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.

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 .

scholarly journals Multicenter Phase Ii Trial of Neoadjuvant Chemotherapy with Mfolfox6 for Stage Ii/Iii Rectal Cancer with a T3/T4 Tumor Fact Trial

2014 ◽  
Vol 25 ◽  
pp. iv201
Author(s):  
H. Yokomizo ◽  
K. Yoshimatsu ◽  
J. Koike ◽  
K. Funahashi ◽  
H. Kan ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Stage Ii ◽  
Multicenter Phase

NSABP FR-2: Phase II study of durvalumab following neoadjuvant chemoRT in stage II-IV rectal cancer.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. TPS727-TPS727
Author(s):  
Thomas J. George ◽  
Greg Yothers ◽  
James J. Lee ◽  
Samuel A. Jacobs ◽  
Melvin Deutsch ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Stage Iv ◽  
Sphincter Preservation ◽  
Stage Ii ◽  
Systemic Steroid ◽  
Clinical Role

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.

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

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14591-14591 ◽  
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]

Phase II trial of neoadjuvant chemotherapy with TS-1/L-OHP (SOX) for resectable advanced rectal cancer (NCCSG-09).

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. e15028-e15028
Author(s):  
Yasumasa Takii ◽  
Satoshi Maruyama ◽  
Mikako Kawahara ◽  
Hitoshi Nogami ◽  
Hajime Yokomizo ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Advanced Rectal Cancer

NSABP FR-2: Phase II study of durvalumab following neoadjuvant chemoRT in stage II-IV rectal cancer.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. TPS264-TPS264
Author(s):  
Thomas J. George ◽  
Greg Yothers ◽  
Samuel A. Jacobs ◽  
Gene Grant Finley ◽  
Hiral D. Parekh ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Stage Iv ◽  
Tumor Infiltrating Lymphocytes ◽  
Sphincter Preservation ◽  
Stage Ii ◽  
Systemic Steroid

TPS264 Background: Clinical improvements for locally advanced rectal cancer have been relatively static over the past few decades. While immunotherapy shows no benefit 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. Using a “window-of-opportunity” study design, this prospective phase II trial will determine the safety and activity of this approach 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 with intent to proceed to surgical resection after CRT. 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, tumor Immunoscore, 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. Support: AstraZeneca-Medimmune, NSABP Foundation. Clinical trial information: NCT03102047.

Neoadjuvant chemotherapy with modified FOLFOXIRI for locally advanced rectal cancer: A single center phase II trial.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 69-69
Author(s):  
Wen Zhang ◽  
Haitao Zhou ◽  
Jun Jiang ◽  
Yuelu Zhu ◽  
Shuangmei Zou ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Folinic Acid ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Locally Advanced ◽  
Venous Invasion ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
R0 Resection

69 Background: Chemoradiotherapy (CRT) remains the standard treatment choice for locally advanced rectal cancer (LARC). Neoadjuvant chemotherapy alone with doublet mFOLFOX6 (folinic acid, 5-fluorouracil, and oxaliplatin) seemed not to influence recurrence free survival with the advantage of less treatment-related complications. This phase II trial was designed to evaluate the efficacy and safety of neoadjuvant triplet chemotherapy with mFOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin, and irinotecan) in patients with LARC (NCT03443661). Methods: Patients with LARC received up to 5 cycles of mFOLFOXIRI (irinotecan 150 mg/m2, oxaliplatin 85 mg/m2, leucovorin 200 mg/m2 were administered on Day 1, fluorouracil 2400 mg/m2 was administered as a continuous intravenous infusion for 48 hours on Day 1, and was repeated every 14 days). Magnetic resonance imaging (MRI) was performed to assess the baseline and post-chemotherapy TN stage. Radical resection was performed within 4–6 weeks of the last dose of chemotherapy if the tumor shrank or remained stable. Adjuvant chemotherapy with mFOLFOX6 or XELOX (oxaliplatin and capecitabine) was recommended. Postoperative radiation was planned for R1 resection, ypT4b, ypN2, and positive circumferential resection margin (CRM). The primary endpoint was the pathological complete response (pCR) rate. Results: Between December 2015 to March 2019, a total of 50 patients were enrolled. 48 (96%) of the patients were clinically node-positive, 28 (56.5%) were CRMnvolved, and 39 (78.4%) were extramural venous invasion (EMVI)-positive. The median cycle of neoadjuvant mFOLFOXIRI chemotherapy was 5 (range, 1–5). A total of 46/50 (92%) patients underwent total mesorectal excision (TME) surgery, all with R0 resection. The pCR rate was 4.3% (2/46). Twenty-three of 46 (50%) patients achieved pathological node-negative status. The proportion of pathologically positive CRM and EMVI were 2.2% and 34.7%, respectively (table). Adjuvant radiotherapy was given to 14/46 (30.4%) patients. The most common Grade 3 or more toxicities included neutrocytopenia (50%), leukopenia (14%), and diarrhea (12%) during neoadjuvant chemotherapy. Clinical meaningful surgical morbidities included pneumonia (n=1), pelvic infection (n=1), and anastomotic fistula (n=1). With a median follow-up time of 33 months (range, 14–73 months), local recurrences and distant metastases were confirmed in 3 (6.5%) and 8 (17.4%) cases, respectively. Conclusions: Neoadjuvant chemotherapy with mFOLFOXIRI yielded a significant down-staging effect with an ordinary pCR rate, and seemed effective in eliminating EMVI and transforming CRM-positive to CRM-negative status in patients with LARC. The preliminary survival results are promising. This regimen could serve as a potential alternative to CRT in selected patients with LARC. Clinical trial information: NCT03443661. [Table: see text]

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