sitesUnited Kingdom
- Study dates
- 9 May 2019to 30 Aug 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with histological diagnosis of E-cadherin negative inoperable or metastatic diffuse gastric cancer (basket cohort), Or inoperable or metastatic triple negative lobular breast cancer (basket cohort) Or inoperable or metastatic CDH1-mutated solid tumour with allele fraction ≥20% (basket cohort) Or recurrent inoperable locally advanced ER positive/HER2 negative lobular breast cancer (breast cohort).
- Assessment of E-cadherin, ER and HER2 status as per local assessment.
- Lobular breast cancer patients previously treated with at least one prior line of therapy including at least one prior line of hormone therapy for advanced disease, but no more than three prior lines of chemotherapy for advanced disease.
- Gastric cancer, triple negative lobular breast cancer or CDH1-mutated solid tumour patients previously treated with at least one prior therapy for advanced disease OR relapsing within one year of completing (neo) adjuvant chemotherapy OR unsuitable for chemotherapy in the opinion of the investigator (for example patient choice not to have chemotherapy, or no suitable chemotherapy agent).
- Measurable disease (RECIST 1.1)
- Haematological and biochemical indices within the ranges shown in protocol. These measurements must be performed within one week (Day -7 to Day 1) before the patient goes in the trial.
Show all 15Show fewer
- Female patients with child-bearing potential must have a negative urine or serum pregnancy test within 7 days prior to start of trial. Both male and female patients of reproductive potential must agree to use two forms of highly effective contraception (see below) for 2 weeks before starting the study treatment, throughout the treatment period and for 90 days after discontinuation of treatment with crizotinib and 2 years after the last dose of fulvestrant.
- NOTE: it is only considered highly effective if the patient is refraining from sexual intercourse during the entire period of risk associated with the study treatments
- The oral contraceptive pill may be ineffective when taken with crizotinib so is not an acceptable means of contraception for female patients during this study but can be used by female partners of male patients.
- 18 years of age or over with written (signed and dated) informed consent and be capable of co-operating with treatment and follow-up.
- World Health Organisation (WHO) performance status 0,1 or 2
- Estimated life expectancy of at least 3 months in the opinion of the investigator
- Pre-/peri-menopausal ER+ lobular breast cancer patients must be willing to receive gosarelin injections every 28 days.
- Signed and dated informed consent.
- Patients willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other procedures.
Who cannot join
- Systemic chemotherapy or investigational medicinal products during the previous four weeks, or hormonal therapy within 7 days except luteinizing hormone-releasing hormone (LHRH) analogues for ovarian suppression. Bisphosphonates or RANK ligand antagonists are permitted for the management of bone metastases.
- Previous treatment with any agent that inhibits ROS1
- Mixed ductal/lobular breast cancer, unless both ductal and lobular components are CDH1 negative by local assessment
- Major surgery (excluding minor procedures, e.g. placement of vascular access) within 4 weeks or radiation therapy within 14 days prior to study entry
- Patients with known symptomatic brain metastases requiring steroids, untreated brain metastases or spinal cord compression
- Any of the following within 12 months prior to study entry: myocardial infarction, uncontrolled angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, or transient ischemic attack. Uncontrolled hypertension or cardiac dysrhythmia including atrial fibrillation.
Show all 20Show fewer
- QT interval, corrected >470 ms or the use of bradycardic agents, drugs which prolong the QT interval and/or anti-arrhythmic agents within 12 days before the first dose of crizotinib or during study treatment.
- Use of drugs that are known potent cytochrome P450 (CYP) 3A4 inhibitors or moderate or strong CYP 3A4 inducers within 12 days before the first dose of crizotinib. Us of CYP3A4 substrates with a narrow therapeutic index (such as ciclosporin) is also not permitted within 12 days prior or during the study treatment.
- Patients on warfarin. Patients requiring anticoagulation for rate-controlled AF or previous venous thromboembolism should be switched to low-molecular weight heparin.
- Known HIV or AIDS-related illness, active infection requiring systemic therapy, or positive HBV or HCV test indicating acute or chronic infection.
- Inability or unwillingness to swallow pills, or (for patients receiving fulvestrant) receive IM injections.
- Other severe acute or chronic medical condition or psychiatric condition, recent or active suicidal ideation or behaviour, or end stage renal disease on haemodialysis, or laboratory abnormality that may increase the risk associated with study participation or investigational products administration or may interfere with the interpretation of results and, in the judgment of the Investigator, would make the patient inappropriate study entry.
- Persisting toxicity related to prior therapy >Grade 1 (except for stable peripheral neuropathy grade ≤2 or alopecia grade ≤2).
- Pregnancy or lactation.
- Diagnosis of other malignancy within 5 years, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the breast or cervix, or low-grade (Gleason ≤6) prostate cancer.
- Is a participant or plans to participate in another interventional clinical trial, whilst taking part in this study. Participation in an observational trial would be acceptable.
- Immunocompromised status due to current known active infection with HIV or due to the use of immunosuppressive therapies for other conditions
- Known prior or suspected hypersensitivity to investigational products or to any of the excipients.
- Patients at risk for gastrointestinal perforation (due to e.g., history of diverticulitis).
- Any other condition which in the Investigator's opinion would not make the patient a good candidate for the clinical trial.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United Kingdom5 sites
Beatson West of Scotland Cancer Centre
Glasgow
Royal Marsden NHS Foundation Trust
London, SW3 6JJ
Guys and St Thomas NHS Foundation Trust
London
University College London Hospital
London
The Christie NHS Foundation Trust
Manchester
About this study
Official title: 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
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.
Read the 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
- Being tested
- Crizotinib Oral Capsule [Xalkori], Fulvestrant 50 MG/ML Prefilled Syringe [Faslodex or generic]
- Keywords
- Advanced E-cadherin negative gastric cancer, Oestrogen receptor positive lobular breast cancer, Crizotinib, Fulvestrant
- Medical subject headings
- Carcinoma, Lobular, Stomach Neoplasms, Triple Negative Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Crizotinib Oral Capsule [Xalkori]Drug
Also called Xalkori
Crizotinib 250 mg Crizotinib 200mg
Fulvestrant 50 MG/ML Prefilled Syringe [Faslodex or generic]Drug
Also called Faslodex
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.
| Study group | Role | What they receive |
|---|---|---|
| Crizotinib Oral Capsule [Xalkori] monotherapy | Active comparator | Arm 1 - Basket cohort (n=29 participants) were treated with Crizotinib Oral Capsule [Xalkori] (250 mg b.d) taken as monotherapy on a continuous dosing schedule. One treatment cycle for Crizotinib is 28 days long. Receives: Drug: Crizotinib Oral Capsule [Xalkori] |
| Crizotinib Oral Capsule [Xalkori] plus Fulvestrant injection | Active comparator | Arm 2 - Lobular Breast Cancer cohort (n=29 participants) were treated with combination therapy. The combination therapy included; Crizotinib Oral Capsule [Xalkori] (250mg b.d.) plus Fulvestrant 50 mg/mL Prefilled Syringe [Faslodex or generic] intramuscular (IM) injection (500 mg per 1 cycle (q28 days, plus loading dose on day 15). Receives: Drug: Crizotinib Oral Capsule [Xalkori]; Drug: Fulvestrant 50 MG/ML Prefilled Syringe [Faslodex or generic] |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Breast Cancer Cohort Participants With Confirmed Response Assessed Using RECIST v1.1
To assess confirmed response rate by RECIST 1.1 of crizotinib and fulvestrant in advanced E-cadherin negative, ER positive lobular breast cancer.
Measured: From Day 1 to Progressive Disease, assessed up to end of study (Approximately 57 months)
Percentage of Basket Cohort Participants With Confirmed Response Assessed Using RECIST v1.1
To assess confirmed response rate (CR/PR outcome) by RECIST 1.1 scan of crizotinib monotherapy in advanced E-cadherin negative, diffuse gastric cancer, triple negative lobular breast cancer or CDH1-mutated solid tumour.
Measured: From Day 1 to Progressive Disease, assessed up to end of study (Approximately 57 months)
Secondary outcomes (3)
Percentage of Participants With Adverse Events (AEs) and Serious AEs (SAEs)
To assess the overall safety and tolerability of crizotinib with fulvestrant in the breast cancer cohort and as monotherapy in the basket cancer cohort. Toxicity will be assessed by CTCAE (version 4) every 4 weeks during study treatment. Adverse events, including serious adverse events, will be recorded until 30 days after the last dose of study treatment with crizotinib.
Measured: From Day 1 to 30 days after last dose of study drug, assessed up to end of study (Approximately 57 months)
Progression-free Survival (PFS) Assessed Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) in Both Basket and Breast Cancer Cohorts
PFS is defined as the time from baseline treatment to the first occurrence of PD, as determined by the investigator using RECIST v1.1, or death from any cause during the study, whichever occurs first. PD is defined as greater than or equal to (>/=) 20 percent (%) relative increase and >/=5 millimeter (mm) of absolute increase in the sum of diameters (SD) of target lesions (TLs), taking as reference the smallest SD recorded since treatment started, or appearance of 1 or more new lesions.
Measured: From Day 1 to disease progression (PD) or death from any cause, assessed up to end of study (Approximately 57 months)
Assessment of Overall Survival in Each Cohort
Overall survival, calculated from day 1 of study treatment to the date of death from any cause.
Measured: From Day 1 to disease progression (PD) or death from any cause, assessed up to end of study (Approximately 57 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Aug 2018
- Study start9 May 2019
- Primary completion30 Aug 2024
- Study completion30 Aug 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (19)Papers the sponsor has linked to this study.
- Other trials for Lobular Breast CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- This multi-centre study design will aim to complete recruitment over 18 months from six high volume centres including the Royal Marsden. Parallel recruitment to breast and basket cancer cohorts will take place for this study.
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- Royal Marsden NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Collaborators
- Pfizer, Breast Cancer Now
- Responsible party
- Sponsor
- Investigators
- Professor Peter Schmid, Study chair, St Bart's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03620643
- Sponsor's protocol ID
- CCR4684
- Acronym
- ROLo
- Status last verified
- Oct 2025
- First submitted
- 4 May 2018
- Last updated
- 30 Oct 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Christgen M, Derksen P. Lobular breast cancer: molecular basis, mouse and cellular models. Breast Cancer Res. 2015 Feb 8;17(1):16. doi: 10.1186/s13058-015-0517-z.
PubMed 25757734Jeanes A, Gottardi CJ, Yap AS. Cadherins and cancer: how does cadherin dysfunction promote tumor progression? Oncogene. 2008 Nov 24;27(55):6920-9. doi: 10.1038/onc.2008.343.
PubMed 19029934Bertucci F, Orsetti B, Negre V, Finetti P, Rouge C, Ahomadegbe JC, Bibeau F, Mathieu MC, Treilleux I, Jacquemier J, Ursule L, Martinec A, Wang Q, Benard J, Puisieux A, Birnbaum D, Theillet C. Lobular and ductal carcinomas of the breast have distinct genomic and expression profiles. Oncogene. 2008 Sep 11;27(40):5359-72. doi: 10.1038/onc.2008.158. Epub 2008 May 19.
PubMed 18490921Cristofanilli M, Gonzalez-Angulo A, Sneige N, Kau SW, Broglio K, Theriault RL, Valero V, Buzdar AU, Kuerer H, Buchholz TA, Hortobagyi GN. Invasive lobular carcinoma classic type: response to primary chemotherapy and survival outcomes. J Clin Oncol. 2005 Jan 1;23(1):41-8. doi: 10.1200/JCO.2005.03.111.
PubMed 15625359Graziano F, Humar B, Guilford P. The role of the E-cadherin gene (CDH1) in diffuse gastric cancer susceptibility: from the laboratory to clinical practice. Ann Oncol. 2003 Dec;14(12):1705-13. doi: 10.1093/annonc/mdg486.
PubMed 14630673Pernot S, Voron T, Perkins G, Lagorce-Pages C, Berger A, Taieb J. Signet-ring cell carcinoma of the stomach: Impact on prognosis and specific therapeutic challenge. World J Gastroenterol. 2015 Oct 28;21(40):11428-38. doi: 10.3748/wjg.v21.i40.11428.
PubMed 26523107Peng Z, Li Z, Gao J, Lu M, Gong J, Tang ET, Oliner KS, Hei YJ, Zhou H, Shen L. Tumor MET Expression and Gene Amplification in Chinese Patients with Locally Advanced or Metastatic Gastric or Gastroesophageal Junction Cancer. Mol Cancer Ther. 2015 Nov;14(11):2634-41. doi: 10.1158/1535-7163.MCT-15-0108. Epub 2015 Sep 1.
PubMed 26330547Turner N, Grose R. Fibroblast growth factor signalling: from development to cancer. Nat Rev Cancer. 2010 Feb;10(2):116-29. doi: 10.1038/nrc2780.
PubMed 20094046Solomon BJ, Mok T, Kim DW, Wu YL, Nakagawa K, Mekhail T, Felip E, Cappuzzo F, Paolini J, Usari T, Iyer S, Reisman A, Wilner KD, Tursi J, Blackhall F; PROFILE 1014 Investigators. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N Engl J Med. 2014 Dec 4;371(23):2167-77. doi: 10.1056/NEJMoa1408440.
PubMed 25470694Shaw AT, Ou SH, Bang YJ, Camidge DR, Solomon BJ, Salgia R, Riely GJ, Varella-Garcia M, Shapiro GI, Costa DB, Doebele RC, Le LP, Zheng Z, Tan W, Stephenson P, Shreeve SM, Tye LM, Christensen JG, Wilner KD, Clark JW, Iafrate AJ. Crizotinib in ROS1-rearranged non-small-cell lung cancer. N Engl J Med. 2014 Nov 20;371(21):1963-71. doi: 10.1056/NEJMoa1406766. Epub 2014 Sep 27.
PubMed 25264305Lennerz JK, Kwak EL, Ackerman A, Michael M, Fox SB, Bergethon K, Lauwers GY, Christensen JG, Wilner KD, Haber DA, Salgia R, Bang YJ, Clark JW, Solomon BJ, Iafrate AJ. MET amplification identifies a small and aggressive subgroup of esophagogastric adenocarcinoma with evidence of responsiveness to crizotinib. J Clin Oncol. 2011 Dec 20;29(36):4803-10. doi: 10.1200/JCO.2011.35.4928. Epub 2011 Oct 31.
PubMed 22042947Lauren Christine Harshman, K.P.G., Laura Polacek, Mary-Ellen Taplin, Atish Dipankar Choudhury, Mark M Pomerantz, Joaquim Bellmunt, Channing Yu, Zijie Sun, Sandy Srinivas, Philip W. Kantoff, Christopher Sweeney. An investigator-initiated phase I study of crizotinib in combination with enzalutamide in metastatic castration-resistant prostate cancer (mCRPC) before or after progression on docetaxel. in ASCO Annual Meeting. 2016. Chicago: J Clin Oncol.
E. L. Kwak, D.R.C., J. Clark, G. I. Shapiro, R. G. Maki, M. J. Ratain, B. Solomon, Y. Bang, S. Ou, R. Salgia. Clinical activity observed in a phase I dose escalation trial of an oral c-met and ALK inhibitor, PF-02341066. in ASCO Annual Meeting. 2009. J Clin Oncol.
Di Leo A, Jerusalem G, Petruzelka L, Torres R, Bondarenko IN, Khasanov R, Verhoeven D, Pedrini JL, Smirnova I, Lichinitser MR, Pendergrass K, Garnett S, Lindemann JP, Sapunar F, Martin M. Results of the CONFIRM phase III trial comparing fulvestrant 250 mg with fulvestrant 500 mg in postmenopausal women with estrogen receptor-positive advanced breast cancer. J Clin Oncol. 2010 Oct 20;28(30):4594-600. doi: 10.1200/JCO.2010.28.8415. Epub 2010 Sep 20.
PubMed 20855825Telford BJ, Chen A, Beetham H, Frick J, Brew TP, Gould CM, Single A, Godwin T, Simpson KJ, Guilford P. Synthetic Lethal Screens Identify Vulnerabilities in GPCR Signaling and Cytoskeletal Organization in E-Cadherin-Deficient Cells. Mol Cancer Ther. 2015 May;14(5):1213-23. doi: 10.1158/1535-7163.MCT-14-1092. Epub 2015 Mar 16.
PubMed 25777964
Study at a glance
From the registry record, last updated by the sponsor on 30 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT03620643
- Acronym / sponsor ID
- ROLo / CCR4684
- Conditions
- Lobular Breast Carcinoma, Gastric Cancer, Triple Negative Breast Cancer, CDH1 Gene Mutation
- Keywords
- Advanced E-cadherin negative gastric cancer, Oestrogen receptor positive lobular breast cancer, Crizotinib, Fulvestrant
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- Royal Marsden NHS Foundation TrustUniversity, hospital or other
- Collaborators
- Pfizer, Breast Cancer Now
- Study start
- 9 May 2019 (actual)
- Primary completion
- 30 Aug 2024 (actual)
- Study completion
- 30 Aug 2024 (actual)
- First posted
- 8 Aug 2018 (actual)
- Results
- Posted 30 Oct 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
- Model description
- This multi-centre study design will aim to complete recruitment over 18 months from six high volume centres including the Royal Marsden. Parallel recruitment to breast and basket cancer cohorts will take place for this study.
| Arm | Type | Receives |
|---|---|---|
| Crizotinib Oral Capsule [Xalkori] monotherapy | Active comparator | Drug: Crizotinib Oral Capsule [Xalkori]Arm 1 - Basket cohort (n=29 participants) were treated with Crizotinib Oral Capsule [Xalkori] (250 mg b.d) taken as monotherapy on a continuous dosing schedule. One treatment cycle for Crizotinib is 28 days long. |
| Crizotinib Oral Capsule [Xalkori] plus Fulvestrant injection | Active comparator | Drug: Crizotinib Oral Capsule [Xalkori], Drug: Fulvestrant 50 MG/ML Prefilled Syringe [Faslodex or generic]Arm 2 - Lobular Breast Cancer cohort (n=29 participants) were treated with combination therapy. The combination therapy included; Crizotinib Oral Capsule [Xalkori] (250mg b.d.) plus Fulvestrant 50 mg/mL Prefilled Syringe [Faslodex or generic] intramuscular (IM) injection (500 mg per 1 cycle (q28 days, plus loading dose on day 15). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Patients with histological diagnosis of E-cadherin negative inoperable or metastatic diffuse gastric cancer (basket cohort), Or inoperable or metastatic triple negative lobular breast cancer (basket cohort) Or inoperable or metastatic CDH1-mutated solid tumour with allele fraction ≥20% (basket cohort) Or recurrent inoperable locally advanced ER positive/HER2 negative lobular breast cancer (breast cohort).
- Assessment of E-cadherin, ER and HER2 status as per local assessment.
- Lobular breast cancer patients previously treated with at least one prior line of therapy including at least one prior line of hormone therapy for advanced disease, but no more than three prior lines of chemotherapy for advanced disease.
- Gastric cancer, triple negative lobular breast cancer or CDH1-mutated solid tumour patients previously treated with at least one prior therapy for advanced disease OR relapsing within one year of completing (neo) adjuvant chemotherapy OR unsuitable for chemotherapy in the opinion of the investigator (for example patient choice not to have chemotherapy, or no suitable chemotherapy agent).
- Measurable disease (RECIST 1.1)
Key exclusion criteria (20 listed)
- Systemic chemotherapy or investigational medicinal products during the previous four weeks, or hormonal therapy within 7 days except luteinizing hormone-releasing hormone (LHRH) analogues for ovarian suppression. Bisphosphonates or RANK ligand antagonists are permitted for the management of bone metastases.
- Previous treatment with any agent that inhibits ROS1
- Mixed ductal/lobular breast cancer, unless both ductal and lobular components are CDH1 negative by local assessment
- Major surgery (excluding minor procedures, e.g. placement of vascular access) within 4 weeks or radiation therapy within 14 days prior to study entry
- Patients with known symptomatic brain metastases requiring steroids, untreated brain metastases or spinal cord compression
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Crizotinib Oral Capsule [Xalkori]Also: XalkoriCrizotinib 250 mg Crizotinib 200mg | Drug | Crizotinib Oral Capsule [Xalkori] monotherapy, Crizotinib Oral Capsule [Xalkori] plus Fulvestrant injection |
| Fulvestrant 50 MG/ML Prefilled Syringe [Faslodex or generic]Also: FaslodexFulvestrant (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. | Drug | Crizotinib Oral Capsule [Xalkori] plus Fulvestrant injection |
Primary outcome
Percentage of Breast Cancer Cohort Participants With Confirmed Response Assessed Using RECIST v1.1
Time frame: From Day 1 to Progressive Disease, assessed up to end of study (Approximately 57 months)
To assess confirmed response rate by RECIST 1.1 of crizotinib and fulvestrant in advanced E-cadherin negative, ER positive lobular breast cancer.
Percentage of Basket Cohort Participants With Confirmed Response Assessed Using RECIST v1.1
Time frame: From Day 1 to Progressive Disease, assessed up to end of study (Approximately 57 months)
To assess confirmed response rate (CR/PR outcome) by RECIST 1.1 scan of crizotinib monotherapy in advanced E-cadherin negative, diffuse gastric cancer, triple negative lobular breast cancer or CDH1-mutated solid tumour.
3 secondary outcomes
Percentage of Participants With Adverse Events (AEs) and Serious AEs (SAEs)
Time frame: From Day 1 to 30 days after last dose of study drug, assessed up to end of study (Approximately 57 months)
Progression-free Survival (PFS) Assessed Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) in Both Basket and Breast Cancer Cohorts
Time frame: From Day 1 to disease progression (PD) or death from any cause, assessed up to end of study (Approximately 57 months)
Assessment of Overall Survival in Each Cohort
Time frame: From Day 1 to disease progression (PD) or death from any cause, assessed up to end of study (Approximately 57 months)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Oct 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 25757734Christgen M, Derksen P. Lobular breast cancer: molecular basis, mouse and cellular models. Breast Cancer Res. 2015 Feb 8;17(1):16. doi: 10.1186/s13058-015-0517-z.
- Background: PubMed 19029934Jeanes A, Gottardi CJ, Yap AS. Cadherins and cancer: how does cadherin dysfunction promote tumor progression? Oncogene. 2008 Nov 24;27(55):6920-9. doi: 10.1038/onc.2008.343.
- Background: PubMed 18490921Bertucci F, Orsetti B, Negre V, Finetti P, Rouge C, Ahomadegbe JC, Bibeau F, Mathieu MC, Treilleux I, Jacquemier J, Ursule L, Martinec A, Wang Q, Benard J, Puisieux A, Birnbaum D, Theillet C. Lobular and ductal carcinomas of the breast have distinct genomic and expression profiles. Oncogene. 2008 Sep 11;27(40):5359-72. doi: 10.1038/onc.2008.158. Epub 2008 May 19.
- Background: PubMed 15625359Cristofanilli M, Gonzalez-Angulo A, Sneige N, Kau SW, Broglio K, Theriault RL, Valero V, Buzdar AU, Kuerer H, Buchholz TA, Hortobagyi GN. Invasive lobular carcinoma classic type: response to primary chemotherapy and survival outcomes. J Clin Oncol. 2005 Jan 1;23(1):41-8. doi: 10.1200/JCO.2005.03.111.
- Background: PubMed 14630673Graziano F, Humar B, Guilford P. The role of the E-cadherin gene (CDH1) in diffuse gastric cancer susceptibility: from the laboratory to clinical practice. Ann Oncol. 2003 Dec;14(12):1705-13. doi: 10.1093/annonc/mdg486.
- Background: PubMed 26523107Pernot S, Voron T, Perkins G, Lagorce-Pages C, Berger A, Taieb J. Signet-ring cell carcinoma of the stomach: Impact on prognosis and specific therapeutic challenge. World J Gastroenterol. 2015 Oct 28;21(40):11428-38. doi: 10.3748/wjg.v21.i40.11428.
- Background: PubMed 26330547Peng Z, Li Z, Gao J, Lu M, Gong J, Tang ET, Oliner KS, Hei YJ, Zhou H, Shen L. Tumor MET Expression and Gene Amplification in Chinese Patients with Locally Advanced or Metastatic Gastric or Gastroesophageal Junction Cancer. Mol Cancer Ther. 2015 Nov;14(11):2634-41. doi: 10.1158/1535-7163.MCT-15-0108. Epub 2015 Sep 1.
- Background: PubMed 20094046Turner N, Grose R. Fibroblast growth factor signalling: from development to cancer. Nat Rev Cancer. 2010 Feb;10(2):116-29. doi: 10.1038/nrc2780.
- Background: PubMed 25470694Solomon BJ, Mok T, Kim DW, Wu YL, Nakagawa K, Mekhail T, Felip E, Cappuzzo F, Paolini J, Usari T, Iyer S, Reisman A, Wilner KD, Tursi J, Blackhall F; PROFILE 1014 Investigators. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N Engl J Med. 2014 Dec 4;371(23):2167-77. doi: 10.1056/NEJMoa1408440.
- Background: PubMed 25264305Shaw AT, Ou SH, Bang YJ, Camidge DR, Solomon BJ, Salgia R, Riely GJ, Varella-Garcia M, Shapiro GI, Costa DB, Doebele RC, Le LP, Zheng Z, Tan W, Stephenson P, Shreeve SM, Tye LM, Christensen JG, Wilner KD, Clark JW, Iafrate AJ. Crizotinib in ROS1-rearranged non-small-cell lung cancer. N Engl J Med. 2014 Nov 20;371(21):1963-71. doi: 10.1056/NEJMoa1406766. Epub 2014 Sep 27.
- Background: PubMed 22042947Lennerz JK, Kwak EL, Ackerman A, Michael M, Fox SB, Bergethon K, Lauwers GY, Christensen JG, Wilner KD, Haber DA, Salgia R, Bang YJ, Clark JW, Solomon BJ, Iafrate AJ. MET amplification identifies a small and aggressive subgroup of esophagogastric adenocarcinoma with evidence of responsiveness to crizotinib. J Clin Oncol. 2011 Dec 20;29(36):4803-10. doi: 10.1200/JCO.2011.35.4928. Epub 2011 Oct 31.
- BackgroundLauren Christine Harshman, K.P.G., Laura Polacek, Mary-Ellen Taplin, Atish Dipankar Choudhury, Mark M Pomerantz, Joaquim Bellmunt, Channing Yu, Zijie Sun, Sandy Srinivas, Philip W. Kantoff, Christopher Sweeney. An investigator-initiated phase I study of crizotinib in combination with enzalutamide in metastatic castration-resistant prostate cancer (mCRPC) before or after progression on docetaxel. in ASCO Annual Meeting. 2016. Chicago: J Clin Oncol.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Professor Peter Schmid study chair
St Bart's Hospital
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Crizotinib Oral Capsule [Xalkori] and Fulvestrant 50 MG/ML Prefilled Syringe [Faslodex or generic] in people with Lobular Breast Carcinoma and Gastric Cancer, run by Royal Marsden NHS Foundation Trust at 5 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Oct 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Breast Cancer Cohort Participants With Confirmed Response Assessed Using RECIST v1.1 (time frame: From Day 1 to Progressive Disease, assessed up to end of study (Approximately 57 months)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03620643, which also lists 19 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Oct 2025.