Thorax Trials

Question 1

What are phase one trials used for ?

Answer 1

• Small cohort

- Usually assessing safety, dose, side effects and benfit

Question 2

What are phase 2 trials used for?

Answer 2

• Larger cohort (100s)
• Can involve a placebo
• Assess feasibility
• Defines test arms for phase 3

Question 3

What are phase 3 trials used for?

Answer 3

• Multinational (1000s)
• Comparison with gold standard of care
• Could change practice

Question 4

How are phase four trials used?

Answer 4

• Multinational (10,000s)
• Mainly pharma
• Long term (>10 years)

Question 5

What is the CHART trial?

Answer 5

• Continuous Hyperfractionated Accelerated Radiation Therapy
• Lung Trial
• 3 x daily treatment with 6hr gaps for 12 consecutive days
• 9% absolute improvement in overall survival at 2 years
• No evidence of long term toxicity compared with standard (60 in 30)
• Did not use modern VMAT
• 61% of patients still died due to persistent local disease
• Labour intensive

Question 6

What was the IDEAL-CRT trial?

Answer 6

• Phase I and II
• How high can radiotherapy dose be escalated
• 73Gy cut off in 30# over 6 weeks
• With chemo-RT (cisplatin and vinorelbine)
• Dose escalation was calculated on an individual patient basis
• Max dose 68Gy to 1cc oesophagus
• Reported disease free survival of 72% at 1 year and 48.5% at 2 years
• Dose escalation with acceptable toxicity did improve survival

Question 7

What is the ADSCan Trial?

Answer 7

• 4 dose escalated and accelerated regimes to compare with standard treatment
• Pick the winner
• Standard Arm: 55Gy in 20# over 26-28 days
• CHART-ED: 54Gy in 36# over 12 days then 10.8Gy in 6# (days 15-17)
• IDEAL: Isotoxic radiotherapy 63-71Gy in 30# over 5 weeks
• I-START: Isotoxic radiotherapy 55–65Gy in 20# over 4 weeks
• ISOTOXIC IMRT: Isotoxic regime IMRT 79.2Gy in 1.8Gy# over 4 weeks BD. Personalised dose escalation based on mean OAR doses.
• Closed June 2021, awaiting results

Question 8

what is the CHECKMATE trial?

Answer 8

• Compares progression free survival and evaluate tumour response
• Uses immunotherapeutic approches
• A: Nivolumab + CCRT followed by nivolumab + ipilimumab maintenance
• B: Nivolumab + CCRT followed by nivolumab maintenance
• C: CCRT followed by durvalumab maintenance
• Resource intensive
• Difficult assessment pathway on to treatment

Question 9

What is KEYNOTE-671?

Answer 9

• Phase III Trial of Pt Chemo +/- pembrolizumab as neoadj/adj therapy
• Patients with resectable stage IIB or IIIA NSCLC
• Arm A: Neoadjuvant pembrolizumab plus chemo followed by surgery and adjuvant pembrolizumab
• Arm B: Neoadjuvant placebo plus chemo followed by surgery and adjuvant placebo
• RT within 4-8 weeks of surgery
• No surgery 60-70Gy in 1.8-2.75Gy
• Gross residual disease 60-70Gy in 1.8-2.0#
• Extracapsular lymphN extension 54-60Gy in 1.8-2.0Gy
• Microscopic +ve margins 54-60Gy in1.8-2.0#

Question 10

What is KEYNOTE-867?

Answer 10

• SABR with or without Pembrolizumab for patients with medically inoperable stages I and IIA NSCLC
• Compare SABR + drug vs SABR + placebo
• Compare event free survival and overall survival
• Peripheral lesions 18Gy in 3#
• Abutting chest wall 11Gy in 5#
• Central lesions 7.5Gy in 8#

Question 11

What is the HALT trial?

Answer 11

• targeted therapy, no dose intensification
• use of SABR to assess oligo-progressive disease to prolong the period of clinical beneift
• patients randomised to receive SABR or no SABR
• Must be < 3 disease sites

Question 12

What is the SARON trial?

Answer 12

• Impact of overall survival of the addition of radical convention and SABR to standard systemic therapy in first line treatment with 1-5 sites

Question 13

What are the SCOPE1 and NEOSCOPE trials?

Answer 13

• SCOPE1 - localised oesoph cancers randomised to receive cisplatin and capecitabeine concurrently with 50Gy in 25# +/- Cetuximab
• Decided cetuximab should not be recommended
• Neoscope compared toxicity and efficacy of 2 pre-op CRT regimens (Oxaliplatin and cape_ or (carboplatin and paclitaxel) with 45Gy in 25#
• Carbo + Pacli passed but Oxali and Cape did not

Question 14

What is the SCOPE2 trial?

Answer 14

• Studies chemoRT including PET response and dose escalation
• Standard arm of 50Gy/25#/5 weeks
• Dose escalation where PTV receives 50Gy/25# and Boost receives 60Gy/25#
• primary outcomes will be 50vs60
• Secondary outcome is PFS, safety and late toxicity, QoL, compliance and dysphagia