Phase II Trial of Sunitinib in Patients With Metastatic Colorectal Cancer After Failure of Standard Therapy

2007 ◽  
Vol 25 (30) ◽  
pp. 4793-4799 ◽  
Author(s):  
Leonard B. Saltz ◽  
Lee S. Rosen ◽  
John L. Marshall ◽  
Robert J. Belt ◽  
Herbert I. Hurwitz ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Growth Factor ◽  
Metastatic Colorectal Cancer ◽  
Dose Reduction ◽  
Phase Ii ◽  
Standard Therapy ◽  
Kinase Inhibitor ◽  
Phase Ii Trial ◽  
Single Agent ◽  
Objective Response

PurposeSunitinib is an oral, multitargeted receptor tyrosine kinase inhibitor of the vascular endothelial growth factor receptor and multiple other growth factor receptors. We assessed the safety and efficacy of sunitinib in patients with metastatic colorectal cancer after failure of standard therapy.Patients and MethodsEighty-four patients were enrolled onto this two-stage phase II trial and were stratified by whether they had received prior bevacizumab (n = 43) or not (n = 41). Treatment comprised sunitinib 50 mg orally daily for 4 weeks, followed by 2 weeks off treatment, in repeated 6-week cycles.ResultsBy Response Evaluation Criteria in Solid Tumors criteria, one patient, who was in the prior bevacizumab cohort, achieved a partial response, and 13 patients (two in the prior bevacizumab cohort and 11 in the no prior bevacizumab cohort) achieved stable disease lasting ≥ 22 weeks. Median time to progression in the prior bevacizumab and bevacizumab-naïve cohorts was 2.2 months (95% CI, 1.9 to 2.3 months) and 2.5 months (95% CI, 2.3 to 3.1 months), respectively, whereas median overall survival time was 7.1 months (95% CI, 4.9 to 10.6 months) and 10.2 months (95% CI, 8.2 to 15.3 months), respectively. The most common adverse events were fatigue, diarrhea, nausea, vomiting, and anorexia. Twenty-six patients (32%) required dose reduction to 37.5 mg/d, and one patient required dose reduction to 25 mg/d.ConclusionSunitinib did not demonstrate a meaningful single-agent objective response rate in colorectal cancer refractory to standard chemotherapy. However, the mechanisms of action and acceptable safety profile of sunitinib warrant further study in combination with standard regimens for metastatic colorectal cancer.

Phase II Trial of Chronomodulated Infusion of High-Dose Fluorouracil and l-Folinic Acid in Previously Untreated Patients With Metastatic Colorectal Cancer

2002 ◽  
Vol 20 (5) ◽  
pp. 1175-1181 ◽  
Author(s):  
H. Curé ◽  
V. Chevalier ◽  
A. Adenis ◽  
N. Tubiana-Mathieu ◽  
G. Niezgodzki ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Folinic Acid ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Objective Response ◽  
World Health ◽  
Fixed Dose ◽  
High Dose

PURPOSE: To study tolerability and efficacy of an intensified chronomodulated schedule of fluorouracil (5-FU) and l-folinic acid (l-FA) as first-line treatment of metastatic colorectal cancer, 5-FU was given near individually determined dose-limiting toxicity in a multicenter phase II trial. PATIENTS AND METHODS: One hundred patients (68 men and 32 women, median age 62 years, World Health Organization performance status ≤ 2) with previously untreated and inoperable metastases received chronomodulated daily infusion of 5-FU/l-FA (from 10:00 pm to 10:00 am with peak at 4:00 am). 5-FU dose was escalated from 900 to 1,100 mg/m2/d with fixed dose of l-FA at 150 mg/m2/d for 4 days every 14 days. RESULTS: 5-FU dose escalation was achieved in 66% of the patients. Grade 3 to 4 toxicities mainly consisted of nausea or vomiting (14% of patients and 1.5% of courses), hand-foot syndrome (38% of patients and 8% of courses), mucositis (26% of patients and 4% of courses), and diarrhea (21% of patients and 2.3% of courses). Objective response rate (ORR) was 41% (95% confidence interval, 31.5% to 50.5%). Twenty patients underwent metastases surgery; among these, 12 had a complete resection. Median progression-free survival was 7 months. Median survival was 17 months; 28% of the patients were alive at 2 years and 18.6% at 3 years. CONCLUSION: The ORR achieved with intensified chronomodulated delivery of 5-FU/l-FA was nearly twice as high as that earlier obtained by our cooperative group using less intensive 5-FU/FA chronotherapy.

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.

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.

Phase II trial of capecitabine +/- erlotinib in advanced colorectal cancer, with retrospective KRAS and primary tumor site analysis.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 781-781
Author(s):  
Daniel Adam Breadner ◽  
Stephen Welch ◽  
Denis Soulieres ◽  
Michael Susmoy Sanatani ◽  
Paul Klimo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Phase Ii ◽  
Combination Chemotherapy ◽  
Kinase Inhibitor ◽  
Phase Ii Trial ◽  
Objective Response ◽  
Growth Factor Receptor ◽  
Wild Type ◽  
Kras Mutations ◽  
Primary Tumor Site

781 Background: Palliative capecitabine (X) monotherapy for advanced colorectal colorectal cancer (aCRC) is generally well tolerated by elderly or frail pts. Epidermal growth factor receptor (EGFR) monoclonal antibodies improve efficacy when added to combination chemotherapy for mCRC. Erlotinib (E), an oral EGFR tyrosine kinase inhibitor (TKI) may add benefit when added to X. We conducted a randomized phase II trial to investigate the novel “all-oral” combination of X and E in aCRC. Methods: Pts with untreated aCRC who were either deemed unfit for, or chose against, combination chemotherapy were randomized to X (1000 mg/m2 PO BID x 14 days) alone or in combination with E (150 mg PO OD) on a 3-week schedule. Primary endpoint was time to disease progression (TTP); secondary endpoints included: objective response rate (ORR), overall survival (OS), and safety. Tumours were designated as left-sided if there were distal to the transverse colon. KRAS status was retrospectively analyzed for 72 of 82 pts. Results: From 2004 to 2008, 82 pts were randomized to X alone (40 pts) or XE (42 pts). TTP was not different between X and XE (7.9 m vs. 9.2 m; p = 0.890), however, KRAS subgroup analysis revealed pts with KRAS mutations did significantly worse when treated with XE compared to X alone (1.9m vs 7.4m; HR = 2.63; P = 0.038). Pts with KRAS wild-type (WT) treated with XE had an improved TTP compared to those treated with X (11.7m vs. 8.4m, HR = 0.73; Wilcoxon P = 0.061). KRAS-WT pts treated with XE with left-sided disease had an improved OS compared to pts with right-sided disease (16m vs. 12.1m, not significant). KRAS-WT pts with left-sided primaries treated with XE had a non-significant improvement in TTP compared to pts treated with X alone (11.7m vs 8.4m). XE was well tolerated but had significantly higher rates of diarrhea and acneform skin rash. Conclusions: The addition of E to X is generally well tolerated but associated with additional toxicities. E may benefit pts with KRAS-wild-type CRC, specifically those with left-sided primary tumours, and likely harms those with KRAS-mutated CRC. Further study of oral EGFR-TKIs in left-sided KRAS-wild-type aCRC is warranted.

Phase II study of sorafenib (BAY 43–9006) in combination with gemcitabine in recurrent epithelial ovarian cancer: A PMH phase II consortium trial

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 5084-5084 ◽  
Author(s):  
S. Welch ◽  
H. Hirte ◽  
R. J. Schilder ◽  
L. Elit ◽  
C. Townsley ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Growth Factor ◽  
Phase Ii ◽  
Kinase Inhibitor ◽  
Single Agent ◽  
Objective Response ◽  
Growth Factor Receptor ◽  
Recurrent Ovarian Cancer ◽  
Ca 125 ◽  
Vegf Receptor

5084 Background: Sorafenib (BAY 43–9006; SOR) is a novel multi-targeted kinase inhibitor that targets the RAF/MEK/ERK signaling pathway, vascular endothelial growth factor (VEGF) receptor, platelet-derived growth factor receptor and flt-3. VEGFR is over-expressed in human ovarian tumors and this is associated with poor prognosis. Gemcitabine (GEM) is known to have single-agent activity in recurrent ovarian cancer (OC). A recent phase I study of GEM/SOR has demonstrated manageable toxicity and some objective responses in recurrent OC patients. We have designed a phase II trial to evaluate the efficacy of this novel combination in patients with recurrent OC. Methods: A two-stage, phase II clinical trial is underway for women with recurrent or refractory OC. Eligible patients may have received up to 2 prior lines of chemotherapy following recurrence, but must be GEM-naive. The treatment consists of SOR, 400mg PO bid continuously, in combination with GEM, IV weekly, 1000 mg/m2. Cycle 1 is an extended cycle of 7 weeks of GEM followed by a 1-week break. GEM is administered weekly for the first 3 weeks of each subsequent 4-week cycle. The primary endpoint is objective response rate, with response evaluated every 8 weeks. Results: 26 patients have been enrolled at 3 centers. 84 cycles have been administered (median 3; range 1–10). Median age was 57 (range: 37–77). 42% were ECOG PS 0 and 58% were PS 1. Of 18 patients evaluable for objective response, 1 patient had a confirmed PR by RECIST criteria and 5 patients had a confirmed PR by CA-125 criteria, yielding a combined RR of 33% in evaluable patients (RR by ITT = 23%). An additional 10 patients had SD. The median time to progression is 7.6 months (95% CI: 5.6-NA). 7 patients are inevaluable for objective response due to the following in cycle 1: withdrawal of consent (3), toxicity (2), and clinical PD (2). 1 patient on-study is yet to have a response evaluation. Grade 3 or 4 toxicities seen in more than 2 patients include: lymphopenia (8), thrombocytopenia (6), hypertension (3), hand-foot syndrome (3), pain (3), neutropenia (3) and hypokalemia (3). Conclusions: The preliminary results show encouraging activity with tolerable toxicity. This trial continues to accrue into a second stage. No significant financial relationships to disclose.

Cetuximab + capecitabine + irinotecan (CCI) versus cetuximab + capecitabine + oxaliplatin (CCO) as first line therapy for patients with metastatic colorectal cancer (CRC): Preliminary results of a randomized phase II trial of the AIO CRC Study Group

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3550-3550 ◽  
Author(s):  
V. Heinemann ◽  
L. Fischer Von Weikersthal ◽  
N. Moosmann ◽  
U. Vehling-Kaiser ◽  
M. Stauch ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Karnofsky Performance Status ◽  
Objective Response ◽  
Standards Of Care ◽  
Preliminary Evaluation ◽  
Randomized Phase Ii

3550 Background: Combinations of infusional 5-FU/FA with either oxaliplatin (FOLFOX) or irinotecan (FOLFIRI) have become standards of care in the treatment of metastatic colorectal cancer. In this trial, 5-FU/FA was replaced by capecitabine, an oral fluoropyrimidine. In addition, cetuximab, an antibody directed against the EGF-receptor was added to further improve treatment efficacy. Methods: Patients (pts) with metastatic CRC (age 18 to 75 years) and measurable disease were randomized to 3-week cycles of therapy. In the CCI-arm, pts received cetuximab (400 mg/m2 iv on day 1 of cycle 1 and 250 mg/m2 iv subsequently), capecitabine (2 × 800 mg/m2 po on days 1 to 14), and irinotecan (200 mg/m2 iv on day 1). In patients >65 years doses of irinotecan and capecitabine were reduced by 20%. In the CCO arm, cetuximab (as described above) was combined with capecitabine (2 × 1000 mg/m2 po on days 1 to 14) and oxaliplatin (130 mg/m2 iv on day 1). Both treatment arms were planned separately according to the optimal design described by Simon (p0 = 0.3, p1 = 0.5, α = 0.1, β = 0.1) with objective response rate (ORR) according to RECIST) as the primary endpoint. Results: The recruitment goal of 92 patients has been achieved. Among evaluable patients, median age in the CCI arm was 63 yrs (range 38–72) and 58 yrs (range 38–74) in the CCO arm. Median Karnofsky performance status was 90% (range 70–100) and 100% (range 70–100), the EGFR-status was positive in 64% and 69% of pts, respectively. The ORR in the CCI arm was 41% (11/27) (95%-CI: 22% to 61%), while in the CCO arm an ORR of 71% (15/21) (95%-CI: 48% to 89%) was documented. Toxicity data were available for 25 pts in each arm. The most common grade 3–4 CTC- toxicities observed in the CCI and the CCO-arm respectively were skin toxicity (4 vs 5 pts), allergic reactions (0 vs 5 pts), diarrhea (5 vs 3pts), neurotoxicity (1 vs 3 pts), and leucopenia (4 vs 5 pts). Conclusion: The preliminary evaluation of this randomized phase II trial suggests the feasibility of both treatment arms. Updated results regarding response rate and progression-free survival will be presented at the meeting. [Table: see text]

Phase II trial of DJ-927, an oral tubulin depolymerization inhibitor, in the treatment of metastatic colorectal cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3591-3591 ◽  
Author(s):  
M. R. Moore ◽  
C. Jones ◽  
G. Harker ◽  
F. Lee ◽  
B. Ardalan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Peripheral Neuropathy ◽  
Metastatic Colorectal Cancer ◽  
Dose Reduction ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Second Line ◽  
Second Line Therapy ◽  
Line Therapy ◽  
Grade 3

3591 Background: DJ-927, a novel oral tubulin depolymerization inhibitor, causes apoptosis and DNA cell division arrest. It is not a substrate for the MDR and has excellent activity in preclinical colorectal cancer models. Methods: We are conducting a two-stage, multi-center, phase II trial to assess the efficacy of DJ-927 administered initially as second-line therapy following failure of irinotecan or oxaliplatin based therapy (n= 39). DJ-927 is given as a single oral dose on day 1 of a 21-day cycle at a dose range of 27 - 35 mg/m2. Results: Thirty-nine patients were enrolled, including 14 with prior irinotecan based therapy and 25 who had received prior oxaliplatin therapy. The median age was 56 years (range: 30–87) and the median ECOG PS at baseline was 1 (range: 0–2). A total of 155 courses (range: 1–24) have been administered with a median of 2 courses. Nine patients required dose reduction due to toxicity. Thirty-seven patients were evaluable for efficacy. There were 2 CRs and 2 PRs (10.3%) reported that were confirmed as per RECIST criteria. Fourteen patients (35.9%) had SD, including 6 patients (15.4%) with SD >12 weeks. The most common Grade 3 or 4 AEs were neutropenia (48.7%), fatigue (10.3%), neuropathy (7.8%), and nausea (5.0%).Six patients experienced febrile neutropenia, all requiring hospitalization but tolerated treatment with subsequent dose reduction. There were 13 episodes (33.3%) of peripheral neuropathy reported; however, only 3 (7.8%) were grade 3 or 4. Six patients withdrew due to adverse events. Conclusions: The results of this study indicate activity of DJ-927 as second line therapy in patients with metastatic colorectal cancer. Severe toxicity was generally limited to reversible neutropenia and peripheral neuropathy. This novel oral agent is well tolerated and warrants further evaluation in combination with other active agents. [Table: see text]

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