A phase II trial of carboplatin (C) and nab-paclitaxel (ABI-007-nab-P) in patients with unresectable stage IV melanoma: Final data from N057E

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 9055-9055
Author(s):  
S. N. Markovic ◽  
V. J. Suman ◽  
L. A. Kottschade ◽  
T. Amatruda ◽  
R. R. McWilliams ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Stage Iv ◽  
Median Number ◽  
Clinical Activity ◽  
Eligibility Criteria ◽  
Unresectable Stage ◽  
Number Of Cycles ◽  
Ecog Ps ◽  
Stage Iv Melanoma

9055 Background: There is increasing evidence that paclitaxel and carboplatin are clinically active in the treatment of metastatic melanoma (MM). Nab-P is an albumin-bound paclitaxel with ability to bind SPARC (secreted protein acid rich in cysteine), that is overexpressed in MM and associated with poor prognosis. This study explores the clinical activity of the combination of nab-P and C in patients (pts) with stage IV melanoma and SPARC correlatives. Methods: A parallel phase II trial was conducted in pts with unresectable stage IV melanoma, who were either chemotherapy naïve (CN) or were previously treated (PT). A treatment regimen consisting of nab-P (100 mg/m2) and C (AUC 2) was administered on days 1, 8, and 15 of a 28 day cycle. The primary aim of this study was to assess whether tumor response rate (CR + PR by RECIST) was ≤15% vs ≥35% in the CN group and ≤5% vs ≥ 20% in the PT cohort. Major eligibility criteria: ≥18 years of age, ECOG PS ≤2, adequate organ function, platinum or taxane naive, peripheral neuropathy < grade 2, and no untreated brain metastasis; no pregnant and/or nursing women. Tumor tissue was tested for SPARC and level 3 immunohistochemical staining was considered positive. Results: 76 pts (41-CN and 35 PT) enrolled from 11/2006 - 7/2007, 3 pts (2-CN, 1-PT) cancelled prior to starting treatment. The median number of cycles administered was 4 (range 1–18-CN and 1–10-PT). There were 11 (28.2%) confirmed responses (1 CR and 10 PRs) in the CN cohort (90% CI: 16.7–42.3%) and 3 (8.8%) confirmed responses (3 PRs) in the PT cohort (90% CI: 2.5–21.3%). Median PFS was 4.5 months (CN) and 4.1 months (PT). Median OS was 11.1 months (CN) and 10.9 months (PT).The most common severe toxicities in both groups (CTCAE ≥ grade 3) included neutropenia, thrombocytopenia, neuro-sensory, fatigue, nausea, and vomiting. PFS was not affected by SPARC positivity; however, based on limited data there is some evidence that OS may be longer with tumoral SPARC positivity (10.0 vs 12.8 mo; SPARC negative vs SPARC positive). Conclusions: The weekly combination of nab-P and C appears to be well tolerated with promising clinical activity as front line or salvage therapy in pts with MM. SPARC positivity may be associated with improved OS. No significant financial relationships to disclose.

scholarly journals A phase II trial of nab-paclitaxel (ABI-007) and carboplatin in patients with unresectable stage IV melanoma

Cancer ◽  
2010 ◽  
Vol 117 (8) ◽  
pp. 1704-1710 ◽  
Author(s):  
Lisa A. Kottschade ◽  
Vera J. Suman ◽  
Thomas Amatruda ◽  
Robert R. McWilliams ◽  
Bassam I. Mattar ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Stage Iv ◽  
Unresectable Stage ◽  
Stage Iv Melanoma

Phase II trial of irinotecan/docetaxel for advanced pancreatic cancer with randomization between irinotecan/docetaxel and irinotecan/docetaxel plus C225, a monoclonal antibody to the epidermal growth factor receptor (EGF-r) : Eastern Cooperative Oncology

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4519-4519 ◽  
Author(s):  
B. A. Burtness ◽  
M. Powell ◽  
J. Berlin ◽  
D. Liles ◽  
A. Chapman ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Median Survival ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Advanced Pancreatic Cancer ◽  
Growth Factor Receptor ◽  
Distant Metastases ◽  
Median Number ◽  
Number Of Cycles ◽  
Ecog Ps

4519 Background: Gemcitabine (G) is standard for metastatic pancreatic cancer (PC), with median survivals of 6 months (m). Second cytotoxic or biologic agents do not substantially advance survival. EGFR is expressed on PC and a phase II trial of G plus cetuximab (C) resulted in favorable 1 year survival. A phase II trial of irinotecan/docetaxel (I/D) chemotherapy reported a median survival for metastatic patients (pts) of 9 m. We conducted this randomized phase II trial to confirm the activity of this non-G regimen, and determine whether combining it with C was feasible and active. The primary endpoint was response. Methods: Pts required histologic confirmation of adenocarcinoma of the pancreas, evidence of distant metastases, ECOG PS 0–1, normal bilirubin, written informed consent, and were randomly assigned to Arm A (N=47) or B (N=45). Imaging with CT or MR within 4 weeks (wk) was used for tumor measurement. Dexamethasone was given 12 hours (h), 1 h before and 12 h after chemotherapy. Pts on Arm A received D 35 mg/m2 over 1 h and I 35 mg/m2 over 30 minutes weekly x 4 in a 6 wk cycle. Pts on Arm B received the same therapy, but C (loading dose 400 mg/m2 wk 1, 250 mg/m2 weekly thereafter) was given before D. Pts not receiving therapeutic anticoagulation received enoxaparin 40 mg per day. Pts were restaged (RECIST) after 2 cycles. Results: Median age Arm A: 59.9, Arm B: 60.2 years. Arm A 55% male, 32% PS 0, 97% EGFR immuno+. Arm B 84% male, 42% PS 0, 97% EGFR +. Median number of cycles for each arm 2 (1 -10). >4 cycles were delivered to 10.5% of pts Arm A, 20.9% Arm B. Grade ¾ neutropenia 26% Arm A, 33% Arm B. Grade 3 nausea 28% Arm A, 18% Arm B; Grade ¾ diarrhea 33% Arm A, 44.4% Arm B. 1 treatment-related death per arm. Median overall survival (OS), with 70.2% of pts known to have died, 6.5m [(95% CI (4.8, 8.6)] in Arm A. With 86.7% of pts known to have died in Arm B, OS 7.4 m [95% CI (4.4, 10.7)]. Response/progression data will be available at time of presentation. Conclusions: Weekly I/D ± C is associated with high rates of grade ¾ neutropenia/diarrhea. Median survival is 6.5m for I/D and 7.4m for I/D/C. Non-G containing therapy is active in metastatic PC. [Table: see text]

Phase II study of bevacizumab in combination with cisplatin and docetaxel as first-line treatment of patients (p) with metastatic non-squamous non-small cell lung cancer (NSCLC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e19023-e19023
Author(s):  
N. Ferrer ◽  
M. Cobo ◽  
A. Paredes ◽  
M. Méndez ◽  
J. Muñoz-Langa ◽  
...  
Keyword(s):  
Phase Ii ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Median Number ◽  
Line Treatment ◽  
Eligibility Criteria ◽  
Platinum Based Chemotherapy ◽  
History Of ◽  
Grade 3 ◽  
Number Of Cycles

e19023 Background: Bevacizumab (B), in addition to platinum-based chemotherapy, is indicated for 1st-line treatment of p with advanced NSCLC other than predominantly squamous cell histology. B has been shown to improve progression free survival (PFS) and overall survival (OS) when combined with cisplatin/gemcitabine and carboplatin/paclitaxel, respectively. However, there are limited data on the safety and efficacy of B in combination with other widely used chemotherapy doublets for NSCLC. This is a single-arm, open- labeled, single-stage phase II trial of cisplatin (C), docetaxel (D) and B for NSCLC. Methods: Eligibility criteria: chemo- naïve, stage IIIB wet or IV, non-squamous NSCLC, PS 0–1, no brain metastases and no history of gross hemoptysis. P received D (75 mg/m2), C (75 mg/m2), and B (15 mg/kg iv) on day 1 every 3 weeks for up to 6 cycles, followed by B 15 mg/kg alone every 3 weeks until disease progression or toxicity. Primary endpoint: PFS. Results: 50 p were enrolled (enrollment completed): 24% female, median age 60 (36–74), PS 1: 64%, adenocarcinoma: 72%; stage IV: 92%. Two p did not start treatment. Median follow-up is 5.3 months (range 0–13.6). Median number of cycles of B was 7 (range 0–18). 56% completed 6 cycles of treatment; 24% received ≥ 12 cycles of B. Most frequent grade ≥ 3 toxicities: diarrhea (14.6%), fatigue (14.6%), dyspnea (9.8%), anorexia (4.9%), alopecia (4.9%), esophagitis (4.9%), constipation (4.9%), mucositis (12.2%), proteinuria (4.9%); hematological toxicities: neutropenia (22%), febrile neutropenia (9.8%), leucopenia (14.6%), lymphopenia (4.9%). Of interest, 41.5% developed grade <3 epistaxis and 17% hypertension (1 p grade 3). One p died due to hemoptysis. 46 p were evaluable for response: 29 PRs (ORR: 63%). 18 of 48 p have experienced progression or death with a median SLP of 7.8 months (95% CI: 6.6-NR). Median OS is 13.5 months (95% CI: 12.7–13.6; 81.2% p censored); 1-year survival is 83.9% (95% CI: 67.4%-92.5%). Conclusions: Treatment with C, D and B, followed by maintenance B in 1st line of advanced non-squamous NSCLC shows an acceptable toxicity profile and promising efficacy. Final results will be presented. [Table: see text]

A phase II trial of oxaliplatin in patients with advanced melanoma

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 18016-18016 ◽  
Author(s):  
J. Lutzky ◽  
Y. Nunez ◽  
P. Graham
Keyword(s):  
Phase Ii ◽  
Stage Iv ◽  
Median Number ◽  
Advanced Melanoma ◽  
Platinum Compound ◽  
Disease Stabilization ◽  
Previously Treated ◽  
Number Of Cycles ◽  
Ecog Ps

18016 Background: Oxaliplatin is a platinum derivative without nephrotoxicity with in vitro activity against human melanoma cell lines. (Mohammed, MQ, 2000; Tashiro, T, 1989). A Phase I trial suggested activity in melanoma (Mathe, G, 1986) but Phase II data is lacking. A non-nephrotoxic platinum compound active in melanoma is of interest in the development of combination chemo-or chemoimmunotherapy. Methods: This was a Phase II prospective study of oxaliplatin in patients with previously treated or refractory advanced melanoma. The primary endpoint was to evaluate the response rate, survival, freedom from progression (FFP) and the tolerability of oxaliplatin in this patient population. Key inclusion criteria were: metastatic (stage IV) or unresectable malignant melanoma progressing following treatment with at least one and at most three chemotherapy regimens. ECOG PS 0–2, measurable disease and adequate organ and marrow function were required. Oxaliplatin 130 mg/m2 was given IV in 250–500 mL D5W over 120 minutes every 21 days for at least 2 cycles. Patients were evaluated for response every 2 cycles. Gehan’s two-stage design was utilized. Results: Ten patients were treated between March 2004 and March 2005. Three patients were female and 3 male with a median age of 62.5 years. All patients had PS 0–1. The median number of cycles was 2 (1–6). Three patients had disease stabilization (SD) for median of 3 months. No objective responses were seen; therefore, the study did not progress to the second stage.All patients have progressed and all have expired but one. Median survival from registration was 168 days (128–383). Toxicities included grade 2 fatigue (2 pts) and grade 2 neuropathy (3 pts); one patient had grade 3 diarrhea. Conclusions: Treatment with oxaliplatin in previously treated patients with melanoma is well tolerated at the dose and schedule studied but did not result in objective responses and further development in this population cannot be recommended. Incorporation into combination regimens in previously untreated patients may be of interest. No significant financial relationships to disclose.

A phase II trial of carboplatin and ABI-007 in patients with unresectable stage IV melanoma, N057E

2008 ◽  
Vol 26 (15_suppl) ◽  
pp. 9044-9044
Author(s):  
L. A. Kottschade ◽  
V. J. Suman ◽  
T. Amatruda ◽  
R. R. McWilliams ◽  
S. R. Dakhil ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Stage Iv ◽  
Unresectable Stage ◽  
Stage Iv Melanoma

scholarly journals Phase II trial of the regulatory T cell-depleting agent, denileukin diftitox, in patients with unresectable stage IV melanoma

BMC Cancer ◽  
2011 ◽  
Vol 11 (1) ◽  
Author(s):  
Sucheta Telang ◽  
Mary Ann Rasku ◽  
Amy L Clem ◽  
Karen Carter ◽  
Alden C Klarer ◽  
...  
Keyword(s):  
T Cell ◽  
Phase Ii ◽  
Regulatory T Cell ◽  
Phase Ii Trial ◽  
Stage Iv ◽  
Denileukin Diftitox ◽  
Unresectable Stage ◽  
Stage Iv Melanoma

Randomized phase II study of biweekly gemcitabine (gem)-paclitaxel (pac), gem-carboplatin (carb) and gem-cisplatin (cis) as first-line treatments in metastatic breast cancer (MBC) after anthracycline failure

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1099-1099 ◽  
Author(s):  
B. Xu ◽  
Z. Jiang ◽  
S. Kim ◽  
S. Yu ◽  
J. Feng ◽  
...  
Keyword(s):  
Performance Status ◽  
Metastatic Breast ◽  
Stage Iv ◽  
Ecog Performance Status ◽  
Eligibility Criteria ◽  
Dominant Type ◽  
Tumor Involvement ◽  
Number Of Cycles ◽  
Ecog Ps ◽  
Tumor Types

1099 Background: Biweekly gem-pac and gem-cis regimens have shown promising activity and safety in different tumor types. In MBC biweekly gem-pac is active and well tolerated. The aim of this multi-country study is to evaluate the efficacy and safety of gem in combination with pac, carb or cis on a biweekly schedule in patients (pts) with MBC. Methods: Major eligibility criteria included: tissue diagnosis of stage IV breast carcinoma; prior anthracycline therapy; ECOG performance status (PS) of 0 or 1; and written informed consent. Pts were randomized to receive gem 2500 mg/m2 in combination with pac 150 mg/m2 (Arm A), carb AUC 2.5 (Arm B) or cis 50 mg/m2 (Arm C) on day 1 of 2-week cycles. The primary endpoint was response rate, with safety a secondary endpoint. Results: This interim analysis was planned to occur when patient enrollment had reached 50% (75/150 pts), at which point there were 26 pts in Arm A, 25 in Arm B and 24 in Arm C, with 12 pts still on treatment. The baseline characteristics were similar in the three arms, including mean age (Arm A 50.2 yr, Arm B 46.1, Arm C 47.3); ECOG PS (PS 0: 50.0%, 64.0%, 54.2%); mean number of sites of tumor involvement (2.9, 2.6, 2.7); dominant type of metastasis (visceral: 73.1%, 80.0%, 79.2%); and disease-free interval (<24 mo: 53.8%, 60.0%, 41.7%). The mean number of cycles was 6.4, 6.0 and 5.8. There was a partial response in 5/26 efficacy qualified pts (19.2%), 5/25 pts (20.0%) and 2/23 pts (8.7%) in Arms A, B and C, respectively, stable disease in 10 pts (38.5%), 9 pts (36.0%) and 9 pts (39.1%), and progressive disease in 5 pts (19.2%), 6 pts (24.0%) and 6 pts (26.1%). There were no treatment-related deaths. Conclusions: The three regimens appear to show activity and have manageable toxicity when given on a biweekly schedule. [Table: see text] No significant financial relationships to disclose.

Sign in / Sign up

Export Citation Format

Share Document