Cambridge Brain Mets Trial 1

Phase 1

Terminated

• Conditions: Lung Cancer; Breast Cancer; Brain Cancer; Advanced Breast Cancer; Advanced Lung Cancer
• Interventions: Drug: Afatinib; Radiation: 2 Gy targeted radiotherapy; Radiation: 4 Gy targeted radiotherapy

• Registration Number: NCT02768337
• Lead Sponsor: Cambridge University Hospitals NHS Foundation Trust

Brief 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.

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 Timeline

• Study Start: 2015-03-10
• Study First Submitted: 2016-04-28
• Study First Submitted QC: 2016-05-10
• Study First Posted: 2016-05-11
• Primary Completion: 2020-08-12
• Study Completion: 2021-08-12
• Status Verified: 2024-01
• Last Update Submitted: 2024-01-30
• Last Update Posted: 2024-01-31

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 26

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm 1: Afatinib only at Recommended Phase 2 dose (RP2D)	Afatinib	No targeted radiotherapy. Afatinib at Recommended Phase 2 Dose for 11 days.
Arm 2: Afatinib RP2D + 2 Gy targeted radiotherapy	2 Gy targeted radiotherapy	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.
Arm 3: Afatinib RP2D + 4 Gy targeted radiotherapy	4 Gy targeted radiotherapy	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.
Arm 3: Afatinib RP2D + 4 Gy targeted radiotherapy	Afatinib	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.
Arm 2: Afatinib RP2D + 2 Gy targeted radiotherapy	Afatinib	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.

Primary Outcome Measures

Name	Time	Method
Ratio of afatinib concentration in: [resected brain metastases] / [plasma] - each measured in (ng/mL) on day 12	Day 12 of treatment

Secondary Outcome Measures

Name	Time	Method
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	From consent to Day 41+/-7 days

Trial Locations

Locations (6)

The Beatson West of Scotland Cancer Centre; 🇬🇧 Glasgow, United Kingdom

Oxford University Hospitals NHS Foundation Trust; 🇬🇧 Oxford, United Kingdom

Clatterbridge Cancer Centre; 🇬🇧 Liverpool, United Kingdom

University Hospitals Birmingham NHS Foundation Trust; 🇬🇧 Birmingham, United Kingdom

Cambridge University Hospitals NHS Foundation Trust; 🇬🇧 Cambridge, England, United Kingdom

The Christie NHS Foundation Trust; 🇬🇧 Manchester, United Kingdom