SCALOP2:A multicenter randomized trial of RT dose escalation and nelfinavir in pancreatic cancer
Mukherjee, S. Qi, C. Shaw, R. Bridgewater, J. Radhakrishna, Ganesh Patel, N. Tranter, B. Parsons, P. Falk, S. Wasan, H.
Mukherjee, S.
Qi, C.
Shaw, R.
Bridgewater, J.
Radhakrishna, Ganesh
Patel, N.
Tranter, B.
Parsons, P.
Falk, S.
Wasan, H.
Citations
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Abstract
Purpose or Objective
The anti-retroviral agent, nelfinavir (N), demonstrated radiosensitising properties in pre-clinical models and showed
promising activity in single arm phase I/II trials in combination with CRT for LAPC. RT dose escalation (BED10 >70) may be
associated with improved survival. SCALOP2 was a phase 1/randomized phase II study. The phase I component established
the MTD of nelfinavir in combination with capecitabine-based CRT following gemcitabine+nab-paclitaxel (GEMABX)
induction chemotherapy in LAPC (previously reported). The 2 x 2 randomized phase II component evaluated whether (1) RT
dose escalation from 50.4Gy/28 fractions [standard dose (SD)] to 60Gy/30 fractions [high dose (HD)], combined with
capecitabine improved OS and (2) adding nelfinavir to CRT improved PFS.
Materials and Methods
Patients with unresectable, histologically/cytologically proven LAPC and WHO PS 0-1 received 3 cycles of induction GEMABX
(standard dose and schedule) followed by restaging. Progression-free patients were randomized to 1 further cycle of
GEMABX followed by A (SD+N), B (SD = control arm), C (HD +N), D (HD), or E (GEMABX x 2 cycles = calibration arm). CRT
capecitabine dose was 830mg/m2 bd on days of RT, nelfinavir 1250mg bd started 7 days before CRT until completing CRT.
Results
Between March 2016 and March 2020, 186 patients were recruited from 21 centres in the UK (phase 1=27; phase 2=159).
106/159 patients were randomized (A=19, B=26, C=19, D=27, E=15). Arm E closed in Nov 2019, taking into consideration
data from the LAPACT trial. The ISDMC recommended closure of the nelfinavir arms in Feb 2020 due to futility. At the time
of analysis, 64/91 patients randomized to CRT arms had died. Median OS was 15.6 mo (60% CI 14.3,18.2) in the SD arms and
16.9 mo (16.2, 17.7) in the HD arms, HR (60% CI) 1.11(0.89,1.38), adjusted one-sided p=Not significant (NS). Of the 76
patients eligible for randomization to N-containing arms, median PFS was 11.1 (10.3, 12.8) in the CRT-only arms (HR (60%
CI) 1.84(1.47,2.3) and 10 mo (60% CI 9.9,10.2) in the CRT+N arms, adjusted one-sided p=NS. Secondary endpoints: Grade 3-4 serious adverse reactions during CRT were reported as follows: 5/45 (11.1%) in SD arms, 4/46 (8.7%) in HD arms, 5/38
(13.2%) in CRT+N arms and 4/38 (10.5%) in CRT-only arms. 1-year local progression (with/without metastasis) and local only (no metastasis) progression rate was 33.3% and 26.7% (SD arms) and 23.9% and 15.2% (HD arms) respectively. Overall
resection rate (11%) and quality of life were similar for all arms.
Conclusion
The addition of nelfinavir and/or RT dose escalation to 60Gy failed to improve outcomes in LAPC. RT dose escalation to
60Gy was well tolerated.
Description
Date
2022
Publisher
Collections
Keywords
Type
Meetings and Proceedings
Citation
Mukherjee S, Qi C, Shaw R, Bridgewater J, Radhakrishna G, Patel N, et al. SCALOP2:A multicenter randomized trial of RT dose escalation and nelfinavir in pancreatic cancer. Radiotherapy and Oncology. 2022 May;170:S77-S8. PubMed PMID: WOS:000806759200078.