Final results of a phase II study of sorafenib in combination with carboplatin and paclitaxel in patients with metastatic or recurrent squamous cell cancer of the head and neck (SCCHN).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5592-5592 ◽  
Author(s):  
George R. Blumenschein ◽  
Bonnie S. Glisson ◽  
Charles Lu ◽  
Anita Lyn Sabichi ◽  
Lawrence E. Ginsberg ◽  
...  
Keyword(s):  
Phase Ii ◽  
Cell Cancer ◽  
Progression Free Survival ◽  
Angiogenic Growth Factors ◽  
Current Standard ◽  
Hand Foot Syndrome ◽  
Current Standard Treatment ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
Ecog Ps

5592 Background: Cytotoxic chemotherapy (CT) is the current standard treatment for metastatic/recurrent SCCHN. The prognosis for these patients (PTS) is poor with a median progression free survival (PFS) of 4 months with CT. Survival in PTS with SCCHN may correlate inversely with the number of angiogenic growth factors secreted. Sorafenib is a potent inhibitor of c-Raf, b-Raf, VEGFR-1/2/3 and PDGFR-β. To investigate the hypothesis that a multi-targeted TKI added to chemotherapy would improve outcomes in patients with metastatic/recurrent SCCHN, we performed a phase II trial of   paclitaxel and carboplatin and sorafenib (PCS). Methods: PTS were required to have ECOG PS 0-1, measurable disease, controlled blood pressure, and may have received one regimen of induction, concomitant or adjuvant CT, but not CT for recurrent/metastatic disease. Sites of primary disease excluded nasopharynx and paranasal sinus. Treatment consisted P 200mg/m2 and C AUC 6 intravenously on day 1 followed by S 400 mg orally bid (days 2-19) in every 3-week cycles.  Primary endpoint was PFS, targeting median PFS of 6 months (M). Secondary endpoints include overall survival (OS), response rate (RR), exploratory biomarkers, and toxicity. Results: Forty-eight PTS with SCCHN were enrolled with 44 PTS evaluable for PFS and response using RECIST. Median age: 56 years (22-79 years), 89% male, median ECOG PS 1.  Median follow-up was 24.1 M.  RR was 55% (n=24), disease control rate was 84% (n=37), median PFS was 8.51 M (95% CI: 5.98 ~ 13 months), and median OS was 22.6 M (95% CI: 13.1 - NA months). Grade ³3 treatment related toxicities included hand-foot syndrome (n=10), neutropenia (n=5), pain (n=6), elevated lipase (n=4), elevated amylase (n=3), anemia (n=3), fatigue (n=2), hypertension (n=2), neuropathy (n=2), febrile neutropenia (n=2), and thrombocytopenia (n=2).  Conclusions: The combination of PCS was well tolerated and had encouraging activity in recurrent/metastatic SCCHN. Blood-based and tissue biomarkers are being analyzed.  Final outcomes, toxicity, and correlative biomarker data will be reported.

scholarly journals Combination Therapy of High-Dose Rabeprazole Plus Metronomic Capecitabine in Advanced Gastro-Intestinal Cancer: A Randomized Phase II Trial

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3084
Author(s):  
Michela Roberto ◽  
Adriana Romiti ◽  
Federica Mazzuca ◽  
Annalisa Milano ◽  
Chiara D’Antonio ◽  
...  
Keyword(s):  
Phase Ii ◽  
Plasma Concentrations ◽  
Progression Free Survival ◽  
High Dose ◽  
Clinical Investigations ◽  
Significant Difference ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
Ecog Ps ◽  
Favorable Safety

Background: In recent years, proton pump inhibitors (PPIs) have been investigated at high-dose to modulate tumor microenvironment acidification thus restoring chemotherapeutic sensitivity. This is the first trial to study activity and safety of repurposing high dose rabeprazole combined with metronomic capecitabine (mCAP). Methods: A phase II study in which patients with gastrointestinal cancer, refractory to standard treatments, who had a life expectancy >3 months, were blind randomized 1:1 to mCAP, 1500 mg/daily, continuously with or without rabeprazole 1.5 mg/kg bid, three days a week. The primary endpoint was 3-months progression-free survival (PFS). The secondary endpoints were clinical benefit (CB) and overall survival (OS). Safety and plasma concentrations of capecitabine and its metabolites (5′-DFUR and 5-FU) were also evaluated. Results: Sixty-seven (median age 69 years; 63% male; 84% colorectal cancer, 76% ECOG-PS ≤ 1; 84% pretreated with two or more lines of chemotherapy) out of 90 patients screened for eligibility, were randomized to receive mCAP+rabeprazole (n = 32) vs. mCAP (n = 35). All patients were evaluable for response. No significant difference between mCAP+rabeprazole vs. mCAP, in terms of 3-months PFS rate (HR = 1.43, 95%CI 0.53–3.85; p = 0.477), median PFS (HR = 1.22, 95%CI 0.75–2.00, p = 0.420), CB (RR = 0.85, 95%CI 0.29–2.44; p = 0.786) and median OS (HR = 0.89, 95%CI 0.54–1.48; p = 0.664) was observed. However, a 3-year OS rate of 10% and 12% was reported in the mCAP-rabeprazole and mCAP groups, respectively. Overall, no grade 3 or 4 toxicity occurred but grade 1 or 2 adverse event of any type were more frequently in the mCAP+rabeprazole group than in the mCAP (OR 2.83, 95%CI 1.03–7.79; p = 0.043). Finally, there was not statistically significant difference in the plasma concentration of capecitabine and its metabolites between the two groups. Conclusions: Although the adjunct of high dose rabeprazole to mCAP was not shown to affect mCAP activity, as PPI are being investigated worldwide as drugs to be repositioned in cancer treatment and also considering the limited sample size as well as the favorable safety profile of the combination in the present study, further clinical investigations are desirable.

Results of the Quad wild type arm of the AGITG ICECREAM study: A randomised phase II study of cetuximab alone or in combination with irinotecan in patients with refractory metastatic colorectal cancer with no mutations in KRAS, NRAS, BRAF or PIK3CA.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 3572-3572 ◽  
Author(s):  
Jeremy David Shapiro ◽  
Subotheni Thavaneswaran ◽  
Craig Underhill ◽  
Kristy Pamela Robledo ◽  
Christos Stelios Karapetis ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Single Agent ◽  
Progression Free Survival ◽  
Wild Type ◽  
Response Characteristics ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
Ecog Ps

3572 Background: Cetuximab (cet) increases survival in RAS wild-type (WT) metastatic colorectal cancer (mCRC) in first-line and chemorefractory patients (pts). Adding irinotecan (iri) to cet in refractory pts who had progressed on iri increased response and delayed progression in the BOND trial, which was conducted prior to recognition that RAS mutations are predictive of EGFR-inhibitor (EGFR-I) resistance. Subsequent trials in chemorefractory pts used single agent EGFR-I as standard. In the era of biomarker selection, the benefit of continuing iri versus single agent EGFR-I had not been resolved. Methods: ICECREAM is a randomised phase II trial evaluating cet v cet + iri in chemotherapy-refractory mCRC, stratified for KRAS G13D mutation (previously reported) or no mutations in KRAS, NRAS, BRAF and PI3KCA (Quad WT ). EGFR-I naïve, ECOG PS 0-1 pts, progressing within 6 months of iri and refractory (or intolerant) to fluoropyrimidine and oxaliplatin were randomised to cet 400mg/m2 IV loading then 250mg/m2 weekly +/- iri 180mg/m2q2 wks. The primary endpoint was progression-free survival at 6 months (6m PFS); secondary endpoints were response rate (RR), overall survival (OS), toxicity and quality of life (QOL). Results: From Nov 2012 to June 2016, 48 Quad WT pts were recruited: 2 ineligible (not iri-refractory, BRAF mutation) wre not included for analyses and a further 2 not evaluable for response. Characteristics were balanced between cet (n = 21) v cet-iri (n = 25), except for sex (male 62 v 72%) and primary site (left 95 v 68%). 6m PFS rate was 14% v 41%; HR 0.39 (95% CI: 0.20–0.78, p = 0.008). RR was 10% (2 PR) v 36% (1 CR, 8 PR); p = 0.04. Toxicities were higher with cet-iri; at least one grade 3/4 adverse event in 50 v 23%. No differences in global or specific QOL were seen. Conclusions: The AGITG ICECREAM trial confirms a significant synergy for the addition of iri to cet and improved PFS in Quad WT chemorefractory mCRC, echoing data in molecularly unselected pts. Clinical trial information: ACTRN12612000901808.

Preliminary results of a randomized phase II study comparing two schedules of temozolomide in combination with sorafenib in patients with advanced melanoma

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 8009-8009 ◽  
Author(s):  
R. K. Amaravadi ◽  
L. M. Schuchter ◽  
A. Kramer ◽  
S. F. Barth ◽  
J. Villanueva ◽  
...  
Keyword(s):  
Brain Metastasis ◽  
Phase Ii ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Prior Therapy ◽  
Optimal Dosing ◽  
Hand Foot Syndrome ◽  
Correlative Studies ◽  
Grade 3 ◽  
Ecog Ps

8009 Background: Sorafenib (SO) is an oral Raf kinase/VEGFR-2 inhibitor that has anti-melanoma activity when given with carboplatin/paclitaxel. The primary objective of this study is to estimate the duration of progression-free survival (PFS) for patients with metastatic melanoma (MM) taking SO + temozolomide (TEM). Secondary objectives are to determine the optimal dosing of TEM when given with SO, response, and toxicity rates. Correlative studies include BRAF genotyping and assessment of intratumoral Raf inhibition. Methods: Patients with MM and ECOG PS<2 are eligible. Prior therapy is allowed. Accrual is designed for 167 patients in one stage. All patients receive SO 400 mg po bid continuously. After one week of SO alone, patients without brain metastasis and no prior TEM are randomized to receive either extended daily dosing (EDD): TEM 75 mg/m2 po qd for 6 /8 weeks (Arm A), or standard dosing (STD): TEM 150 mg/m2 po qd for days1–5/28 (Arm B). Patients with prior TEM use are treated with EDD (Arm C) and patients with brain metastasis without prior TEM are treated with STD (Arm D). Responses are assessed using RECIST criteria. Results: 65 patients were evaluated for toxicity. Of these, 58 received SO + TEM and were evaluable for response (Table). SO + TEM resulted in a 24% overall response rate (ORR) [95% CI 11–41%] in patients without brain metastasis or prior TEM and 20% ORR [95% CI 3–56%] in patients with brain metastasis and no prior TEM. Observed grade 3 toxicities attributable to study medication were: hand-foot syndrome (12%), rash (8%), nausea (5%), anorexia (8%), and hypertension (3%). Nausea and anorexia were more prevalent with STD. Tumor blocks and 8 paired biopsy samples have been collected for correlative studies. Conclusions: Initial phase II results demonstrate encouraging antitumor activity and safety profile for SO + TEM in MM. Updated PFS data, response and toxicity rates, and correlative results will be presented. [Table: see text] [Table: see text]

Efficacy of first-line bevacizumab (BEV)-based therapy for metastatic triple-negative breast cancer (TNBC): Subgroup analysis of TURANDOT.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 1040-1040 ◽  
Author(s):  
Moshe J. Inbar ◽  
Istvan Lang ◽  
Zsuzsanna Kahan ◽  
Richard Greil ◽  
Semir Beslija ◽  
...  
Keyword(s):  
Subgroup Analysis ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase Iii ◽  
First Line ◽  
Hand Foot Syndrome ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
One Year ◽  
Ecog Ps

1040 Background: The randomized phase III TURANDOT trial compared first-line BEV plus paclitaxel (PAC) vs BEV plus capecitabine (CAP) in HER2-negative metastatic BC (mBC). BEV-based regimens are often favored in TNBC [Dawood 2012] because of efficacy in subgroup analyses and a lack of effective treatments. We performed an exploratory subgroup analysis of TURANDOT to provide more data on BEV-based therapy in TNBC. Methods: Patients (pts) with HER2-negative mBC who had received no prior chemotherapy for mBC were randomized to either BEV–PAC (BEV 10 mg/kg d1 and 15 + PAC 90 mg/m2 d1, 8, and 15 q4w) or BEV–CAP (BEV 15 mg/kg d1 + CAP 1000 mg/m2bid d1–14 q3w). The primary endpoint was overall survival (OS); secondary endpoints included objective response rate (ORR), progression-free survival (PFS), and safety. Results: Of 561 pts treated, 130 had TNBC. Baseline characteristics were typical of a poor-prognosis population and generally balanced between treatment arms, although fewer pts receiving BEV–PAC than BEV–CAP had ECOG PS 1/2 (25% vs 40%, respectively), positive lymph nodes (56% vs 72%), metastatic disease at first diagnosis (19% vs 30%), and liver metastases (27% vs 43%). Median age was 54 vs 56 years, respectively. At data cut-off, median follow-up was 21.4 vs 19.2 mo for BEV–PAC and BEV–CAP, respectively. The safety profiles in the TNBC subgroup were similar to the overall population. The predominant grade ≥3 AEs were hematologic AEs and neuropathy with BEV–PAC and hand-foot syndrome and diarrhea with BEV–CAP. Conclusions: One-year OS rates up to 78% in TURANDOT are among the highest seen in TNBC. BEV-based therapy is a valid option in a setting with limited active treatments. BEV–PAC may be favored based on 1-year OS, PFS, and ORR. Clinical trial information: NCT00600340. [Table: see text]

Palbociclib (P) in patients (pts) with soft tissue sarcoma (STS) with CDK4 amplification: Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 11565-11565
Author(s):  
Scott Schuetze ◽  
Michael Rothe ◽  
Pam K. Mangat ◽  
Liz Garrett-Mayer ◽  
Funda Meric-Bernstam ◽  
...  
Keyword(s):  
Treatment Options ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
Stage Design ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
Ecog Ps ◽  
Stage 1 ◽  
Anti Tumor Activity

11565 Background: TAPUR is a phase II basket study evaluating anti-tumor activity of commercially available targeted agents in pts with advanced cancers with genomic alterations. Results in a cohort of STS pts with CDK4 amplification treated with P are reported. Methods: Eligible pts had advanced STS, no standard treatment options, measurable disease, ECOG PS 0-2, and adequate organ function. Genomic testing was performed in CLIA-certified, CAP-accredited site selected labs. Pts received P at 125 mg orally once daily for 21 days, followed by 7 days off until disease progression. Pts matched to P had CDK4 amplification and no RB mutations. Simon 2-stage design tested the null disease control (DC) - defined as partial (PR), complete response (CR) or stable disease at 16+ weeks (SD 16+) - rate of 15% vs. 35% (power = 0.85; α = 0.10). If ≥2 of 10 pts in stage 1 have DC, 18 more pts are enrolled. If ≥7 of 28 pts have DC, the null DC rate is rejected. Secondary endpoints are progression-free survival (PFS), overall survival (OS) and safety. Results: 29 pts (66% male) with STS with CDK4 amplification were enrolled from July 2016 to Nov 2019. 1 pt was not evaluable and excluded from efficacy analyses. Demographics and outcomes are summarized in Table. One pt with partial response (PR) and 12 pts with SD16+ were observed for DC and objective response (OR) rates of 48% (95% CI: 31%, 62%) and 3.7% (95% CI: 0.1%, 19%), respectively, and the null DC rate of 15% was rejected (p<0.001). 9/13 pts with DC continued on treatment for >32 weeks. 14 pts had at least one grade 3-4 AE at least possibly related to P with the most common being low WBC/platelets. Other grade 3 AEs included increased alanine aminotransferase, anemia, and fatigue. Conclusions: Monotherapy P demonstrated anti-tumor activity in heavily pre-treated pts with STS with CDK4 amplification. Additional study is warranted to confirm the efficacy of P in pts with STS with CDK4 amplification. Clinical trial information: NCT02693535. [Table: see text]

Randomized phase II study of maintenance vandetanib (ZD6474) in small cell lung cancer (SCLC) patients who have a complete or partial response to induction therapy: NCIC CTG BR.20

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7522-7522 ◽  
Author(s):  
A. M. Arnold ◽  
M. Smylie ◽  
K. Ding ◽  
Y. Ung ◽  
B. Findlay ◽  
...  
Keyword(s):  
Partial Response ◽  
Phase Ii ◽  
Randomized Study ◽  
Progression Free Survival ◽  
P Value ◽  
Cancer Society ◽  
Randomized Phase Ii ◽  
Secondary Endpoints ◽  
Dose Modifications ◽  
Ecog Ps

7522 Background: Vandetanib (V) is an inhibitor of vascular endothelial and epidermal growth factor receptors. This trial sought to determine whether maintenance V, given after standard chemotherapy (CT) and radiation (RT), prolonged progression-free survival (PFS) in responding patients with SCLC. Secondary endpoints: overall survival (OS) and toxicity. Methods: Phase II randomized, study of V 300 mg PO daily or placebo (P). Eligibility: complete (CR) or partial response (PR) to platinum-based CT, ECOG PS 0–2 and completion of RT (thoracic or prophylactic cranial). Statistics: 80% power to detect a 2.5 months improvement in median PFS (estimate for P of 4 months) using a 1-sided 10% level test (100 eligible patients; 77 events). Results: Between May 2003 and March 2006, 107 patients were accrued from 17 centres. Median follow up: 13.5 months. 46 had limited disease (LD); 61 extensive disease (ED). There were fewer PS 0 patients (11 vs. 20), and fewer had CR to initial CT (4 vs. 8) in the V arm. V patients were more likely to experience toxicity and require dose modification. The most frequent toxicities leading to dose modifications were gastrointestinal and rash. Clinically asymptomatic QTc prolongation was observed in 8 V patients. 83 of 107 patients developed progressive disease (43 on V; 40 on P). The median PFS for V was 2.7 months (80% C.I.: 1.1 –4.5) and 2.8 months for P (80% C.I.: 1.9 –5.6); estimated hazard ratio (HR) was 1.01 for V vs P (80% C.I.: 0.75 –1.36, 1-sided P-value = 0.51). Median OS for V was 10.6 months vs. 11.9 months for P; HR was 1.43 for V vs. P (80% C.I.: 1.00 –2.05, 1-sided P-value = 0.90). In a planned subgroup analysis, a significant interaction was noted (P-value = 0.01); with LD patients randomized to V having a longer OS (HR: 0.45, 1-sided P-value = 0.07), whereas ED patients randomized to V had a shorter OS compared to P (HR: 2.27, 1-sided P-value = 0.996). Conclusion: V failed to demonstrate efficacy as maintenance therapy for SCLC. Future targeted therapies should probably be explored concurrently with chemotherapy. This study was supported by the Canadian Cancer Society and AstraZeneca. [Table: see text]

Docetaxel, oxaliplatin, and capecitabine (TEX regimen) for patients with metastatic gastric cancer: Interim results from a phase II trial by the German AIO Group

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4554-4554 ◽  
Author(s):  
M. H. Moehler ◽  
P. Thuss-Patience ◽  
D. Arnold ◽  
W. Grothe ◽  
A. Stein ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Phase Ii ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Distant Metastases ◽  
Response Assessment ◽  
Metastatic Gastric Cancer ◽  
Phase Ii Trials ◽  
Grade 3 ◽  
Ecog Ps

4554 Background: Combination regimens of 3 drugs have shown promising activity as treatment for patients (pts) with metastatic gastric cancer (GC). Docetaxel combined with cisplatin and 5-FU (CF) improved overall survival and response rates when compared to standard CF. However, the identification of less toxic and more convenient variants of this regimen is still important. We have previously established a regimen with docetaxel (T) combined with oxaliplatin (E) and capecitabine (X) in a phase I trial [Grothe et al., Proc. ASCO 2006]. Results of a preplanned interim analysis of subsequent multicenter phase II trials of the TEX regimen are presented here. Methods: Pts with metastatic or locally advanced GC, adequate organ function, ECOG PS 0–2, and no prior chemotherapy for advanced disease (adjuvant allowed) were enrolled. TEX regimen was administered as defined: T 35 mg/m2 and E 70 mg/m2 on days (d) 1 and 8, with X 800 mg/m2 bid on d1–14 every 22 days Toxicity assessment was done 3-weekly while CT scans were repeated 9-weekly. Results: 35 of 48 pts were enrolled until 06/08: 28 male / 7 female, median age 59 (36–81) years, ECOG PS 0/1/2 69%/31%/0%, gastric / gastroesophageal cancer 60%/40%, distant metastases 96%, tumor in situ 37%. The most common toxicities reported were (CTC grade [gr] 3/4): diarrhea 20%/3%, vomiting 11%/3%, asthenia and neurotoxicity each 9%/0%. Mucositis and hand-foot-syndrome were observed in (grade 1+2 / grade 3) 29%/0% and 26%/3%, respectively. Hematoxicity was mild with grade 3 anemia in 10% and no other grade 3/4 toxicity except one episode of febrile neutropenia . Of 25 pts evaluable so far, first tumor response assessment revealed (RECIST criteria) partial response in 36% and stable disease in 40% of patients. Conclusions: TEX is a safe and tolerable regimen for patients with metastatic gastric cancer. Preliminary efficacy results indicate promising activity. Mature data including progression free survival will be presented at the meeting. [Table: see text]

A phase II study of sunitinib in recurrent or metastatic endometrial carcinoma: A trial of the PMH Phase II Consortium

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5576-5576
Author(s):  
S. Welch ◽  
H. J. Mackay ◽  
H. Hirte ◽  
G. F. Fleming ◽  
R. Morgan ◽  
...  
Keyword(s):  
Phase Ii ◽  
Kinase Inhibitor ◽  
Phase Ii Study ◽  
Objective Response ◽  
Progression Free Survival ◽  
Open Label ◽  
Second Stage ◽  
Best Response ◽  
Grade 3 ◽  
Ecog Ps

5576 Background: Endometrial cancer (EC) is the most common gynecologic malignancy. Vascular endothelial growth factor (VEGF) overexpression in EC correlates with poor outcome, thus targeting VEGF is a rational therapeutic approach. We have conducted a two-stage open-label phase II study in advanced EC with sunitinib, an oral tyrosine kinase inhibitor of multiple VEGF receptors. Methods: Eligible pts have recurrent or metastatic EC and have received up to 1 prior chemotherapy (CT) regimen for metastatic disease. Sunitinib is given at 50 mg daily (OD) for 4 consecutive weeks (wks) followed by 2 wks off. Dose could be reduced to 37.5 mg OD and then 25 mg OD in the setting of toxicity. Imaging is repeated every 12 wks. Primary objectives are objective response rate (ORR by RECIST) and rate of 6-month progression-free survival (PFS). If 1 or more responses occur in the first 15 evaluable pts, the study would continue to a second stage (total = 30 pts). Secondary objectives are time to progression (TTP), overall survival (OS), and safety. Results: We report the results of the first stage of this study. Sixteen pts have been treated (median age: 63; range 41–74) with 37 cycles of sunitinib (median 2; range: 1–7). Baseline ECOG PS was 0 (7 pts), 1 (8 pts), or 2 (1 pt). Histology was endometrioid (7 pts), serous (5 pts), clear cell (1 pt), or mixed/other (3 pts). Most pts had high-grade histology (G3: 8; G2: 4; G1: 2; GX: 2). Nine pts had prior adjuvant CT, 8 pts had 1 prior CT for advanced EC, 4 pts had prior hormones and 7 pts had prior radiotherapy. Partial response was achieved by 2 pts (ORR = 12.5%), and 2 other pts had a best response of stable disease; 3 of these pts remained progression-free > 6 months. Median TTP = 2.5 months (95% CI: 2.47-NR), and median OS = 6.2 months (95% CI: 5.1-NR). Grade 3/4 adverse events (AE) in >10% of pts were fatigue (7 pts, 44%) and hypertension (5 pts, 31%). Dose reduction was required for 11 of 16 pts (69%). Two pts were inevaluable after receiving <2 cycles due to AE (grade 4 hyponatremia; grade 3 fatigue) and 1 other pt has yet to complete 2 cycles. Conclusions: Sunitinib shows preliminary activity in EC. This trial will proceed to a second stage of accrual to further explore the efficacy and safety of sunitinib in advanced EC. [Table: see text]

Phase II study of biweekly administration of CPT-11 and gemcitabine in chemotherapy-naive patients with metastatic pancreatic cancer in Japan.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15150-e15150
Author(s):  
Ryoji Takada ◽  
Tatsuya Ioka ◽  
Nobuko Ishida ◽  
Takuo Yamai ◽  
Nobuyasu Fukutake ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Phase Ii ◽  
Combination Chemotherapy ◽  
Phase Ii Study ◽  
Single Agent ◽  
Progression Free Survival ◽  
Current Standard ◽  
Free Survival ◽  
Metastatic Pancreatic Adenocarcinoma ◽  
Grade 3

e15150 Background: The current standard therapies for metastatic pancreatic adenocarcinoma in Japan are the single-agent Gemcitabine (Gem) or S-1 and Gem plus erlotinib. Irinotecan (CPT-11) is one of the promising drugs for Gem-refractory PC pts. Both Irinotecan and Gem have shown activity against these diseases with different mechanisms and are non-cross-resistant with each other. Japanese pts have the different metabolism with Irinotecan rather than pts in western countries. Methods: The aim of this phase II study was to evaluate the efficacy and safety of CPT-11 and Gem in Japanese pancreatic cancer pts. Patients with MPC and PS 0-2 were enrolled in this phase II trial. CPT-11, 100mg/m (2), was administered in 90 min. and Gem, 1000mg/m (2), was administered in 30 min. soon after CPT-11 on day1. Chemotherapy was repeated biweekly. Results: From May 2002 to May 2006 40 pts, with median age of 62 (40-74) years, were enrolled in this study. The overall response rate (RR) was 15% with disease control rate of 50%. The median progression-free survival (PFS) was 4.0 months (range: 1.0-15.0 months), and median overall survival (OS) was 7.5 months (range: 3.0-24.0 months). Grade 3/4 anemia, leucopenia occurred in 26.3, 5.2% of pts. The most common non-hematologic toxities were fatigue, diarrhea, nausea/vomiting and anorexia. Grade 3 diarrhea and nausea occurred in 10.5% of pts. Conclusions: The combination chemotherapy with Gem and CPT-11 showed favorable RR as expected and the treatment was manageable in Japanese pts with MPC. We plan to evaluate this combination chemotherapy for MPC pts after progression of FOLFIRINOX in near the future. Clinical trial information: UMIN000009963.

A phase I/II study of cetuximab (cet) in combination with S-1 and oxaliplatin (SOX) in first-line treatment for metastatic colorectal cancer (mCRC) (JACCRO CC-06).

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 571-571 ◽  
Author(s):  
Akihito Tsuji ◽  
Yu Sunakawa ◽  
Tadamichi Denda ◽  
Yasutaka Takinishi ◽  
Masahito Kotaka ◽  
...  
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Maximum Tolerated Dose ◽  
Safety And Efficacy ◽  
Dose Adaptation ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
Early Tumor ◽  
Ecog Ps ◽  
Level 2

571 Background: Both SOX and cet are effective treatments each other in patients (pts) with mCRC. COIN trial indicated that the use of cet in combination with capacitabine and oxaliplatin should not be recommended. However, the safety and efficacy of cet plus SOX are not clear. To evaluate the safety and clinical efficacy of the combination, we conducted a multi-center phase I/II study. Methods: In this trial, we assigned pts with KRAS wild type (wt), EGFR-expressing tumor and no prior chemotherapy to receive cet (initial dose 400, and 250 mg/m2 weekly) followed by SOX (oxaliplatin on day 1 and S-1 40 mg/m2 twice daily on days 1-14). The treatment was repeated every 3 weeks. The phase I part was designed to determine the maximum tolerated dose (MTD) and recommended dose (RD) according to the dose adaptation schedule of oxaliplatin (100 mg/m2 for level 1 and 130 mg/m2 for level 2). In the following phase II part, the enrolled pts were treated with the RD. The primary endpoint was response rate (RR) evaluated by the external review board according to RECIST criteria v1.1. Secondary endpoints included PFS, OS, and safety. In addition, we prospectively evaluated early tumor shrinkage (ETS). Results: A total of 67 pts were enrolled from January 2012 to February 2013. In the phase I part, level 2 was determined to be the RD. The MTD was not determined because dose limiting toxicity was not confirmed in level 2. In the phase II part, 59 pts including 6 pts of phase I cohort were assessable for the efficacy. The median age was 64 years, 51% of pts were male, and ECOG PS 0 was observed in 85% of pts. The median course of treatment was 5 (range 1-14). The RR was 62.7% (95%CI, 50.4 to 75.1) and ETS was observed in 72% of pts. In safety analysis, grade 3 or worse adverse events were platelet count decreased (13.1%), neutropenia (8.2%), anorexia (11.7%), rash acneform (6.7%) and peripheral neuropathy (3.3%). Conclusions: We determined the RD of cet plus SOX treatment in pts with mCRC. This combination is tolerable at full doses of cet and SOX, with manageable toxicities, and demonstrates advantages in RR for pts with KRAS wt tumor. Updated safety and efficacy data will be presented. Clinical trial information: UMIN000007022.

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