Phase II trial of erlotinib in advanced pancreatic cancer (PC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4609-4609
Author(s):  
P. Tang ◽  
S. Gill ◽  
H. J. Au ◽  
E. X. Chen ◽  
D. Hedley ◽  
...  
Keyword(s):  
Disease Control ◽  
Phase Ii ◽  
Dose Escalation ◽  
Kinase Inhibitor ◽  
Phase Ii Trial ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Study Endpoint ◽  
Primary Study ◽  
Kras Mutations

4609 Background: The epidermal growth factor receptor (EGFR) is a potentially important target in PC. Benefit from erlotinib (Tarceva), an oral EGFR tyrosine kinase inhibitor has been associated with the presence of a skin rash. The purpose of this study was to determine the efficacy of erlotinib, dosed to achieve a rash, in patients (pts) with PC. Methods: Erlotinib was given at an initial dose of 150 mg/day to eligible pts with locally advanced (LA) or metastatic PC who had progressed or were unable to tolerate gemcitabine-based chemotherapy. The dose of erlotinib was increased by 50mg every 2 weeks (maximum 300 mg/day) until > grade 1 rash (CTCAE v 3.0) or other dose-limiting toxicities occurred. Erlotinib pharmacokinetic (PK) studies were performed. Baseline tumor tissue was collected for analysis of Kras mutations, EGFR by IHC and FISH. The primary endpoint of this two- stage phase II trial was prolonged disease control (PR + SD > 8 wks) with a rate of >20% assumed to be significant . Results: Fifty pts were accrued (median age 61, M:F = 25:25, ECOG 0:1:2 = 5:41:4, LA:Metastatic = 5:45, prior gemcitabine none:adjuvant:palliative = 2:16:35). 47 and 40 pts were evaluable for toxicity and response, respectively. Dose-escalation to 200–300 mg of erlotinib was possible in 9 pts. Most common treatment adverse events (TAEs) of any grade were: rash (35 pts, 74.5%), diarrhea (18 pts, 38.3 %), and fatigue (8 pts, 17%). Grade 3+ TAEs were rash in 2 pts and diarrhea in 2 pts. Best response was SD in 14 pts, 0.35 (95% CI: 0.2–0.5). Prolonged disease control (SD > 8 wks) was observed in 10/40 evaluable pts, 0.25 (95% CI: 0.12–0.38), which met the primary study endpoint. Median TTP was 1.6 mo (95% CI:1.6–2.1), mOS 4.1 mo (95% CI:3.2–7.3), and 6 mo OS rate was 39% (95%CI: 24–61%). PK and correlative data are being analyzed and will be presented. Conclusions: Erlotinib is associated with prolonged stable disease in a subset of pts with advanced refractory PC. Dose escalation in the absence of toxicity is feasible and safe. [Table: see text]

Imatinib in locally advanced dermatofibrosarcoma protuberans (DFSP): A phase II trial of the Dermatologic Cooperative Oncology Group (DeCOG)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 9561-9561 ◽  
Author(s):  
S. Ugurel ◽  
J. Utikal ◽  
P. Mohr ◽  
P. Helmbold ◽  
C. Pfoehler ◽  
...  
Keyword(s):  
Side Effects ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Locally Advanced ◽  
Distant Metastases ◽  
Initial Response ◽  
Study Endpoint ◽  
Primary Study ◽  
Imatinib Treatment ◽  
Study Results

9561 Background: DFSP is known for its low metastatic potential but locally infiltrative growth, hereby enforcing extensive and often multiple surgical procedures. DFSP cells were recently shown to display chromosomal translocations of the regions 17q22 and 22q13, resulting in an autocrine growth stimulation loop via the platelet-derived growth factor (PDGF) pathway. The tyrosine kinase inhibitor imatinib blocks PDGF signal transduction, thus offering a new therapeutic option for DFSP patients. This multicenter phase II trial was aimed to investigate the efficacy of imatinib in locally advanced DFSP. Methods: The primary study endpoint was objective response, secondary endpoints were safety and relapse-free survival. Patients with histological proof of locally advanced primary or relapsed DFSP, measurable tumor parameters according to RECIST, and no evidence of distant metastases were eligible. Patients received imatinib 600 mg/d PO. Tumor measurements were performed at week 6 and 12, and every 8 weeks thereafter. At the end of imatinib treatment, at the earliest after week 12, residual tumors were surgically excised with histological proof of tumor-free margins. Results: By January 2006, nine out of 13 recruited patients were evaluable for response (per protocol, PP), three are still on treatment and one stopped treatment after 12 days due to side effects. Among the nine PP patients, seven partial responses, one stabilization, and one progression were observed. Five responders showed an ongoing tumor shrinkage until complete surgical excision, whereas two patients revealed an initial response at 6 weeks, followed by a disease progression at 12 weeks. None of the patients developed distant metastases under treatment or thereafter. Side effects were mostly mild to moderate (CTC grade 1–2). Severe side effects (CTC grade 3–4), reversible angina pectoris and septicemia, respectively, were observed in two patients. Conclusions: The study results indicate imatinib as a potent systemic treatment option in locally advanced DFSP. However, a subset of DFSP patients appeared resistant to imatinib, either primarily after treatment onset, or secondarily after showing an initial response. No significant financial relationships to disclose.

Final analysis of a multicenter, randomized phase II trial comparing three different chemoradiotherapy regimens in the treatment of patients with locally advanced, nonmetastatic pancreatic cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4610-4610
Author(s):  
R. Wilkowski ◽  
S. Boeck ◽  
S. Ostermaier ◽  
R. Sauer ◽  
M. Herbst ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Objective Response ◽  
Locally Advanced ◽  
Study Endpoint ◽  
Hematological Toxicity ◽  
Primary Study ◽  
Grade 3

4610 Background: To date, no standard treatment approach for patients (pts) with non-resectable, locally advanced pancreatic cancer (PC) is defined. Methods: Within a prospective phase II trial treatment-naive pts with locally advanced PC and adequate organ function were randomly assigned to three different CRT regimens; all pts received a conventionally fractionated radiotherapy of 50 Gy (with a daily dose of 2.0 Gy) and were randomized to either concurrent 5-FU as a 24h-infusion (350 mg/m2/d on each day of radiotherapy, RT-5FU arm), concurrent low-dose gemcitabine 300 mg/m2 and cisplatin 30 mg/m2 on days 1, 8, 22, and 29 (RT-GC arm), or the same concurrent treatment followed by a sequential chemotherapy with full- dose gemcitabine (1000 mg/m2) and cisplatin (50 mg/m2) every two weeks (RT-GC+GC arm). Treatment duration in the RT- GC+GC arm was upon disease progression or unacceptable toxicity. The primary study endpoint was the overall survival (OS) rate after 9 months (mo); secondary endpoints included response rate (WHO criteria), progression-free survival (PFS), resectability and toxicity. Results: Ninety-five patients (median age 64 years, 54% male, 50% KPS 90–100%) were recruited from 12 German centers. Seventy patients were evaluable for objective response: the intent-to-treat response rate (CR+PR) was 19% in the RT-5FU arm, 22% in the RT-GC arm and 13% in the RT-GC+GC arm, respectively. Overall, 18 pts (19%) underwent surgical resection after initial CRT (R0 in 8 pts). After a median follow-up of 8.6 mo, median PFS was estimated with 4 mo (RT-5FU), 5.6 mo (RT-GC) and 6 mo (RT- GC+GC), respectively (p=0.21). The corresponding median OS times were 9.6 mo, 9.3 mo and 7.3 mo (p=0.61). Hematological grade 3/4 toxicities were higher in the two gemcitabine/cisplatin-containing arms, but no grade 3/4 febrile neutopenia was observed. Regarding non-hematological toxicity, nausea/vomiting were more frequently in the RT-GC and RT-GC+GC arm, whereas diarrhea was more frequent in the RT-5FU arm. Conclusions: Based on these data, gemcitabine/cisplatin-based CRT does not achieve a higher clinical efficacy compared to RT-5FU, and is associated with increased hematological toxicity. [Table: see text]

Phase II trial of 5-fluorouracil, adriamycin and cisplatin (FAP) followed by radiation and 5-fluorouracil in locally advanced pancreatic cancer

1989 ◽  
Vol 25 (2) ◽  
pp. 131-134 ◽  
Author(s):  
D. J. TH. Wagener ◽  
Q. G. C. M. van Hoesel ◽  
S. H. Yap ◽  
W. J. Hoogenraad ◽  
Th. Wobbes ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Locally Advanced Pancreatic Cancer

Phase II study of sunitinib administered in a continuous daily dosing regimen in patients (pts) with advanced GIST

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 9532-9532 ◽  
Author(s):  
S. George ◽  
P. G. Casali ◽  
J. Blay ◽  
A. Le Cesne ◽  
A. R. Tyler ◽  
...  
Keyword(s):  
Phase Ii ◽  
Clinical Benefit ◽  
Kinase Inhibitor ◽  
Continuous Treatment ◽  
Study Endpoint ◽  
Primary Study ◽  
Open Label ◽  
Early Results ◽  
Imatinib Resistant ◽  
Grade 3

9532 Background: Sunitinib malate (SU11248) is an oral multitargeted tyrosine kinase inhibitor with antitumor and antiangiogenic activities due to inhibition of KIT, VEGFRs, PDGFRs, RET, and FLT3. In previous phase I/II and III trials in pts with imatinib-resistant GIST, sunitinib demonstrated efficacy and favorable clinical tolerability when administered in 6-week treatment cycles consisting of 4 weeks sunitinib (50 mg QD), followed by 2 weeks off treatment. The current study examined continuous sunitinib dosing as a way to avoid potential reactivation of tumor cells during the off-treatment period. Methods: This open-label, multicenter, phase II trial was designed to evaluate the efficacy, safety, and tolerability of sunitinib administered once daily using a continuous-treatment regimen in pts with imatinib-resistant GIST. Treatment is initiated with 37.5 mg sunitinib daily, with the option to titrate dosing on an individual basis depending on tolerability. The primary study endpoint is clinical benefit rate, defined as percent of evaluable pts with confirmed CR, PR, or SD ≥24 weeks using RECIST. Secondary endpoints included ORR, TTP, PFS, OS, and safety/tolerability measures. Results: Of 28 pts who had started treatment at the time of this analysis, early results were available for 17 pts from two centers. The most commonly occurring treatment-related adverse events were stomatitis, hand-foot syndrome, gastroesophageal reflex, and fatigue, which were generally grade 1. Two pts experienced treatment-related grade 3 hypertension, and another exhibited grade 3 asymptomatic neutropenia. Five pts have been evaluated for benefit after 8 weeks of treatment. Stable disease (which is the clinical benefit typically observed in GIST pts treated with sunitinib) was demonstrated in all five pts. Expanded safety/tolerability and efficacy results will be available for presentation. Conclusions: Continuous dosing of sunitinib is feasible and appears to be associated with acceptable tolerability in pts with imatinib-refractory GIST, similar to the extensive experience documented with intermittent sunitinib dosing. It is possible that continuous daily dosing of sunitinib may further improve the outcomes of pts with GIST. [Table: see text]

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 trial of S-1 and concurrent radiotherapy in patients with locally advanced pancreatic cancer

2008 ◽  
Vol 63 (3) ◽  
pp. 535-541 ◽  
Author(s):  
Hee Man Kim ◽  
Seungmin Bang ◽  
Jeong Youp Park ◽  
Jinsil Seong ◽  
Si Young Song ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Locally Advanced Pancreatic Cancer ◽  
Concurrent Radiotherapy
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