Cambridge Brain Mets Trial 1 (CamBMT1)
|Lung Cancer Breast Cancer Brain Cancer Advanced Breast Cancer Advanced Lung Cancer||Drug: Afatinib Radiation: 2 Gy targeted radiotherapy Radiation: 4 Gy targeted radiotherapy||Phase 1 Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Other
|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|
- Ratio of afatinib concentration in: [resected brain metastases] / [plasma] - each measured in (ng/mL) on day 12 [ Time Frame: Day 12 of treatment ]
- 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 ]
|Study Start Date:||February 2015|
|Estimated Study Completion Date:||December 2019|
|Estimated Primary Completion Date:||October 2019 (Final data collection date for primary outcome measure)|
Arm 1: Afatinib only at Recommended Phase 2 dose (RP2D)
No targeted radiotherapy. Afatinib at Recommended Phase 2 Dose for 11 days.
Other Name: Giotrif
Experimental: Arm 2: Afatinib RP2D + 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.
Other Name: GiotrifRadiation: 2 Gy targeted radiotherapy
Experimental: Arm 3: Afatinib RP2D + 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.
Other Name: GiotrifRadiation: 4 Gy 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 afatiinib 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02768337
|Contact: Nicola Ramenatte||+44 1223 email@example.com|
|Cambridge University Hospitals NHS Foundation Trust||Recruiting|
|Cambridge, England, United Kingdom, CB2 2QQ|
|The Beatson West of Scotland Cancer Centre||Recruiting|
|Glasgow, United Kingdom|
|The Christie NHS Foundation Trust||Recruiting|
|Manchester, United Kingdom|
|Principal Investigator:||Richard Baird, MD PhD||Cambridge University Hospitals NHS Foundation Trust|