Phase II study of epacadostat with pembrolizumab in metastatic or unresectable gastroesophageal junction and gastric adenocarcinoma requiring paired biopsies.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. TPS191-TPS191
Author(s):  
Adel Kardosh ◽  
Diane Tseng ◽  
Bita Sahaf ◽  
Ativ Zomet ◽  
Julia Krupa ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Gastric Adenocarcinoma ◽  
Phase Ii ◽  
Response Rate ◽  
Performance Status ◽  
Gastroesophageal Junction ◽  
Single Agent ◽  
The United States ◽  
Ecog Performance Status ◽  
Major Health Problem

TPS191 Background: Gastroesophageal junction (GEJ) and gastric adenocarcinomas constitute a major health problem worldwide. Gastric cancer is the fourth most prevalent malignancy and the second leading cause of cancer death worldwide. Furthermore, the incidence of adenocarcinoma of the esophagus, GEJ and gastric cardia has risen faster than any other malignancy in the last 25 years in the United States and other Western countries. Cytotoxic chemotherapy remains the standard treatment, with progression free survival (PFS) for advanced disease of 4 to 6 months and median overall survival (OS) of 7 to 10 months. Pembrolizumab, a PD-1 inhibitor, was recently approved for advanced gastric or gastroesophageal junction adenocarcinoma whose tumors express PD-1, on the basis of a response rate of 13% seen in KEYNOTE 059 (NCT02335411). Combination immunotherapies are hypothesized to build on this response. Methods: This is a single arm, phase II clinical trial of epacadostat, a novel inhibitor of the enzyme indoleamine 2,3 dioxygenase-1 (IDO-1), in combination with pembrolizumab, in metastatic or unresectable gastroesophageal junction or gastric adenocarcinoma. A 6-month PFS of 20% with single agent pembrolizumab is the basis for the null hypothesis. We will enroll 30 patients over 18 months and follow patients for at least 6 months. This design has 80% power to reject a 20% PFS rate, if the true PFS is 39%. Eligible patients must have: adenocarcinoma of the distal esophagus, gastroesophageal junction or stomach; progression on at least one line of prior therapy for metastatic disease, and for HER2+ disease should have received prior trastuzumab; ECOG performance status 0 or 1; willing to undergo two newly-obtained biopsies - before and on-treatment, provided the procedure is not deemed high-risk and is clinically feasible. Notably, PDL-1 expression is not required. The primary endpoint is 6-month PFS, with secondary endpoints of response rate (RR), OS, and the safety and tolerability of the combination. Furthermore, comprehensive immune profiling from patient blood and tumor tissue will be performed. The study opened to accrual in September 2017 (NCT03196232). Clinical trial information: NCT03196232.

A phase II study of S-1 for previously treated small cell lung cancer (SCLC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e19074-e19074
Author(s):  
K. Kudo ◽  
F. Ohyanagi ◽  
A. Horiike ◽  
E. Miyauchi ◽  
I. Motokawa ◽  
...  
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Performance Status ◽  
Single Agent ◽  
Progression Free Survival ◽  
Median Number ◽  
Ecog Performance Status ◽  
Treatment Regimens ◽  
Platinum Based Chemotherapy ◽  
Previously Treated

e19074 Background: S-1 is a novel oral 5-fluorouracil derivative that exhibits obvious activity against various tumor types including NSCLC. However, the effects of S-1 against SCLC have not been reported. The present phase II trial assesses the efficacy and safety of S-1 in previously treated SCLC patients. Methods: Eligible patients had pathologically documented SCLC that relapsed after platinum-based chemotherapy, ECOG performance status (PS) 0–2, and adequate bone marrow, kidney and liver function. Patients with untreated or symptomatic brain metastasis were excluded. Treatment comprised the oral administration of S-1 at 40 mg/m2 twice each day for 28 days every 6 weeks. The primary end point was the objective tumor response rate (RECIST). Secondary endpoints included progression-free survival and overall survival. Results: Twenty-six evaluable patients were enrolled (Simon's two-stage optimal design; α = 0.1; β = 0.1; P0 = 0.05; P1 = 0.25) with the following characteristics: male: female, 22/4; median age, 68 (33 - 79) y; PS0–1, n = 21; PS2, n = 5. The median number of prior treatment regimens was 2 (1–3). S-1 was administered for a mean of 1.3 cycles (1 - 5). One patient (3.8%) partially responded, 10 (38.5%) had stable and 15 (57.7%) had progressive disease. The overall response rate was 3.8% and the disease control rate was 42.3%. The median time to progression was 33 days. The median survival time was 8.0 months and the 1-year survival rate was 23%. This regimen was well tolerated. The common grade 3/4 toxicities included neutropenia (7.7%), leukopenia (7.7%), anemia (7.7%), hyponatremia (7.7%), rush (7.7%), infection (7.7%), and diarrhea (3.8%). None of the patients developed febrile neutropenia and no deaths were attributed to treatment. Conclusions: S-1 is well tolerated but has low activity as a single agent in previously treated patients with SCLC. No significant financial relationships to disclose.

Phase II study of cetuximab in combination with carboplatin and docetaxel for patients with advanced/metastatic non-small cell lung cancer (NSCLC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7643-7643 ◽  
Author(s):  
C. P. Belani ◽  
S. Ramalingam ◽  
M. Schreeder ◽  
R. Steis ◽  
R. Guidice ◽  
...  
Keyword(s):  
Disease Progression ◽  
Phase Ii ◽  
Advanced Nsclc ◽  
Response Rate ◽  
Phase Ii Study ◽  
Performance Status ◽  
Single Agent ◽  
Stage Iiib ◽  
Duration Of Treatment ◽  
Ecog Performance Status

7643 Background: Cetuximab, a chimeric IgG1 monoclonal antibody against the external domain of the epidermal growth factor receptor (EGFR), has demonstrated single-agent activity against NSCLC. When administered in combination with carboplatin and docetaxel, a commonly used regimen for advanced NSCLC, cetuximab exhibits synergistic interaction in preclinical studies. Therefore, we conducted a phase II study to evaluate the efficacy of the combination of cetuximab, carboplatin, and docetaxel for the treatment of advanced NSCLC. Methods: Chemotherapy-naive patients = 18 years with histologically/cytologically confirmed stage IIIB (w/ effusion) or stage IV NSCLC received cetuximab (400 mg/m2 on day 1 and 250 mg/m2 on days 8 and 15) plus docetaxel (75 mg/m2 on day 1) and carboplatin (AUC=6 on day 1) every 21 days for up to 6 cycles. Thereafter, patients without evidence of disease progression (CR/PR/SD) were continued on single-agent cetuximab (250 mg/m2/week) for a maximum of 1 year or until disease progression. The primary endpoint was response rate. Results: 81 patients were enrolled and 76 are evaluable for response. Patient characteristics included: gender male/female, 43/38; median age 63 years (range 42–83); ECOG performance status 0/1/, 31/50; and stage IIIB/IV- 5/76. The median number of cycles administered was 4 (range 1–6). The response rate (CR/PR) was 14.5% (95% CI, 7.5 to 24.4), with a median progression-free survival of 4.7 months and a median overall survival of 11 months. With combination therapy, the salient grade 3/4 events were neutropenia (28%), febrile neutropenia (3.8%), hypotension (4%), hypokalemia and hypomagnesemia (5%), hypersensitivity (1%), acne-like rash (3%), peripheral neuropathy (1%), and myalgia (1%). Twenty-five patients received maintenance therapy with single-agent cetuximab (median duration of treatment was 12 weeks) and this was well tolerated. Conclusions: This large multicenter phase II study of the novel combination of cetuximab with docetaxel and carboplatin shows promising efficacy for patients with advanced and metastatic NSCLC and has an acceptable toxicity profile. No significant financial relationships to disclose.

A phase II clinical trial utilizing maximum medical and surgical cytoredutive treatments for patients with metastatic colorectal cancer to the liver

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15130-e15130
Author(s):  
S. D. Glisson ◽  
R. V. LaRocca ◽  
J. B. Hargis ◽  
A. Cervera ◽  
G. Goldsmith ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Liver Resection ◽  
Liver Metastases ◽  
Phase Ii ◽  
Wedge Resection ◽  
Performance Status ◽  
Single Agent ◽  
Phase Ii Clinical Trial ◽  
Ecog Performance Status ◽  
Intention To Treat

e15130 Background: The median overall survival (‘OS‘) for patients with mCRC treated with chemotherapy is about 20.4 months. Combination chemotherapy with surgical cytoreduction for patients with liver metastases are evaluated in a phase II clinical trial. Methods: Patients with newly diagnosed mCRC to the liver or recurrent CRC after 5FU failure were consented to receive further chemotherapy with at least irinotecan-based chemotherapy, oxaliplatin-based chemotherapy, and with the intention to treat the liver metastases with either RFA and/or liver resection between chemotherapy regimens whenever possible. Bevacizamab and cetuximab were considered options for treatment after their respective FDA approvals. Chemotherapy was given until there was treatment failure. The primary endpoint was OS. Results: Between 2001 and 2004 thirty-seven patients aged 41 to 79 were consented. One remained alive by December 2008. Only patients with an ECOG performance status of 0–1 were consented. Twenty had been treated with 5FU for a stage III CRC befored developing mCRC. All patients received irinotecan in the form of FOLFIRI, IFL, or as a single agent. Thirty-six also received oxaliplatin in the form of either FOLFOX4 or 6. Twenty-two patients received cetuximab as a single agent. Some regimens were augmented with bevacizumab. Fourteen patients could not undergo resection or RFA because of performance status or progression. Three required radiation to the CNS or distant bone. There were eleven patients who underwent RFA of at least one liver metastasis. There were ten patients who underwent liver resection. One patient underwent both RFA and liver resection at two different times. Another patient underwent RFA, adrenalectomy and wedge resection of the lung at three different times. He remained alive at 78 months at the time of submission. Median OS was 34.5+ months at the time of submission. Patient survival ranged from 15 to 86 months. There were no deaths associated with any surgical intervention. Conclusions: OS was improved in mCRC patients or recurrent CRC patients who had potentially ablatable or resectable liver lesions at the time of their diagnosis and who were treated with available aggressive medical and surgical therapies. [Table: see text]

A combination chemotherapy of weekly paclitaxel and doxifluridine (5’-DFUR: an intermediate metabolite of capecitabine) in patients with unresectable or recurrent gastric cancer in an outpatient setting. Final results of a multicenter phase II trial

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15050-15050
Author(s):  
S. Yoshino ◽  
T. Nishimura ◽  
S. Hazama ◽  
M. Oka ◽  
H. Ozasa ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Adverse Events ◽  
Phase Ii ◽  
Response Rate ◽  
Performance Status ◽  
Single Agent ◽  
Outpatient Setting ◽  
Eligibility Criteria ◽  
Line Therapy ◽  
Recurrent Gastric Cancer

15050 Background: Paclitaxel (PTX) and 5’-DFUR have single-agent activity in gastric cancer and have distinct mechanisms of action and no overlap of key toxicities. Synergistic interaction between PTX and 5’-DFUR is mediated by taxane-induced up-regulation of thymidine phosphorylase, which converts 5’-DFUR to 5-FU. We conducted a combination phase II study of PTX and 5’-DFUR in patients with unresectable or recurrent gastric cancer to evaluate the efficacy and safety in an outpatient. Methods: Eligibility criteria included patients with histologically proven unresectable or recurrent gastric cancer who had measurable lesions fitting RECIST, up to one prior chemotherapy, a performance status of 0–2 and adequate organ function. According to our results of phase I study (Proc ASCO 2004, Abstr. 4228), the treatment included PTX 70 mg/m2 i.v. on days 1, 8, and 15 every 4 weeks and 5’-DFUR 600 mg/body p.o. everyday until there was disease progression or the appearance of unacceptable toxicity. Primary endpoint was: RR; and secondary endpoints were OS, PFS, TTF and onset rate of adverse events. Results: Between June 2004 and July 2006, 42 patients were enrolled in this study: including 34 men; 8 women; median age of 70 years (range, 44–85 years); and PS levels were, zero with 27, one with 13 and two with 2 patients. In 42 eligible patients, clinical usefulness was evaluated resulting in response rate of 40.5% (CR, 1; PR, 16; SD, 17; PD, 6; and NE, 2 patients). The first-line therapy involved 28 patients in whom the response rate was 50.0%. The second-line therapy involved 13 patients (all TS-1 failure) in whom the response rate was 23.1%. OS was 371 days, PFS was 170 days and TTF was 147 days. All patients were treated in outpatient. Severe adverse events were found in 2 patients to discontinue the present treatment, though other adverse events were relatively mild without death due to the present therapy. Commonly observed grade 3/4 adverse events were neutropenia (26.2%), appetite loss (4.8%), neuropathy (4.8%), and fatigue (4.8%). Conclusions: The outpatient combination of a weekly PTX and 5’-DFUR chemotherapy is active and well tolerated. No significant financial relationships to disclose.

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.

Validation of the Functional Assessment of Cancer Therapy-Ovarian (FACT-O) Symptom Index (FOSI) in a phase II clinical trial of pertuzumab in patients with advanced ovarian cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 16021-16021 ◽  
Author(s):  
J. Beaumont ◽  
S. Yount ◽  
D. Lalla ◽  
D. Lubeck ◽  
M. Derynck ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Clinical Trial ◽  
Phase Ii ◽  
Performance Status ◽  
Advanced Ovarian Cancer ◽  
Phase Ii Clinical Trial ◽  
Response To Treatment ◽  
Ecog Performance Status ◽  
Symptom Index ◽  
Cross Sectional

16021 Background: The FOSI is a very brief(8-item) index derived from the FACT-O to measure symptom response to treatment for ovarian cancer(OC). We evaluated its performance in a single arm Phase II clinical trial. Methods: The FOSI was administered to patients with advanced OC participating in a single arm Ph II clinical trial of pertuzumab(Gordon et al, JCO (2006) v24:4324;2006)). Pertuzumab, a humanized HER2 antibody is the first in a new class of investigational agents known as HER dimerization inhibitors(HDIs). Patients completed the FOSI at D1 of each 3 week cycle, up to 17 cycles. Validation analyses focused on data from the first 4 cycles and included Cronbach's alpha coefficients plus cross-sectional and longitudinal comparisons of groups defined by ECOG performance status (PS). Results: 62 patients completed the FOSI at baseline (B), 54 at cycle 2, 44 at cycle 3 and 27 at cycle 4. The FOSI showed acceptable internal consistency reliability with alphas of 0.73 to 0.80. The FOSI differentiated patients with PS 0 from those with PS =1 at each cycle (Table). There was a difference in FOSI scores in patients with worsened PS from those whose PS improved or was unchanged at cycle 2 only (p<0.001). The ES (mean change/ SD of change scores) for the group with worsened PS was -0.77. The minimally important difference was estimated to be 2–3 points. Conclusions: The FOSI is a valid symptom measure in this population of OC patients, demonstrating acceptable reliability, validity and responsiveness to clinical change. [Table: see text] No significant financial relationships to disclose.

Phase II single institution study of sequential biochemotherapy (BCT) for patients (pts) with stage IV melanoma (M)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8580-8580
Author(s):  
P. R. Bojanapally ◽  
D. T. Alexandrescu ◽  
V. Rusciano ◽  
P. H. Wiernik ◽  
J. P. Dutcher
Keyword(s):  
Median Survival ◽  
Phase Ii ◽  
Performance Status ◽  
Single Agent ◽  
Stage Iv ◽  
Experimental Therapy ◽  
Ecog Performance Status ◽  
Maximum Benefit ◽  
Prospective Phase ◽  
Metastatic Sites

8580 Background: The utility of BCT for M remains controversial. A prospective phase II study was conducted to assess the clinical benefit of BCT in patients with stage IV M. Methods: Between March 2005 and March 2006 11 pts (6 Male and 5 Female with a median age of 54 (range 36 - 82)) with metastatic M were treated with paclitaxel 225 mg/m2 via continuous 24 hour IV infusion every 3 wks for 4 cycles or maximum benefit followed by HD IL2, 1.33 mg/m2 every 8 hours for 5 days of wk1 and wk3 based on pts tolerance to a maximum of 12 doses per wk. 2 Male pts received IL2 followed by paclitaxel. Pts had a ECOG performance status of 0 - 2, with a median time of 60 months since diagnosis of disease (range 7 to 240 months). 11 pts (92%) had multiple metastatic sites (50% had lung mets, 58% had liver mets) and 4 pts (33%) had prior chemotherapy or immunotherapy. Results: Of the 13 assessable pts one achieved a PR after paclitaxel and CR after IL2 continuing at 20+ months. One had SD for 1 year after receiving HD IL2 and SD for 6 months while on paclitaxel independently, One had PR for 6 months on paclitaxel and one had MR with paclitaxel for 3 months. 9 pts (69%) had PD on paclitaxel and again on IL2, with a median survival from treatment of 7 months, 2 of these got no IL2 due to rapid PD. An overall response rate of 30% (1 CR on paclitaxel + IL2 , 1 PR on paclitaxel, 2 SD (including MR) on paclitaxel) was seen with a median survival from treatment of 15 months. Conclusions: In this study there may be prolonged survival among responders, which may be due to synergy of sequential BCT, or may reflect single agent activity of each drug. BCT should still be considered as an experimental therapy and further evaluated. No significant financial relationships to disclose.

Phase II study of irinotecan and paclitaxel for patients with recurrent small cell lung cancer (SCLC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18011-18011
Author(s):  
T. K. Owonikoko ◽  
S. Ramalingam ◽  
J. Forster ◽  
Y. Shuai ◽  
T. Evans ◽  
...  
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Study ◽  
Performance Status ◽  
Treatment Options ◽  
Objective Response ◽  
Ecog Performance Status ◽  
Stage Design ◽  
Prior Chemotherapy Regimen ◽  
Version 2.0

18011 Background: Recurrent SCLC has a poor prognosis and is devoid of treatment options that improve overall survival. Irinotecan and paclitaxel are both active agents against SCLC, and have synergistic preclinical interactions. We conducted a phase II study to evaluate the efficacy and safety of the combination of irinotecan and paclitaxel for patients with recurrent SCLC. Methods: Patients with SCLC who relapsed following one prior chemotherapy regimen were eligible. Other pertinent inclusion criteria were: ECOG performance status 0–2, adequate bone marrow, hepatic and renal function and willingness to provide informed consent. Patients with untreated brain metastasis were excluded. Paclitaxel (75 mg/m2) and irinotecan (50 mg/m2) were administered on days 1 & 8 of every 3-week cycle. Treatment was continued until progression up to a maximum of 6 cycles or unacceptable toxicity. The primary endpoint was response rate. Toxicity was graded by CTC version 2.0. The simon two-stage design was utilized and the estimated sample size was 55 patients (stage I - 23 patients; stage 2 - 32 patients). The study has a 90% power to detect a response rate of 30%, with an alpha error rate of 10%. Results: 55 patients have been enrolled and complete data are available for 32 patients at the time of this report. Patient baseline characteristics are: male 53%, PS 0–44%; PS 1–47% and PS 2–6%. The median age is 61 years. Fifteen patients received ≥ 4 cycles. Salient grades 3–5 toxicities seen: neutropenia (13%), fatigue (13%); diarrhea (3%), hypersensitivity (3%) and hyponatremia (3%).The objective response rate is 37% (95% CI 19%-55%) with 9 PRs and 1 CR. Additional 8 patients (24%) had stable disease. The median survival is 19.6 weeks (95% CI 15.1–29.4) and the 1-year survival rate is 15%. Conclusions: The combination of irinotecan and paclitaxel is well tolerated and has promising anti-cancer activity in recurrent SCLC. Updated data on all 55 patients will be available at the time of the presentation. No significant financial relationships to disclose.

Docetaxel-carboplatin chemotherapy in combination with cetuximab in patients with locally advanced or metastasized non-small cell lung cancer (NSCLC): Interim results of the nonrandomized phase II study TaxErb

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e19062-e19062
Author(s):  
J. R. Fischer ◽  
F. Griesinger ◽  
T. Fink ◽  
E. Buchholz ◽  
T. Salm ◽  
...  
Keyword(s):  
Phase Ii ◽  
Partial Remission ◽  
Response Rate ◽  
Phase Ii Study ◽  
Performance Status ◽  
Locally Advanced ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Ecog Performance Status ◽  
Benefit Risk Assessment

e19062 Background: Combination chemotherapy with carboplatin-docetaxel has been shown to be effective and safe for patients with locally advanced or metastasized NSCLC. The monoclonal anti-EGRF antibody cetuximab has the potential to improve response rates and survival without a substantial increase in toxicity when given in combination with chemotherapy. Methods: Open, non-controlled phase II study with a planned sample size of 70 pts. Pts with locally advanced or metastasized NSCLC, ECOG performance status ≤ 2 and no prior systemic chemotherapy were treated with carboplatin AUC5 (d 1) q4w for 4–6 cycles and docetaxel 35 mg/m2 (d1, 8, 15) q4w; cetuximab 400 / 250 mg/m2 (d 1) q1w until progression or intolerable toxicity (12 month max.). The primary endpoint was response rate defined as complete or partial remission according to RECIST. Secondary endpoints were toxicity, 1 year survival, median and progression free survival. Results: Subject of the interims analysis were 27 pts (25 stage IV, 2 stage IIIb). ECOG 0/1/2 was 33.3%/59.3%/3.7% (1 no data). 63% had prior surgery, 93% prior radiotherapy and all had adjuvant or inductive chemotherapy. Pts received a mean of 3 ± 1.4 cycles docetaxel-carboplatin-cetuximab. 49 adverse events were grade 1–2 and 12 grade 3–5. Skin toxicity (49%; 95%CI: 30%-68%; 41% G1/2, 8% G3/4), dyspnoea (35%; 95%CI: 17%-53%) and diarrhoea (23%; 95%CI: 7 %-39%; 19% G1/2, 4% G3) were most frequent. 11 pts (41%) had toxicity leading to dose reduction. 0 pts had complete and 11 pts had partial remission resulting in a response rate of 40.7% (95%CI: 22%-59%) based on intention to treat. 6 pts had stable disease (22.2%; 95%CI: 7%-38%). 5 pts were not evaluable for response. Conclusions: The combination of carboplatin-docetaxel-cetuximab has an overall acceptable tolerability. With a preliminary response rate of 40.7% the benefit risk assessment was found to be favourable and the study was continued. [Table: see text]

Bevacizumab (Bmab) in combination with uracil-tegafur (UFT) and oral leucovorin (LV) in elderly patients (≥ 75 years old) with metastatic colorectal cancer (mCRC): A multicenter phase II trial (J-BLUE study).

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 588-588
Author(s):  
Mitsuo Shimada ◽  
Tomohiro Nishina ◽  
Jun Higashijima ◽  
Toshikazu Moriwaki ◽  
Toshiki Masuishi ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Elderly Patients ◽  
Phase Ii ◽  
Performance Status ◽  
Progression Free Survival ◽  
Open Label ◽  
Effective Treatment Option ◽  
Ecog Performance Status ◽  
Eligibility Criteria ◽  
Ecog Ps

588 Background: Now fluoropyrimidine plus Bmab is considered a recommendable option to the majority of elderly mCRC patients who are deemed inappropriate for the standard doublet chemotherapy with biologics. Our previous phase II study of UFT/ LV in elderly mCRC patients (≥75 years old) had demonstrated acceptable safety and efficacy (overall response rate [ORR] 33%, progression-free survival [PFS] 5.3 months, overall survival [OS] 18 months). The aim of the present study was to investigate the efficacy and safety of Bmab in combination with UFT/LV for elderly mCRC patients. Methods: This study was designed as a single-arm, open-label, multicenter, cooperative group (SGOSG-TCTG) clinical trial (trial registration: UMIN000003515). Key eligibility criteria included age ≥75 years, ECOG performance status (PS) 0 or 1, first-line chemotherapy, measurable lesions, and preserved organ functions. Patients received UFT 300mg/m2/day and LV 75mg/body/day on days 1-21 followed by 7 days rest, and intravenous administration of Bmab 5mg/kg on days 1 and 15. Treatment repeated every 28 days. The primary endpoint was PFS, and secondary endpoints were ORR, OS, and safety. Results: A total of 55 patients were enrolled from 15 institutions between Aug 2008 and Mar 2012. Among them, 52 eligible patients were evaluated. Median age was 80 years (range: 75-87). ECOG PS 0 was 73%. Median PFS was 8.2 months (95% confidence interval [CI], 6.2-10.3, events in 86.5%). Confirmed ORR was 40.4% (95% CI, 27.0-54.9%). Median OS was 18.7 months (95% CI, 10.3-27.0, events in 48%). The most common grade ≥3 treatment-related adverse events were hypertension (11.5%), fatigue (7.7%), nausea (5.8%), and diarrhea (5.8%). The treatment-related death occurred in 2 (3.8%) patients. Main reasons for discontinuation of treatment were disease-progression (62.5%) and toxicity (27.1%). Conclusions: Bmab in combination with UFT/LV is tolerable and effective treatment option for elderly patients (≥75 years old) with mCRC. Further trial with Bmab plus UFT/LV targeting elderly mCRC patients would be warranted. Clinical trial information: 000003515.

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