Phase I/II Trial of Capecitabine, Oxaliplatin, and Radiation for Rectal Cancer

2003 ◽  
Vol 21 (16) ◽  
pp. 3098-3104 ◽  
Author(s):  
Claus Rödel ◽  
Gerhard. G. Grabenbauer ◽  
Thomas Papadopoulos ◽  
Werner Hohenberger ◽  
Hans-Joachim Schmoll ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Tumor Regression ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Sphincter Preservation ◽  
Phase Iii ◽  
Grade 3

Purpose: The purpose of this study was to establish the feasibility and efficacy of preoperative radiotherapy (RT) with concurrent capecitabine and oxaliplatin (XELOX-RT) in patients with rectal cancer. Patients and Methods: Thirty-two patients with locally advanced (T3/T4) or low-lying rectal cancer received preoperative RT (total dose, 50.4 Gy). Capecitabine was administered concurrently at 825 mg/m2 bid on days 1 to 14 and 22 to 35, with oxaliplatin starting at 50 mg/m2 on days 1, 8, 22, and 29 with planned escalation steps of 10 mg/m2. End points of the phase II study included downstaging, histopathologic tumor regression, resectability of T4 disease, and sphincter preservation in patients with low-lying tumors. Results: Dose-limiting grade 3 gastrointestinal toxicity was observed in two of six patients treated with 60 mg/m2 of oxaliplatin. Thus, 50 mg/m2 was the recommended dose for the phase II study. Toxicities observed at this dose level were generally mild, with only two cases of short-lived grade 3 diarrhea. Myelosuppression, mainly leukopenia, was restricted to grade 2 in 19% of patients. T-category downstaging was achieved in 17 (55%) of 31 operated patients, and 68% of patients had negative lymph nodes. Pathologic complete response was found in 19% of the resected specimens. Radical surgery with free margins could be performed in 79% of patients with T4 disease, and 36% of patients with tumors ≤ 2 cm from the dentate line had sphincter-saving surgery. Conclusion: Preoperative XELOX-RT is a feasible and well tolerated treatment. This regimen is proposed for phase III evaluation comparing standard fluorouracil-based therapy with XELOX chemoradiotherapy.

Multicenter Phase II Trial of Chemoradiation With Oxaliplatin for Rectal Cancer

2007 ◽  
Vol 26 (1) ◽  
pp. 110-117 ◽  
Author(s):  
Claus Rödel ◽  
Torsten Liersch ◽  
Robert Michael Hermann ◽  
Dirk Arnold ◽  
Thomas Reese ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Tumor Regression ◽  
Pathologic Complete Response ◽  
Sensory Neuropathy ◽  
Multimodality Treatment ◽  
Complete Response ◽  
Sphincter Preservation ◽  
Phase Iii ◽  
Multicenter Phase ◽  
Grade 3

PurposeTo evaluate the activity and safety of preoperative radiotherapy (RT) and concurrent capecitabine and oxaliplatin (XELOX-RT) plus four cycles of adjuvant XELOX in patients with rectal cancer.Patients and MethodsOne hundred ten patients with T3/T4 or N+ rectal cancer were entered onto the trial in 11 investigator sites and received preoperative RT (50.4 Gy in 28 fractions). Capecitabine was administered concurrently at 1,650 mg/m2on days 1 to 14 and 22 to 35, and oxaliplatin was administered at 50 mg/m2on days 1, 8, 22, and 29. Surgery was scheduled 4 to 6 weeks after completion of XELOX-RT. Four cycles of adjuvant XELOX (capecitabine 1,000 mg/m2bid on days 1 to 14; oxaliplatin 130 mg/m2on day 1) were administered. The main end points were activity as assessed by the pathologic complete response (pCR) rate and the feasibility of postoperative XELOX chemotherapy.ResultsAfter XELOX-RT, 103 of 104 eligible patients underwent surgery; pCR was achieved in 17 patients (16%), one patient had ypT0N1 disease, and 53 patients showed tumor regression of more than 50% of the tumor mass. R0 resections were achieved in 95% of patients, and sphincter preservation was accomplished in 77%. Full-dose preoperative XELOX-RT was administered in 96%. Grade 3 or 4 diarrhea occurred in 12% of patients. Postoperative complication occurred in 43% of patients. Sixty percent of patients received all four cycles of adjuvant XELOX, with sensory neuropathy (18%) and diarrhea (12%) being the main grade 3 or 4 toxicities.ConclusionPreoperative XELOX-RT plus four cycles of adjuvant XELOX is an active and feasible treatment. This regimen is proposed for phase III evaluation comparing standard fluorouracil-based treatment with XELOX- based multimodality treatment.

Neoadjuvant cetuximab, capecitabine, and radiotherapy (RT) in locally advanced resectable rectal cancer: results of a phase II trial

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15029-e15029
Author(s):  
V. Velenik ◽  
J. Ocvirk ◽  
I. Oblak ◽  
F. Anderluh
Keyword(s):  
Rectal Cancer ◽  
Phase Ii ◽  
Tumor Regression ◽  
Anal Verge ◽  
Locally Advanced ◽  
Advanced Rectal Cancer ◽  
Sphincter Preservation ◽  
Open Label ◽  
Resectable Rectal Cancer ◽  
Grade 3

e15029 Background: Preoperative chemoradiotherapy (CRT) with capecitabine is a treatment of choice for locally advanced rectal cancer. The radiosensitizing effect of cetuximab, an EGFR-targeting monoclonal antibody, may further enhance the tumor response. The aim of this prospective, nonrandomized, open-label phase II study was to establish the efficacy and safety profile of cetuximab combined with capecitabine and concurrent RT for locally advanced resectable rectal cancer. Methods: Patients (pts) with stage II or III rectal cancer confirmed by MRI were treated with capecitabine 1250 mg/m2 twice daily for 2 weeks. Cetuximab 400mg/m2 was intravenously administered on week 3, followed by cetuximab 250mg/m2/week and capecitabine 825 mg/m2 bid including weekends during RT. The RT dose was 45 Gy (25×1.8 Gy, 3D conformal technique), starting on week 4. Total mesorectal excision was scheduled 4–6 weeks after completion of CRT. Tumor regression grades (TRG) were evaluated on surgical specimens according to Dworak. The primary endpoint was complete pathologic response (pCR). Results: Thirty-seven pts were eligible for safety and efficacy analyses. Median age was 55 (range: 33–72) years, 81% of pts were male. Three pts (8.1%) had T3N0 tumors, 1 pt (2.7%) T2N1, 13 pts (35%) T3N1, 1 pt (2.7%) T2N2, 15 pts (40.5%) T3N2 and 4 pts (11%) T4N2. The median tumor distance from anal verge was 6 (range: 1–11) cm. All pts received 45 Gy RT. Dose reduction/treatment interruption was necessary for 9/37 (24.3%) pts owing to hypersensitivity reaction (n=4), hepatotoxicity grade 3 (n=1) or diarrhea grade 3 (n=4). Other grade 3 toxicities included dermatitis (n=6, 16.2%), anorexia (n=1, 2.7%) and infection (n=1, 2.7%). TRG 4 (pCR) was recorded in 3 pts (8.1%) and TRG 3 in 7 pts (18.9%). T-, N- and overall downstaging rates were 56.8%, 81.1% and 73.0%, respectively. The total sphincter preservation rate was 75.7%; in 17 pts whose tumors were located ≤5 cm of the anal verge, the rate was 53%. Conclusions: Preoperative CRT with cetuximab and capecitabine is safe and feasible. A high pathologic downstaging rate was achieved, although the pCR rate appeared to be in the range previously reported for CRT with capecitabine. No significant financial relationships to disclose.

A phase II study of complete neoadjuvant therapy in rectal cancer (CONTRE): The Brown University Oncology Group.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 335-335 ◽  
Author(s):  
Kimberly Perez ◽  
Victor Pricolo ◽  
Matthew Vrees ◽  
Thomas A. DiPetrillo ◽  
Nicholas Oldenberg ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Pathologic Complete Response ◽  
Neoadjuvant Treatment ◽  
Complete Response ◽  
Stage Ii ◽  
R0 Resection ◽  
Pelvic Mri ◽  
Grade 3

335 Background: While preoperative chemoradiation followed by surgery is the standard approach for patients (pts) with newly diagnosed clinical stage II-III rectal cancer, many are unable to tolerate postoperative adjuvant chemotherapy which may compromise disease-free and overall survival. CONTRE is a multicenter phase II study designed to determine the feasibility of administering all chemotherapy prior to surgery and to assess its impact on pathologic complete response (pCR) and complete (R0) resection Methods: Pts with T3-4 and/or N1-2 rectal cancer, staged by endorectal ultrasound (ERUS) and pelvic MRI, receive modified (m) FOLFOX6 every 2 weeks x 8 cycles, followed by repeat MRI and proctoscopy to assess response. Pts then receive 50.4 Gy IMRT with 5-FU 225 mg/m2/day or capecitabine 825mg/m2 BID, 5 days per week during radiation, followed by surgery 4-8 weeks later. Results: Thus far, we have enrolled 36 of a planned 39 pts (median age 58, range 30-79; T2-1, T3-30, T4-2; N1-20, N2-7). 28 of the first 30 (93%) completed 8 cycles of mFOLFOX6. 26 pts have completed chemoradiation while 2 chose to proceed directly to surgery. All patients opted to receive capecitabine during radiation. Grade 3/4 toxicities during chemotherapy and chemoradiation have included diarrhea (16%) and neutropenia (12%), with grade 3 renal and cardiac toxicities reported in one patient each. A clinical complete response after chemotherapy alone was achieved in 3 of 29 (10%). Of the first 21 pts undergoing surgery, pCR has been achieved in 6 (29%) and R0 resections in 100%. Thus far, all pts have been able to undergo sphincter-sparing resections. Study accrual will be completed by the meeting. Conclusions: A larger proportion of stage II-III rectal cancer pts are able to complete mFOLFOX6 (>90% in our cohort) when administered prior to chemoradiation and surgery. Complete neoadjuvant treatment may represent a well-tolerated alternative to the current standard treatment sequence and a platform for the evaluation of novel therapeutics such as targeted agents during preoperative therapy. Funded in part by LIFEcycle, Inc. Clinical trial information: NCT01363843.

624 A PHASE III STUDY ON NEOADJUVANT TORIPALIMAB PLUS CHEMOTHERAPY VERSUS NEOADJUVANT CHEMOTHERAPY FOR LOCALLY RESECTABLE ESOPHAGEAL SQUAMOUS CELL CARCINOMA

2021 ◽  
Vol 34 (Supplement_1) ◽  
Author(s):  
Yan Zheng ◽  
Jiangong Zhang ◽  
Wenqun Xing
Keyword(s):  
Phase Ii ◽  
Checkpoint Inhibitors ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Disease Free Survival ◽  
Complete Response ◽  
Phase Iii ◽  
R0 Resection ◽  
Phase Iii Trial ◽  
Free Survival

Abstract   In recent years, immune checkpoint inhibitors (ICIs) have shown promising results in the treatment of ESCC. More than 20 phase II clinical trials have been launched to explore combinations of ICIs in the neoadjuvant setting for ESCC. Based on our phase II clinical trial, a two-arm phase III trial was launched in our Hospital. Methods A two-arm phase III trial was launched in April 2020 in our Hospital. Patient recruitment will be completed within 18 months. The primary endpoint is event-free survival (EFS). The secondary endpoints include pathologic complete response (pCR), disease-free survival (DFS) rate, overall response rate (ORR), R0 resection rate, major pathologic response (MPR), adverse events (AEs), complication rate and quality of life (QOL). A biobank of pretreatment, resected tumor tissue and paired blood samples will be built for translational research in the future. Results Until Dec. 2021, one hundred and twenty ESCC patients recruited in the trial. The trial is ongoing. Conclusion This RCT directly compares NAC with neoadjuvant toripalimab plus chemotherapy in terms of EFS for locally advanced ESCC. The results may usher in a new era of resectable ESCC treatment.

Phase II study of preoperative panitumumab, 5-fluorouracil, and oxaliplatin with concurrent radiotherapy in locally advanced rectal cancer: Preliminary safety results (StarPan /STAR-02 Study)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4110-4110
Author(s):  
C. Pinto ◽  
F. Di Fabio ◽  
E. Maiello ◽  
P. Di Tullio ◽  
S. Pini ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Moderate Increase ◽  
Concurrent Radiotherapy ◽  
Grade 3

4110 Background: The aim of this phase II study is to assess the activity of preoperative external radiotherapy combined with panitumumab, oxaliplatin and 5-fluorouracil in locally advanced rectal cancer patients (pts). Methods: Pts entering the study had histologically-proven rectal adenocarcinoma, either uT3N+ or T4 N-/+ stage, with location <12 cm from the anal margin. Panitumumab was administered at a dose of 6 mg/kg IV, 2 weeks before the start of chemoradiotherapy, and then in combination with chemoradiotherapy, every 2 weeks for 3 times. 5-fluorouracil and oxaliplatin were administered according to an established schedule of STAR-01 Study (oxaliplatin 60 mg/m2 IV weekly for six times, and 5- fluorouracil 225 mg/m2/day continuous infusion IV d 1–38). Radiotherapy was delivered up to a dose of 50.4 Gy in daily fractions of 1.8 Gy. Rectal surgery was performed 7–8 weeks after the end of neoadjuvant treatment. Eight courses of adjuvant chemotherapy with FOLFOX4 plus panitumumab at a dose of 6 mg/kg, every 2 weeks, were given after surgery. The primary endpoint of the study was the complete pathological response rate. Results: From February 2007 to December 2008, 35 out of the 55 planned pts were enrolled. Twenty nine pts completed neoadjuvant treatment and 20 underwent surgery (15 pts ongoing). The characteristics of 29 pts were: males 19 (65.5%) and females 10 (34.5%); median age 58 years (range 39–78); median Karnofsky PS 100 (range 70–100); stage: uT3N+ 22 (75.9%), uT4N- 3 (10.3%), uT4N+ 4 (13.8%). The most frequent grade 1–4 side-effects were acneiform rash (96.2%), diarrhea (51.7%) and fatigue (14.3%). Grade 3 diarrhea was registered in 35.7% pts, and grade 3–4 cutaneous toxicity in 51.8%. No grade 3–4 hematological toxicity was found. The median cumulative dose of delivered radiotherapy was 50.4 Gy. The planned dose of panitumumab, 5-fluourouracil and oxaliplatin was administered in 83%, 72% and 67% of pts, respectively. Conclusions: Despite the moderate increase of diarrhea, these early results demonstrate that panitumumab can be safety added to 5-fluorouracil/oxaliplatin-based chemoradiotherapy, without compromising the concurrent radiotherapy dose. No significant financial relationships to disclose.

Preoperative chemoradiation with S-1 plus oxaliplatin in patients with locally advanced rectal cancer: Results of a phase II study and the role of apparent diffusion coefficient (ADC) by diffusion-weighted magnetic resonance imaging (DW MRI) for prediction of pathologic responses.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 629-629
Author(s):  
E. M. Lee ◽  
J. L. Hong ◽  
J. L. Lee ◽  
S. Y. Kim ◽  
Y. S. Park ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Phase I ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Preoperative Chemoradiation ◽  
Curative Surgery

629 Background: We conducted a phase II study of preoperative chemoradiation (CRT) with S-1, a novel oral fluoropyrimidine, plus oxaliplatin in patients (pts) with locally advanced rectal cancer. Tumor ADCs were measured by DW-MRI and were evaluated as a predictive marker for pathologic responses. Methods: Radiotherapy was delivered to a total 50.4 Gy. The recommended doses were determined by a previous phase I study; oxaliplatin 50 mg/m2/week on D1, 8, 22 and 29, and S-1 80 mg/m2/day on D1-14 and D22-35. Total mesorectal excision was performed within 6 ± 2 weeks. Primary endpoint was pathologic complete response (pCR) rate. The value of tumor ADCs by DW-MRI was measured before and after CRT, and was correlated with pathologic responses after surgery. Results: A total of 38 patients were enrolled; 22 (57.9%) were men and the median age was 54 years (range, 28-67). Of 35 patients who underwent curative surgery, 28 patients underwent sphincter-saving operations. There was no grade 4 toxicity, and grade 3 toxicities included leukopenia (2.7%), neutropenia (2.7%), anorexia (2.7%), nausea (2.7%) and diarrhea (8.8%). The pCR rate was 25.7% (8/35, 95% CI [10.9-42.1]) and additional 10 patients (28.6%) showed near total regressions of tumor. Tumor ADCs by DW-MRI were calculated in 38 patients (including phase I part). The post-CRT ADC and the ADC changes (ΔADC) were significantly correlated with pCR rate (post-CRT ADC: 1.52±0.46 vs. 1.07±0.58, p=0.037, ΔADC: 44.5% vs. -7.6%, p=0.026). Conclusions: Preoperative CRT with S-1 plus oxaliplatin showed promising results in pathologic responses and favorable toxicities profiles. Tumor ADC by DW-MRI seems to be a useful method for predicting responses. No significant financial relationships to disclose.

A randomized phase II study of capecitabine-based chemoradiation with or without bevacizumab in resectable locally advanced rectal cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 3571-3571 ◽  
Author(s):  
Mercedes Martinez Villacampa ◽  
Jaume Capdevila ◽  
Jose Luis Manzano ◽  
Carles Pericay ◽  
Ramon Salazar ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Locally Advanced ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Correct Selection ◽  
Randomized Phase Ii ◽  
Grade 3 ◽  
The Impact

3571 Background: The addition of bevacizumab (BEV) to capecitabine (CAP)-based chemoradiation (CRT) has shown encouraging efficacy in locally advanced rectal cancer (LARC), in nonrandomized studies. This randomized phase II study investigated the effect of adding BEV to preoperative CAP-based CRT in patients (pts), with LARC. Methods: The primary end point was pathologic complete response (pCR). A two-stage design was used. Assuming a minimum pCR rate of at least 15% in one of the arms, a difference between the two arms of 10%, and accepting a probability of correct selection of 87%, 41 pts per arm were needed. Patients with LARC (Stages II-III assessed by MRI) and ECOG PS <2 were randomized to concurrent radiotherapy 45Gy/25f/5 weeks + CAP (825mg/m²/bid) + BEV every 2 weeks (5 mg/kg for 3 doses) (arm A) or the same schedule without BEV (arm B). Surgery was scheduled 6-8 weeks after completing CRT. Results: 90 pts were randomized (arm A/B: 44/46). Patient’s characteristics were well balanced between both arms: male 61%, median age 62 years, median distance from anal verge 7 cm, T3 79%, N+ 87%. 40 (91%)/43 (93%) of pts (arm A/B) finalized the planned CRT + surgery treatment. Overall grade 3-4 toxicity rates were 18 % and 13% (arm A/B, p=0.50); no grade 3-4 hematological toxicity was reported. Postoperative complications were 19(43%)/17(37%)(arm A/B). Efficacy data on patients who actually underwent surgery are reported in the table. Conclusions: The addition of BEV to CAP-based preoperative CRT has shown to be feasible and safe in the local control of LARC. No differences in pCR were observed and longer follow-up is needed to assess the impact on survival endpoints. [Table: see text]

Phase Ib/II study of neoadjuvant chemoradiotherapy with CRLX101 and capecitabine for locally advanced rectal cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15144-e15144 ◽  
Author(s):  
Andrew Wang ◽  
Autumn Jackson McRee ◽  
A. William Blackstock ◽  
Bert H. O'Neil ◽  
Dominic T. Moore ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Single Agent ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Neoadjuvant Chemoradiotherapy ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Phase Ib ◽  
Grade 3

e15144 Background: There is strong interest in the development of novel agents to further improve the therapeutic ratio of neoadjuvant chemoradiotherapy for rectal cancer. CRLX101 is an investigational nanoparticle-drug conjugate with a camptothecin payload. The purpose of this Phase Ib/II study is to assess toxicity and to evaluate whether the addition of CRLX101 to chemoradiotherapy can improve pathologic complete response (pCR) for rectal cancer. Methods: This is a single-arm multicenter Phase Ib/II study examining the addition of CRLX101 to a standard capecitabine-based chemoradiotherapy regimen. Phase Ib employs a 3+3 dose escalation design with starting dose of 12 mg/m2 every other week (QOW). Dose level +1 was 15 mg/m2 (MTD for CRLX101 single agent QOW). Upon reaching MTD for QOW dosing, protocol was modified to evaluate QW CRLX101 dosing starting at 12 mg/m2 and 15 mg/m2as +1 level. Secondary endpoints included pCR and clinical outcome. Results: A total of 32 patients were enrolled on the trial. 26/32 had T3-4, 9/32 had N2 and 16/32 had N1 disease. For QOW dosing, 9 patients completed treatment without DLT and MTD was identified as 15 mg/m2 QOW. 14 patients were treated on the Phase II portion of the study at 15 mg/m2 QOW prior to the initiation of weekly dosing Phase Ib cohorts. For QW dosing, 0/3 patients experienced DLT at 12 mg/m2 and 1/6 patients experienced DLT at 15 mg/m2. The DLT was skin desquamation requiring treatment delay. QW MTD was identified as 15 mg/m2. Toxicities (all grade 3 except lymphopenia) that could possibly be attributed to CRLX101 are in Table 1. Full clinical and pathologic staging were available for 29/32 patients. Mean neoadjuvant rectal (NAR) score was 19 with standard deviation of 15. At the weekly MTD, 3/6 patients had pCR. Conclusions: CRLX101 weekly at 15 mg/m2+ standard capecitabine-based chemoradiotherapy appears to be well tolerated, with promising pCR rates that warrants further evaluation. A larger PhII trial should be considered with this regimen. Clinical trial information: NCT02010567. [Table: see text]

Totally neoadjuvant chemoradiation therapy with mFOLFOX6 in locally advanced rectal cancer: A single arm phase II study (FOTAC).

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. TPS816-TPS816
Author(s):  
Jianwei Zhang ◽  
Yue Cai ◽  
Huabin Hu ◽  
Jian Xiao ◽  
Dianke Chen ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Phase Ii Study ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Neoadjuvant Chemoradiation ◽  
Chemoradiation Therapy ◽  
Neoadjuvant Chemoradiation Therapy

TPS816 Background: Preoperative 5-Fluorouracil based chemoradiotherapy is the standard of treatment for locally advanced rectal cancer. About 15% to 18% of patients would achieve pathologic complete response (pCR) after 5-Fluorouracil based chemoradiation. And the survival outcome of patients with pCR was much better than that of non-pCR. In our previous FOWARC study, in the group of preoperative systemic chemotherapy with mFOLFOX6 combined with radiation, the pCR rate was up to 27.5%. In another study, adding mFOLFOX6 after neoadjuvant chemo radiation in locally advanced rectal cancer improve the pCR rate to 38%. This phase II study aimed to explore whether totally neoadjuvant chemoradiation therapy with mFOLFOX6 could further improve the pCR rate in locally advanced rectal cancer. Methods: The primary endpoint is the pathologic complete response rate (pCR).The secondary endpoint included 3-year disease free survival rate, 3-year local recurrence rate, and safety. We hypothesized that totally neoadjuvant chemoradiation therapy with mFOLFOX6 could improve the pCR rate from 18% to 45% with 5% type I error and 80% power. Fifty patients met inclusion criteria will be enrolled in the trial. All patients will receive long term radiation for 25 times and 50Gy before surgery. Four cycles of mFOLFOX6 would be performed every 2 weeks during radiotherapy, and another 4-6 cycles would be added after radiotherapy and before operation. Totally, the patients will receive 8-10 cycles of chemotherapy before surgery. MRI of the pelvic will be performed every 4 cycles of the therapy to assess clinical response. Then the patient will receive total mesorectal excision at least 8 weeks after radiotherapy. The post-operative chemotherapy will be omitted and all the patients go to surveillance. Clinical trial information: NCT02887313.

Voltage: Investigator-initiated clinical trial of nivolumab monotherapy and subsequent radical surgery following preoperative chemoradiotherapy in patients with microsatellite stable locally advanced rectal cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 3606-3606 ◽  
Author(s):  
Takayuki Yoshino ◽  
Hideaki Bando ◽  
Yuichiro Tsukada ◽  
Koji Inamori ◽  
Satoshi Yuki ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Rectal Cancer ◽  
Phase I ◽  
Phase Ii ◽  
Tumor Regression ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Fisher Exact Test

3606 Background: Chemoradiotherapy (CRT) with surgery (S) is standard for patients (pts) with locally-advanced rectal cancer (LARC), and nivolumab (nivo) is active in microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC). We studied nivo and radical S following CRT (50.4 Gy with capecitabine 1,650 mg/m2) in T3–4 NanyM0 LARC. Methods: Phase I included testing of a recommended phase II dosing schedule (RP2S). Efficacy and safety were studied in phase II pts and those given RP2S in phase I. In Cohort A-1, for microsatellite stable (MSS) LARC pts, the primary endpoint was centrally confirmed pathologic complete response (pCR) rate using AJCC tumor regression grading. The estimated required sample size assuming null and alternative hypotheses pCR = 10% and 30% was 37 pts, with a 1-sided alpha of 5% and power of 90%. Cohort A-2 was exploratory and included a maximum of 5 MSI-H pts. Results: Nivo 240 mg q2 weeks x 5 cycles, following CRT but pre-S, was the RP2S. From 1/17 to 6/18, 37 pts were enrolled in Cohort A-1. Eleven pts (30%; 90% CI 18-44%) showed pCR (AJCC grade (gr) 0). Including the 3 pts (8%) graded AJCC 1, 14 (38%) had major pathologic responses. In addition, clinical CR was observed in 1 pt (3%) refusing S after nivo. Both MSI-H LARC Cohort A-2 pts showed pCRs. Immune-related severe adverse events were observed in 2 pts (gr 3 myasthenia and gr 2 interstitial nephritis); both fully recovered and had S. No treatment-related deaths were observed. pCR rates of 60% (6/10) and 19% (5/27) (p = 0.038, Fisher exact test) were seen in pts with tumor cells with PD-L1 ≥1% and < 1% IHC staining, respectively, performed on biopsy samples taken pre-CRT. Rates of 62% (8/13) and 10% (1/10) (p = 0.029) were seen in 23 pts with samples analyzable by flow cytometry, according to CD8+ lymphocyte /regulatory T cell (CD8/Treg) ratios ≥2 and < 2, respectively. Conclusions: A promising pCR rate of 30%, with mild toxicity, was shown in MSS LARC pts treated with nivo plus radical S. PD-L1 expression and elevated CD8/Treg ratio may be better predictors of nivo benefit, warranting further study in a larger cohort. Clinical trial information: NCT02948348.

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