Preoperative chemoradiotherapy in non-small cell lung cancer (NSCLC) patients with operable stage IIIB disease. A phase II trial of the Swiss Group for Clinical Cancer Research (SAKK)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18021-18021 ◽  
Author(s):  
M. Pless ◽  
R. Stupp ◽  
R. Kann ◽  
A. Zouhair ◽  
M. Mayer ◽  
...  
Keyword(s):  
Phase Ii ◽  
Primary Endpoint ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Objective Response ◽  
Locally Advanced ◽  
Stage Iiib ◽  
R0 Resection ◽  
Clinical Cancer Research ◽  
Concomitant Boost

18021 Background and Methods: Outcome of patients (pts) with locally advanced NSCLC treated with radio- or chemoradiotherapy is poor. This two-stage phase II trial (planned sample size 46) aimed at evaluating feasibility and outcome of a tri-modality concept of neoadjuvant chemotherapy (CT), radiotherapy (RT) followed by definitive surgery in operable, stage IIIB NSCLC pts. Treatment consisted of 3 cycles of cisplatin (100 mg/m2) and docetaxel (85 mg/m2) followed by accelerated, concomitant boost RT (44 Gy/22 fx) and surgery. Primary endpoint is event-free survival at 1 year. Operable pts up to age 75 and a performance status of 0–1 with stage IIIB NSCLC (pleural effusion excluded) were eligible. Results: Forty-five eligible pts (46 accrued) with a median age was 60 years (range 28–70) were treated between September 2001 and May 2006. Tumor location was right-sided in 28 pts and left-sided in 17 pts. Histology was squamous cell 42%, large cell 11%, adeno-13% and undifferentiated carcinoma 33%. N3-disease was present in 29%, T4 stage in 78%. CT (45 pts) and RT (34 pts) were delivered as prescribed in >80% of cycles. The median time from enrollment to surgery was 3.7 months (2.8 - 5.2). The objective response rate after CT was 53% (95% c.i. 38–68%), after additional RT 67% (51–80%). Surgery (pneumonectomy in 17) was performed in 31 pts (69%), with an R0 resection in 24 pts. Median duration of hospitalization was 12 days (8–134). Two pts died in the perioperative phase due to ARDS and a cerebro-vascular event, respectively. Mature results of the primary endpoint and overall survival will be available at the ASCO meeting. Conclusions: Combined multimodality treatment strategy is feasible in a subgroup of patients, with acceptable toxicity. About two thirds of patients responded to the induction therapy, and were able to undergo subsequent surgery. 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]

Triple induction chemotherapy and chemoradiotherapy in locally advanced esophageal cancer: Final results of a multicenter phase II trial

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4568-4568
Author(s):  
W. M. Eisterer ◽  
A. De Vries ◽  
B. Spechtenhauser ◽  
D. Kendler ◽  
A. Königsrainer ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
R0 Resection ◽  
Ecog Performance Status ◽  
Blurred Vision ◽  
Hyperfractionated Radiotherapy

4568 Background: Surgery is the standard treatment for patients with resectable esophageal carcinoma, but 5-year survival rates rarely exceed 20%. Neoadjuvant chemoradiotherapy (CRT) may lead to downstaging of the tumor and thus improve the possibility of complete oncologic resection. Docetaxel (Dx) showed considerable activity in combination with hyperfractionated radiotherapy and only moderate toxicity. We evaluated a triple neoadjuvant regime including Dx in patients with locally advanced esophageal adenocarcinoma (AC) or squamos cell carcinoma (SCC). Methods: 24 patients (pts) with AC (n=8) or SCC (n=16) medically fit, no prior therapy, ECOG-performance status = 2 were included. Pts received 2 cycles of cisplatin (Cis) 15mg/ms2 d1–5, 5-fluorouracil (5-FU) 750mg/m2 continuous infusion (CI) d1–5, and Dx 75mg/m2 d1 repeated every 29 days followed by radiotherapy (RT) 39.6 Gy total dose (daily fraction 1.8Gy) concomitant to Dx 15mg/m2 on days 1, 8, 15, 22 and 5-FU 300mg/m2 CI on the days of RT followed by resection or definitive RT up to 59.6 Gy in case of inoperability. Results: See table . Grade 3/4 toxicity (n/%): neutropenia 10/43%, diarrhea 4/18%, alopecia 2/9%; deep vein thrombosis 1/5%, blurred vision 1/5%, fever 1/5%, pulmonary embolus 1/5%, arterial hypertension 1/5%. 1 pt died 39 days post resection due to fatal anastomical bleeding. 6/16 operated pts (37%) showed morbidity (anastomical stenosis/insufficiency, fistula, nervus recurrens palsy). 4/22 pts (18%) died 7- 25 months after therapy due to metastatic disease. At a median follow-up of 12 months 18 pts (82%) are alive, median survival has not been reached yet. Conclusions: Triple induction CT and CRT with Dx, Cis, and 5-FU is safe, feasible, and effective with CPR in 31%, downstaging in 81% and R0-resection in 100% of pts. Main toxicities are neutropenia (43%) and postoperative morbidity (37%). A follow-up phase II trial of triple induction therapy in combination with an EGFR-directed antibody is planned. [Table: see text] No significant financial relationships to disclose.

Phase II study of perioperative chemotherapy with cisplatin (C) and pemetrexed (P) in non-small cell lung cancer (NSCLC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e17535-e17535
Author(s):  
Aamer Farooq ◽  
Grace K. Dy ◽  
Todd L. Demmy ◽  
Paul Bogner ◽  
Cynthia Nowadly ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Clinical Stage ◽  
Performance Status ◽  
Bronchopleural Fistula ◽  
Objective Response ◽  
Disease Free Survival ◽  
R0 Resection ◽  
Ecog Performance Status ◽  
N2 Disease

e17535 Background: Pathological complete response (pCR) with neoadjuvant chemotherapy is associated with improved survival in many solid tumors. We evaluated efficacy and tolerability of neoadjuvant plus adjuvant C+P in this phase II trial. Methods: We recruited patients (pts) with clinical stage IB-IIIA (TNM 7th ed) NSCLC, ECOG performance status (PS) 0-1 in this single-arm phase II trial using two-stage design with 90% power to detect pCR rate of >10% (vs null hypothesis of <2%). Pre-treatment mediastinal biopsy was required. Protocol was amended in 2009 to exclude squamous histology. Pts received 3 cycles of C 75mg/m2 + P 500mg/m2 (day 1 every 21 days) followed by surgical resection. Two cycles were delivered adjuvantly within 60-80 days after surgery. The primary end point was pCR. Secondary endpoints were objective response rate (ORR), overall survival (OS), disease-free survival (DFS), and adverse events (AEs). Results: 38 pts were enrolled with median age of 62 yrs, 19 males: 19 females. 74% (N=28) had ECOG PS 0. Preoperatively, 26% (N=10) had squamous histology, 29% (N=11) had biopsy-proven N2 involvement. Median of 4 cycles were administered. ORR was 29% (11 pts with PR). 4 pts did not undergo surgery (3 had disease progression; one became hypoxic during intubation in the OR). Resection status was R2 in 9% (3 of 34 pts), remaining pts had R0 resection. 6 pts had documented N2 clearance; median DFS (mDFS) and OS (mOS) of these pts have not reached (NR) vs 15 and 24 months respectively, in pts with persistent N2 disease. CTC grade 3+ nonhematologic AEs (<10%) include arterial thrombosis, bronchopleural fistula, empyema, hyperglycemia, fatigue and tinnitus. There was no pCR seen and thus accrual to 2nd stage was not pursued. There was no correlation between DFS or OS with ORR or pre-operative stage. There was statistically signification association between DFS with histology (favoring squamous, p=0.03) and post-op stage (p=0.024). The table shows mDFS and mOS in months according to pre-op stage. Conclusions: While the primary endpoint was not met, this regimen is active and well-tolerated perioperatively in NSCLC pts. [Table: see text]

Activity of cabazitaxel in patients with metastatic or inoperable locally advanced dedifferentiated liposarcoma: European Organization for Research and Treatment of Cancer (EORTC) Phase II trial 1202.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 11556-11556
Author(s):  
Roberta Sanfilippo ◽  
Richard L Hayward ◽  
Jammbe Musoro ◽  
Charlotte Benson ◽  
Michael Gordon Leahy ◽  
...  
Keyword(s):  
Phase Ii ◽  
Primary Endpoint ◽  
Phase Ii Trial ◽  
Objective Response ◽  
Locally Advanced ◽  
Soft Tissue Sarcomas ◽  
Phase Iii ◽  
European Organization ◽  
Drug Clinical Trial ◽  
Stage 1

11556 Background: The optimal treatment for patients with advanced dedifferentiated (DD) liposarcoma (LPS) remains uncertain. Single agents which are most effective include doxorubicin and ifosfamide but, as with soft tissue sarcomas (STS) in general, objective response rates (ORR) and progression free survival (PFS) are very modest. Cabazitaxel exerts its effect through inhibition of microtubular disassembly and has been shown to be relatively safe, effective and well-tolerated. EORTC 1202 assessed whether cabazitaxel demonstrated sufficient antitumor activity in patients with metastatic or inoperable locally advanced DD LPS to justify further investigation in a phase III setting. Methods: This was an international multi-center, open label single arm phase II trial. Eligible patients with metastatic or inoperable locally advanced DD LPS were treated with cabazitaxel 25mg/m² IV infusion over 1 hour every 21 days. Primary endpoint was PFS rate at 12 weeks assessed by local investigator per RECIST 1.1. Based on a Simon two-stage design, at least 4 out of 17 (Stage 1) and 11 out of 37 (Stage 2) eligible and evaluable patients who are progression-free at 12 weeks were needed. Results: Forty patients were registered by 10 institutions in 4 countries between March 2015 and March 2019, with 2 patients being ineligible. Among the 38 eligible patients who started treatment, 3 (7.5 %) were still on treatment at the time of analysis. The number of cycles ranged from 1 to 30, with a median of 5; 26 patients (65%) received at least 4 cycles of cabazitaxel. Among the first 17 (Stage 1) and 37 (Stage 2), 11 and 20 patients were progression-free at 12 weeks respectively, satisfying the study decision rules. The PFS rate at 12 weeks for all 38 eligible patients was 52.6% (conditional 1-sided 95 % CI 38.3 – 100). Two patients (5.3%) achieved a confirmed partial response (PR) and 23 stable disease (SD) (60.5%). Disease control (PR+SD) was achieved in 25 patients (65.8%). Median PFS was 7.4 months (95%CI 2.8-10.3). The most common cabazitaxel -related grade >3 adverse events in all 40 registered patients were neutropenia (60%), febrile neutropenia (25%), fatigue (12.5%), and anemia (10%). There were no cabazitaxel-related deaths. Conclusions: EORTC 1202 met its primary endpoint, with 20/37 pts (54%) being progression-free at 12 weeks. Results of this trial confirm activity of cabazitaxel in patients with metastatic or inoperable locally advanced DD LPS and warrant further exploration of the drug. Clinical trial information: NCT01913652 .

Phase II Trial of Chronomodulated Infusion of High-Dose Fluorouracil and l-Folinic Acid in Previously Untreated Patients With Metastatic Colorectal Cancer

2002 ◽  
Vol 20 (5) ◽  
pp. 1175-1181 ◽  
Author(s):  
H. Curé ◽  
V. Chevalier ◽  
A. Adenis ◽  
N. Tubiana-Mathieu ◽  
G. Niezgodzki ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Folinic Acid ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Objective Response ◽  
World Health ◽  
Fixed Dose ◽  
High Dose

PURPOSE: To study tolerability and efficacy of an intensified chronomodulated schedule of fluorouracil (5-FU) and l-folinic acid (l-FA) as first-line treatment of metastatic colorectal cancer, 5-FU was given near individually determined dose-limiting toxicity in a multicenter phase II trial. PATIENTS AND METHODS: One hundred patients (68 men and 32 women, median age 62 years, World Health Organization performance status ≤ 2) with previously untreated and inoperable metastases received chronomodulated daily infusion of 5-FU/l-FA (from 10:00 pm to 10:00 am with peak at 4:00 am). 5-FU dose was escalated from 900 to 1,100 mg/m2/d with fixed dose of l-FA at 150 mg/m2/d for 4 days every 14 days. RESULTS: 5-FU dose escalation was achieved in 66% of the patients. Grade 3 to 4 toxicities mainly consisted of nausea or vomiting (14% of patients and 1.5% of courses), hand-foot syndrome (38% of patients and 8% of courses), mucositis (26% of patients and 4% of courses), and diarrhea (21% of patients and 2.3% of courses). Objective response rate (ORR) was 41% (95% confidence interval, 31.5% to 50.5%). Twenty patients underwent metastases surgery; among these, 12 had a complete resection. Median progression-free survival was 7 months. Median survival was 17 months; 28% of the patients were alive at 2 years and 18.6% at 3 years. CONCLUSION: The ORR achieved with intensified chronomodulated delivery of 5-FU/l-FA was nearly twice as high as that earlier obtained by our cooperative group using less intensive 5-FU/FA chronotherapy.

A phase II trial of irinotecan, 5-fluorouracil and leucovorin in patients with previously untreated advanced colorectal cancer (CRC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14599-14599
Author(s):  
N. Lee ◽  
S. Bae ◽  
S. Lee ◽  
D. Kim ◽  
K. Kim ◽  
...  
Keyword(s):  
Continuous Infusion ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Objective Response ◽  
Tumor Control ◽  
Ecog Performance Status ◽  
Grade 3 ◽  
Ecog Ps

14599 Background: We prospectively conducted a phase II trial to test the efficacy and safety of irinotecan, 5-fluorouracil and leucovorin (FOLFIRI) regimens for the first-line treatment of previously untreated patients with recurrent or metastatic advanced CRC. Methods: Thirty-four previously untreated patients with advanced CRC were enrolled in this study from June 2001 to December 2006. Eligible patients had histologically confirmed adenocarcinoma, no prior systemic therapy in palliative setting, ECOG PS = 2, adequate organ function, written informed consent and at least one measurable disease. The patients received either irinotecan 180 mg/m2 on day 1 with a LV bolus of 200 mg/m2 and a FU bolus of 400 mg/m2, and this was followed by a FU continuous infusion of 600 mg/m2 on day 1 and day 2 (the classic FOLFIRI regimen), or they were treated with a LV bolus of 400 mg/m2 and a FU bolus of 400 mg/m2 followed by a FU continuous infusion of 2,400 mg/m2 for 46 hours (the simplified FOLFIRI regimen), and these treatments were repeated every 2 weeks until disease progression. Results: There were 13 females and 21 males with median age of 54 years (range: 41–79). The most common metastatic sites were lung and liver. A total of 262 cycles were administrated with median 6 cycles per patient (range: 1–22). All pts were evaluable for toxicity, and 30 pts for response to the treatment. The objective response rate was 26.4% with 2 complete responses respectively. Sixteen (47%) pts had stable disease and 7 (20.5%) had a progression. The tumor control rate was 73.4%. The median TTP was 5.3 months, and the overall survival was 10.1 months. The prognostic factor for longer TTP and survival was the ECOG performance status (PS). The type of regimens was not affected on response rate, TTP and survival. The chemotherapy was generally well tolerated and the most common grade 3–4 toxicities were neutropenia, diarrhea. The non- hematological toxicities were similar for both treatment groups, with more frequent grade =3 neutropenia being noted for the simplified FOLFIRI regimen. Conclusions: The FOLFIRI regimen was demonstrated to have a moderate antitumor activity with acceptable toxicity profiles, and tend to show more favorable outcome for patients with good ECOG PS. No significant financial relationships to disclose.

A randomized phase II trial of weekly docetaxel plus either cisplatin or oxaliplatin in patients with previously untreated advanced gastric cancer: Preliminary results

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4566-4566
Author(s):  
S. Sym ◽  
S. Park ◽  
J. Park ◽  
K. Kwon ◽  
I. Jung ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Objective Response ◽  
Progression Free Survival ◽  
Tolerability Profile ◽  
Preliminary Results ◽  
Weekly Docetaxel ◽  
Randomized Phase Ii ◽  
Significant Difference

4566 Background: Docetaxel, in combination with cisplatin or oxaliplatin, has demonstrated efficacy against AGC. This randomized phase II trial evaluated two weekly docetaxel-based regimens to see which would be most promising according to objective response rate (ORR) as first-line therapy in AGC. Methods: Chemotherapy-naïve patients with measurable unresectable and/or metastatic gastric adenocarcinoma and a performance status ≤2 were randomly assigned to receive docetaxel (35 mg/m2) weekly on days 1 and 8 of a 21-day cycle plus either cisplatin (60 mg/m2 on day 1) (arm A) or oxaliplatin (120 mg/m2 on day 1) (arm B). Toxicity was assessed on days 1, 8, and 21 of each cycle, and response was evaluated every 2 cycles. Results: Between March 2007 and December 2008, 61 eligible patients entered. In Arm A, 29 patients were evaluable for objective response and 31 for safety. In Arm B, 28 patients were evaluable for objective response and 30 for safety. Median age was 52 years and disease status was comparable for both arms. Ten of 29 (34.5%) patients had a confirmed objective response in the arm A (95% confidence interval [CI] 17.1–51.8%) and 11 of 28 (39.2%) patients had a confirmed objective response in the arm B (95% CI 21.1- 57.2%). No significant difference was noted between the arms both for ORR (p=0.202) or for disease control (58.6% and 82.1%, respectively, p=0.082). Median progression free survival time was 4.4 month in the arm A and 4.3 months in the arm B (Hazard ratio = 0.936; 95% CI, 0.503–1.744; p = 0.836). There was no relevant difference in the occurrence of overall grade ¾ toxicity between the two arms (51.6% vs. 46.6%, respectively; p=0.800). Neutropenia was the most common grade 3/4 toxicity (32.3% vs. 36.6%, respectively). There was one treatment related death in Arm B. Conclusions: The preliminary results showed that both treatment arms have similar clinical efficacy as front-line treatment in AGC. Each regimen has a manageable tolerability profile. The accrual is ongoing. No significant financial relationships to disclose.

Survival analysis of induction cisplatin (CDDP)-docetaxel (DOC)-bevacizumab (BEV) chemotherapy followed by maintenance BEV-pemetrexed (PEM) therapy in advanced nonsquamous non-small cell lung cancer (NonSq NSCLC): A phase II trial from Okayama Lung Cancer Study Group 0903.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e19040-e19040
Author(s):  
Naoyuki Nogami ◽  
Katsuyuki Hotta ◽  
Toshiyuki Kozuki ◽  
Hiroshige Yoshioka ◽  
Akihiro Nishiyama ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Maintenance Therapy ◽  
Phase Ii ◽  
Primary Endpoint ◽  
Phase Ii Trial ◽  
Objective Response ◽  
Stage Iv ◽  
Induction Phase ◽  
Lung Cancer Study Group ◽  
Platinum Based Chemotherapy

e19040 Background: BEV maintenance therapy and PEM maintenance therapy in platinum-based chemotherapy yield a significant survival advantage in CALGB and PARAMUNT trials, respectively, but each agent gave only modest impact on survival. We conducted a phase II trial of CDDP-DOC-BEV therapy followed by maintenance BEV-PEM therapy inchemo-naïve advanced NonSq NSCLC. Methods: Forty-one patients (pts) participated in the induction phase, specified as four cycles of induction CDDP (80 mg/m2), DOC (60 mg/m2) and BEV (15 mg/kg) on day 1 of a 21-day cycle. Pts who had not progressed during CDDP-DOC-BEV received maintenance BEV (15 mg/kg) and PEM (500 mg/m2) on day 1 of a 21-day cycle until disease progression. The primary endpoint was PFS, and the secondary endpoints included OS, toxicity, and response. Survival time was calculated from the date of registration. Results: Pt characteristics were as follows: median age: 62 yrs; 76% male; 32% PS 0; 73% stage IV; 93% Ad; 5% EGFR-mutant and 2% ALK-mutant. At the time of this analysis, 34 pts (83%) discontinued the treatment, mainly due to progressive disease (53%). The principal toxicity was myelosuppression (gr. 4 hematological: 21 pts [51%]), and grs. 3/4 febrile neutropenia was observed in 10 (24%) despite no treatment-related deaths. The objective response rate and disease control rate (DCR, % pts with CR/PR/SD) was 82.9% and 97.6%, respectively. Median follow-up time was 15.6 months, and 1-yr PFS rate was 34.2% with 95% confidence interval (CI) of 20.3-48.5%, which met the primary endpoint. Also, 1-yr OS rate was 75.6% (95%CI: 59.4-86.1%). Exploratory analysis for pts with both EGFR- and ALK-wild-typed NonSq NSCLC (n = 16) demonstrated 1-yr PFS and OS rates of 50.0% (24.5-71.1%) and 87.5% (58.6-96.7%), respectively. Also, pts with maintenance therapy (n = 34) had 1-yr PFS and OS rates of 41.2% (24.8-56.9%) and 82.4% (64.9-91.7%), respectively. Conclusions: CDDP-DOC-BEV followed by BEV-PEM maintenance seems highly effective despite moderately toxic profiles in chemo-naïve pts with advanced NonSq NSCLC. Clinical trial information: UMIN000004127.

Phase II trial of the c-Met inhibitor tepotinib in advanced lung adenocarcinoma with MET exon 14 skipping mutations.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20541-e20541
Author(s):  
Paul K. Paik ◽  
Enriqueta Felip ◽  
Remi Veillon ◽  
Jürgen Scheele ◽  
Rolf Bruns
Keyword(s):  
Lung Adenocarcinoma ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Objective Response ◽  
Elevated Serum ◽  
Stage Iiib ◽  
Met Inhibitor ◽  
Grade 3 ◽  
Lung Adenocarcinomas ◽  
Platinum Doublet

e20541 Background: Approximately 3-4% of lung adenocarcinomas express a truncated form of c-Met (c-Metex14) due to mutation-induced exon 14 skipping. c-Metex14 accumulates on the cell surface and is constitutively active with the ability to drive NSCLC. Data suggest that lung adenocarcinomas harboring c-METex14 are sensitive to c-Met kinase inhibitors. The highly selective c-Met inhibitor tepotinib is well tolerated and active at an oral dose of 500 mg QD. This single-arm phase II trial (NCT02864992) is investigating the efficacy and safety of tepotinib in patients (pts) with advanced lung adenocarcinoma harboring METex14. Methods: Adults with stage IIIB/IV lung adenocarcinoma who have failed 1 or 2 lines of systemic therapy, including a platinum doublet-containing regimen, are eligible. Tumors must harbor mutations that are known to cause exon 14 skipping, confirmed by a central laboratory, but not activating EGFR mutations or ALK rearrangements. Pts receive tepotinib 500 mg QD until disease progression, intolerable toxicity, or withdrawal from treatment for other reasons. The primary endpoint is objective response rate. Secondary endpoints include progression-free and overall survival, safety, pharmacokinetics, and quality of life. Recruitment of 60 patients in Europe, USA, and Japan is planned. Results: Four pts (age 64–77 years; 3 stage IV, 1 stage IIIB, all Caucasian males) have been enrolled. All had received two prior chemotherapy regimens including a platinum doublet. Pts have currently completed 1–5 cycles of tepotinib therapy. The majority of adverse events observed to date have been grade 1/2 in severity; grade 3 disease-related dyspnea, pulmonary embolism, and pleural effusion were observed in one patient and grade 3 tepotinib-related elevated serum amylase in another. Of the 3 pts with post-baseline tumor evaluations, two have had an unconfirmed partial response and the third (with only one post-baseline assessment) stable disease. Conclusions: These initial data suggest that the efficacy of tepotinib 500 mg QD is comparable to that of less selective c-Met inhibitors in pts with c-METex14 NSCLC (ORR > 40%). Tepotinib is also well tolerated. Recruitment to the trial is ongoing. Clinical trial information: NCT02864992.

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.

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