Neoplasms

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Symptoms and General Pathology

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Breast Neoplasms

Brain Neoplasms

Neoplasm Metastasis

Lung Neoplasms

Breast Diseases

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Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Central Nervous System Neoplasms

Nervous System Neoplasms

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Central Nervous System Diseases

Antineoplastic Agents

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Amino Acids

Afatinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

No targeted radiotherapy. Afatinib at Recommended Phase 2 Dose for 11 days.

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.

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.

2 Gy targeted radiotherapy

4 Gy targeted radiotherapy

Richard Baird, MD PhD

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.

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.

Cambridge Brain Mets Trial 1

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

Spots Global Cancer Trial Database for 4 gy targeted radiotherapy