Lung CancerPhase 1/2CamBMT1NCT02768337
Cambridge Brain Mets Trial 1
A Phase 1/2 study testing Afatinib, 2 Gy targeted radiotherapy and 4 Gy targeted radiotherapy in people with Lung Cancer and Breast Cancer, run by Cambridge University Hospitals NHS Foundation Trust at 6 sites in United Kingdom.
Trial summary
Proof of principle phase 1b / randomised phase 2 study of afatinib penetration into cerebral metastases for patients undergoing neurosurgical resection, both with and without prior low-dose, targeted radiotherapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lung Cancer, Breast Cancer, Brain Cancer
- What is being tested?
- Afatinib, 2 Gy targeted radiotherapy and 4 Gy targeted radiotherapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 6 sitesUnited Kingdom
- Study dates
- 10 Mar 2015to 12 Aug 2021
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
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
- Operable brain metastases from likely breast or lung origin as determined by local MDT. Both of the following groups of patients may be considered eligible:
- Patients with a past history of histologically/cytologically confirmed breast or lung cancer, now presenting with a new likely brain metastasis from that primary.
- Patients presenting with new, primary (breast/lung) tumours, plus synchronous, operable brain metastases, without pre-op tissue diagnosis.
- ECOG performance score 0, 1 or 2.
- Aged 18 years or older.
- Written informed consent.
- Patients are allowed to take oral corticosteroids however the plan should be for them to receive a stable dose of corticosteroids for at least 3 days before neurosurgery (i.e. trial days 10, 11, 12)
Who cannot join
- The presence of any of the following will preclude patient inclusion:
- History or presence of existing interstitial lung disease.
- Current clinically significant impairment of cardiac function (greater than Class II according to New York Heart Association [NYHA] classification).
- Unstable ischemic heart disease within the last 6 months, including myocardial infarction.
- Presence of QTc interval prolongation >480 ms.
- Clinically significant corneal or conjunctival eye disease.
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- Clinically significant skin diseases such as psoriasis, rash or atopic dermatitis.
- Clinically significant impairment of GI function or GI disease including total gastrectomy that may alter the absorption of afatinib.
- Clinically significant, active peptic ulcer disease.
- Known positive test for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) antibody or patients with any untreated serious infections.
- Pregnancy and contraception:
- Female patients of child bearing potential must have a negative serum or urine pregnancy test within 14 days prior to registration/randomisation, and must use an effective method of contraception at least 1 week prior to treatment, during treatment and for at least 28 days after the final dose of study drug. Acceptable methods are:
- True abstinence (this must be the patients usual and preferred lifestyle, not just for the duration of the study) Oral contraceptive (either combined or progestogen alone) Contraceptive implant, injections or patches Vaginal ring Intrauterine device (IUD, coil or intrauterine system) Condom and cap Diaphragm plus spermicide Tubal Ligation
- A female patient of child bearing potential is defined as a sexually mature woman not surgically sterilized or not post-menopausal for at least 24 consecutive months if aged 55 years or younger or 12 months if aged 56 years or older.
- Men must use one of the following, reliable forms to contraception for the entire duration of treatment and for 28 days after the final dose of study drug:
- Condom plus spermicide even if female partner is using another method of contraception (Men should also use a condom to protect male partners, or female partners who are pregnant or breast feeding, from exposure to the study medicine in semen).
- True abstinence (this must be the patients usual and preferred lifestyle, not just for the duration of the study)
- Concurrent severe and/or uncontrolled medical conditions (due to concurrent disease other than cancer) which in the opinion of the investigator could compromise participation in the study.
- Known or suspected active drug or alcohol abuse.
- Administration of chemotherapy, immunotherapy, radiotherapy or any investigational cancer therapy within 5 half-lives of the prior therapy or 2 weeks of first dose of afatinib, whichever is longer. Continuation of established endocrine therapy is allowed and no washout period is required. Established endocrine therapy (which may include GnRH analogues) is that which has been administered for at least 2 weeks prior to starting afatinib on Day 1
- Known hypersensitivity to afatinib or its excipients.
- Toxicities of prior therapies that have not resolved to ≤CTCAE Grade 1.
- Any of the following laboratory test findings:
- Haemoglobin <90 g/L Absolute neutrophil count <1 x 109 /L Platelet count <100 x 109 /L AST or ALT >2.5 x upper limit of normal range (ULN) Total serum bilirubin >1.5 x ULN Creatinine >1.5 x ULN Creatinine clearance <30mL/min (Cockcroft-Gault)
- Patients taking potent P-gp inducers/inhibitors (see section 15.9)
- Any other reason which, in the opinion of the Investigator, interferes with the ability of the patient to participate in the study.
- Patients unable to comply with the protocol.
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United Kingdom6 sites
University Hospitals Birmingham NHS Foundation Trust
Birmingham
Cambridge University Hospitals NHS Foundation Trust
Cambridge, England, CB2 2QQ
The Beatson West of Scotland Cancer Centre
Glasgow
Clatterbridge Cancer Centre
Liverpool
The Christie NHS Foundation Trust
Manchester
Oxford University Hospitals NHS Foundation Trust
Oxford
About this study
Official title: Cambridge Brain Mets Trial 1: A Proof-of-principle Phase 1b/Randomised Phase 2 Study of Afatinib Penetration Into Cerebral Metastases for Patients Undergoing Neurosurgical Resection, Both With and Without Prior Low-dose, Targeted Radiotherapy
Proof of principle phase 1b / randomised phase 2 study of afatinib penetration into cerebral metastases for patients undergoing neurosurgical resection, both with and without prior low-dose, targeted radiotherapy.
Read the detailed description
Brain metastases occur in 20-40% of all patients with cancer, with an incidence 10 times higher than that of primary malignant brain tumours. patients with brain metastases are an underserved population. Overall they have a poor prognosis with a median survival of 1-2 months with corticosteroids and only 5-7 months after whole brain radiotherapy. An important factor in the poor prognosis of patients with brain metastases is the inability of many drugs to penetrate the blood-brain-barrier into tumour tissue.Combination therapy with surgical excision, radiotherapy and novel drugs could potentially improve the prognosis for some patients.
CamBMT1 is an open label, 3 Arm randomised Phase 2 trial investigating whether administration of a low dose of targeted radiotherapy during afatinib treatment could increase the concentration of drug penetration into brain metastases.
Eligible patients in Phase 2 will be randomised to 1 of 3 Arms:
Arm 1: no radiotherapy Arm 2: 2Gy radiotherapy Arm 3: 4Gy radiotherapy All patients will also receive 11 days of afatinib treatment at the recommended Phase 2 dose, previously determined in a Phase 1b safety run-in phase.
On Day 10, of afatinib treatment patients randomised to Arms 2 or 3 will receive their allocated dose of radiotherapy On Day 12, patients will undergo neurosurgical resection of their brain metastasis/ses.
Patients will be followed up on Day 22-28 and on Day 41 +/- 7 days
For the primary outcome measure, samples for measurement of plasma concentration of afatinib will be taken pre-treatment, on day 10 and Day 12 post-resection. Tumour tissue from the resected brain metastasis will be taken on day 12 for measurement of afatinib concentration. The primary outcome measure is the ratio of these concentrations.
The patient population studied will be breast/likely breast or lung/likely lung primary cancers with operable brain metastases.
- Being tested
- Afatinib, 2 Gy targeted radiotherapy, 4 Gy targeted radiotherapy
- Keywords
- brain metastasis, operable brain metastasis
- Medical subject headings
- Lung Neoplasms, Breast Neoplasms, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AfatinibDrug
Also called Giotrif
2 Gy targeted radiotherapyRadiation
4 Gy targeted radiotherapyRadiation
| Study group | Role | What they receive |
|---|---|---|
| Arm 1: Afatinib only at Recommended Phase 2 dose (RP2D) | Other | No targeted radiotherapy. Afatinib at Recommended Phase 2 Dose for 11 days. Receives: Drug: Afatinib |
| Arm 2: Afatinib RP2D + 2 Gy targeted radiotherapy | Experimental | Patient will receive the RP2D of afatinib for 11 days and will receive targeted radiotherapy at a dose level of 2 Gy on Day 10 of treatment. Receives: Drug: Afatinib; Radiation: 2 Gy targeted radiotherapy |
| Arm 3: Afatinib RP2D + 4 Gy targeted radiotherapy | Experimental | Patient will receive the RP2D of afatinib for 11 days and will receive targeted radiotherapy at a dose level of 4 Gy on Day 10 of treatment. Receives: Drug: Afatinib; Radiation: 4 Gy targeted radiotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Ratio of afatinib concentration in: [resected brain metastases] / [plasma] - each measured in (ng/mL) on day 12
Measured: Day 12 of treatment
Secondary outcomes (1)
Safety of afatinib alone and combined with targeted low-dose radiotherapy - assessed by number of participants with treatment- related adverse events as assessed by CTCAE v4.0
Measured: From consent to Day 41+/-7 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 May 2016 (estimated)
- Study start10 Mar 2015
- Primary completion12 Aug 2020
- Study completion12 Aug 2021
Why it stopped: Slow recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Lung CancerStudies 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 1/2
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cambridge University Hospitals NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Collaborators
- Boehringer Ingelheim, Cancer Research UK, University of Cambridge, The Brain Tumour Charity
- Responsible party
- Principal investigator, Richard D. Baird MD PhD, Cambridge University Hospitals NHS Foundation Trust
- Investigators
- Richard Baird, MD PhD, Principal investigator, Cambridge University Hospitals NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02768337
- Sponsor's protocol ID
- CamBMT1
- Other IDs
- 2013-002398-23, 1200.206, 146009
- Acronym
- CamBMT1
- Status last verified
- Jan 2024
- First submitted
- 28 Apr 2016
- Last updated
- 31 Jan 2024
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 31 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cambridge Brain Mets Trial 1: A Proof-of-principle Phase 1b/Randomised Phase 2 Study of Afatinib Penetration Into Cerebral Metastases for Patients Undergoing Neurosurgical Resection, Both With and Without Prior Low-dose, Targeted Radiotherapy
- ClinicalTrials.gov ID
- NCT02768337
- Acronym / sponsor ID
- CamBMT1 / CamBMT1
- Keywords
- brain metastasis, operable brain metastasis
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow recruitment
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Cambridge University Hospitals NHS Foundation TrustUniversity, hospital or other
- Collaborators
- Boehringer Ingelheim, Cancer Research UK, University of Cambridge, The Brain Tumour Charity
- Study start
- 10 Mar 2015 (actual)
- Primary completion
- 12 Aug 2020 (actual)
- Study completion
- 12 Aug 2021 (actual)
- First posted
- 11 May 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Proof of principle phase 1b / randomised phase 2 study of afatinib penetration into cerebral metastases for patients undergoing neurosurgical resection, both with and without prior low-dose, targeted radiotherapy.
Detailed description
Brain metastases occur in 20-40% of all patients with cancer, with an incidence 10 times higher than that of primary malignant brain tumours. patients with brain metastases are an underserved population. Overall they have a poor prognosis with a median survival of 1-2 months with corticosteroids and only 5-7 months after whole brain radiotherapy. An important factor in the poor prognosis of patients with brain metastases is the inability of many drugs to penetrate the blood-brain-barrier into tumour tissue.Combination therapy with surgical excision, radiotherapy and novel drugs could potentially improve the prognosis for some patients.
CamBMT1 is an open label, 3 Arm randomised Phase 2 trial investigating whether administration of a low dose of targeted radiotherapy during afatinib treatment could increase the concentration of drug penetration into brain metastases.
Eligible patients in Phase 2 will be randomised to 1 of 3 Arms:
Arm 1: no radiotherapy Arm 2: 2Gy radiotherapy Arm 3: 4Gy radiotherapy All patients will also receive 11 days of afatinib treatment at the recommended Phase 2 dose, previously determined in a Phase 1b safety run-in phase.
On Day 10, of afatinib treatment patients randomised to Arms 2 or 3 will receive their allocated dose of radiotherapy On Day 12, patients will undergo neurosurgical resection of their brain metastasis/ses.
Patients will be followed up on Day 22-28 and on Day 41 +/- 7 days
For the primary outcome measure, samples for measurement of plasma concentration of afatinib will be taken pre-treatment, on day 10 and Day 12 post-resection. Tumour tissue from the resected brain metastasis will be taken on day 12 for measurement of afatinib concentration. The primary outcome measure is the ratio of these concentrations.
The patient population studied will be breast/likely breast or lung/likely lung primary cancers with operable brain metastases.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Arm 1: Afatinib only at Recommended Phase 2 dose (RP2D) | Other | Drug: AfatinibNo targeted radiotherapy. Afatinib at Recommended Phase 2 Dose for 11 days. |
| Arm 2: Afatinib RP2D + 2 Gy targeted radiotherapy | Experimental | Drug: Afatinib, Radiation: 2 Gy targeted radiotherapyPatient will receive the RP2D of afatinib for 11 days and will receive targeted radiotherapy at a dose level of 2 Gy on Day 10 of treatment. |
| Arm 3: Afatinib RP2D + 4 Gy targeted radiotherapy | Experimental | Drug: Afatinib, Radiation: 4 Gy targeted radiotherapyPatient will receive the RP2D of afatinib for 11 days and will receive targeted radiotherapy at a dose level of 4 Gy on Day 10 of treatment. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Operable brain metastases from likely breast or lung origin as determined by local MDT. Both of the following groups of patients may be considered eligible:
- ECOG performance score 0, 1 or 2.
- Aged 18 years or older.
- Written informed consent.
- Patients are allowed to take oral corticosteroids however the plan should be for them to receive a stable dose of corticosteroids for at least 3 days before neurosurgery (i.e. trial days 10, 11, 12)
Key exclusion criteria (27 listed)
- History or presence of existing interstitial lung disease.
- Current clinically significant impairment of cardiac function (greater than Class II according to New York Heart Association [NYHA] classification).
- Unstable ischemic heart disease within the last 6 months, including myocardial infarction.
- Presence of QTc interval prolongation >480 ms.
- Clinically significant corneal or conjunctival eye disease.
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 |
|---|---|---|
| AfatinibAlso: Giotrif | Drug | Arm 1: Afatinib only at Recommended Phase 2 dose (RP2D), Arm 2: Afatinib RP2D + 2 Gy targeted radiotherapy, Arm 3: Afatinib RP2D + 4 Gy targeted radiotherapy |
| 2 Gy targeted radiotherapy | Radiation | Arm 2: Afatinib RP2D + 2 Gy targeted radiotherapy |
| 4 Gy targeted radiotherapy | Radiation | Arm 3: Afatinib RP2D + 4 Gy targeted radiotherapy |
Primary outcome
Ratio of afatinib concentration in: [resected brain metastases] / [plasma] - each measured in (ng/mL) on day 12
Time frame: Day 12 of treatment
1 secondary outcome
Safety of afatinib alone and combined with targeted low-dose radiotherapy - assessed by number of participants with treatment- related adverse events as assessed by CTCAE v4.0
Time frame: From consent to Day 41+/-7 days
Results and safety
The study was stopped early (reason given: Slow recruitment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jan 2024.
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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.
Richard Baird, MD PhD principal investigator
Cambridge University Hospitals NHS Foundation Trust
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Afatinib, 2 Gy targeted radiotherapy and 4 Gy targeted radiotherapy in people with Lung Cancer and Breast Cancer, run by Cambridge University Hospitals NHS Foundation Trust at 6 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 7 inclusion and 27 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: stopped early, as of the sponsor's last update on 31 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
The study was stopped early (reason given: Slow recruitment). Results are not available in the source record.
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?
Ratio of afatinib concentration in: [resected brain metastases] / [plasma] - each measured in (ng/mL) on day 12 (time frame: Day 12 of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 31 Jan 2024; AzTrials last refreshed its copy on 1 Nov 2026.