A phase II study of single agent abraxane as second-line therapy in patients with advanced urothelial carcinoma

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16058-e16058
Author(s):  
S. S. Sridhar ◽  
C. M. Canil ◽  
A. Eisen ◽  
I. F. Tannock ◽  
J. J. Knox ◽  
...  
Keyword(s):  
Phase Ii ◽  
Joint Pain ◽  
Urothelial Cancer ◽  
Single Agent ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Line Therapy ◽  
Metastatic Urothelial Cancer ◽  
Cancer Setting

e16058 Background: Metastatic urothelial cancer progressing on or after first-line platinum-based chemotherapy is incurable and has a very poor prognosis. There is no standard second-line therapy, but the taxanes including paclitaxel, have previously shown activity. Abraxane (ABI-007) is a novel well tolerated albumin-bound nanoparticle formulation of paclitaxel. The goal of this study was to determine the efficacy and tolerability of single agent Abraxane in the second-line metastatic urothelial cancer setting. Methods: Patients with measureable metastatic urothelial cancer, who progressed on or after first-line cisplatin based chemotherapy were enrolled onto this phase II, two-stage multicenter trial. Patients received Abraxane 260 mg/m2 intravenously every 3 weeks. Clinical evaluation, CBC and blood chemistries were performed every cycle and restaging CT scans every 2 cycles. Results: Fourteen patients have been enrolled to date. Patient demographics: M: F 12:2; mean age 64 (range 45–80); ECOG 0:1:2 4:5:5. A total of 57 cycles, avg 4 cycles/ patient (range 1–9) have been administered. There were three dose delays due to neuropathy, pain, and low neutrophil count respectively. There were two dose reductions due to fatigue and neuropathy. Most frequent adverse events (AE) were fatigue, alopecia, anorexia, cough and joint pain; the most frequent grade 3+ AE were fatigue, joint pain, hypertension, joint stiffness and back pain. Fourteen patients are currently evaluable for best response using RECIST criteria. There have been 5 partial responses (PR), 5 stable disease (SD) and 4 progressive disease (PD). Conclusions: Single agent Abraxane was well tolerated in the 2nd line, cisplatin refractory/resistant metastatic urothelial cancer setting. Preliminary efficacy results are encouraging with a clinical benefit rate of 71% (10 out of 14 evaluable pts having either SD or PR). Stage 1 response criteria have been met and accrual is ongoing to a total of 48 patients. No significant financial relationships to disclose.

Second-line therapy with pemetrexed after gemcitabine failure in patients with unresectable locally advanced or metastatic pancreatic cancer: A multicenter phase II trial

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4124-4124 ◽  
Author(s):  
S. Boeck ◽  
K. Weigang-Koehler ◽  
M. Fuchs ◽  
E. Kettner ◽  
D. Quietzsch ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Survival Rate ◽  
Phase Ii ◽  
Single Agent ◽  
Locally Advanced ◽  
Metastatic Pancreatic Cancer ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Line Therapy

4124 Background: There is no established second-line therapy for advanced pancreatic cancer after failure of standard first-line treatment with gemcitabine. In view of the urgent need of such therapy and the observation of clinically meaningful responses with pemetrexed in previously untreated pancreatic cancer, this phase II study evaluated pemetrexed as second-line therapy. Methods: This study was planned to evaluate the efficacy and safety of pemetrexed in 54 patients (pts) with unresectable locally advanced or metastatic pancreatic cancer (stage II-IV), ECOG performance status ≤2 and estimated life expectancy of ≥12 weeks (wks) after failure of first-line gemcitabine single agent or combination therapy. Pemetrexed was started at 500 mg/m2 q3w (10 min infusion), with vitamin B12 and folic acid supplementation. Dose escalation by 100 mg/m2 every other cycle and an unlimited number of cycles were allowed. Primary endpoint was the 3-month survival rate. Results: A total of 189 treatment cycles (median 2, range 1–20) was given to 52 pts (60% male, median age 63 yrs, median time since initial diagnosis 32 wks, 89% stage IV disease). Doses were escalated in 2 pts (4%) and reduced due to toxicity in 9 pts (17%); median dose per cycle was 500 mg/m2 (range 212–700 mg/m2). The 3-month survival rate was 75% (95% CI 63.2–86.8%). At a median follow-up of 20 wks, the median overall survival estimate was 20 wks, with 9 pts alive including 1 still on pemetrexed. Median TTP was 7 wks (range 1–62 wks). The overall response rate was 3.8% (0 CR, 2 PR); 12 pts (23%) had SD for ≥6 wks, 9 of them for ≥12 wks. CA 19–9 decreased at least once by ≥ 50% in 12 pts (23%). Grade 3/4 hematological toxicity rates per pt were as follows: neutropenia 17.3% (febrile neutopenia: 3.8%), leukopenia 15.4%, thrombopenia 5.8% and anemia 3.8%. Conclusion: Pemetrexed is a feasible option for second-line therapy with mild toxicity and encouraging activity in unresectable locally advanced or metastatic pancreatic cancer after gemcitabine failure. [Table: see text]

Intravenous vinorelbine as first-line and second-line therapy in advanced breast cancer.

1995 ◽  
Vol 13 (11) ◽  
pp. 2722-2730 ◽  
Author(s):  
B L Weber ◽  
C Vogel ◽  
S Jones ◽  
H Harvey ◽  
L Hutchins ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Single Agent ◽  
Objective Response ◽  
Advanced Breast ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Line Therapy

PURPOSE We evaluated single-agent intravenous (IV) vinorelbine as first- and second-line treatment for advanced breast cancer (ABC) in patients who were not resistant to anthracyclines. Objective tumor response (TR) and toxicity were assessed. PATIENTS AND METHODS A total of 107 women were enrolled onto this multicenter, nonrandomized, open-label phase II study. Patients were stratified into first- and second-line treatment groups, based on prior treatment history. Vinorelbine was initially given at 30 mg/m2/wk, with dose modification for toxicity as indicated. Therapy was continued until disease progression or severe toxicity mandated withdrawal or until the patient asked to be removed from the study. RESULTS The objective response rate for all patients was 34% (95% confidence interval [CI], 25% to 44%): 35% (95% CI, 23% to 48%) for first-line patients and 32% (95% CI, 20% to 47%) for second-line patients. Nine first-line and three second-line patients obtained a complete response (CR). The median duration of objective response was 34 weeks in both groups. The overall survival durations of first- and second-line patients were 67 weeks and 62 weeks, respectively. Granulocytopenia was the predominant dose-limiting toxicity. Two patients died on study as a result of granulocytopenic sepsis. CONCLUSION Single-agent vinorelbine is an effective and well-tolerated agent for first- and second-line therapy of ABC. The results of this study confirm the findings of similar international trials and suggest vinorelbine should be considered a valid treatment option for patients with ABC and a potential component in future combination regimens for this disease.

Gemcitabine in combination with oxaliplatin as second-line therapy of advanced and metastatic NSCLC

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18157-18157
Author(s):  
A. J. Alencar ◽  
M. Blaya ◽  
L. Raez ◽  
N. Farfan ◽  
G. Lopes ◽  
...  
Keyword(s):  
Organ Failure ◽  
Response Rate ◽  
Performance Status ◽  
Single Agent ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Line Therapy ◽  
Multi Organ Failure

18157 Background: Single agent gemcitabine is active as second line therapy in NSCLC. Oxaliplatin may be non-cross resistant with the other platinum-containing agents used as first-line therapy in NSCLC. The combination of gemcitabine and oxaliplatin (GEMOX) is synergistic in pre-clinical models. Methods: A phase II, non-randomized trial was designed to assess the efficacy and tolerability of gemcitabine 1,000 mg/m2 over 100 min in combination with oxaliplatin 100 mg/m2 over 2 hours both given on days 1 and 15 of each 28-day cycle. Patients with NSCLC were eligible if they had progressed after first line treatment. Primary endpoint was tumor response rate. Planned sample size is 30 patients over a period of 2 years. Functional Assessment of Cancer Therapy- Lung (FACT-L) v.4 questionaire was used to assess quality of life of patients on therapy. Results: Twenty-two patients have been enrolled. 13 males (59%) and 9 females (41%). 15 Hispanic (68%), 4 Caucasian (18%), and 3 African-American (13%). Median age is 55 yrs. Histologic subtypes are as follows: adenocarcinoma, 12; NSCLC not otherwise specified 7; squamous cell carcinoma, 3. Nine patients had an ECOG performance status (PS) of 0 (41%) and 13 had a PS of 1 (59%). Two patients were never smokers. A total of 56 cycles have been administered (median 2, range 1 to 6). GEMOX as second-line therapy was given to 18 patients (81%), third-line to 4 patients (18%). Two patients died on study from disease progression leading to respiratory and multi-organ failure. The following Grade 3 and 4 adverse events were seen in 2 patients each: fatigue, dyspnea, anemia, and multi-organ failure. Cancer pain was seen in 1 patient. Twenty patients are available for assessment of response. Two patients had a confirmed partial response (10%) and another eight had stable disease (40%). Preliminary results of FACT-L analysis in 19 pts shows improvement in Lung Cancer Subscale (LCS) score in 25% of the patients after 2 cycles of therapy. Conclusions: Combination gemcitabine and oxaliplatin is active and well tolerated as second line treatment for NSCLC. Improvement of LCS score after 2 cycles suggests a clinical benefit that is beyond the observed response rate of 10%. No significant financial relationships to disclose.

E7208: A randomized phase II trial of irinotecan and cetuximab (IC) versus IC plus ramucirumab (ICR) in second line therapy of KRAS wild type colorectal cancer (CRC).

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. TPS793-TPS793 ◽  
Author(s):  
Howard S. Hochster ◽  
Paul J. Catalano ◽  
Edith P. Mitchell ◽  
Deirdre Jill Cohen ◽  
Peter J. O'Dwyer ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Bowel Perforation ◽  
Second Line ◽  
Wild Type ◽  
First Line ◽  
Second Line Therapy ◽  
Line Therapy ◽  
Randomized Phase Ii ◽  
Grade 3

TPS793 Background: Anti-angiogenic therapy for CRC has been accepted as standard therapy with approval of bevacizumab (bev) in both first-line and second-line settings. At the time this study was started, the benefit of continuing an anti-angiogenic in second line therapy was unproven. Ramucirumab (RAM, IMC 1121b) is a humanized antibody directed against the VEGF-R2 receptor, which may prove to have different activity compared to anti-VEGF antibody (bev). Additionally, while combining the anti-EGFR antibody, cetuximab (CMAB), with bev in first-line unselected patients was not effective, it is unknown whether the same may be true with RAM plus CMAB in a second-line setting for KRAS-selected patients. Methods: The study was designed as a randomized phase II trial with 147 patients assigned to IC = irinotecan (I) 180 mg/m2 IV plus CMAB 500 mg/m2 IV q2w versus ICR = IC plus RAM 8 mg/kg IV q2w. Eligibility included prior treatment on one prior oxaliplatin and bev-containing regimen and progression within 42 days of last bev, PS 0-1, KRAS codon 12,13 wild-type and standard other chemo and bev criteria. Doses were modified for neutropenia, diarrhea, mucositis, rash and grade 3 other toxicities. The study was activated 10/8/10. The first 35 patients were enrolled and accrual was held 6/24/12 for toxicity analysis per protocol. More grade 3 events of mucositis, diarrhea, neutropenia and perforation events (including peri-rectal abscesses) were seen in the ICR arm. The study has been modified reflect the actual doses received, and now uses modified ICR (mICR) = I 150 mg/m2, CMAB 400 mg/m2 and RAM 6 mg/kg IV q2w. The study was re-activataed in May 2014. An additional 100 pts will be accrued to the revised study, giving 85% power to detect improved median PFS from 4.5 to 7.65 months. New eligibility criteria include any progression from first-line chemo (on or off), normal albumin, no bowel perforation or obstruction in last 6 months. This study is now open to accrual in ECOG-ACRIN and in SWOG with endorsement, and via CTSU. Clinical trial information: NCT01079780.

A multi-center phase Ib/II study of nal-irinotecan, 5-fluouracil and leucovorin in combination with nivolumab as second-line therapy for patients with advanced unresectable biliary tract cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS4154-TPS4154
Author(s):  
Vaibhav Sahai ◽  
Tyler Howard Buckley ◽  
Kent A. Griffith ◽  
Mark Zalupski
Keyword(s):  
Dose Level ◽  
Biliary Tract ◽  
Single Agent ◽  
Objective Response ◽  
Cell Subset ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Phase Ib ◽  
Line Therapy

TPS4154 Background: Patients (pts) with advanced biliary tract cancers (BTC) have poor prognosis despite systemic chemotherapy, and treatment beyond first-line platinum doublet remains investigational. The immunomodulatory properties of conventional cytotoxic therapy, particularly in regard to the upregulation of PD-L1 expression rendering tumor cells more sensitive to T cell-mediated lysis and neoantigen production, rapid emergence of chemotherapy resistance, and known modest efficacy of single agent PD-1 antibody in BTC provide a rationale for combining chemotherapy and immunotherapy. This multi-center, phase Ib/II, single-arm study is designed to investigate the role of nal-irinotecan, 5-FU and leucovorin in combination with nivolumab as second-line therapy in pts with advanced BTC. Methods: Key eligibility criteria include histologically confirmed advanced, unresectable biliary carcinoma (intra- or extra-hepatic and gallbladder) with progression or intolerance of first-line systemic therapy (excluding irinotecan and PD-1/PD-L1 antibody), measurable disease per RECIST v1.1, ECOG PS 0-1, Child Pugh A or B7, and absence of autoimmune disease or chronic steroid use. Primary objective of the phase Ib portion is to determine the recommended phase 2 dose, and of the phase II portion is to evaluate the median progression-free survival. Secondary objectives include evaluation of objective response rate per immune related (ir)RECIST, median OS and safety in this patient population. Exploratory objectives include identification of biomarker predictors of response and mechanisms of resistance through serial biopsies and blood collection (pre, on and post therapy), including sequential whole exome/transcriptomic analysis and immune cell subset analysis (tissue and blood). Therapy includes nal-irinotecan 70 mg/m2, leucovorin 200 (dose level -1) or 400 mg/m2 (dose level 0), 5-fluouracil 2400 mg/m2 IV over 46 hours, and nivolumab 240 mg on day 1 every 2 weeks for 6 months. In the absence of disease progression, pts may continue therapy for up to 2 years. Accrual goal is 30 evaluable pts. Using a null hypothesis value of median PFS of 2.9 months, and an alternative hypothesis of 5.0 months, this ongoing study has > 80% power, with a two-sided alpha of 0.05 to identify treatment efficacy of study arm. Clinical trial information: NCT03785873.

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