PD-1 antibody combined with COX inhibitor in MSI-h/dMMR or high TMB colorectal cancer: A single arm phase II study.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. TPS729-TPS729
Author(s):  
Zehua Wu ◽  
Yanhong Deng ◽  
Jianwei Zhang ◽  
Huabin Hu ◽  
Yue Cai ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Phase Ii ◽  
Objective Response ◽  
Progression Free Survival ◽  
Tumor Mutation Burden ◽  
Mutation Burden ◽  
Cox Inhibitor ◽  
Duration Of Response ◽  
Colorectal Cancer Patients ◽  
To Receive

TPS729 Background: Programmed death protein 1 (PD-1) antibody has been to approved in patients with MSI-H/dMMR colorectal cancer and has achieved significant efficacy. It's also reported that tumor mutation burden (TMB) may be another biomarker of response to PD-1 therapy. But there were about 50-60% of patients with MSI-H/dMMR were insensitive to PD-1 antibody. Cyclooxygenase (COX) inhibitor has been proved to prevent adenomas in colorectal and it is safe for most of the patients. Preclinical data demonstrate that inhibition of COX synergizes with anti-PD-1 blockade in inducing eradication of tumors. Methods: This single arm, phase II trial will assess the efficacy and safety of combination of PD-1 antibody and COX inhibitor in patients with MSI-H/dMMR or high tumor mutation burden colorectal cancer. Patients diagnosed with MSI-H/dMMR or high tumor mutation burden colorectal cancer which was unresectable and had at least one lines of chemotherapy fail or refuse to receive chemotherapy were eligible. Eligible patients were assigned to receive BAT1306 (100 mg once every three weeks) plus COX inhibitor (aspirin 200 mg every day or Celebrex 400 mg every day). Chest/abdomen/pelvic CT with IV contrast will be performed to assess clinical response. The primary endpoint is objective response rate (ORR). Secondary endpoints include progression-free survival (PFS), overall survival (OS), disease control rate (DCR), safety and duration of response. Adverse events are graded per NCI CTCAE v4.03 and will be monitored for 30 days after treatment. Patients will be followed for survival. Planned enrollment is 54 patients. Clinical trial information: NCT03638297.

Phase II trial of oxaliplatin as first-line chemotherapy in metastatic colorectal cancer patients. Digestive Group of French Federation of Cancer Centers.

1998 ◽  
Vol 16 (8) ◽  
pp. 2739-2744 ◽  
Author(s):  
Y Bécouarn ◽  
M Ychou ◽  
M Ducreux ◽  
C Borel ◽  
F Bertheault-Cvitkovic ◽  
...  
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Sensory Neuropathy ◽  
Progression Free Survival ◽  
Free Survival ◽  
Duration Of Response ◽  
Grade 3 ◽  
Colorectal Cancer Patients ◽  
Peripheral Sensory

PURPOSE To evaluate the objective tumor response rate and safety profile of oxaliplatin when administered to patients with previously untreated metastatic colorectal adenocarcinoma. PATIENTS AND METHODS A total of 39 patients were entered onto this phase II trial. One patient was excluded for having had a second cancer, so the study was based on 38 patients. Patients were treated with oxaliplatin 130 mg/m2 as a 2-hour infusion on day 1, every 21 days. Patients were assessed for response every three courses. All clinical and radiologic data were reviewed by an external panel of experts, with their assessment being considered definitive. RESULTS Nine partial responses (PRs) were observed (response rate, 24.3%; 95% confidence interval, 11.8% to 41.2%). The median duration of response was 216+ days. Fifteen patients (40.5%) had stable disease and 13 (35.2%) had progressive disease. The median progression-free survival time for all patients was 126+ days (range, 21 to 447+). The main toxicity was peripheral sensory neuropathy. Grade 3 neurotoxicity (National Cancer Institute common toxicity criteria [NCI-CTC]) was reported in 13%. Hematologic and gastrointestinal toxicities were mild. The incidence of grade 3 neutropenia was 5.2%, while that of grade 3 or 4 thrombopenia was 7.9%. Vomiting (grade 3 or 4) occurred in 7.9% of patients and grade 3 diarrhea in 2.6%. CONCLUSION This phase II study provides clear evidence of the safety and efficacy of oxaliplatin monotherapy at this dose and schedule in patients with previously untreated metastatic colorectal carcinoma.

A phase II trial of salvage treatment with gemcitabine and S-1 combination in heavily pretreated patients with metastatic colorectal cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3595-3595
Author(s):  
Sun Jin Sym ◽  
Junshik Hong ◽  
Hee Kyung Ahn ◽  
Jinny Park ◽  
Eun Kyung Cho ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Disease Control ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Treatment Options ◽  
Objective Response ◽  
Progression Free Survival ◽  
Median Number ◽  
Heavily Pretreated

3595 Background: We conducted a phase II trial of gemcitabine with S-1 to evaluate the activity and toxicity of such a combination in heavily pre-treated patients (pts) with metastatic colorectal cancer (mCRC) who have progressed after treatment with fluoropyrimidines-, oxaliplatin- and irinotecan-containing regimens. Methods: 36 pts were enrolled, with the following characteristics: 19 females (53%), median age 57 (28-72), 30 EOGO PS 0-1 (83%). S-1 was given orally (30 mg/m2) b.i.d for 14 consecutive days and gemcitabine (1000 mg/m2) was given on days 1 and 8, every 21 days, until disease progression and for a maximum of 9 cycles. The primary endpoint was objective response rate (ORR). Results: The median number of cycles was 5 (range 1-9), ORR was 16.7% (95% confidence interval [CI] 4.5-28.9%) and disease control rate was 61.1% (95% CI 45.2-77.0%) with 6 partial responses and 16 stable diseases. Median duration of disease control was 5.8 months (95% CI 4.1-7.5 months). Median progression-free survival was 3.7 months (95% CI 2.2-5.2 months) and median overall survival was 10.0 months (95% CI 7.4-12.7 months). Grade 3-4 toxicities were rare (neutropenia 12%, anemia 11%, leucopenia 6%, thrombocytopenia 3% and diarrhea 3%). Conclusions: Combination chemotherapy with gemcitabine and S-1 was a convenient, well tolerated and efficacious for heavily pre-treated pts with mCRC. This regimen warrants further evaluation in pts with good PS but no further treatment options.

A phase II trial of salvage treatment with gemcitabine and S-1 combination in heavily pretreated patients with metastatic colorectal cancer.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 488-488 ◽  
Author(s):  
Sun Jin Sym ◽  
Junshik Hong ◽  
Hee Kyung Ahn ◽  
Jinny Park ◽  
Eun Kyung Cho ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Disease Control ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Treatment Options ◽  
Objective Response ◽  
Progression Free Survival ◽  
Median Number ◽  
Ecog Ps

488 Background: We conducted a phase II trial of gemcitabine with S-1 to evaluate the activity and toxicity of such a combination in heavily pre-treated patients (pts) with metastatic colorectal cancer (mCRC) who have progressed after treatment with 5-fluorouracil (5-FU), oxaliplatin and irinotecan. Methods: 34 pts were enrolled, with the following characteristics: 17 (50%) females, median age 57 years (28-72), 28 (82%) ECOG PS 0-1. S-1 was given orally (30 mg/m2) b.i.d for 14 consecutive days and gemcitabine (1000 mg/m2) was given on days 1 and 8, every 21 days, until disease progression and for a maximum of 9 cycles. The primary endpoint was objective response rate (ORR). Results: The median number of cycles was four (range 1-9). ORR was 14.7% (95% confidence interval [CI] 2.8-26.6) and disease control rate was 58.8% (95% CI 42.2-75.3) with five partial responses and fifteen stable diseases. Median duration of disease control was 5.1 months (95% CI 3.3-7.0). Median progression-free survival was 3.2 months (95% CI 2.3-4.1) and median overall survival was 11.8 months (95% CI 7.0-16.5). Grade 3-4 toxicities were neutropenia (12%), anemia (12%), thrombocytopenia (3%) and diarrhea (3%). Conclusions: Combination chemotherapy with gemcitabine and S-1 was well tolerated and efficacious for heavily pre-treated mCRC pts, and could be an alternative for pts with good PS but no further treatment options.

Randomized Multicenter Phase II Trial of Two Different Schedules of Capecitabine Plus Oxaliplatin as First-Line Treatment in Advanced Colorectal Cancer

2003 ◽  
Vol 21 (7) ◽  
pp. 1307-1312 ◽  
Author(s):  
Werner Scheithauer ◽  
Gabriela V. Kornek ◽  
Markus Raderer ◽  
Birgit Schüll ◽  
Katharina Schmid ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Survival Time ◽  
Phase Ii ◽  
Advanced Colorectal Cancer ◽  
Response Rate ◽  
Progression Free Survival ◽  
Synergistic Activity ◽  
Free Survival ◽  
Multicenter Phase ◽  
To Receive

Purpose: Capecitabine and oxaliplatin, two new agents with potential synergistic activity, have demonstrated promising antitumor efficacy in advanced colorectal cancer (ACC). Preclinical and clinical evidence indicating that dose intensification of the oral fluorouracil prodrug might result in improved therapeutic results led us to the present randomized multicenter phase II study. Patients and Methods: Eighty-nine patients with bidimensionally measurable ACC previously untreated for metastatic disease were randomly allocated to receive oxaliplatin 130 mg/m2 day 1 plus capecitabine 2,000 mg/m2/d days 1 to 14 every 3 weeks (arm A) or to receive oxaliplatin 85 mg/m2 days 1 and 14 combined with capecitabine 3,500 mg/m2 days 1 to 7 and 14 to 21 every 4 weeks (arm B). In both treatment arms, chemotherapy was continued for a total of 6 months unless there was prior evidence of progression of disease. Results: Patients allocated to the high-dose capecitabine combination arm B had a higher radiologically confirmed response rate (54.5% v 42.2%) and a significantly longer median progression-free survival time than those allocated to control arm A (10.5 v 6.0 months; P = .0013). Median overall survival times cannot be calculated for either treatment arm at this point. Despite a 34% higher dose intensity of capecitabine in arm B, there was no difference in hematologic toxicity between treatment arms (neutropenia/thrombocytopenia: 60%/43% in arm B v 56%/33% in arm A). Similarly, the incidence rate and degree of nonhematologic adverse events were comparable: The most commonly encountered symptoms (all grades, arm A and arm B) included nausea/emesis (A: 58%; B: 62%), diarrhea (A: 44%; B: 31%), peripheral sensory neuropathy (A: 80%; B: 83%), and fatigue (A: 40%; B: 50%). Conclusion: Results of this study indicate that both combination regimens are feasible, tolerable, and clinically active. The dose-intensified bimonthly capecitabine arm, however, seems to be more effective in increasing both response rate and progression-free survival time.

scholarly journals RaPiDS (GOG-3028): randomized Phase II study of balstilimab alone or in combination with zalifrelimab in cervical cancer

2021 ◽  
Author(s):  
David M O’Malley ◽  
Leslie M Randall ◽  
Camille Gunderson Jackson ◽  
Robert L Coleman ◽  
John L Hays ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Progression Free Survival ◽  
Platinum Based Chemotherapy ◽  
Duration Of Response ◽  
Chemotherapy Patients ◽  
Investigational Agents

Balstilimab (anti-programmed death 1) and zalifrelimab (anti-CTLA-4) are two new checkpoint inhibitors that have emerged as promising investigational agents for the treatment of cervical cancer, particularly in the setting of previously-treated, recurrent/metastatic disease. Here we describe the rationale and design of RaPiDS (NCT03894215), a two-arm Phase II study evaluating the safety, tolerability and efficacy of balstilimab administered alone or in combination with zalifrelimab in patients with advanced cervical cancer who progressed after first-line, platinum-based chemotherapy. Patients will be randomized in a 1:1 ratio. The primary end point is objective response rate, and key secondary objectives include safety, duration of response, progression-free survival, overall survival and quality of life outcomes.

scholarly journals Olaparib with or without bevacizumab or bevacizumab and 5-fluorouracil in advanced colorectal cancer: Phase III LYNK-003

2021 ◽  
Author(s):  
Tae Won Kim ◽  
Julien Taieb ◽  
Ellen B Gurary ◽  
Nati Lerman ◽  
Karen Cui ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Advanced Colorectal Cancer ◽  
Objective Response ◽  
Progression Free Survival ◽  
Response Duration ◽  
Standard Of Care ◽  
Phase Iii ◽  
Clinical Trial Registration ◽  
Duration Of Response ◽  
Reduced Toxicity

Oxaliplatin-based chemotherapy with a regimen such as FOLFOX with or without targeted therapy is a standard of care option for advanced colorectal cancer; however, long-term exposure to oxaliplatin is associated with cumulative toxicity. Growing evidence suggests maintenance therapy with a less intensive regimen after platinum-based induction therapy can provide continuing benefit with reduced toxicity. We describe the rationale and design of the Phase III LYNK-003 trial, which will evaluate the efficacy and safety of olaparib with or without bevacizumab compared with 5-fluoruracil plus bevacizumab in patients with unresectable or metastatic colorectal cancer that has not progressed on an induction course of FOLFOX plus bevacizumab. The primary end point is progression-free survival by independent central review; secondary end points include overall survival, objective response, duration of response and safety. Clinical trial registration: NCT04456699

A phase II trial of salvage treatment with gemcitabine and S-1 combination in heavily pretreated patients with metastatic colorectal cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14137-e14137
Author(s):  
Sun Jin Sym ◽  
Junshik Hong ◽  
Minkyu Jung ◽  
Jinny Park ◽  
Eun Kyung Cho ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Disease Control ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Objective Response ◽  
Progression Free Survival ◽  
Median Number ◽  
Heavily Pretreated ◽  
Number Of Cycles

e14137 Background: We conducted a phase II trial of gemcitabine with S-1 to evaluate the activity and toxicity of such a combination in heavily pre-treated patients (pts) with metastatic colorectal cancer (mCRC) who have progressed after treatment with 5-fluorouracil, oxaliplatin and irinotecan. Methods: Between Dec 2009 and Nov 2011, 23 pts were enrolled, with the following characteristics: 12 males and 11 females, median age 57 years (28-72). S-1 was given orally (30 mg/m2) b.i.d for 14 consecutive days and gemcitabine (1000 mg/m2) was given on days 1 and 8, every 21 days, until disease progression and for a maximum of 9 cycles. The primary endpoint was objective response rate (ORR). Results: The median number of cycles was four (range 1-9). OR was 8.7% (95% confidence interval [CI] 0-20.2) and disease control rate was 56.5% (95% CI 36.4-76.9) with two partial responses and eleven stable diseases. Median duration of disease control was 8.5 months (95% CI 3.8-13.2). Median progression-free survival was 3.2 months (95% CI 1.9-4.5) and median overall survival was 11.8 months (95% CI 4.0-19.5). Grade 3-4 toxicities were neutropenia (8%) and thrombocytopenia (4%). Conclusions: Combination chemotherapy with gemcitabine and S-1 was well tolerated and efficacious for refractory mCRC pts.

Sorafenib and irinotecan combination for pre-treated RAS-mutated metastatic colorectal cancer patients: A multicentre randomized phase II trial (NEXIRI 2).

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 635-635 ◽  
Author(s):  
Emmanuelle Samalin ◽  
Christelle De La Fouchardiere ◽  
Simon Thezenas ◽  
Valérie Boige ◽  
Hélène Senellart ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Randomized Study ◽  
Progression Free Survival ◽  
Fixed Dose ◽  
Randomized Phase Ii ◽  
Heavily Pretreated ◽  
Colorectal Cancer Patients

635 Background: Sorafenib and irinotecan (NEXIRI regimen) showed promising activity with a disease control rate (DCR) of 65% in heavily pretreated mutated (mt) KRAS metastatic colorectal cancer (mCRC) patients in a phase I/II trial (Samalin et al. 2014).This multicentre randomized phase II trial aimed to determine the 2-month progression-free survival rate (2-PFS) of NEXIRI versus irinotecan or sorafenib monotherapy in mtRAS mCRC patients after failure of all approved active drugs at the time of the study. Methods: Patients PS ≤ 1 with progressive measurable and non-resectable mtKRAS (then RAS) mCRC pre-treated with irinotecan, oxaliplatin, fluoropyrimidines and bevacizumab (none regorafenib), were randomized in 3 arms: NEXIRI (irinotecan IV 120 (C1), 150 (C2) and 180mg/m² (C3) if diarrhea grade < 1 in a biweekly regimen combined with a fixed dose of sorafenib, 400mg twice daily) versus irinotecan alone (180mg/m²) versus sorafenib alone until progression or toxicity, with cross over to NEXIRI at progression for the monotherapy arms. The primary endpoint was the 2-PFS (RECIST v1.1). Pharmacokinetic, pharmacogenetics and pathologic translational studies were undertaken. Results: We included 173 patients (median age 62 [31-82]; PS 0/1: 38/61%) between 2012/09 and 2014/07 in 17 French centres. Main results are shown below (median follow-up 17.5 months). Conclusions: We confirmed the NEXIRI regimen efficacy in a randomized study for refractory mtRAS mCRC patients. These results justify comparing this combination to regorafenib or TAS 102 monotherapies in this population. Ancillary studies are ongoing to identify biomarkers. Clinical trial information: NCT01715441. [Table: see text]

Mature overall survival (OS) results from the LUME-Meso study of nintedanib (N) + pemetrexed/cisplatin (PEM/CIS) vs placebo (P) + PEM/CIS in chemo-naïve patients (pts) with malignant pleural mesothelioma (MPM).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 8506-8506 ◽  
Author(s):  
Anna K. Nowak ◽  
Federica Grosso ◽  
Nicola Steele ◽  
Silvia Novello ◽  
Sanjay Popat ◽  
...  
Keyword(s):  
Randomized Study ◽  
Objective Response ◽  
Progression Free Survival ◽  
Primary Analysis ◽  
Double Blind ◽  
Abl Kinases ◽  
Duration Of Response ◽  
Grade 3 ◽  
Ecog Ps ◽  
To Receive

8506 Background: LUME-Meso is a Phase (Ph) II/III, double-blind, randomized study. N targets MPM by inhibiting VEGFR 1–3, PDGFR α/β, FGFR 1–3, Src and Abl kinases. Primary analysis of the Ph II data demonstrated improved progression-free survival (PFS; hazard ratio [HR]=0.56; 95% confidence interval [CI] 0.34–0.91; p=0.017). Mature Ph 2 OS and updated PFS results are reported here. Methods: Pts with unresectable MPM (ECOG PS 0–1) were stratified by histology (epithelioid/biphasic) and randomized 1:1 to receive ≤6 cycles PEM (500 mg/m2)/CIS (75 mg/m2) Day 1 + N or P (200 mg bid, Days 2–21), followed by N or P monotherapy until progression or toxicity. The primary endpoint was PFS. The primary OS analysis and updated PFS analysis were performed as predefined. Results: 87 pts were randomly assigned (N=44, P=43). OS benefit favored N over P treatment (HR=0.77; 95% CI 0.46–1.29; p=0.319; 62 [71%] OS events) and was greatest in epithelioid pts (HR=0.70; 95% CI 0.40–1.21; p=0.197) with a median (m) OS gain of 5.4 months (mOS [95% CI]: 20.6 [16.2–28.8] N vs 15.2 [12.2–23.6] P). Updated PFS results (HR=0.54; 95% CI 0.33–0.87; p=0.010) also showed greatest benefit for epithelioid pts (HR=0.49; 95% CI 0.30–0.82; p=0.006) with a mPFS gain of 4.0 months (mPFS [95% CI]: 9.7 [7.2–12.4] N vs 5.7 [5.5–7.0] P). Improved forced vital capacity, objective response rates and duration of response were also observed with N treatment. Drug-related adverse events (AEs) in N- vs P-treated pts were 97.7% vs 97.6%. Grade ≥3 AEs of note included neutropenia (27.3% vs 4.9%), ALT (11.4% vs 0) and GGT (6.8% vs 0) elevations, and diarrhea (6.8% vs 0). AEs led to trial discontinuation in only 3 (6.8%) N vs 7 (17.1%) P pts. Conclusions: Mature Ph II OS data show that adding N to standard 1st-line treatment gives a strong signal towards improved OS. Updated PFS confirmed the primary analysis; AEs were manageable. The greatest clinical benefit was observed in pts with epithelioid histology. Median survival of 20.6 months in epithelioid pts treated with N is unprecedented in advanced MPM trials. Ph III is actively recruiting in this pt population. Clinical trial information: NCT01907100.

Phase II study of FOLFIRI + ramucirumab with recurrent colorectal cancer refractory to adjuvant chemotherapy with oxaliplatin / fluoropyrimidine (RAINCLOUD).

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. TPS882-TPS882
Author(s):  
Naotoshi Sugimoto ◽  
Chu Matsuda ◽  
Taishi Hata ◽  
Taroh Satoh ◽  
Masakazu Ikenaga ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Phase Ii ◽  
Progression Free Survival ◽  
Recurrent Colorectal Cancer ◽  
Eligibility Criteria ◽  
Meaningful Improvement ◽  
Significance Level ◽  
Registration Number ◽  
The One ◽  
Colorectal Cancer Patients

TPS882 Background: The RAISE study demonstrated the superiority of FOLFIRI + ramucirumab (Ram) to FOLFIRI in second-line metastatic colorectal cancer patients progressed after oxaliplatin, fluoropyrimidine with bevacizumab. But no prospective data is existed that the efficacy and toxicity of FOLFIRI + Ram pretreated oxaliplatin, fluoropyrimidine without an anti-angiogenesis therapy. Methods: RAINCLOUD study is a multicenter single-arm phase II trial. Key eligibility criteria is as follows: histologically or cytologically confirmed colorectal cancer, confirmed recurrent colorectal cancer, refractory to fluoropyrimidine, refractory or intolerant of oxaliplatin without pretreated anti-angiogenesis therapy, has measureable or non-measurable lesion, PS = 0 or 1, has adequate coagulation function, 20 years or older. Primary endpoint of this study is progression-free survival. Secondary endpoints are overall survival, time to treatment failure, response rate, disease control rate and safety. Patients receive FOLFIRI (irinotecan: 180 mg/m2, l-levofolinate: 200 mg/m2, bolus fluorouracil: 400mg/m2, and continuous fluorouracil: 2400 mg/m2) plus Ram (8 mg/kg) every two weeks until progression or the development of unacceptable toxicity. We hypothesized that threshold of PFS in FOLFIRI + Ram is 3.9 months and expected PFS is 6.9 months and designed to have an 80% power to detect clinically meaningful improvement in PFS at the one-sided significance level of 0.05, minimal patient registration number is 44 in order that power 1-β outperforms 0.8. Taking a few ineligibility patients and dropout patients into consideration, number of target patients is set to be 48. Study recruitment started on September 2017. The association of exploratory biomarker study will be planned. Clinical trial information: UMIN000028677.

Sign in / Sign up

Export Citation Format

Share Document