Randomized phase II trial of ficlatuzumab with or without cetuximab in pan-refractory, advanced head and neck squamous cell carcinoma (HNSCC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 6015-6015
Author(s):  
Julie E. Bauman ◽  
Nabil F. Saba ◽  
Denise Roe ◽  
Jessica R. Bauman ◽  
John M. Kaczmar ◽  
...  
Keyword(s):  
Lower Bound ◽  
Phase Ii ◽  
Primary Endpoint ◽  
Performance Status ◽  
Primary Objective ◽  
Phase Iii ◽  
Platinum Resistance ◽  
Eligibility Criteria ◽  
Immune Biomarkers ◽  
Hpv Status

6015 Background: Cetuximab (C), an anti-EGFR monoclonal antibody (mAb), is approved for advanced HNSCC but benefits a minority. Crosstalk between the EGFR and hepatocyte growth factor (HGF)/cMet pathways is a known resistance mechanism. HGF is also immunosuppressive within the tumor microenvironment. A Phase I study confirmed the safety of C and ficlatuzumab (F), an IgG1 anti-HGF mAb, with preliminary efficacy and biomarker data suggesting that dual pathway inhibition may overcome tumor-intrinsic or immune cetuximab resistance. Methods: The primary objective of this phase II randomized, non-comparative trial was to evaluate the efficacy of F (20 mg/kg every 2 wks), with or without C (500 mg/m2 every 2 wks), in pan-refractory, advanced HNSCC. Eligibility criteria included recurrent/metastatic HNSCC, performance status (PS) 0-1, C resistance (defined as progression on or within 6 months of exposure), and resistance to or ineligibility for platinum and anti-PD1 mAb. Randomization was stratified by HPV status and center. The primary endpoint was median progression-free survival (mPFS). An arm was deemed worthy of further study if the lower bound of the 90% 1-sided confidence interval (CI) excluded the historical control of 2 months. Secondary objectives included overall response rate (ORR) in the overall and HPV-stratified populations. A Bayesian continuous monitoring rule for futility was applied. Results: 60 patients were randomized and 58 treated between Jan 2018 and Dec 2020 (27 to F; 33 to FC). Baseline characteristics were balanced across major prognostic variables including age, PS, HPV status, platinum resistance, and PD1 mAb exposure. Median time since prior cetuximab was 3.5 months (range 0-48 months). Grade ≥3 adverse events attributed to F included: pneumonitis (2); edema (3); diarrhea (1); LFT elevation (1); rash (2); electrolyte abnormality (2). The Table presents efficacy data. The F arm stopped for futility after 26 evaluable subjects accrued. The FC arm completed accrual and met the primary endpoint; 32 evaluable subjects had mPFS of 3.6 months (lower bound 90% 1-sided CI: 2.3 months) and ORR of 19% (6/32). All responses were in HPV- subjects, including 2 complete (CR) and 4 partial responses (PR) to the FC combination and 1 PR to F monotherapy. The mPFS and ORR for the HPV- population (n = 16) on FC were 3.8 months and 38% (6/16). Mechanistic signaling and immune biomarkers are under analysis. Conclusions: The well-tolerated FC combination met the primary PFS endpoint in pan-refractory, advanced HNSCC with notable activity in HPV- HNSCC, warranting phase III investigation. Clinical trial information: NCT03422536. [Table: see text]

Phase II study with preoperative oxaliplatin (O), cisplatin (P), 5-fluorouracil (F) (OPF) and radiation (XRT) in patients with esophageal (ES), gastroesophageal (GE), and gastric (G) cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15612-e15612
Author(s):  
M. Pera ◽  
R. Gallego ◽  
M. Martin-Richard ◽  
C. Montagut ◽  
M. Iglesias ◽  
...  
Keyword(s):  
Phase Ii ◽  
Median Overall Survival ◽  
Phase Ii Study ◽  
Performance Status ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Surgical Oncology ◽  
Primary Objective ◽  
Ecog Performance Status ◽  
Eligibility Criteria

e15612 Background: A phase I study showed the feasibility of the triplet combination (OPF) with XRT in ES and GE cancer (Maurel et al, IJRBOP, 2005). We conducted a phase II study to evaluate the efficacy of the regimen. Methods: Enrolled pts had resectable, high-risk (HR) based on endoscopic ultrasonography (EUS) (uT3, uN1 or uT4 if deemed resectable) ES, GE and G cancer. The primary objective was to determine the pathologic complete response (pCR). If 2 or more pCR were reported in the first 18 pts treated, enrollment continues with 23 additional pts. Eligibility criteria: squamous cell or adenocarcinoma of the ES, GE or G cancer and ECOG Performance status (PS) 0–1. Staging was done with EUS and computed spiral tomography. Laparoscopic staging was mandatory for pts with ES, GE and G adenocarcinoma. Pts received 2 cycles of O 85 mg/m2, P 55 mg/m2, F (3 g/m2 in 96h CI) q4w, with concomitant 45 Gy XRT in 25 fractions; surgery was planned 5–8 weeks after XRT. All pathological specimens were reviewed by a unique pathologist and regression analysis was recorded using Cologne (C) and M.D.Anderson (MDA) classification for ES and European Journal of Surgical Oncology (EJSO) for GE and G. Results: Between 5/04 to 12/07, 41 pts were enrolled in 5 Spanish Institutions. Median age 62 yrs (39–75 yrs); Male/female 83%/17%; PS 0/1 27%/73%; ES/GE/G 39%/32%/29%; EUS stageT3N0 (20%), T2–3N1 (65%) and T4 (10%). G3/4 adverse events included asthenia (27%), infection (7%), diarrhea (7%) and stomatitis (5%). There were 2 toxic deaths. Of the 31 pts who underwent surgery, there were R0=94%/R1=3%/R2= 3%. 7/41 pts (17%) achieved pCR. Using C and MDA classification, 9/14 (61%) and 12/14 (85%) ES achieved grade IV/III and P0/P1 regression, respectively. With EJSO classification 3/17 (18%) GE and G tumors achieved pCR. Median time to progression or death (PFS) was 16.2 (CI:12.2-NR) months (mo). Median overall survival (OS) was 28.9 mo. (CI: 22.5-NR). Conclusions: Although in the whole group pCR, PFS and OS does not appear superior to results achieved in other trials with preoperative P/F/XRT in HR pts, the OPF regimen seems specially active in ES cancer. No significant financial relationships to disclose.

Randomized phase II study of pharmacodynamic separation (PDS) of pemetrexed (Pem) and erlotinib (Erl) versus pem alone in patients (pts) with advanced non-small cell lung cancer (NSCLC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8097-8097 ◽  
Author(s):  
Tianhong Li ◽  
Bilal Piperdi ◽  
William Vincent Walsh ◽  
Mimi Kim ◽  
Rasim Gucalp ◽  
...  
Keyword(s):  
Phase Ii ◽  
Primary Endpoint ◽  
Performance Status ◽  
Progression Free Survival ◽  
Dose Schedule ◽  
Phase Iii ◽  
Smoking History ◽  
Clinical Activity ◽  
P Value ◽  
Randomized Phase Ii

8097 Background: Preclinical and phase I studies showed that PDS optimizes cytotoxicity of concurrent EGFR inhibitors and chemotherapy. We conducted a randomized phase II trial to assess relative efficacy of Pem alone (Arm A) versus Pem +Erl on a PDS dose-schedule (Arm B) as 2nd-line therapy in pts with advanced NSCLC (NCT00950365). Methods: Eligible pts were randomized 2:1 (Arm B: A), stratified by sex, smoking history, and performance status (0/1 vs 2). Accrual was restricted to non-squamous histology in 2009. Treatment: Arm A – Pem 500 mg/m2IV on day 1; Arm B – Pem + Erl 150 mg po QD on days 2-17. 1 cycle = 3 weeks. Primary endpoint was progression-free survival (PFS). 50 pts in Arm B were needed to detect an increase in median PFS from ~3 to 4.5 months. Results: 83 pts were entered. Age: 63 yo. Female: 42 (53%). Smoking ≥15PY: 58 (72%). Nonsquamous: 78 (99%). The primary endpoint of the study was met: Efficacy results from 79 eligible pts showed 1.6-fold longer PFS in Arm B (4.6 m) compared to Arm A (2.8 m). Although the study was not designed to directly compare two arms, p value was 0.052. Toxicity: G3/4 Hem (A/B): 8(30%)/12(23%); Neutropenia with infection (A/B): 0/3(6%). G3/4 Non-Hem (A/B): skin rash: 0/3(6%); diarrhea: 0/2(4%); joint pain: 1(4%)/6(11.5%). Treatment related death (A/B): 0/1. Interstitial lung disease (A/B): 0/1. Conclusions: PDS of Pem and Erl is well tolerated and has promising clinical activity in 2nd-line non-squamous NSCLC. Ongoing correlative studies aim to identify a subgroup of patients who might benefit most from this treatment, which will guide the design of a confirmatory phase III study. (UL1 RR024146, P30CA093373, Lilly, Astellas) Clinical trial information: NCT00950365. [Table: see text]

VinCaP: A phase II trial of vinflunine chemotherapy in locally-advanced and metastatic carcinoma of the penis (CRUK/12/021).

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 547-547
Author(s):  
Lisa M. Pickering ◽  
Holly Tovey ◽  
Tony Elliott ◽  
Stephanie M. Burnett ◽  
Amit Bahl ◽  
...  
Keyword(s):  
Phase Ii ◽  
Primary Endpoint ◽  
Performance Status ◽  
Single Agent ◽  
Locally Advanced ◽  
Metastatic Carcinoma ◽  
Primary Analysis ◽  
Ecog Performance Status ◽  
Eligibility Criteria ◽  
Exact Design

547 Background: Platinum-based combination chemotherapy regimens are used in the treatment of carcinoma of the penis, but toxicity limits their value for patients with metastatic disease. This trial aims to define both the toxicity and the rate of disease control for the non-platinum cytotoxic agent Vinflunine. Methods: A phase II single-arm trial was designed to demonstrate a clinical benefit rate of at least 40% and to exclude a rate of less than 15% (p0 = 0.15, p1 = 0.40, α = 0.05, β = 0.80, Fleming-A’hern exact design). 22 evaluable patients were required. Key eligibility criteria included measurable, histologically-proven squamous cell carcinoma of the penis staged as M1; or M0, Tx, N3; or M0, Tx, N2 and deemed inoperable by multidisciplinary team; or M0, T4 any N. Patients were required to have ECOG performance status of 0, 1 or 2 and adequate hepatic and renal function. Treatment comprised four 21-day cycles of vinflunine (320mg/m2) with RECIST v1.1 restaging following cycle 4 (response primary endpoint). Patients deemed to be benefitting from treatment were permitted to continue vinflunine at the discretion of the treating clinician until progression or unacceptable toxicity. Results: 25 patients were recruited from 8 UK centres between June 2014 and May 2017. Median age was 68 years; 19 patients had metastatic (M1) disease. All patients have completed trial treatment and primary endpoint assessment. Data cleaning for the primary analysis is currently in progress, with the snapshot for the primary analysis due in October 2017 and primary analysis to be presented to the trial oversight committees in November 2017. Conclusions: It is hoped that single-agent vinflunine will be associated with a favourable toxicity profile combined with meaningful clinical responses. The results will be available for presentation at the meeting. Clinical trial information: NCT02057913.

Randomized phase II/III trial comparing gemcitabine/carboplatin (GC) and methotrexate/carboplatin/vinblastine (M-CAVI) in patients (pts) with advanced urothelial cancer (UC) unfit for cisplatin-based chemotherapy (CHT): Phase III results of EORTC study 30986.

2010 ◽  
Vol 28 (18_suppl) ◽  
pp. LBA4519-LBA4519 ◽  
Author(s):  
M. De Santis ◽  
J. Bellmunt ◽  
G. Mead ◽  
J. M. Kerst ◽  
M. G. Leahy ◽  
...  
Keyword(s):  
Renal Function ◽  
Phase Ii ◽  
Impaired Renal Function ◽  
Performance Status ◽  
Primary Objective ◽  
Error Rates ◽  
Phase Iii ◽  
Logrank Test ◽  
Randomized Phase Ii ◽  
Grade 3

LBA4519 Background: About 50% of pts with advanced UC are not eligible for cisplatin based CHT (“unfit”) due to impaired renal function, performance status (PS) or comorbidity. This is the first randomized phase II/III trial comparing two chemotherapy regimens in this pts group. Methods: The primary objective of the phase III part of this study was to compare the overall survival (OS) of CHT naïve pts with measurable disease and an impaired renal function (GFR<60 but >30 ml/min) and/or PS 2 who were randomized to receive either GC (G 1000 mg/m2 d1 and 8 and C AUC 4.5) q21 days or M-CAVI (M 30 mg/m2 d1 and 15 and 22, C AUC 4.5 d1 and VI 3 mg/m2 d1 and 15 and 22) q28 days. In order to detect an increase of 50% in median survival on GC compared to M-CAVI (13.5 versus 9 months) based on a two sided logrank test at error rates alpha=0.05 and beta=0.20, 225 pts were required. Secondary endpoints were overall response rate (ORR) and progression free survival (PFS). Results: 238 pts, 119 in each arm, were randomized between January 2001 and March 2008 by 29 institutions. The median follow-up is 4.5 years. Two pts were ineligible and two other pts never started treatment. Best ORRs (CR + PR) were 41.2% (36.1% confirmed response) on GC versus 30.3% (21.0% confirmed response) on M-CAVI (p = 0.08). Median OS was 9.3 months on GC and 8.1 months on M-CAVI (p = 0.64). There was no difference in PFS between the two arms (p = 0.78). OS, PFS and ORR were similar in each of the risk groups (reason unfit for cisplatin and Bajorin risk group). Severe acute toxicity (SAT) (death, grade 4 thrombocytopenia with bleeding, or grade 3/4 renal toxicity, neutropenic fever or mucositis) was observed in 9.3% of pts on GC (2 toxic deaths) and 21.2% on M-CAVI (4 toxic deaths). The most common grade 3/4 toxicities were leucopenia (44.9%, 46.6%), neutropenia (52.5%, 63.5%), febrile neutropenia (4.2%, 14.4%), thrombocytopenia (48.3%, 19.4%), and infection (11.8%, 12.7%) on GC and M-CAVI, respectively. Conclusions: There were no significant differences in efficacy between the two treatment groups. The incidence of SATs was slightly higher on M-CAVI. [Table: see text]

A phase I/II study of biweekly docetaxel (D) in combination with fixed-dose cisplatin plus fluorouracil (CF) in patients (pts) with advanced esophageal cancer (AEC) (JCOG0807).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15016-e15016
Author(s):  
Shuichi Hironaka ◽  
Yasuhiro Tsubosa ◽  
Junki Mizusawa ◽  
Takayuki Kii ◽  
Ken Kato ◽  
...  
Keyword(s):  
Phase I ◽  
Peer Review ◽  
Primary Endpoint ◽  
Performance Status ◽  
Treatment Compliance ◽  
Phase Iii ◽  
Fixed Dose ◽  
Open Label ◽  
Eligibility Criteria ◽  
Grade 3

e15016 Background: Thougha triplet chemotherapy with D plus CF (DCF) has shown promising activity, high incidence of adverse events (AEs) especially in febrile neutropenia (FN) was observed in previous studies for head and neck cancer (TAX323, 324) and gastric cancer (TAX325). To reduce its AEs with keeping activity, we conducted a multicenter open-label phase I/II study of biweekly D plus CF for AEC. Methods: Eligibility criteria included histologically proven AEC with measurable disease, age 20 to 75, non-resectable or recurrent disease, performance status (PS) 0 to 1. Pts received escalating doses of D (dose level (DL) 1: 30 mg/m2, DL 2: 40 mg/m2, on days 1, 15) in combination with fixed dose of CF (cisplatin 80 mg/m2 on day 1, fluorouracil 800 mg/m2on days 1-5) repeated every 4 weeks with 3+3 design in phase I part (P-I). The primary endpoint of P-I was dose limiting toxicity (DLT) and that of phase II part (P-II) was response rate (RR) defined by central peer review. Based on a SWOG two stage design (p0=35%, p1=50%; one-sided a=0.1, β =0.2) at least 22 responders among 50 eligible pts should be observed to satisfy the primary endpoint. Results: Between Feb 2009 and Mar 2010, 62 pts were enrolled for P-I and P-II. In P-I, 10 pts were enrolled with DLT of 0/3 in DL1 and 2/7 in DL2. Considering DLT and treatment compliance, the recommended dose for P-II was determined as DL1. Thus, 3 (P-I) and additional 52 pts (P-II) were analyzed: 53 for efficacy (excluded 2 ineligible pts) and 55 for safety. Pts characteristics were as follows: male/female 49/6, age median 61 (range 44 to 75), PS 0/1 39/16. The RR was 62% (95% confidence interval, 48-75%, p<0.0001) by central peer review. Median OS and PFS were 11.1 and 5.8 months. Grade 3/4 toxicity was observed in neutropenia (25%), anemia (36%), hyponatremia (29%), anorexia (24%) and nausea (11%). No grade 3/4 FN was observed. Treatment related death occurred in one patient due to pneumonitis. Conclusions: Biweekly D (30mg/m2) combined with CF showed promising activity and tolerability. A phase III study comparing CF with DCF is warranted. Clinical trial information: UMIN000001737.

Randomized, phase II study of ficlatuzumab with or without cetuximab in patients with pan-refractory, recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS6594-TPS6594
Author(s):  
Julie E. Bauman ◽  
Denise Roe ◽  
Nabil F. Saba ◽  
Jessica Ruth Bauman ◽  
John M. Kaczmar ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Resistance Mechanism ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Platinum Resistance ◽  
Intrinsic Resistance ◽  
Eligibility Criteria ◽  
Randomized Phase Ii ◽  
Clinical Resistance

TPS6594 Background: Patients with pan-refractory R/M HNSCC, with clinical resistance to cytotoxic therapy, anti-EGFR molecular targeting, and immunotherapy, have poor survival. An established tumor-intrinsic resistance mechanism to cetuximab, an anti-EGFR IgG1 monoclonal antibody (mAb), is activation of the hepatocyte growth factor (HGF)/cMet pathway, which converges with the EGFR network at both the PI3K/Akt and MAPK nodes allowing for reciprocal compensation. Moreover, over-expression of HGF in the tumor microenvironment is immunosuppressive. Convergent data suggest that HGF/cMet pathway inhibition concurrent with EGFR blockade may overcome cetuximab resistance. We previously reported a Phase I study of ficlatuzumab, a humanized anti-HGF IgG1 mAb, with cetuximab in cetuximab-resistant R/M HNSCC. The combination showed promising safety, overall response rate (ORR) and progression-free survival (PFS). Preliminary biomarker analyses showed that high circulating cMet was associated with poor PFS whereas serum Veristrat, a proteomic classifier associated with worse prognosis in the setting of anti-EGFR monotherapy, was not. An increase in total peripheral T cells, particularly the CD8+ subset, was associated with treatment response while progression was associated with expansion of a unique myeloid population. We designed a follow-on randomized phase II trial evaluating ficlatuzumab with or without cetuximab in pan-refractory, R/M HNSCC with signaling and immune correlatives. Methods: This is a multicenter phase II trial with a randomized, non-comparative, two-arm design (ficlatuzumab 20 mg/kg with or without cetuximab 500 mg/m2 every 2 weeks) in patients with pan-refractory R/M HNSCC. Key eligibility criteria include: R/M HNSCC; cetuximab resistance (progression during or within 6 months of cetuximab-radiation or palliative cetuximab); platinum resistance; prior exposure to anti-PD1 mAb; ECOG 0-1; consent to baseline research biopsy. The primary objective is to evaluate the efficacy of each arm as measured by PFS. To test the hypothesis that either regimen improves historical PFS from 2 to 3.33 months requires 66 eligible patients. Key secondary endpoints are ORR and survival. Mechanistic biomarkers include tumor HGF/cMet pathway activation, tumor and peripheral immune profiles, soluble cMet, and serum Veristrat. Thirty-five of 66 subjects have enrolled at 6 centers. A Bayesian continuous monitoring rule for futility has not been triggered for either arm. Clinical trial information: NCT03422536 .

SWOG 0941: A phase II study of sorafenib and erlotinib in patients (pts) with advanced gallbladder cancer or cholangiocarcinoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4113-4113 ◽  
Author(s):  
Anthony B. El-Khoueiry ◽  
Cathryn J Rankin ◽  
Syma Iqbal ◽  
Kenneth C. Micetich ◽  
Omar Kayaleh ◽  
...  
Keyword(s):  
Growth Factor ◽  
Gallbladder Cancer ◽  
Primary Endpoint ◽  
Performance Status ◽  
Objective Response ◽  
Tumor Biology ◽  
Primary Objective ◽  
Prognostic Impact ◽  
Eligibility Criteria ◽  
Histologic Diagnosis

4113 Background: The treatment of pts with advanced biliary cancers represents a therapeutic challenge. The vascular endothelial growth factor and epidermal growth factor receptor pathways play an important role in biliary carcinogenesis, as evidenced by their up-regulation and prognostic impact. Methods: The primary objective was progression free survival (PFS) (improvement in PFS from 4 to 8 months); secondary endpoints included overall survival (OS), objective response rate, and toxicity. A two-stage design was used; if 13 or more eligible pts of the 25 initially accrued were alive without progression at 4 months, an additional 25 were to be accrued. Eligibility criteria included no prior treatment for advanced or metastatic disease, histologic diagnosis of gallbladder cancer or cholangiocarcinoma, presence of measurable disease, Zubrod performance status 0-1, AST/ALT ≤ 5 IULN, total bilirubin ≤1.5 IULN, adequate hematologic function. Pts were treated with sorafenib 400 mg PO BID and erlotinib 100 mg PO q daily continuously. Restaging scans were performed every 8 weeks. Results: 32 eligible pts were accrued. 30 pts were evaluable for response. 2 patients (7 %) had an unconfirmed partial response (95% CI:1%-23%), and 8 pts (27%) had stable disease. Median PFS was 2 months (95% CI: 2-3 months). 22/32 patients progressed or died within 4 months of registration. Median OS was 6 months (95% CI: 3 -7 months). The study failed to meet its primary endpoint to proceed to the second stage of accrual. There were 3 deaths on study, 1 of which was possibly related to treatment. 19 patients (59%) had grade 3 or 4 toxicities: AST/ALT (22%), bilirubin (16%), alkaline phosphatase (16%), hypertension (16%), diarrhea (9%), hepatic infection (6%). Conclusions: This multicenter study was the first to evaluate the combination of sorafenib and erlotinib in pts with advanced biliary cancers. Despite manageable toxicity, the study failed to meet its primary endpoint. Correlative studies on collected tissue and blood are ongoing; improved pt selection based on tumor biology and molecular markers is necessary for future evaluation of targeted therapies in this disease.

PEAK (study 20070509): A randomized phase II study of mFOLFOX6 with either panitumumab (pmab) or bevacizumab (bev) as first-line treatment (tx) in patients (pts) with unresectable wild‑type (WT) KRAS metastatic colorectal cancer (mCRC).

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 446-446 ◽  
Author(s):  
Lee Steven Schwartzberg ◽  
Fernando Rivera ◽  
Meinolf Karthaus ◽  
Gianpiero Fasola ◽  
Jean-Luc Canon ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Performance Status ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Ecog Performance Status ◽  
Eligibility Criteria ◽  
Prior Therapy ◽  
Randomized Phase Ii

446 Background: Pmab has demonstrated significant improvement in progression-free survival (PFS) in pts with WT KRAS mCRC as 1st-line tx in a phase III trial comparing pmab + FOLFOX4 vs FOLFOX4 alone. Here, we describe the results of PEAK, a multicenter, randomized phase II study evaluating pmab + mFOLFOX6 and bev + mFOLFOX6 in pts with previously untreated WT KRASmCRC. Methods: Pts were randomized 1:1 to pmab 6.0 mg/kg + mFOLFOX6 Q2W or bev 5.0 mg/kg + mFOLFOX6 Q2W. Pt eligibility criteria included: WT KRASmCRC, ECOG performance status ≤ 1, and no prior chemotherapy, anti-VEGF tx, or anti-EGFR tx for mCRC. The primary endpoint was PFS; secondary endpoints included overall survival (OS), objective response rate (ORR), and safety. No formal hypothesis was tested. Results: 285 pts with WT KRASmCRC were randomized and 278 pts received tx. Demographics were balanced between arms. Intent-to-treat efficacy results are shown (Table). Worst grade 3/4 adverse events (AE) occurred in 86% of pts in the pmab + mFOLFOX6 arm vs 76% of pts in the bev + mFOLFOX6 arm. Grade 5 AEs occurred in 5% of pts in the pmab + mFOLFOX6 arm and 6% of pts in the bev + mFOLFOX6 arm. Tx discontinuation due to any AE was 24% in the pmab + mFOLFOX6 arm and 27% in the bev + mFOLFOX6 arm. Conclusions: In this estimation study of pts with WT KRASmCRC without any prior therapy for mCRC, PFS and ORR were similar between arms. The median OS was not reached in the pmab + mFOLFOX6 arm. The safety profile for both arms was consistent with previously reported studies of either combination. Tx discontinuation rates due to AEs were similar between arms. Clinical trial information: NCT00819780. [Table: see text]

Efficacy and safety of perioperative chemotherapy with 5FU-cisplatine-cetuximab in gastric and gastroesophageal junction adenocarcinomas (GGOJA): A single-arm multicenter phase II trial (FFCD 0901).

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 154-154 ◽  
Author(s):  
Christophe Mariette ◽  
Guillaume Piessen ◽  
Carole Monterymard ◽  
Denis Pezet ◽  
Aurelie Ferru ◽  
...  
Keyword(s):  
Phase Ii ◽  
Primary Endpoint ◽  
Performance Status ◽  
Gastroesophageal Junction ◽  
Objective Response ◽  
Tumour Response ◽  
Primary Objective ◽  
Perioperative Chemotherapy ◽  
Efficacy And Safety ◽  
Grade 3

154 Background: Whilst perioperative chemotherapy (CT) combined with radical surgery offers a survival benefit over surgery alone in GGOJA, 3-year survival still needs to be improved. The purpose of this phase II study was to evaluate the efficacy and safety of the perioperative use of cetuximab combined with 5-fluorouracil and cisplatin in operable GGOJA. Methods: Untreated operable patients with a WHO Performance Status (PS) ≤ 2 and age ≤ 75 years, with localised GGOJA received 6 cycles of intravenous Cetuximab (500mg/m²), Cisplatine (50mg/m²) and LV5FU2s (folinic acid 400mg/m², 5FU bolus 400mg/m², and continuous infusion of 5FU 2400mg/m²) every 2 weeks. Surgery was planned 3-4 weeks after the end of neaodjuvant CT and postoperative CT planned for 6-8 weeks after surgery. The primary objective was a combined evaluation of tumoral response, assessed by centrally reviewed computed tomography, and major toxicities leading to neoadjuvant CT being discontinued. Sample size (63 patients) was calculated using Bryant and Day design (α=5%, Power=80%), expecting a rate of objective response of 45% and a percentage of patients without major toxicities of 90%. Results: 65 patients were enrolled from 2011 to 2013 with a median age of 60.5 years. 83.1% were men, 98.5% had a WHO PS<2, 30.8% had a gastric and 69.2% a junctional tumour, 28.5% had a stage II and 71.4% of patients a stage III tumour. With regard to the primary endpoint, 64 patients were evaluated, 29.7% (n=19) had an objective morphological tumour response and 95.3% (n=61) did not stop treatment prematurely due to major toxicity. 58 patients (89.2%) completed neoadjuvant CT as planned. The median duration of CT was 2.3 months and grade 3-4-5 toxicities were observed in 61.5% of patients. 60 patients (92.3%) underwent surgical resection with 24 significant complications (41.7%) and 2 postoperative deaths (3.4%). On histological analysis, 40 patients (71.4%) were non responders. Conclusions: Adding cetuximab to the neoadjuvant chemotherapy regimen in operable GGOJA is safe but does not show enough efficacy in the present study to meet the primary endpoint. Clinical trial information: NCT01360086.

Adjuvant chemotherapy versus perioperative chemotherapy (CTx) for resectable gastric signet ring cell (SRC) gastric cancer: A multicenter, randomized phase II study (PRODIGE 19).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4019-4019 ◽  
Author(s):  
Clarisse Eveno ◽  
Antoine Adenis ◽  
Olivier Bouche ◽  
Karine Le Malicot ◽  
Vincent Hautefeuille ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Primary Endpoint ◽  
Performance Status ◽  
Tumor Stage ◽  
Primary Objective ◽  
Signet Ring Cell ◽  
Phase Iii ◽  
R0 Resection ◽  
Intrinsic Resistance ◽  
Stage Ib

4019 Background: The incidence of SRC gastric cancers is markedly increasing in Western countries. SRC cancers may harbor intrinsic resistance to chemotherapy (CTx) leaving many clinicians unsure of the benefits of delaying surgery to pursue a neoadjuvant approach. The primary objective of this study was to assess whether upfront surgery plus adjuvant CTx would provide enough survival benefit for study in a phase III trial when compared to perioperative CTx. Methods: Patients with stage IB-III SRC gastric cancer were randomly assigned to receive upfront surgery plus adjuvant CTx (epirubicin, cisplatin and 5-fluorouracil [ECF regimen], 6 cycles; experimental arm [SurgFirst]) or perioperative CTx (ECF, 3 cycles before and 3 cycles after surgery; control arm [CTxFirst]). Randomization (1:1) was stratified by tumor stage, tumor location, performance status and center. The primary endpoint was overall survival (OS) at 2 years (OS2; target (H1): OS2 > 26%). Results: 83 eligible patients were included in 27 centers from 11/12 to 09/16 (median age, 61 years (range: 32-80 years); male, 59%; ECOG PS 0-1, 99%). Results were (CTxFirst/SurgFirst): full completion of CTx, 87%/77%; surgical resection, 82.5%/90%; major postoperative complications (Clavien Dindo III-IV), 24%/23%; R0 resection rate, 88%/78%; OS2, 60%/53.5%; and median OS, 39/28 months (exploratory hazard ratio, 0.71 [95%CI: 0.40-2.64]). Conclusions: This trial met its primary endpoint (OS2 > 26% in the experimental arm). With OS2 rates > 50%, both CTx modalities deserve further evaluation in Phase III studies in stage IB-III SRC gastric cancer. Clinical trial information: NCT01717924.

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