Phase II trial of stereotactic ablative radiation (SAbR) for oligoprogressive kidney cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4564-4564
Author(s):  
Raquibul Hannan ◽  
Michael Christensen ◽  
Aurelie Garant ◽  
Hans J. Hammers ◽  
Waddah Arafat ◽  
...  
Keyword(s):  
Phase Ii ◽  
Local Control ◽  
Systemic Therapy ◽  
Kinase Inhibitor ◽  
Primary Objective ◽  
Related Quality ◽  
Health Related ◽  
Secondary Endpoints ◽  
Grade 3

4564 Background: Metastatic renal cell carcinoma (mRCC) patients on systemic therapy may experience oligoprogression. SAbR has been demonstrated to be safe and is associated with high local control rates in mRCC. In this prospective phase II single arm trial, we investigated SAbR to control oligoprogressive mRCC. Methods: Patients with mRCC who demonstrated response to systemic therapy with subsequent radiographic evidence of three or fewer sites of progression were treated with SAbR to all progressive sites. Systemic therapy was held during SAbR at the discretion of the treating oncologist. Follow-up included radiographic imaging at three-month intervals. Sequential SAbR for continued oligoprogression was allowed. The primary objective was extension of ongoing systemic therapy by >6 months in 40% of the patients. Progression was defined by any of these 3 criteria: (1) local failure at a radiated site; (2) progression ineligible for additional SAbR (>3 sites) or involving >30% of metastasis; or (3) progression as clinically determined by treating physicians. An exact binomial test was used to test the probability of postponing systemic therapy. Secondary endpoints focused on overall survival (OS), local control (LC) rates, toxicity, and health-related quality of life (QOL). Results: The trial completed accrual with enrollment of 20 patients who received SAbR to a total of 36 sites. At enrollment four, twelve, three, and one patients were on first, second, third, and fourth line of systemic therapy, respectively. Eleven were on immunotherapy and nine on a tyrosine-kinase inhibitor. Three patients required repeat SAbR to a new site for sequential disease control. At a median follow-up of 8.3 months (interquartile range 3.9 – 15.1), SAbR extended the duration of the ongoing systemic therapy by >6 months in 12 out of 17 patients (70.6%, 95% CI: 48.9%-92.3%). Thirteen out of 20 patients progressed with a median PFS of 8.7 months (95% CI: 3.2-12.4). Five patients died and the OS did not reach the median. LC was 36/36 (100%). Treatment related grade 1 and grade 2 toxicity was experienced by three and one patient, respectively; no grade 3 toxicities were reported. When compared to baseline, no significant decline in QOL was detected. Conclusions: SAbR extended PFS of ongoing systemic by >6 months in oligoprogressive patients with mRCC. SAbR was safe and did not adversely affect QOL. These data support further evaluation of SAbR for oligoproressive mRCC in a prospective randomized setting. Clinical trial information: NCT03696277.

Randomized phase II trial of the multi-kinase inhibitor sorafenib versus interferon (IFN) in treatment-naïve patients with metastatic renal cell carcinoma (mRCC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4501-4501 ◽  
Author(s):  
B. Escudier ◽  
C. Szczylik ◽  
T. Demkow ◽  
M. Staehler ◽  
F. Rolland ◽  
...  
Keyword(s):  
Phase Ii ◽  
Kinase Inhibitor ◽  
Phase Ii Trial ◽  
Prognostic Score ◽  
Primary Objective ◽  
Phase Iii ◽  
First Line ◽  
First Line Therapy ◽  
Randomized Phase Ii ◽  
Grade 3

4501 Background: Sorafenib, an oral multi-kinase inhibitor that targets tumor growth and vascularization, significantly prolonged PFS in a Phase III trial with previously treated mRCC patients. This randomized Phase II trial investigated the efficacy and tolerability of sorafenib compared with IFN in first-line therapy of patients with clear-cell RCC. Methods: Untreated patients with mRCC were stratified by MSKCC prognostic score and randomized to receive continuous oral sorafenib 400 mg bid or IFN 9 million units tiw, with an option of dose escalation (600 mg bid sorafenib) or crossover from IFN to sorafenib upon disease progression. The study assessed PFS at 99 events as primary objective, best response (RECIST), overall survival, health-related quality of life, and adverse events (AEs). Results: Baseline characteristics of 188 patients (sorafenib n=97; IFN n = 91) were: median age 62.0 years; MSKCC score: 57% low, 41% intermediate, 1% high; prior nephrectomy: 82%; ECOG 0:1, 55.3%:44.7%. As of January 6, 2006, PFS events have been reported for 64 (34%) patients. Preliminary data showed drug-related AEs of any severity (sorafenib vs IFN) in 50.5% vs 51.6% of patients (≥grade 3: 8.2% vs 11.0%), including diarrhea (24.7% vs 5.5%), fatigue (14.4% vs 20.9%), fever (2.1% vs 18.7%), hypertension (13.4% vs 0%), nausea (5.2% vs 13.2%), flu-like syndrome (1.0% vs 6.6%), hand-foot skin reaction (6.2% vs 0%), and rash/desquamation (4.1% vs 0%). Drug-related metabolic/laboratory abnormalities at grade 3 (no grade 4) comprised hypophosphatemia (21.7% vs. 0%), lipase elevation (5.6% vs. 11.1%), anemia (0% vs. 5.3%) and hypoalbuminemia (0% vs. 3.6%). Five patients receiving IFN withdrew from treatment due to AEs, whereas only one patient withdrew from sorafenib. Conclusions: Sorafenib was generally well tolerated in RCC patients in the first-line setting, with relatively infrequent drug-related AEs ≥grade 3. Full PFS data will be presented at the meeting. [Table: see text]

First-in-human dose-finding study of the ALK/EGFR inhibitor AP26113 in patients with advanced malignancies: Updated results.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8031-8031 ◽  
Author(s):  
D. Ross Camidge ◽  
Lyudmila Bazhenova ◽  
Ravi Salgia ◽  
Glen J. Weiss ◽  
Corey J. Langer ◽  
...  
Keyword(s):  
Phase Ii ◽  
Stable Disease ◽  
Kinase Inhibitor ◽  
Dose Finding ◽  
Anaplastic Lymphoma ◽  
Human Dose ◽  
Advanced Malignancies ◽  
Grade 3 ◽  
Egfr Tki

8031 Background: AP26113 is a novel tyrosine kinase inhibitor (TKI) that potently inhibits mutant activated forms of anaplastic lymphoma kinase (ALK+) and epidermal growth factor receptor (EGFRm), and TKI-resistant forms including L1196M (ALK) and T790M (EGFR). AP26113 does not inhibit native EGFR. Methods: The dose finding phase (3+3 design) of this phase I/II open-label, multicenter study is ongoing in pts with advanced malignancies (except leukemia) refractory to available therapies or for whom no standard treatment exists. Initial dosing is orally once daily. Results: As of 14 Jan 2013, 44 pts were enrolled: 30 mg n=3, 60 mg n=3, 90 mg n=8, 120 mg n=8, 180 mg n=11, 240 mg n=9, 300 mg n=2; 64% female, median age 60 yrs; diagnoses: non-small cell lung cancer (NSCLC, n=37), other (n=7). 26 pts discontinued: 18 disease progression, 6 adverse event (AE), 2 deaths (sudden death, hypoxia; both possibly related). Most common AEs: nausea (45%), fatigue (39%), diarrhea (27%); most common grade 3/4 treatment-related AE: diarrhea (5%). 2 dose limiting toxicities observed: grade 3 ALT increase, 240 mg; grade 4 dyspnea, 300 mg. Doses <300 mg are being explored further. 21 pts had ALK+ history (18 NSCLC, 3 other). Among 18 evaluable ALK+ pts, 10 responded. 15 ALK+ pts had 0 (n=3) or 1 (n=12) prior ALK TKI (crizotinib); of these, 2/3 and 8/12 pts (67%) responded, including 2 complete responses. The longest response is 40 wks (ongoing). 4 of 5 ALK+ pts with untreated or progressing CNS lesions at baseline and with follow-up scans had evidence of radiographic improvement in CNS, including 1 pt resistant to crizotinib and LDK378 (overall response = stable disease). 16 pts had EGFRm history (15 NSCLC, 1 SCLC); 14 pts had ≥1 prior EGFR TKI. Of 12 EGFRm pts with a follow-up scan, 1 pt (prior erlotinib) responded at 120 mg (duration 21 wks, ongoing), 6 pts had stable disease (2 ongoing, duration 7-31 wks). Conclusions: AP26113 has promising anti-tumor activity in ALK+ pts, with initial evidence of activity in EGFRm pts, and is generally well tolerated. Phase II will begin after the recommended phase II dose is determined, with 4 cohorts: crizotinib-naïve NSCLC; crizotinib-resistant NSCLC; EGFR TKI-resistant NSCLC; other tumors. NCT01449461. Clinical trial information: NCT01449461.

Phase II study of the FGFR inhibitor AZD4547 in previously treated patients with FGF pathway-activated stage IV squamous cell lung cancer (SqNSCLC): LUNG-MAP sub-study SWOG S1400D.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9055-9055 ◽  
Author(s):  
Charu Aggarwal ◽  
Mary Weber Redman ◽  
Primo Lara ◽  
Hossein Borghaei ◽  
Philip C. Hoffman ◽  
...  
Keyword(s):  
Phase Ii ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Grade 5 ◽  
Duration Of Response ◽  
Secondary Endpoints ◽  
Previously Treated Patients ◽  
Previously Treated ◽  
Grade 3

9055 Background: LungMAP is a National Clinical Trials Network umbrella trial for previously-treated SqNSCLC. S1400D is a phase II biomarker-driven therapeutic sub-study evaluating the FGFR inhibitor AZD4547 in patients (pts) with FGFR positive chemo-refractory SqNSCLC. Methods: Eligible pts had tumor FGFR alteration and/or mutation by next generation sequencing (Foundation Medicine), measurable disease, Zubrod PS 0-2, progression after 1 line of systemic therapy, and adequate end organ function. Receipt of prior immunotherapy was allowed. Eligible pts received AZD4547 80 mg bid orally. Primary endpoint was overall response rate (ORR) by RECIST; secondary endpoints included progression-free survival (PFS) and duration of response (DoR). Originally designed as a randomized trial of AZD4547 versus docetaxel, it was redesigned to be a single arm AZD4547 trial with the emergence of immunotherapy as standard 2ndline therapy. Forty pts were required to rule out an ORR of < = 15% if the true ORR was > 35% (90% power, alpha 0.05). Results: 93 pts (13% of pts screened on S1400) were assigned to S1400D; 43 were enrolled with 28 receiving AZD4547. Pt characteristics: median age 66.3 y (49-88), female (n = 8, 29%), & Caucasian (n = 25; 89%). Biomarker profile: FGFR1 amplification (n = 38; 86%); FGFR3 S249C (n = 4; 9%); FGFR3 amplification (n = 3; 7%); and FGFR3 fusion (n = 2; 5%). Nine pts (26%) had more than one biomarker alteration. The study was closed at interim analysis for futility in October 2016. Treatment related Grade 3 AEs were seen in 5 pts (dyspnea, fatigue, hyponatremia, lung infection & retinopathy); 1 pt had Grade 4 sepsis. There were no Grade 5 AEs. Median follow up among alive pts was 4.3 months (mos). Of 25 response evaluable pts, one with FGFR3 S249C had unconfirmed PR (4%, 95% CI 1-20%) with DoR of 1.5 mos. Median PFS was 2.7 mos (95% CI 1.4 - 4.3 mos). Conclusions: This is the first Phase II trial to evaluate AZD4547 as a targeted approach in pts with previously treated FGFR-altered SqNSCLC. AZD4547 had an acceptable safety profile but minimal activity in this biomarker-enriched cohort. Evaluation of other targeted agents in LUNG-MAP is currently ongoing. Clinical trial information: NCT02965378.

A phase II trial of cabozantinib and erlotinib for patients with EGFR and c-Met co-expressing metastatic pancreatic adenocarcinoma (PDAC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16764-e16764
Author(s):  
Anita Ahmed Turk ◽  
Amikar Sehdev ◽  
Safi Shahda ◽  
Bert O'Neil ◽  
Paul R. Helft ◽  
...  
Keyword(s):  
Phase Ii ◽  
Kinase Inhibitor ◽  
Phase Ii Study ◽  
Metastatic Pancreatic Adenocarcinoma ◽  
Prior Chemotherapy Regimen ◽  
40Mg Daily ◽  
Clinical Responses ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
Improvement In Survival

e16764 Background: Both EGFR and the c-MET receptors are overexpressed in a majority of PDACs. Inhibition of both receptors simultaneously may be required for anti-tumor activity. Erlotinib, an EGFR inhibitor, has modest activity in metastatic PDAC and is approved by the FDA in combination with gemcitabine. Cabozantinib is a tyrosine kinase inhibitor targeting AXL, FLT-3, KIT, MER, MET, RET, ROS1, TIE-2, TRKB, TYRO3, and VEGFR-1, -2, and -3. Preclinical data suggests that the addition of cabozantinib to erlotinib leads to tumor shrinkage and improvement in survival in a KPC PDAC mouse model compared to gemcitabine alone. This phase II study tests this hypothesis in patients with metastatic PDAC that co-express c-MET and EGFR. Methods: Key eligibility includes patients (pts) with metastatic PDAC with EGFR and c-MET overexpression (as determined by centrally tested IHC of 2+ or greater) that have progression on one prior chemotherapy regimen. Patients were treated with cabozantinib (40mg daily) and erlotinib (100mg daily) continuously. This dosing is based on previous combination data in NSCLC. This is a single arm two-stage phase II study with a primary endpoint of overall response rate. Secondary endpoints include of PFS, DCR and OS. Results: From October 2017 to October 2019, 43 pts were screened with 7 pts (median age 62 [range 51-76)] enrolled and treated on study. Pts had a median of 1 line of prior systemic chemotherapy. Most common reason for screen failure was due to lack of co-expression of c-MET and EGFR. EGFR IHC expression was +2 in 4 pts, +3 in 3 pts; c-MET IHC expression was +2 in 5 pts and +3 in 2 pts. Most common any-grade adverse events attributable to cabozantinib and erlotinib include: diarrhea (71%), AST increase (43%), fatigue (43%), nausea (43%), and rash (43%). Only one grade 3 event of fatigue occurred. All pts had clinical and/or radiographic progression within 1-2 months after initiating study therapy. Conclusions: The combination of cabozantinib and erlotinib was well tolerated with manageable toxicity. Due to lack of clinical responses, this study has been terminated due to futility. Clinical trial information: NCT03213626 .

Endoscopic Fundoplication

2017 ◽  
Vol 12 (3) ◽  
pp. 180-185 ◽  
Author(s):  
Michael I. Ebright ◽  
Praveen Sridhar ◽  
Virginia R. Litle ◽  
Chaitan K. Narsule ◽  
Benedict D. Daly ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Health Related Quality ◽  
Atypical Symptoms ◽  
Related Quality ◽  
Health Related ◽  
Quality Of Life Index ◽  
Grade 3 ◽  
Laparoscopic Techniques

Objective Transoral incisionless fundoplication (TIF) is a completely endoscopic approach to treat gastroesophageal reflux disease (GERD). We previously reported our initial results demonstrating safety and early effectiveness. We now present an updated experience describing outcomes with longer follow-up. Methods For a three-year period, TIF procedures were performed on 80 patients. Preoperative workup routinely consisted of contrast esophagram and manometry. PH testing was reserved for patients with either atypical symptoms or typical symptoms unresponsive to protonpump inhibitors (PPIs). Heartburn severity was longitudinally assessed using the GERD health-related quality of life index. Safety analysis was performed on all 80 patients, and an effectiveness analysis was performed on patients with at least 6-month follow-up. Results Mean procedure time was 75 minutes. There were seven (8.75%) grade 2 complications and one (1.25%) grade 3 complication (aspiration pneumonia). The median length of stay was 1 day (mean, 1.4). Forty-one patients had a minimum of 6-month of follow-up (mean, 24 months; range, 6–68 months). The mean satisfaction scores at follow-up improved significantly from baseline ( P < 0.001). Sixty-three percent of patients had completely stopped or reduced their PPI dose. Results were not impacted by impaired motility; however, the presence of a small hiatal hernia or a Hill grade 2/4 valve was associated with reduced GERD health-related quality of life scores postoperatively. Conclusions At a mean follow-up of 24 months, TIF is effective. Although symptoms and satisfaction improved significantly, many patients continued to take PPIs. Future studies should focus on longer-term durability and comparisons with laparoscopic techniques.

QOLP-04. THE KETOGENIC DIET PLUS STANDARD CARE FOR RECENTLY DIAGNOSED GLIOBLASTOMA: A PHASE 1 SAFETY AND FEASIBILITY TRIAL

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi183-vi183
Author(s):  
Jethro Hu ◽  
L J Amaral ◽  
Gillian Gresham ◽  
Thomas Nelson ◽  
Amelia Welborn ◽  
...  
Keyword(s):  
Ketogenic Diet ◽  
Phase 1 ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Primary Objective ◽  
Feasibility Trial ◽  
Phase 2 Trial ◽  
Related Quality ◽  
Health Related ◽  
Grade 3

Abstract INTRODUCTION There is abundant interest in the potential therapeutic and supportive role of a ketogenic diet (KD) for glioblastoma patients. We conducted a single-arm phase 1 trial to assess the safety and feasibility of KD plus standard-of-care (SOC) in glioblastoma patients (NCT03451799). METHODS Adults within 3 months of diagnosis participated in a 16-week intervention of a classic 3:1 KD (grams fat : grams carbohydrate + protein) with dietitian support. Blood glucose and ketone levels were assessed twice daily (Keto-Mojo), with remote monitoring of daily weight and activity (Fitbit). The primary objective was to assess safety (weight stability, CTCAE) and feasibility (maintaining ketosis &gt; 0.3mM for &gt; 50% of study period). Secondary objectives included assessments of progression-free survival (PFS), overall survival (OS), health-related quality of life (HRQOL), and cognition (MoCA). RESULTS From 04/2018-02/2021, 14 patients were evaluable: female:male, 8:6, median age 55 years, KPS 80, BMI 24.5. MGMT promoter methylation: 6 present, 7 absent, 1 indeterminate. Adherence to KD was high, with all patients maintaining ketosis ( &gt; 0.3mM) &gt; 50% and 11 patients maintaining ketosis &gt; 85% of study days. Adverse events (&gt; Grade 2) potentially attributable to KD: appetite loss (Grade 2: 2); fatigue (Grade 2: 5); flu-like symptoms (Grade 2: 1); constipation (Grade 2: 5, Grade 3: 1). No patients were removed from study for safety reasons. HRQOL was stable, with improvements in role function (not statistically significant). MoCA score improved in 10/14 patients. Median PFS and OS from KD initiation were 11.7 and 29.1 months, respectively. CONCLUSION Our findings suggest that a supervised KD plus SOC is safe and feasible in glioblastoma patients. KD was well-tolerated with encouraging trends in HRQOL and cognition. PFS and OS in this small trial compare favorably to historical control. A multicenter phase 2 trial powered to assess efficacy is planned.

CheckMate 067: 6.5-year outcomes in patients (pts) with advanced melanoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9506-9506
Author(s):  
Jedd D. Wolchok ◽  
Vanna Chiarion-Sileni ◽  
Rene Gonzalez ◽  
Jean-Jacques Grob ◽  
Piotr Rutkowski ◽  
...  
Keyword(s):  
Systemic Therapy ◽  
Objective Response ◽  
Progression Free Survival ◽  
Additional Treatment ◽  
Advanced Melanoma ◽  
Phase 3 ◽  
Primary Endpoints ◽  
Secondary Endpoints ◽  
Grade 3

9506 Background: In the phase 3 CheckMate 067 trial, a durable and sustained clinical benefit was achieved with nivolumab (NIVO) + ipilimumab (IPI) and NIVO alone vs IPI at 5-y of follow-up (overall survival [OS] and progression-free survival [PFS] rates: 52%, 44%, 26% and 36%, 29%, 8%, respectively). Here we report 6.5-y efficacy and safety outcomes. Methods: Eligible pts with previously untreated unresectable stage III or IV melanoma were randomly assigned in a 1:1:1 ratio and stratified by PD-L1 status, BRAF mutation status, and metastasis stage. Pts received NIVO 1 mg/kg + IPI 3 mg/kg for 4 doses Q3W followed by NIVO 3 mg/kg Q2W (n = 314), NIVO 3 mg/kg Q2W + placebo (n = 316), or IPI 3 mg/kg Q3W for 4 doses + placebo (n = 315) until progression or unacceptable toxicity. Co-primary endpoints were PFS and OS with NIVO + IPI or NIVO vs IPI. Secondary endpoints included objective response rate (ORR), descriptive efficacy assessments of NIVO + IPI vs NIVO alone, and safety. Results: With a minimum follow-up of 6.5 y, median OS was 72.1 mo with NIVO + IPI, 36.9 mo with NIVO, and 19.9 mo with IPI (table). Median time from randomization to subsequent systemic therapy was not reached (NR; 95% CI, 59.6–NR) with NIVO + IPI, 25.2 mo (95% CI, 16.0–43.2) with NIVO, and 8.0 mo (95% CI, 6.5–8.7) with IPI; 36%, 49%, and 66% of pts, respectively, received any subsequent systemic therapy. Median treatment-free interval (which excluded pts who discontinued follow-up prior to initiation of subsequent systemic therapy) was 27.6 mo (range, 0–83.0), 2.3 mo (range, 0.2–81.6), and 1.9 mo (range, 0.1–81.9) with NIVO + IPI, NIVO, and IPI, respectively. Of the pts alive and in follow-up, 112/138 (81%; NIVO + IPI), 84/114 (74%; NIVO), and 27/63 (43%; IPI) were off treatment and never received subsequent systemic therapy; 7, 8, and 0 pts, respectively, were still on treatment. Grade 3/4 treatment-related adverse events were reported in 59% of NIVO + IPI-treated pts, 24% of NIVO-treated pts, and 28% of IPI-treated pts. Since the 5-y analysis, no new safety signals were observed and no additional treatment-related deaths occurred. Conclusions: This 6.5-y analysis represents the longest follow-up from a phase 3 melanoma trial in the modern checkpoint inhibitor combination therapy and targeted therapy era. The results show durable improved outcomes with NIVO + IPI and NIVO vs IPI in pts with advanced melanoma. We observed improvement in OS, PFS, and ORR with NIVO + IPI over NIVO alone. Clinical trial information: NCT01844505. [Table: see text]

scholarly journals Report of a Multicenter Phase II Trial Testing a Combination of Biweekly Bevacizumab and Daily Erlotinib in Patients With Unresectable Biliary Cancer: A Phase II Consortium Study

2010 ◽  
Vol 28 (21) ◽  
pp. 3491-3497 ◽  
Author(s):  
Sam J. Lubner ◽  
Michelle R. Mahoney ◽  
Jill L. Kolesar ◽  
Noelle K. LoConte ◽  
George P. Kim ◽  
...  
Keyword(s):  
Growth Factor ◽  
Phase Ii ◽  
Kinase Inhibitor ◽  
Evaluation Criteria ◽  
Growth Factor Receptor ◽  
Primary Objective ◽  
Clinical Activity ◽  
Biliary Cancer ◽  
Vegf Inhibitor ◽  
Grade 3

Purpose Biliary cancers overexpress epidermal growth factor receptor (EGFR), and angiogenesis has been correlated with poor outcome. Erlotinib, an EGFR tyrosine kinase inhibitor, and bevacizumab, a vascular endothelial growth factor (VEGF) inhibitor have each been shown to have activity in biliary cancer. The primary objective of this study was to evaluate the response rate by Response Evaluation Criteria in Solid Tumors (RECIST). Secondary end points included overall survival (OS), time to progression (TTP), VEGF levels, and molecular studies of EGFR and k-ras. Patients and Methods Eligible patients had advanced cholangiocarcinoma or gallbladder cancer. Patients were treated with bevacizumab 5 mg/kg intravenously on days 1 and 15 and erlotinib 150 mg by mouth daily on days 1 through 28. Responses were evaluated by RECIST. VEGF levels were collected, and samples were analyzed for EGFR mutation by polymerase chain reaction. Results Fifty-three eligible patients were enrolled at eight sites. Of 49 evaluable patients, six (12%; 95% CI, 6% to 27%) had a confirmed partial response. Stable disease was documented in another 25 patients (51%). Rash was the most common grade 3 toxicity. Four patients had grade 4 toxicities. Median OS was 9.9 months, and TTP was 4.4 months. Low repeats (< 16) in EGFR intron 1 polymorphism and G>G k-ras Q38 genotype (wild type) were associated with improved outcomes. Conclusion Combination chemotherapy with bevacizumab and erlotinib showed clinical activity with infrequent grade 3 and 4 adverse effects in patients with advanced biliary cancers. On the basis of preliminary molecular analysis, presence of a k-ras mutation may alter erlotinib efficacy. The combination of bevacizumab and erlotinib may be a therapeutic alternative in patients with advanced biliary cancer.

Phase II study of neoadjuvant chemotherapy (NAC) with S-1 and cisplatin (CDDP) for patients (pts) with metastatic or locally unserectable gastric cancer (MGC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4078-4078
Author(s):  
A. Nashimoto ◽  
H. Yabusaki ◽  
S. Nakagawa
Keyword(s):  
Overall Survival ◽  
Phase Ii ◽  
Distal Gastrectomy ◽  
Phase Ii Study ◽  
Performance Status ◽  
Tumor Location ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
Univariate Analyses

4078 Background: To improve the poor prognosis of pts with MGC, we conducted a phase II study to evaluate the feasibility and efficacy of intensive NAC to enhance surgical respectability and survival. Methods: Eligible criteria included histologically proven metastatic or locally unserectable gastric adenocarcinoma and measurable or evaluable disease, PS 0–2 and sufficient organ functions. The primary endpoint was overall survival and the secondary endpoints were overall resonse rate (ORR) and toxicities. Since Oct. 2000, chemotherapy-naïve 120 pts with MGC have received S-1 (80 mg/m2 orally intake for 21 consecutive days) and CDDP (50 mg/m2 intravenous drip infusion on day 8) as NAC. Treatment was repeated every 5 weeks. The median administered courses were three (range: 1–7), and median follow up periods were 13.8 months. Results: The proportion of the duration as an outpatient- therapy was 86%. 77.5% of pts (93/120) went to surgical resection; 36 had distal gastrectomy and 57 had total gastrectomy. ORR was 62.5% (CR 1, PR 74), and 61.7%, 75.7%, 28.6% and 23.8% for primary lesion, metastatic lymph nodes, liver metastases and peritoneal metastasis, respectively. Toxicity (grade 3/4): neutropenia 7.5%, thrombocytopenia 6.7%, anemia 6.7%, anorexia 5.8%, nausea 2.5%; no treatment related death. Survival: median 23 months; 1 year 79%; 4 year 31% in all pts, and 42 months; 83%; 38% in pts with gastrectomy, respectively. In univariate analyses, overall survival (OS) was predicted by the responder, limited tumor location, H0, P0, but not by age, sex, histological type, gross type, T-factor, N-factor, or performance status. In multivariate analyses, H0, P0 and responder independently predicted OS. In pts with gastrectomy, H0, curative resection, PS0 and responder predicted OS. Conclusions: NAC with S-1 and CDDP was feasible and useful for pts with MGC and resulted in a promising survival rate. No significant financial relationships to disclose.

Phase II trial of sorafenib in esophageal (E) and gastroesophageal junction (GEJ) cancer: Response and prolonged stable disease observed in adenocarcinoma.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 91-91
Author(s):  
Geoffrey Y. Ku ◽  
Yelena Yuriy Janjigian ◽  
Manish A. Shah ◽  
Jessica Herrera ◽  
Laura H. Tang ◽  
...  
Keyword(s):  
Phase Ii ◽  
Stable Disease ◽  
Kinase Inhibitor ◽  
Phase Ii Trial ◽  
Gastroesophageal Junction ◽  
Single Agent ◽  
Progression Free Survival ◽  
Complete Response ◽  
Secondary Endpoints ◽  
Grade 3

91 Background: Sorafenib is a tyrosine kinase inhibitor targeting VEGFr, PDGFr, Raf and other pathways. Encouraging response and survival were observed in a phase II trial of sorafenib with chemotherapy in GE cancer (J Clin Oncol 27:2947;2010). We performed a phase II trial of single-agent sorafenib with the primary endpoint of progression-free survival (PFS). Secondary endpoints include response and toxicity. Methods: Patients (Pts) with measurable metastatic E and GEJ cancer with ≤3 prior chemotherapy regimens were treated with sorafenib 400 mg BID. CT scans were performed monthly for the first 2 months, then every 2 months. Results: Thirty-five patients have been accrued, with 34 evaluable; median age 62, 31 male, 4 female, median KPS 80%, E 25, GEJ 10, adenocarcinoma (AC) 30 squamous 5, median no. of prior therapies 2. Of 31 response-evaluable Pts, 1 (3%) ongoing complete response was noted (34+ months) in a Pt with E AC with biopsy-proven lymph node recurrence after chemoradiation and surgery; 23 Pts (74%) had stable disease. Median PFS is 3.7 months (95% CI 1.9 to 4 months), with median overall survival 8.9 months (95% CI 6.9 to 11.6 months). Four patients remain on treatment. Significant grade 3 toxicities included hand foot reaction (3 Pts), rash (1 Pt), dehydration (3 Pts) and fatigue (2 Pts). Twenty-seven of 33 tumors (82%) tested positive for phospho-ERK by immunohistochemistry. Conclusions: Encouraging activity in terms of PFS has been noted in this heavily pre-treated population. Updated data will be presented. Supported by a grant from Bayer. Clinical trial information: NCT00917462.

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