A SARC phase II multicenter trial of imatinib mesylate (IM) in patients with aggressive fibromatosis

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 9515-9515 ◽  
Author(s):  
R. Chugh ◽  
R. G. Maki ◽  
D. G. Thomas ◽  
D. Reinke ◽  
J. K. Wathen ◽  
...  
Keyword(s):  
Phase Ii ◽  
Primary Endpoint ◽  
Phase Ii Trial ◽  
Case Reports ◽  
Point Mutations ◽  
Case Series ◽  
Aggressive Fibromatosis ◽  
Median Number ◽  
Fresh Tissue ◽  
Maximum Change

9515 Background: Aggressive fibromatosis (desmoid tumors, AF) are uncommon, locally aggressive, connective tissue neoplasms. Existing literature on systemic treatment of AF is sparse and consists mostly of case reports and small case-series. Based on previous observation of regression of AF treated with IM and tumoral expression of IM targets, SARC (Sarcoma Alliance for Research through Collaboration) included the treatment of AF onto a multi-institution phase II trial of IM in sarcoma. Here we report early clinical and laboratory results of the AF group. Methods: Eligible patients had histologically proven AF, unresectable or difficult to resect without considerable functional impairment. Patients were treated with IM 300 mg po BID (BSA≥1.5m2). The primary endpoint was complete (CR) or partial response(PR) at two months or stable disease (SD) or better at four months. Tumor DNA was extracted from available formalin fixed paraffin embedded tissue specimens and analyzed via allelic PCR and genomic DNA sequence analysis for specific point mutations in PDGFRα exons 12/14/18, PDGFRβ exons 12/18, KIT exons 9/11/13/17, and bRAF. Results: 51 patients were enrolled from 10/02 to 12/05 at 5 institutions, with 45 patients currently evaluable. The median age is 37 (range 14–67), and median number of prior therapies is 1 (range 0–3). 36 patients (80%) reached the primary endpoint of CR/PR at 2 months or SD or better at 4 months. The median time to treatment failure is 6.8 months (95% C.I. 5.8–17.1). Thus far, the maximum change in the largest dimension of the tumor ranged from a 21% increase to a 45% decrease. In 22 available tumor specimens, deletions within PDGFRαE12 and E18 were noted in 1 and 3 patients, respectively, while a wildtype genotype was found in other regions. Conclusions: IM has activity in AF, the mechanism of which remains unclear. While this is the largest reported phase II trial of AF, further improvement in evaluating clinical efficacy in this disease is clearly necessary. We plan an analysis of the maximum change in largest tumor dimension for each patient, which will be particularly beneficial in AF as responses often occur late. We have not as yet identified a laboratory predictor of clinical benefit. Further investigation of other potential targets in fresh tissue is warranted. [Table: see text]

A review of 565 phase II trial abstracts from ASCO 2005: Design characteristics of contemporary trials evaluating cytotoxic versus non-cytotoxic regimens

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 6569-6569
Author(s):  
C. Elser ◽  
G. Pond ◽  
E. Chen ◽  
L. Siu
Keyword(s):  
North America ◽  
Phase Ii ◽  
Primary Endpoint ◽  
Phase Ii Trial ◽  
Median Number ◽  
Cytotoxic Agents ◽  
Targeted Agents ◽  
Time To Event ◽  
Phase Ii Trials ◽  
Number Of Patients

6569 Background: New phase II trial designs have been proposed to accommodate the non-cytotoxic nature of molecularly targeted agents. In particular, the use of alternative endpoints and controls has been suggested. The objectives of this survey are to review the designs of contemporary phase II trials, to compare trials of cytotoxic versus non-cytotoxic regimens, and to identify predictors of acceptance for presentation. Methods: Abstracts of phase II trials of systemic anticancer therapy published in the 2005 ASCO Proceedings were hand searched. The trial context, type of intervention, trial design, endpoints, and completeness of reporting were assessed. Results: Our search yielded 565 abstracts: 72% were multi-center, 44% North American, 25% clearly identified as industry-sponsored, the median number of patients was 44 (range 8–346). Only 83% explicitly reported the study phase, 29% the primary endpoint, 11% the number of stages, and 5% the statistical design. For design properties, 16% used multiple arms and 6% used enrichment. Of trials reporting the primary endpoint, 48% used radiological or marker response and 22% time-to-event endpoints. The median number of endpoints was 4 (range 1–8). Non- cytotoxic regimens, which included targeted agents, hormone- or immunotherapy, constituted 22% of the trials reviewed, purely cytotoxic regimens 60%, the remaining 18% contained combinations of both. Trials of non-cytotoxic and combination regimens were more likely to report the primary endpoint (p=0.02), use time-to-event endpoints (p=0.006), have multiple arms, use enrichment, be conducted in North America, be industry-sponsored, and be accepted for oral or poster presentation (all p<0.001). Other predictors of publication type in multivariate analysis were multi-centricity, higher number of patients, industry involvement, and being conducted in North America (all p<0.05). Conclusions: Design properties of contemporary phase II trials of non-cytotoxic agents differ from trials of cytotoxic chemotherapy, and are more likely to be accepted for presentation at ASCO. Proposed new trial designs start to be more widely adopted. Most abstracts incompletely report design properties. No significant financial relationships to disclose.

Denosumab and pembrolizumab in clear cell renal carcinoma (KEYPAD): A phase II trial (ANZUP1601).

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. TPS367-TPS367
Author(s):  
Craig Gedye ◽  
Abhishek Jagdish Joshi ◽  
Alison Yan Zhang ◽  
Andrew James Martin ◽  
Anthony M. Joshua ◽  
...  
Keyword(s):  
Disease Progression ◽  
Phase Ii ◽  
Kinase Inhibitors ◽  
Clear Cell ◽  
Phase Ii Trial ◽  
Case Reports ◽  
Cell Cancer ◽  
Tumour Response ◽  
Predictive Biomarkers ◽  
Progression Free Survival

TPS367 Background: Inhibitors of the programmed death-1 pathway (PD-1) are effective in clear cell renal cell cancer (ccRCC). Preclinical data and case reports suggest that denosumab, an inhibitor of Receptor Activator of Nuclear Factor κ-B Ligand (RANKL) signaling, could potentiate the anti-tumour effects of anti-PD1 inhibitors without overlapping toxicities. We aim to determine the activity and safety of combining denosumab and pembrolizumab in advanced ccRCC. Methods: This single arm, multi-center, phase II trial will recruit 70 participants with metastatic or unresectable ccRCC, progressing during or after treatment with vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors, and with no prior treatment with immunotherapy or denosumab. Participants will receive pembrolizumab 200mg IV every 3 weeks plus denosumab 120mg SC on days 1, 8 and 22 and then every 3 weeks until disease progression, prohibitive toxicity or maximum treatment of 24 months. Response will be assessed at weeks 12, 18, 24, then every 12 weeks until disease progression. Bloods for translational studies are collected at baseline, week 6 and on disease progression. The primary endpoint is objective tumour response rate (OTRR) per RECIST 1.1. Secondary endpoints include OTRR per iRECIST, progression free survival (PFS), time to OTRR, time to first skeletal related event, adverse events, and frequency of treatment delays/discontinuations. Correlative studies will include identification of prognostic and/or predictive biomarkers relating to immune and RANKL signaling. A sample size of 70 provides 90% power with a 1-sided type 1 error rate of 10% to distinguish the observed OTRR (and PFS at 6 months) from an OTRR of 40% (worthy of pursuit) versus 25% (not worthy of pursuit). 15 sites are open across Australia. As of September 23, 2020, 40 patients have been recruited. Clinical trial information: NCT03280667 .

Reversion of Chemoresistance in Aggressive Lymphoma by Quinine. A Phase II Trial.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4572-4572
Author(s):  
Pierre Soubeyran ◽  
Amine Masmoudi ◽  
Christele Blanc-Bisson ◽  
Isabelle Soubeyran ◽  
Ricardo Bellott ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Cell Lymphoma ◽  
Previous History ◽  
Dose Intensity ◽  
B Cell Lymphoma ◽  
Median Number ◽  
Aggressive Lymphoma ◽  
History Of ◽  
Resistance To Chemotherapy

Abstract Multidrug resistance has been one of the most studied mechanisms of cancer cell resistance to chemotherapy. Evidence of its involvement in hematological malignancies is known since many years. One well-designed phase I trial showed that about 20 to 25% of patients strictly resistant to EPOCH schedule could become responsive again by the addition of Dex-verapamil (J Clin Oncol1995; 13:1995–2004). We decided to perform a phase II trial to evaluate whether quinine could reverse resistance to chemotherapy in aggressive lymphoma. Methods: Patients included had all received at least two lines of chemotherapy including CEOP (cyclophosphamide 750mg/m2, epirubicine 60mg/m2, vincristine 1.4mg/m2 IV day 1 and prednisone 40mg/m2 orally day1 to day 7) and were demonstrated as strictly refractory to CEOP i.e. either no change or progression. Q-CEOP was administered as follows: quinine 30-mg/kg/day for two days from d0 to d1 as a continuous infusion, CEOP at the beginning of d1. Results: 15 patients have been included with the following characteristics: median age: 52 years (32–64), 66% stage III–IV, 60% elevated LDH. The median number of previous regimens was 3 (2–5). 13 patients had diffuse large B cell lymphoma including 3 with previous history of follicular lymphoma. Two had mantle cell lymphoma. Seven patients were included directly since they were initially refractory to CEOP while eight were shown refractory after two further cycles of CEOP. Epirubicin pharmacokinetics was not influenced by quinine. Mean dose intensity of epirubicin was 94%. Toxicity was mild. 4 responses were observed at the end of treatment including 2 complete and 2 partial responses (26%, IC 95%: 8–55%). Only the 2 CR patients are still alive with no evidence of disease at 35+ and 61+ months. Conclusion: These results add further arguments to confirm that MDR1 plays a significant role in resistance to chemotherapy in lymphoma. Quinine allowed unexpected long term remission in 2 responding patients.

A Phase II Open-Label, Multi-Center Study of Anti-CCR4 Monoclonal Antibody Mogamulizumab (KW-0761) in Patients with Previously Treated Peripheral T-Cell Lymphoma(PTCL)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1763-1763 ◽  
Author(s):  
Pier Luigi Zinzani ◽  
Bertrand Coiffier ◽  
John Radford ◽  
Dolores Caballero ◽  
Paul Fields ◽  
...  
Keyword(s):  
T Cell ◽  
Phase Ii ◽  
Research Funding ◽  
Phase Ii Trial ◽  
Median Number ◽  
Advisory Board ◽  
Japanese Study ◽  
Duration Of Response ◽  
Previously Treated ◽  
Grade 3

Abstract Background CC chemokine receptor 4 (CCR4) is the receptor for macrophage-derived chemokine (MDC/CCL22) and thymus activation-regulated chemokine (TARC/CCL17). CCR4 is expressed on tumour cells in approximately 30-65% of patients with PTCL (Ogura, 2014). PTCL-NOS patients who are CCR4 positive have been reported to have a poorer prognosis compared to CCR4 negative patients (Ishida T CCR 2004). Mogamulizumab (KW-0761) is a defucosylated, humanized, IgG1 Mab with enhanced antibody dependent cellular cytotoxicity, that binds to CCR4. Mogamulizumab was evaluated in both phase 1 and 2 trials in Japanese patients. A phase II trial in PTCL and cutaneous T-cell lymphoma (CTCL) patients (Ogura, 2014) reported an overall response rate (ORR) of 35% in patients who relapsed after last systemic therapy (ORR was 34% in PTCL), leading to its approval in Japan in patients with previously treated CTCL and PTCL, in addition to its first indication, previously treated adult T-cell leukemia-lymphoma. Here we report the preliminary results of a European phase II trial of mogamulizumab in patients with relapsed/refractory PTCL. Methods A multi-center phase II study of mogamulizumab monotherapy was conducted to determine efficacy, safety and immunogenicity in patients with CCR4+ PTCL. The primary endpoint was ORR and secondary endpoints included duration of response, progression-free survival (PFS) and overall survival (OS). At least 34 evaluable patients were needed to detect a significant improvement over 15% assuming 80% power and a 0.0240 alpha significance level (assumes 35% ORR for alternative). Patients received mogamulizumab once weekly for 4 weeks and subsequently once every 2 weeks until progressive disease (PD) or unacceptable toxicity at a dose of 1.0 mg/kg. Responses were assessed every 8 weeks according to IWG criteria (Cheson et al 2007). Results Based on a preliminary analysis of the data, a total of 38 patients received at least one administration of mogamulizumab and were evaluable for safety analysis; (Male/female 23/15 ;Median age 58.5 years (range 19-87)). Three patients are still ongoing in the study (1 complete response (CR) and 2 stable disease (SD)). ECOG performance status at baseline was 0 (32%); 1 (29%); 2 (39%) and 92% of patients had stage III (32%) or IV (61%) disease. The median number of prior treatments was 2 (range 1-8). Only 17 patients (49%) responded to the last treatment administered prior to study entry. The median number of mogamulizumab administrations was 6 (range 1-32). The majority of adverse events (AEs) were CTCAE grade 1-2. Skin rash related to drug was observed in 32% of patients (12/38) and related AEs > grade 3 occurred in 32% (12) of patients. Infusion related reactions occurred in 3 patients (2 were CTCAE grade 2 and 1 was grade 3). Thirty-five patients were evaluable for efficacy. The ORR rate was 11% and the stable disease rate was 34% with a SD or better rate of 46%. The response by histological subtype is specified in the table below. The median duration of response (including SD) is 2.9 months. The median PFS is 2.1 months. Two patients (ALCL-ALK-neg and PTCL-NOS) proceeded to allogeneic SCT. Although the ORR in this study was less than seen in the Japanese study, the PFS was comparable. There were differences in patient population/study conduct between the Japanese study and this study, respectively, which included: inclusion of only relapsed patients (100% vs 49%), ECOG PS 2 (0% vs 39%) and response assessments (after 4 and 8 weeks versus 8 weekly from week 8). Conclusions Based on preliminary data, mogamulizumab demonstrates a SD or better rate of 46% and an ORR of 11% with an acceptable safety profile in this phase II study of heavily pre-treated relapsed/refractory PTCL patients. TableBest Overall Response by Histological subtypeNo of subjectsCR/PR n (%)SDn (%)>SD n (%)PTCL-NOS152* (13%)6 (40%)8 (53%)AITL122 (17%)3 (25%)5 (42%)TMF301 (33%)1 (33%)ALCL-ALK neg402 (50%)2 (50%)ALCL-ALK pos1000Efficacy Evaluable Subjects354 (11%)12 (34%)16 (46%) *One patient had CR by CT scan but did not have bone marrow done for confirmation of CR Disclosures Zinzani: Sandoz: Consultancy; Celgene International Sàrl: Advisory Board, Advisory Board Other, Honoraria, Speakers Bureau; MundiPharma International Ltd: Advisory Board, Advisory Board Other, Honoraria, Speakers Bureau; Pfizer Inc: Advisory Board Other, Honoraria, Speakers Bureau; Takeda Pharmaceutical Company Limited: Advisory Board Other, Honoraria, Speakers Bureau; F. Hoffmann-La Roche Ltd: Advisory Board Other, Honoraria; GlaxoSmithKline: Advisory Board, Advisory Board Other, Honoraria; Gilead: Advisory Board, Advisory Board Other; Bayer AG: Advisory Board Other, Consultancy. d'Amore:CTI Life Sciences: Speakers Bureau; Mundipharma: Speakers Bureau; Takeda/Seattle Genetics : Speakers Bureau; Sanofi-Aventis: Research Funding; Amgen: Research Funding; Roche: Research Funding; Kyowa-Kirin: Advisory Board Other. Haioun:Roche: Honoraria; Celgene: Honoraria; Takeda: Honoraria; Pfizer: Honoraria; Janssen: Honoraria. Morschhauser:Genentech: Honoraria; Bayer: Honoraria; Spectrum: Honoraria; Mundipharma: Honoraria; Gilead: Honoraria.

Identification of predictive markers of clinical activity from a phase II trial of single agent pertuzumab (rhuMab 2C4), a HER dimerization inhibitor, in advanced ovarian cancer (OC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3001-3001 ◽  
Author(s):  
L. Amler ◽  
M. S. Gordon ◽  
A. Strauss ◽  
N. Rabbee ◽  
M. K. Derynck ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Single Agent ◽  
Advanced Ovarian Cancer ◽  
Ca 125 ◽  
Clinical Activity ◽  
Fresh Tissue ◽  
Formalin Fixed Paraffin ◽  
Heavily Pretreated ◽  
Dimerization Inhibitor

3001 Background: Pertuzumab (P), a humanized HER2 antibody, represents a new class of targeted agents called HER dimerization inhibitors (HDIs). P inhibits dimerization of HER2 with EGFR, HER3 and HER4, and subsequently inhibits signaling through MAP and PI3 kinases. Interim data from a phase II trial suggested that P has activity in OC, especially in a subset of tumors with activated HER2 (Abstract #5051 ASCO 2005). Methods: 123 pts with relapsed OC were treated with P. Cohort 1 was treated with 840mg followed by 420mg and cohort 2 with 1050mg every 3 weeks. Fresh tissue biopsies were mandated from Cohort 1, and archival formalin fixed paraffin tissue (FFPET ) were obtained from both cohorts. Molecular expression studies from FFPET and fresh tissue were conducted. Results: From final data of 117 evaluable pts, 5 pts had objective partial responses (RR = 4.3%). Eight pts (6.8%) had SD for ≥ 6 months, and an additional 4 pts (3.4%) had SD with CA-125 reduction of ≥50%. Overall rate of activity = 14.5%. Of the 65 fresh tumor biopsies, 28 were evaluable and 8 (28.6%) were positive for phosphorylated HER2 (pHER2) by ELISA. Among pts who had pHER2 status determined, TTP was 20.9 weeks for pHER2+ pts (n=8), compared to 5.8 weeks for pHER2- (n = 20). Data from microarray expression profiling were analyzed with respect to pHER2 status from the same tumors. The expression levels of HER2, EGFR and HER3 in combination with the expression of certain HER ligands may be predictive of pHER2 status. We have extended these analyses to qRT-PCR from macrodissected FFPET of HER receptors and ligands. This was analyzed with respect to clinical outcome. Preliminary analyses of expression data suggest that HER receptors and ligands may be promising candidates for diagnostic markers. Updated data in 78 OC pts will be presented. Conclusions: Clinical activity was observed in 14.5% of pts with heavily pretreated OC (PRs, SD ≥ 6 months, and SD with CA-125 reductions of ≥50%). This study suggests that P may be active in OC, and that specific HER receptors and ligands may be promising diagnostics for identifying tumors responsive to P. [Table: see text]

Phase II trial of irinotecan/docetaxel for advanced pancreatic cancer with randomization between irinotecan/docetaxel and irinotecan/docetaxel plus C225, a monoclonal antibody to the epidermal growth factor receptor (EGF-r) : Eastern Cooperative Oncology

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4519-4519 ◽  
Author(s):  
B. A. Burtness ◽  
M. Powell ◽  
J. Berlin ◽  
D. Liles ◽  
A. Chapman ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Median Survival ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Advanced Pancreatic Cancer ◽  
Growth Factor Receptor ◽  
Distant Metastases ◽  
Median Number ◽  
Number Of Cycles ◽  
Ecog Ps

4519 Background: Gemcitabine (G) is standard for metastatic pancreatic cancer (PC), with median survivals of 6 months (m). Second cytotoxic or biologic agents do not substantially advance survival. EGFR is expressed on PC and a phase II trial of G plus cetuximab (C) resulted in favorable 1 year survival. A phase II trial of irinotecan/docetaxel (I/D) chemotherapy reported a median survival for metastatic patients (pts) of 9 m. We conducted this randomized phase II trial to confirm the activity of this non-G regimen, and determine whether combining it with C was feasible and active. The primary endpoint was response. Methods: Pts required histologic confirmation of adenocarcinoma of the pancreas, evidence of distant metastases, ECOG PS 0–1, normal bilirubin, written informed consent, and were randomly assigned to Arm A (N=47) or B (N=45). Imaging with CT or MR within 4 weeks (wk) was used for tumor measurement. Dexamethasone was given 12 hours (h), 1 h before and 12 h after chemotherapy. Pts on Arm A received D 35 mg/m2 over 1 h and I 35 mg/m2 over 30 minutes weekly x 4 in a 6 wk cycle. Pts on Arm B received the same therapy, but C (loading dose 400 mg/m2 wk 1, 250 mg/m2 weekly thereafter) was given before D. Pts not receiving therapeutic anticoagulation received enoxaparin 40 mg per day. Pts were restaged (RECIST) after 2 cycles. Results: Median age Arm A: 59.9, Arm B: 60.2 years. Arm A 55% male, 32% PS 0, 97% EGFR immuno+. Arm B 84% male, 42% PS 0, 97% EGFR +. Median number of cycles for each arm 2 (1 -10). >4 cycles were delivered to 10.5% of pts Arm A, 20.9% Arm B. Grade ¾ neutropenia 26% Arm A, 33% Arm B. Grade 3 nausea 28% Arm A, 18% Arm B; Grade ¾ diarrhea 33% Arm A, 44.4% Arm B. 1 treatment-related death per arm. Median overall survival (OS), with 70.2% of pts known to have died, 6.5m [(95% CI (4.8, 8.6)] in Arm A. With 86.7% of pts known to have died in Arm B, OS 7.4 m [95% CI (4.4, 10.7)]. Response/progression data will be available at time of presentation. Conclusions: Weekly I/D ± C is associated with high rates of grade ¾ neutropenia/diarrhea. Median survival is 6.5m for I/D and 7.4m for I/D/C. Non-G containing therapy is active in metastatic PC. [Table: see text]

A phase II trial of oral S-1 combined with gemcitabine in patients with unresectable biliary tract cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15527-e15527 ◽  
Author(s):  
K. Nakamura ◽  
T. Yamaguchi ◽  
K. Sudo ◽  
T. Hara ◽  
T. Denda ◽  
...  
Keyword(s):  
Biliary Tract ◽  
Phase Ii ◽  
Biliary Tract Cancer ◽  
Bile Ducts ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Median Number ◽  
High Response Rate ◽  
Eligibility Criteria ◽  
Tract Cancer

e15527 Background: Optimal chemotherapy for unresectable biliary tract cancer is yet to be defined. We have conducted the phase II trial of Gemcitabine (GEM) with S-1, oral fluorouracil prodrug tegafur combined with two modulators, 5-chloro-2, 4-dihydropridine and potassium oxonate to evaluate the activity and toxicity of such combination in patients with unresectable biliary tract cancer. Methods: Eligibility criteria were pathologically-proven biliary tract cancer, appropriate performance status 0 to 2, age 20 to 79 years, adequate hematological, renal and liver functions, no prior chemotherapy, and written informed consent. S-1 was given orally (30mg/m2) bid for 14 consecutive days and GEM (1000mg/m2) was given on day 8 and 15. Cycle was repeated every 21 days. Results: 30 patients with unresectable biliary tract cancer (Gall-bladder: intrahepatic bile ducts: extrahepatic bile ducts=7:16:7) were enrolled from March 2007 to December 2008. Patients characteristics were: median age; 67 (46–79), male/female; 20/10, PS 0/1/2; 16/13/1. Median number of cycles was 8 (range 1 to 14). Out of total 26 evaluable patients, objective responses were observed in 9 patients (30%); 16 patients achieved stable disease and 1 patients showed disease progression. Median survival was 390 days (95% c.i.: 290 - 490 days). The grade 3–4 toxicities observed were leucopenia (20%), neutropenia (40%), anemia (17%), thrombocytopenia (37%), anorexia (7%), fever (10%), rash (7%) and interstitial pneumonia (7%). Conclusions: The combination chemotherapy with GEM and S-1 was well tolerated and high response rate has been observed. This result is very promising but survival benefit against GEM monotherapy should be demonstrated in future phase 3 studies. No significant financial relationships to disclose.

Gemcitabine and oxaliplatin (GEMOX) alone or in combination with cetuximab as first-line treatment for advanced biliary cancer: Final analysis of a randomized phase II trial (BINGO).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4032-4032 ◽  
Author(s):  
David Malka ◽  
Laetitia Fartoux ◽  
Vanessa Rousseau ◽  
Tanja Trarbach ◽  
Eveline Boucher ◽  
...  
Keyword(s):  
Phase Ii ◽  
Primary Endpoint ◽  
Mutational Analysis ◽  
Metabolic Response ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Objective Response ◽  
First Line ◽  
Open Label ◽  
Randomized Phase Ii

4032 Background: Gemcitabine-platinum chemotherapy (CTx) regimens are widely accepted as first-line standard of care for patients (pts) with advanced biliary cancers (ABC). EGFR overexpression has been observed in ABC, suggesting that the combination with anti-EGFR monoclonal antibodies may be appropriate. Methods: Patients with ABC, WHO performance status (PS) 0-1, and without prior palliative CTx were eligible for this international, open-label, two-stage, non-comparative, randomized phase II trial. Patients received GEMOX (gemcitabine, 1 g/m² [10 mg/m²/min] at day [D]1 + oxaliplatin, 100 mg/m² at D2, arm A) or GEMOX + cetuximab (500 mg/m² at D1 or 2, arm B), every 2 weeks. The primary endpoint was crude 4-month progression-free survival (PFS) rate (H0, <40%; H1, ≥60%; planned sample size, 100 pts, increased to 150 pts by amendment to allow subgroup analyses). Secondary endpoints were objective response rate (ORR), disease control rate (DCR), PFS, overall survival (OS), and toxicity (NCI-CTC v3.0). Exploratory endpoints included early metabolic response as assessed by PET at 1 month, and tumor KRAS mutational analysis. Results: From Oct. 2007 to Dec. 2009, we enrolled 150 pts (median age, 62 years; male, 57%; metastatic, 79%; cholangiocarcinoma, 84%; median follow-up, 30 months) (Table). Conclusions: GEMOX-cetuximab regimen was well tolerated and met its primary endpoint (4-month PFS ≥60%). However, median PFS and OS were similar in both arms. Exploratory analyses (e.g., KRAS tumor status) are underway to identify pt subgroups deriving benefit from the addition of cetuximab to CTx. [Table: see text]

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.

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