505TiP REGINA: A phase II trial of neoadjuvant regorafenib (rego) in combination with nivolumab (nivo) and short-course radiotherapy (SCRT) in intermediate-risk, stage II-III rectal cancer (RC)

TPS727 Background: Locally advanced rectal cancer remains a clinical challenge with few improvements noted over the past few decades. Although immunotherapy has no current clinical role in microsatellite stable (MSS) colorectal cancer, preclinical models suggest that radiotherapy (RT) can enhance neoantigen presentation, modulate the microenvironment, and improve the likelihood of anti-tumor activity with checkpoint inhibitor use. This prospective phase II trial will test that hypothesis in addition to confirming safety of this approach using a “window-of-opportunity” study design with the anti-PD-L1 agent durvalumab (MEDI4736). Methods: This multi-center phase II trial is currently enrolling patients (pts) with rectal cancer who are undergoing standard NCCN guideline-compliant neoadjuvant chemoradiotherapy (CRT). Eligibility includes pts with MSS stage II-IV rectal cancer with adequate organ function and pre-treatment diagnostic tumor available for profiling who are undergoing CRT with intentions to proceed to surgical resection. Stage IV disease must be limited such that the primary pelvic tumor requires definitive management. Standard ineligibility criteria include active infections, systemic steroid use, or other conditions making immunotherapy use unsafe. Treatment includes durvalumab (750mg IV infusion once every 2 wks) for 4 total doses beginning within 3-7 days after CRT completion. Surgery must be within 8-12 wks of the final CRT dose. Primary endpoint is a demonstrated improvement in Neoadjuvant Rectal Cancer (NAR) score compared to historical controls targeting a 20% relative risk reduction in DFS and 3-4% absolute OS improvement. Secondary endpoints include OS, DFS, toxicity, pCR, cCR, therapy completion, negative surgical margins, sphincter preservation, off-target “abscopal” effects for the subset of stage IV pts, and exploratory assessments of tumor infiltrating lymphocytes, circulating immunologic profiles, and molecular predictors of response. A safety run-in phase has completed as a precedent to full enrollment. Enrollment now continues to 47 total pts to achieve 41 surgically evaluable pts. NCT03102047. Support: AstraZeneca-Medimmune, NSABP Foundation Clinical trial information: NCT03102047.

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Effect of neoadjuvant chemotherapy and early chemotherapeutic response evaluation for low/intermediated-risk mid-low stage II/III rectal cancer: A prospective, open-label, single-arm, phase II trial.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e16133 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e16133-e16133

Author(s):

Xiangbing Deng ◽

Liang Bi ◽

Qingbin Wu ◽

Du He ◽

Hongfeng Gou ◽

...

Keyword(s):

Rectal Cancer ◽

Neoadjuvant Chemotherapy ◽

Likelihood Ratio ◽

Phase Ii ◽

Local Control ◽

Phase Ii Trial ◽

Stage Ii ◽

Early Assessment ◽

Tumor Length ◽

Chemotherapeutic Response

e16133 Background: Neoadjuvant chemoradiotherapy (NCRT) is the standard of care for stage II/III rectal cancer (RC) for its local-control effect. As advancement in surgery, local relapse was no longer the primary cause of failures, especially in low/intermediated-risk stage II/III RCs, in which benefit of radiotherapy in local control wasn’t shown in our previous trial. Distant relapse has become the major form of recurrences, and occurs at an increased rate when chemotherapy was delayed. This trial explores the effect of neoadjuvant chemotherapy (NCT), and the possibility of early assessment of chemotherapeutic response in low/intermediated-risk stage II/III RCs. Methods: This prospective, single arm, phase II trial planned to enroll 60 low/intermediate-risk stage II/III mid-low RCs (low: cT3a-bN0-1M0 MRF(-); mid: cT3a-c or T4aN0-1M0). 4 cycles of CAPOX NCT were scheduled. Rectal MRI, transanal US, endoscopy, CT were examined prior to treatment and after every two cycles. The primary outcome was the clinicopathological response, defined as pathological TRG0-1, TRG2 without tumor length increase, or TRG3 with tumor length regression over 30%. This study was approved by the Ethics Committees of West China Hospital and registered at ClinicalTrials.gov (NCT03666442). Results: From Dec. 2017 to Oct. 2019, 61 eligible patients were enrolled. Two patients received 3 cycles and 2 had only 2 cycles of chemotherapy due to intolerable adverse effects; 57 cases finished 4 cycles. In pathological evaluation, 13 patients (21.3%) were complete response (pTRG0) with one positive node in one patient; 5 cases were pTRG1; 26 were pTRG2; 17 had no response (pTRG3). 48 cases (78.7%) were responders. In the ROC curve predicting the responder via the 2-cycle regression in tumor length, the AUC was 0.864 (95%CI (0.764,0.963), p < 0.001), and the best cutoff regression rate after 2 cycles NCT was 27%. With this cutoff, the sensitivity was 83.3%; specificity was 84.6%; accuracy was 83.6%; positive likelihood ratio was 5.42; negative likelihood ratio was 0.20. Conclusions: NCT achieve more favorable pCR and tumor response rate in low/intermediated-risk stage II/III RCs, comparing to previous studies. The tumor regression after 2 cycles NCT had good accuracy in diagnosing the chemotherapeutic response. This early assessed chemosensitivity may become another feature for tailored use of neoadjuvant treatments, further cohort study will be conducted. Clinical trial information: NCT03666442 .

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PALAESTRA: A phase II trial with short-course radiotherapy followed by chemotherapy as palliative treatment in esophageal adenocarcinoma

Annals of Oncology ◽

10.1093/annonc/mdz247.097 ◽

2019 ◽

Vol 30 ◽

pp. v298

Author(s):

D. Borg ◽

J. Sundberg ◽

E. Brun ◽

E. Kjellén ◽

K. Petersson ◽

...

Keyword(s):

Esophageal Adenocarcinoma ◽

Phase Ii ◽

Palliative Treatment ◽

Phase Ii Trial ◽

Short Course ◽

Short Course Radiotherapy

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Altered fractionation short-course radiotherapy for stage II-III rectal cancer: a retrospective study

Radiation Oncology ◽

10.1186/s13014-020-01566-8 ◽

2020 ◽

Vol 15 (1) ◽

Author(s):

Hans Geinitz ◽

Carsten Nieder ◽

Lukas Kocik ◽

Christine Track ◽

Johann Feichtinger ◽

...

Keyword(s):

Rectal Cancer ◽

Retrospective Study ◽

Stage Ii ◽

Altered Fractionation ◽

Short Course ◽

Short Course Radiotherapy

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EP-1424: Palliative short-course radiotherapy in rectal cancer: a phase II study

Radiotherapy and Oncology ◽

10.1016/s0167-8140(16)32674-3 ◽

2016 ◽

Vol 119 ◽

pp. S662-S663

Author(s):

V. Picardi ◽

F. Deodato ◽

G. Macchia ◽

A. Guido ◽

L. Giaccherini ◽

...

Keyword(s):

Rectal Cancer ◽

Phase Ii ◽

Phase Ii Study ◽

Short Course ◽

Short Course Radiotherapy

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First toxicity and efficacy analysis of a phase II trial of a novel 5-FU-oxaliplatin based chemoradiation schema for stage II and III rectal carcinoma

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.14591 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 14591-14591 ◽

Cited By ~ 1

Author(s):

E. M. Rishe ◽

S. Malamud ◽

K. Hu ◽

W. Enker ◽

P. Kozuch ◽

...

Keyword(s):

Rectal Cancer ◽

Phase Ii ◽

Phase Ii Trial ◽

Neoadjuvant Treatment ◽

Standard Of Care ◽

Neoadjuvant Chemoradiation ◽

Stage Ii ◽

Efficacy Analysis ◽

Significant Toxicity ◽

Grade 3

14591 Background: 5-FU based neoadjuvant chemoradiation (CRT) has become the standard of care for stage 2 and 3 rectal cancer (ca). Pathologic complete responses (pCR) and downstaging have been associated with improved survival outcomes. The addition of oxaliplatin or irinotecan to neoadjuvant treatment has led to improved pCR and downstaging. The feasibility and efficacy of “total” oxaliplatin therapy (pre and postoperative oxaliplatin) for stage 2 and 3 rectal ca patients has yet to be defined. Objective: To determine the feasibility, toxicity and efficacy of neoadjuvant oxaliplatin, 5-FU and RT followed by surgery, with postop adjuvant modified FOLFOX6. Methods: Single institution, single arm phase II trial of oxaliplatin 60mg/m2 weekly for 6 weeks with continuous infusion 5- FU 225 mg/m2/excision. Postoperative therapy consisted of mFOLFOX6 every 2 weeks for 6 cycles. Eligibility included previously untreated, histologically proven rectal cancer, T3–4N0M0 or TanyN+M0 (stage II-III). Results: 15 pts have been enrolled in this study. One died of disease prior to CRT. Eight pts have completed total oxaliplatin therapy. One pt had 1 cycle deleted due to grade 2 neuropathy. Prior to adjuvant therapy 2 pts dropped out: 1 from pulmonary symptoms and one asthenia. Two pts attained a pCR and 6 attained downstaging. Significant toxicity has been limited to grade 3 neuropathy in one pt (completely resolved) and one grade 3 GI toxicity (self limited). Conclusions: Early analysis shows the feasibility of pre and post operative oxaliplatin based therapy. The limited data permit only observation of pCR and tumor downstaging rates but toxicity outcomes are encouraging. Further accrual and follow-up will better define efficacy and toxicity of this regimen. [Table: see text]

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