Phase II study of combination therapy with S-1 and cetuximab in patients with KRAS wild-type unresectable colorectal cancer who had previously received irinotecan, oxaliplatin, and fluoropyrimidines (KSCC0901).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 3558-3558
Author(s):  
Kazuma Kobayashi ◽  
Yasunori Emi ◽  
Yoshihiro Kakeji ◽  
Takao Takahashi ◽  
Eiji Oki ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Combination Therapy ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Performance Status ◽  
Dihydropyrimidine Dehydrogenase ◽  
Treatment Protocol ◽  
Progression Free Survival ◽  
Wild Type ◽  
Open Label

3558 Background: Anti-epidermal growth factor receptor (anti-EGFR) antibodies alone or in combination with irinotecan (Iri) can be considered standard third-line therapy for KRAS wild-type (wKRAS) unresectable colorectal cancer (UNCRC). However, some UNCRC patients (pts) cannot tolerate Iri-containing therapy. S-1, an oral fluorouracil (FU) derivative, enhances the anti-tumor effect by inhibiting dihydropyrimidine dehydrogenase activity and reducing digestive toxicity. Combination therapy with cetuximab (C-mab) may restore 5-FU resistance in 5-FU–resistant CCs. Therefore, we examined the efficacy of S-1+C-mab therapy in wKRAS UNCRC pts, who had previously received Iri, oxaliplatin (OX), and FUs. Methods: The study design was multicenter, single-arm, open-label phase II study. The major inclusion criteria were written informed consent; histologically proven CRC and clinically proven UNCRC; presence of measurable lesions; previous therapy with Iri, OX, and 5-FU; documented progressive disease after 5-FU–based chemotherapy; wKRAS tumors; age ≥ 20 years; performance status (PS) 0–1; and adequate organ function. The treatment protocol was as follows: weekly durable intravenous (DIV) C-mab administration at 400 mg/m2 (day 1) and 250 mg/m2/week (except day 1) and oral administration of 80 mg/m2/day S-1 on days 1–28 of each 42-day cycle. The primary endpoint was progression-free survival (PFS). A sample size of 39 was planned for a threshold PFS of 3.5 months and expected value of 6.0 months, with one-sided alpha of 0.05 and beta of approximately 0.2. Results: One patient was ineligible; 38 pts (PS 0/1, 32/6; 1/2/>3 prior chemotherapy regimens, 4/23/11) were enrolled from 10/2009 to 12/2010. The median PFS (central review) was 5.5 months (90% CI: 4.4 – 5.7); median overall survival (OS), 13.1 months; and the best ORR, 36.8%. The most common grade 3–4 adverse events were neutrophils, hypokalemia, rash, and dry skin. Conclusions: This study showed that S-1+C-mab may be a promising and well-tolerated treatment choice of wKRAS UNCRC, who had previously heavily treated by Iri, OX and FUs.

Phase II Study of Uracil-Tegafur With Leucovorin in Elderly (≥ 75 years old) Patients With Colorectal Cancer: ECOG 1299

2007 ◽  
Vol 25 (34) ◽  
pp. 5397-5402 ◽  
Author(s):  
Howard S. Hochster ◽  
Weixiu Luo ◽  
Elizabeta C. Popa ◽  
Bruce T. Lyman ◽  
Mary Mulcahy ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Elderly Patients ◽  
Survival Time ◽  
Phase Ii ◽  
Performance Status ◽  
Progression Free Survival ◽  
Open Label ◽  
Old Patients ◽  
Gi Toxicity ◽  
Grade 3

Purpose To evaluate the tolerability and effectiveness of uracil-tegafur (UFT) with leucovorin (LV) in the treatment of elderly patients with advanced colorectal cancer. Patients and Methods Patients ≥ 75 years of age with previously untreated colorectal cancer were eligible for this phase II, single-arm, open-label, multicenter cooperative group clinical trial. UFT 100 mg/m2 plus LV 30 mg orally every 8 hours for 28 days every 35 days was administered until progression. Results Fifty-eight patients were enrolled between June 2000 and July 2001, and 55 were treated. The median age of treated patients was 81 years (range, 75 to 90 years), 26 patients were (47%) women, and 80% had good performance status (0 to 1). The observed overall response rate was 22% (95% CI, 11.8% to 35.0%). The estimated median overall survival time was 13.0 months (95% CI, 9.6 to 17.4 months), and median progression-free survival time was 4.6 months (95% CI, 2.6 to 6.7 months). Among the 56 treated patients (including one ineligible patient), 31 (55%) experienced grade 3 to 4 toxicities, most commonly diarrhea (25%) and GI toxicity (36%), with patients older than 85 years of age at highest risk. Conclusion The results of this trial support the efficacy of oral UFT/LV in elderly patients with colorectal cancer. The regimen is tolerated moderately well overall, particularly as compared with other fluoropyrimidine regimens, although there is increased GI toxicity in the most elderly. These results suggest that studies using newer oral fluoropyrimidine analogs should be investigated in this patient population.

scholarly journals Randomized Phase II Study of SOX+B-mab Versus SOX+C-mab in Patients With Previously Untreated Recurrent Advanced Colorectal Cancer With Wild-Type KRAS (MCSGO-1107 Study)

2021 ◽  
Author(s):  
Yujiro Nishizawa ◽  
Naotsugu Haraguchi ◽  
Hirotoshi Kim ◽  
Yoshihito Ide ◽  
Ken Nakata ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Phase Ii ◽  
Progression Free Survival ◽  
Efficacy And Safety ◽  
Wild Type ◽  
Open Label ◽  
Randomized Phase Ii ◽  
Early Tumor ◽  
Patient Prognosis ◽  
Clinical Trials Registry

Abstract Background: Although chemotherapy for metastatic colorectal cancer (mCRC) has improved, the standard chemotherapy regimens for patients with RAS wild-type mCRC remain debated.Methods: This randomized phase II, open-label, multicenter study compared the efficacy and safety of S-1 and oxaliplatin (SOX)+bevacizumab (B-mab) with SOX+cetuximab (C-mab) in patients with previously untreated recurrent advanced CRC with wild-type KRAS. Between February 2012 and October 2016, 45 patients were enrolled.Results: Overall response rates were 59.1% and 43.5% (p=0.29) and disease control rates were 90.9% and 91.3% (p=0.96) in the SOX+B-mab and SOX+C-mab groups, respectively. Median overall survival (OS) was 25.3 and 15.5 months (HR=0.607, p=0.167) and median progression-free survival (PFS) were 11.7 and 5.5 months (HR=0.558, p=0.077) in the SOX+B-mab and SOX+C-mab groups, respectively. The OS and PFS of patients with early tumor shrinkage (ETS) were not significantly different in the SOX+B-mab group. However, they were significantly better when ETS was ≥20 in the SOX+C-mab group (p=0.032 and p=0.003, respectively).Conclusions: The efficacy and safety of SOX+B-mab and SOX+C-mab for wild-type KRAS recurrent advanced CRC as first-line chemotherapy were almost the same. Consideration of the treatment strategy based on ETS may improve patient prognosis, especially in patients receiving the SOX+C-mab regimen.Trial registration: UMIN Clinical Trials Registry (UMIN000006706)Date of registration: NOV/11/2011URL of trial registry record:https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000007920

A phase II study of oxaliplatin reintroduction in patients pretreated with oxaliplatin and irinotecan for advanced colorectal cancer (RE-OPEN study).

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 758-758
Author(s):  
Mitsukuni Suenaga ◽  
Nobuyuki Mizunuma ◽  
Satoshi Matsusaka ◽  
Eiji Shinozaki ◽  
Masato Ozaka ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Phase Ii ◽  
Primary Endpoint ◽  
Stable Disease ◽  
Tumor Response ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Complete Response ◽  
Open Label ◽  
Treatment Start

758 Background: Re-introduction of oxaliplatin (L-OHP) for patients with metastatic colorectal cancer (mCRC) refractory to standard chemotherapy regimens including L-OHP, irinotecan (CPT-11), and fluorouracil was thought to be effective approach. We performed a single arm, open-label phase II study (UMIN ID: 000004884), and the reported results of interim analysis were promising. Methods: Patients with prior chemotherapy including L-OHP and CPT-11 achieved tumor response or stable disease during prior L-OHP based therapy, and 6 months or over from confirmed progression disease during previous L-OHP based therapy was eligible for this study. Patients received FOLFOX regimens every two weeks. Primary endpoint was disease control rate (DCR) after 12 weeks of treatment start. Tumor response was evaluated by RECIST v1.1, and DCR was defined as complete response (CR), partial response (PR) or stable disease. This trial followed a Simon’s two-stage minimax design. Assuming the expected and threshold DCR after 12 weeks of treatment start would be 40% and 20%, 33 patients (18 in Step I and 15 in Step II) were required with a one sided α-level of 5% and a power of 80%. Results: Between February 2011 and August 2013, 33 patients were enrolled in this study. Characteristics of patients were as follows (n=33): median age of 62 years (35-77); male/female: 19/14; ECOG PS0: 84.8%; and colon/rectum: 14/19. All patients received mFOLFOX6 regimen. The DCR after 12 weeks of treatment start was 39.4% (95% CI: 21.8-57.0%), and the primary endpoint was met. The response Rate (CR or PR) was 6.1%. The median number of courses of chemotherapy was five, and the median total dose of L-OHP was 366.9 mg/m2. The median progression free survival was 98 days and the median overall survival was 300 days. The incidence of allergic reaction was 24.4% and peripheral neuropathy was 90.9%, graded as mild to moderate events. There were no other severe adverse events and treatment related deaths. Conclusions: Reintroduction of L-OHP was effective and could be a new salvage option for patients with mCRC refractory to previous L-OHP based therapy. Clinical trial information: 000004884.

Multicenter, open-label phase II study of daily oral regorafenib for chemotherapy-refractory, metastatic and locally advanced angiosarcoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 11561-11561
Author(s):  
Mark Agulnik ◽  
Steven Ian Robinson ◽  
Scott H. Okuno ◽  
Brittany Siontis ◽  
Steven Attia ◽  
...  
Keyword(s):  
Phase Ii ◽  
Primary Endpoint ◽  
Phase Ii Study ◽  
Performance Status ◽  
Locally Advanced ◽  
Survival Rates ◽  
Progression Free Survival ◽  
Open Label ◽  
Tie2 Receptor ◽  
Open Label Phase

11561 Background: Angiosarcoma has a particularly poor prognosis with 5-year overall survival rates of approximately 30-40%. Treatment of locally advanced and metastatic angiosarcoma is inadequate. Data strongly suggest concurrent, potent inhibition of VEGFR and Tie2 represents an attractive therapeutic strategy in angiosarcoma. Regorafenib displays potent VEGFR and Tie2 receptor inhibition and also possesses activity against additional potential targets in angiosarcoma including PDGFRs, RAF, KIT and FGFR, amongst others. Methods: A multicenter phase II study of regorafenib in patients with locally advanced or metastatic angiosarcoma was conducted through the Midwest Sarcoma Trials Partnership. Adequate performance status, organ function, measurable disease (RECIST 1.1) and 1-4 prior therapies were required. Regorafenib 160 mg PO daily was given in 28-day cycles (21 days on, 7 days off) until disease progression (PD) or unacceptable toxicity. The primary endpoint was progression-free survival (PFS), assessed at 16 weeks. Secondary endpoints include overall response rate (ORR), clinical benefit rate (CBR), OS, and safety and tolerability. A Simon 2-stage design was used. Results: After final enrollment of the second stage, a total of 31 pts were enrolled at 6 sites, 23 are evaluable for response. Median age was 65 (range 30-91); 50% were female, 67.7% had metastatic disease. PFS at 4 months is 52.2% with a median PFS and OS of 3.55 and 11.4 months. 1 confirmed CR and 2 PR, 12 SD and 8 PD were observed. ORR and CBR are 14.29 and 65.2%, respectively. No uncommon grade 3-4 adverse events were observed. 6 pts were non-evaluable due to refusal of further therapy and 2 patients progressed prior to first evaluation. Conclusions: Regorafenib was well tolerated in this study of pretreated patients with angiosarcomas and met its primary endpoint with a median PFS > 45% at 4 months. Treatment was feasible and did not reveal any previously unreported toxicities. Efficacy outcomes were complicated by early withdrawals of patients. RECIST responses were encouraging and regorafenib has a clinically meaningful 4-month PFS. Clinical trial information: NCT02048722 .

Phase II study of the anti-ganglioside GD3 mouse/human chimeric antibody KW2871 combined with high dose interferon-a2b in patients with metastatic melanoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8547-8547
Author(s):  
Stergios J. Moschos ◽  
Ahmad A. Tarhini ◽  
Thomas Gajewski ◽  
Andrew Mark Scott ◽  
Yan Lin ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Phase Ii ◽  
Immune Cells ◽  
Phase Ii Study ◽  
Performance Status ◽  
Progression Free Survival ◽  
Chimeric Antibody ◽  
High Dose ◽  
Open Label

8547 Background: Immunotherapy has demonstrated notable effects in metastatic melanoma (MM) with durable responses achieved by high-dose IL-2 and IFNα2b, leading to approval of these therapies for treatment of melanoma. However, complete responses occur in only a minority of patients. KW2871 is a chimeric monoclonal antibody (mAb) targeting the GD3 ganglioside with demonstrated antitumor activity and enhancement of antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). IFNα2b has potent immunoregulatory, anti-proliferative, differentiation-inducing, pro-apoptotic, and anti-angiogenic properties against a variety of malignancies including melanoma. Combining high dose IFNα2b (HDI) + KW2871 was hypothesized to have synergistic anti-tumor activity due to (1) the ability of HDI to enhance KW2871 induced ADCC in vitro (Liu, Cancer Immun 2002); (2) improved mAb targeting due to increased GD3 expression and induced inflammatory cytokines (TNF-α, IL-4 and IFN-γ) (Hoon, Cancer Res, 1991); (3) increased tumor-infiltrating immune cells (Kirkwood, Cancer 2002; Moschos, J Clin Oncol 2006). Methods: This is an open label, dose-escalation, phase II study of KW2871 plus HDI in patients with measurable MM. Primary objectives are progression-free survival (PFS) and safety. Secondary objectives include assessment for tumor response by RECIST, ADCC, CDC, pharmacokinetics, human antichimeric antibodies (HACA), tumor-infiltrating immune cells, biomarkers and OS. Patients with measurable disease by RECIST, stable brain metastases, and performance status ECOG 0 or 1 are eligible. Patients with severe comorbidities or autoimmune disease or prior exposure to anti-GD3 antibodies are excluded. Sequential enrollment to cohorts of KW2871 at 5, 10 , 20 mg/m2 IV every 2 week in combination with HDI 20 MU/m2 IV once daily x 5 Days for 4 weeks, then 10 MU/m2 SC three times weekly until disease progression. Results: To date, Cohort 1 (5 mg/m2 KW2871) and Cohort 2 (10 mg/m2 KW2871) have been completed safely. Cohort 3 (20 mg/m2 KW2871) has enrolled of 18 of 27 planned patients. Conclusions: Will be presented at study completion.

Phase II study of panitumumab monotherapy in chemotherapy-naïve frail or elderly patients with unresectable, RAS wild-type colorectal cancer: OGSG 1602.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 106-106 ◽  
Author(s):  
Katsuya Ohta ◽  
Takeshi Kato ◽  
Masahiro Goto ◽  
Tetsuji Terazawa ◽  
Shingo Noura ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Alternative Hypothesis ◽  
Performance Status ◽  
Single Agent ◽  
P Value ◽  
Intensive Chemotherapy ◽  
Wild Type ◽  
Grade 3

106 Background: Single agent of panitumumab (Pmab) is expected to be well tolerated and to improve survival in first-line setting in patients (pts) who are not eligible for intensive chemotherapy, although the efficacy and safety of Pmab for chemotherapy-naïve frail or elderly Japanese pts with wild-type (wt) RAS unresectable colorectal cancer (CRC) have not been yet studied. Methods: We conducted a multi-center phase II study. Pts aged over 76 years, or over 65 who were considered unsuitable for intensive chemotherapy. Pmab 6 mg/kg was administered intravenously every 2 weeks. The primary endpoint was disease control rate (DCR), and secondary endpoints included progression-free survival (PFS), overall survival (OS), response rate (RR), time to treatment failure (TTF), and the incidence of grade 3 or 4 toxicities. Sample size was set to 36 with exact p-value of 0.05, a power of 0.90, the null of hypothesis of 45% and alternative hypothesis of 70% based on the Clopper-Pearson method. Results: A total 36 pts were enrolled in February 2017 to August 2018. Two pts were excluded; one was a lack of image examination at baseline, and the other was a lack of measurable lesion. The median age was 81 (67-88), with 29 pts (85%) being aged over 76 years. There were 33 (92%) pts with performance status (PS) 0/1, while two (6%) and one (3%) pts were PS 2/3, respectively. Twenty-eight pts (78%) had left-sided CRC, while eight pts had right-sided CRC. The RR was 50.0% (95%CI, 32.4-67.6) including three cases (8.8%) of complete response, and SD was 26.5%, yielding 76.5% of DCR (p < 0.001, 90% confidence interval [CI], 61.5-87.7). The RR with left sided tumor was 65% (95%CI, 44.3-82.8), while that pts with right-sided tumor was 0% (95%CI, 0.0-36.9)(p = 0.003). The major grade 3 or 4 nonhematologic toxicities were rash (n = 6, 17%), hypomagnesemia (n = 4, 11%), fatigue (n = 3, 8%), paronychia (n = 3, 6%), and hyponatremia (n = 3, 6%). The grade 3 hematologic toxicities was neutropenia (n = 1, 3%). Conclusions: Pmab monotherapy showed the favolable efficacy and feasibility in the frail or elderly pts with RAS wt, unresectable CRC. The survival analysis including OS, PFS and TTF is awaiting. Clinical trial information: UMIN000024528.

scholarly journals Phase II Study of Biweekly Pemetrexed Plus Irinotecan as Second-Line Therapy for Metastatic Colorectal Cancer

2010 ◽  
Vol 2010 ◽  
pp. 1-7 ◽  
Author(s):  
C. Louvet ◽  
T. André ◽  
E. Gamelin ◽  
M. Hebbar ◽  
M. Mabro ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Vitamin Supplementation ◽  
Open Label ◽  
Common Grade ◽  
Duration Of Response ◽  
Grade 3

Background. This open-label, single-arm, two-stage, Phase II study investigated the efficacy and safety of bi-weekly pemetrexed combined with irinotecan, in patients with metastatic colorectal cancer (mCRC), after first-line chemotherapy using FOLFOX regimen.Patients and methods. Patients received pemetrexed 400 mg/m²as a 10-minute intravenous infusion (with vitamin supplementation) followed by irinotecan 180 mg/m²as a 90-minute infusion on day 1 of a 14-day cycle, for a maximum of 12 cycles. The primary endpoint was response rate (RR;H0≤5%,Ha≥20%,α=0.05, power = 90%). Secondary endpoints were duration of response, progression-free survival (PFS), overall survival (OS), and toxicities.Results. Partial response was observed in six out of 44 patients enrolled in the study (RR = 13.6%). The median PFS and OS were 4.0 and 13.9 months, respectively. The most common grade 3-4 toxicities were fatigue: 20.5% of patients, neutropenia: 18.6%, diarrhea: 13.6%, elevated transaminases: 9.5%, anemia: 9.3%, and vomiting: 6.8%.Conclusion. Pemetrexed plus irinotecan administered every two weeks is an active and well-tolerated regimen in mCRC patients pretreated with FOLFOX regimen. However, this regimen does not seem to provide clinically relevant advantage over historical data of a classical FOLFIRI regimen.

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