Phase II study of induction therapy with gemcitabine and nab-paclitaxel followed by consolidation with mFOLFIRINOX in patients with metastatic pancreatic cancer.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 233-233
Author(s):  
Ramesh K. Ramanathan ◽  
Peter Lee ◽  
Joseph W. Leach ◽  
Stephen Patrick Anthony ◽  
Glen J. Weiss ◽  
...  
Keyword(s):  
Phase Ii ◽  
Induction Therapy ◽  
Phase Ii Study ◽  
Performance Status ◽  
Preliminary Evidence ◽  
Induction Phase ◽  
Novel Approach ◽  
Early Image ◽  
Adequate Organ Function ◽  
One Year

233 Background: We designed a phase II study to evaluate the efficacy, toxicity and feasibility of administering nab-paclitaxel/gemcitabine (NabP-Gem) followed by mFOLFIRINOX in MPC. Methods: Eligible patients had evidence of untreated MPC with performance status of ECOG 0-1 and adequate organ function. Induction therapy was with Nab-P (125 mg/m2) and Gem (1000 mg/ m2) weekly x 3 every 4 weeks for a maximum of 6 months (6 cycles). mFOLFIRINOX every 2 weeks (Consolidation regimen) was initiated after 6 cycles of the Induction regimen, or earlier in case of progression, and given upto 6 months (12 cycles). The FOLFIRINOX regimen (NEJM,364:1817-25: 2011) was modified to omit the bolus 5FU and requires addition of granulocyte growth factor prophylaxis. A primary endpoint is to increase 1 year survival (n=30) to >70%, (95% confidence intervals for one year survival rate is +/- 20%). Results: As of 9/1/2012, 26 of 30 subjects have been accrued. M/F ratio is 58%/42%, median is 65 years. In 20 patients treated on the induction phase, 75% have a > 90% decrease in CA 19-9 levels. The partial response rate (PR) in the first 19 patients who have completed 4 cycles is 50%. Early image analysis on 9 subjects with concurrent CT and PET showed 44% PR (RECIST 1.1) but 89% by CHOI and PET criteria. A novel approach to interrogate tumor texture composition demonstrated substantial change in lesion texture following induction therapy. To date selected Grade > 3 adverse events are neutropenia (n=8), fatigue (n=5), thromboembolic events (n=4), peripheral neuropathy (n=3), dehydration (n=2), anemia (n=3), thrombocytopenia (n=2), febrile neutropenia (n=2) and myalgias (n=2). Among 26 patients who have received at least one cycle of NabP-Gem, ten dose reductions and four dose delays were seen. To date, 11 patients have begun the Consolidation regimen with mFOLFIRINOX. Conclusions: The induction NabP-Gem regimen shows preliminary evidence of substantial activity similar to published reports (JCO.29:4548-54: 2011). Study will now evaluate the safety, efficacy and feasibilty of the Consolidation regimen with mFOLFIRINOX. Supported by the Seena Magowitz Foundation. Clinical trial information: NCT01488552.

Imatinib mesylate in advanced chordoma: A multicenter phase II study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 10003-10003 ◽  
Author(s):  
S. Stacchiotti ◽  
S. Ferrari ◽  
V. Ferraresi ◽  
G. Grignani ◽  
F. Crippa ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Collaborative Study ◽  
Dose Intensity ◽  
Preliminary Evidence ◽  
Tissue Response ◽  
Single Institution ◽  
Multicenter Phase ◽  
Prospective Phase ◽  
One Year

10003 Background: The antitumor activity of Imatinib in chordoma was preliminarily shown in a compassionate series of 18 pts. This prospective Phase II collaborative study was planned thereafter. Methods: From November 2004 to April 2006, 55 pts with progressing advanced chordoma were enrolled in this Phase II study. Cases were provided by 13 Italian centers and one Swiss. Imatinib was given at the planned dose of 800 mg/day (for a received dose intensity in excess of 600 mg/day), until evidence of progression. Mean age was 59 yrs, (range 24–86); PS 0–3 (=2 in 22%); site of origin was the sacrum in 60%, spine in 25%, skull base in 15%; the disease was metastatic in 43% and localized advanced in 57%. All tumors were positive for PDGFRB/PDGFB. Results: In 44 pts evaluable for antitumor response, 37 (84%) had stable disease as their best RECIST response, which was maintained for more than 6 months in 32, for a clinical benefit rate (CR+PR+SD=6mos) of 73%. In 7 of these SD pts (16%), a degree of objective tumor shrinkage was reported. Centralized radiological review is underway, focusing on non-dimensional, “tissue” response, and results thereof will be presented. In 39 pts who were symptomatic at baseline, subjective improvement of symptoms was claimed by 25 (64%). On ITT analysis, median PFS was 32 wks, with 38% of pts free from progression at one year, and 16% on treatment at 18 months. Most frequent drug-related adverse events were nausea (35%) and vomiting (30%), edema (30%), skin rash (28%), G1–3 anemia (24%), asthenia (17%), G1–3 leucopenia (13%). Conclusions: Preliminary evidence of Imatinib efficacy in chordoma was provided in a single-institution, compassionate setting, and is now confirmed by this multicenter Phase II study. On the basis of these data, an international effort on molecular-targeted therapy with Imatinib in advanced chordoma is warranted. No significant financial relationships to disclose.

Phase II study of induction therapy with gemcitabine and nab-paclitaxel followed by consolidation with mFOLFIRINOX in patients with metastatic pancreatic cancer.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 224-224 ◽  
Author(s):  
Ramesh K. Ramanathan ◽  
Peter Lee ◽  
John E. Seng ◽  
Stephen Patrick Anthony ◽  
Peter J. Rosen ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Optimal Sequence ◽  
Induction Regimen ◽  
Early Progression ◽  
Adequate Organ Function ◽  
One Year ◽  
To Receive ◽  
Dose Reductions ◽  
Clinical Trial Information

224 Background: FOLFIRINOX or NabP-Gem are now standard mPC regimens.The optimal sequence is not known.This phase II study evaluated the feasibility of NabP-Gem followed by FOLFIRINOX. Methods: Eligible pts had evidence of untreated mPC, ECOG 0-1 and adequate organ function. Pts received Nab-P (125 mg/m2) and Gem (1000 mg/ m2) weekly x 3 (Induction ) every 4 weeks for upto 6 cycles. FOLFIRINOX, q2 weeks (Consolidation regimen) was initiated after 6 cycles of the Induction regimen, or earlier in case of progression, and given for a maximum of 6 months (12 cycles). mFOLFIRINOX (NEJM, 364:1817-25: 2011) has been modified with growth factor prophylaxis and omission of bolus 5FU. One endpoint is to increase 1 year survival to > 70%, (n=30, 95% CI is +/- 20%). Results: Accrual goals have been met (n=31). The M/F ratio is 55%/45%, median is 66 years. In 23 pts with elevated baseline CA19-9 levels treated with NabP-Gem, 83% had a > 90% decrease. The response rate with the NabP-Gem regimen is 43%. Selected therapy related Grade > 3 adverse events during the course of both NabP-Gem and FOLFIRINOX therapy are: neutropenia (39%), fatigue (32%), anemia (19%), thrombocytopenia (16%), thromboembolic events (3%), peripheral neuropathy (16%), leukopenia (16%), nausea (3%), vomiting (3%), diarrhea (7%), and neutropenic fever (3%). During the course of NabP-Gem, 14 dose reductions and four dose delays were seen. Two pts had early progression at cycle 4 or less and were switched to the Consolidation regimen. Seventy one % (22/31) of pts went on to receive FOLFIRINOX (4 pts still on study), 4 received FOLFIRI, and one pt received FOLFOX as Consolidation therapy. One-year survival is projected to be 50-60%. Conclusions: The induction NabP-Gem regimen shows evidence of substantial activity similar to published reports (JCO.29:4548-54: 2011). The induction-consolidation strategy is feasible in selected patients. Cumulative side effects predominantly fatigue and neuropathy will require appropriate dose reductions or treatment breaks. (Supported by the Seena Magowitz foundation). Clinical trial information: NCT01488552.

The Pitfalls of Early Publication of Data in Acute Myeloid Leukemia: A Report from the Eastern Cooperative Oncology Group (ECOG).

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1952-1952 ◽  
Author(s):  
Jacob M. Rowe ◽  
Xiaopan Yao ◽  
Peter A. Cassileth ◽  
Frederick R. Appelbaum ◽  
Peter H. Wiernik ◽  
...  
Keyword(s):  
Older Adults ◽  
Clinical Trials ◽  
Phase Ii ◽  
Induction Therapy ◽  
Survival Data ◽  
Phase Ii Study ◽  
Cooperative Group ◽  
Autologous Transplant ◽  
Gm Csf ◽  
One Year

Abstract Results from clinical trials may change with time. Data presented in initial abstracts or early reports are often different from what appears in subsequent publications, sometimes due to a more rigorous analysis (as in initial response rates) or to maturity of data (as in reports of survival). Survival curves usually provide projected data based on Kaplan-Meier analyses. Such data may change with time when unexpected events occur (as, for example, relapse after T-cell depleted allogeneic transplants) or more patients advance to the initially projected time point. For AML, several groups have reported that there are very few relapses beyond 3 years. At issue is the optimal time for reporting these survival data. Table 1 reports data from 6 consecutive clinical trials addressing induction and post-remission questions in AML patients performed by ECOG. These data compare the 3-year overall survival (OS) and disease-free survival (DFS) for the identical cohorts of patients as presented at 1 year and at 3 years after completion of the study accrual. PC 486 was a phase II study of induction therapy followed by allogeneic or autologous transplant without prior consolidation. E 3489 was a US intergroup study in which patients received post-induction therapy using an allogeneic transplant (allo), an autologous transplant (auto) or chemotherapy (chemo). E1490 was a study in older adults of induction and consolidation with GM-CSF or placebo. E2491 was an intergroup study comparing ATRA induction versus standard chemotherapy in patients with APL. After consolidation, patients were randomized to maintenance with ATRA versus observation (obs). E3993 was a study in older adults comparing priming with GMCSF or placebo. E4995 was a phase II study of intensified induction and consolidation followed by an autologous transplant. For the same cohorts of patients the 3-year OS tends to decrease as the time from completion of study accrual increases. When looking at the DFS, while a decrease may also occur, in several studies there was an improved DFS with time (for example, in E2491, chemo to ATRA, or in E3993 with GM-CSF priming). There were no changes in either OS or DFS beyond 3 years (data not shown). Table 1: Three-year OS and DFS Presented at Different Time Points OS (%) DFS (%) Study One year Three years One year Three years PC 486 auto or allo HSCT 42 → 38 45 → 39 E 3489 allo HSCT 50 → 50 48 → 47 auto HSCT 47 → 46 39 → 39 chemo 56 → 51 36 → 36 E 1490 Induction / consolidation GM-CSF 23 → 22 23 → 24 placebo 15 → 12 16 → 15 E2491 APL induction+ maintenance ATRA + ATRA 87 → 84 72 → 73 ATRA + obs 83 → 80 61 → 60 chemo + ATRA 81 → 75 43 → 58 chemo + obs 54 → 45 16 → 18 E 3993 Induction/consolidation GM-CSF priming 13 → 11 5 → 10 placebo 14 → 14 9 → 9 E 4995 Induction / consolidation / auto HSCT 54 → 48 63 → 53 In conclusion: For large cooperative group studies, treatment results in AML presented one year from conclusion of study accrual are unlikely to dramatically alter the overall results. Nonetheless, some differences may occur, both in OS and DFS, warranting caution in interpreting the data and comparing with other published reports. Such differences are likely to be even greater if data are presented upon completion of study accrual, prior to one year - although, in a cooperative group setting, this should be balanced against the need to release data for future planning. Publication of interim data, before conclusion of the study accrual, may be misleading and are to be strongly discouraged. Three years appear to be the appropriate time for the publication of definitive survival data.

A phase IB/II randomized study of mFOLFIRINOX (mFFOX) + pegylated recombinant human hyaluronidase (PEGPH20) versus mFFOX alone in patients with good performance status metastatic pancreatic adenocarcinoma (mPC): SWOG S1313 (NCT #01959139).

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 208-208 ◽  
Author(s):  
Ramesh K. Ramanathan ◽  
Shannon McDonough ◽  
Philip Agop Philip ◽  
Sunil R. Hingorani ◽  
Jill Lacy ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Performance Status ◽  
Randomized Study ◽  
Dose Finding ◽  
Type 1 Error ◽  
Randomized Phase Ii ◽  
Metastatic Pancreatic Adenocarcinoma ◽  
Adequate Organ Function ◽  
The Impact

208 Background: PEGPH20 degrades hyaluronan (HA), a major component of the stroma, increases delivery of gemcitabine and prolongs survival in preclinical models. We evaluated the activity of PEGPH20 in combination with mFFOX in mPC , unselected for tumor HA. Methods: Pertinent eligibility: untreated mPC, PS of 0-1 and adequate organ function. Standard FFOX was modified to add prophylactic growth factor support and omit bolus 5FU. Due to increased thromboembolic (TE) events with PEGPH20, an amendment instituted LMWH prophylaxis in the PEGPH20 arm only. Following a dose finding cohort of mFFOX + PEGPH20, the Phase II study randomized patients (1:1) to the combination arm or mFFOX alone (n = 138). The primary endpoint was overall survival (OS), with a null median OS of 10 mo and an alternative of 15 mo (1-sided type 1 error 0.1, 80% power). Results: PEGPH20 at 3 mcg/kg, q2 weeks was more tolerable than twice weekly dosing. The randomized phase II study began May 2015. The planned interim futility analysis when 35 deaths occurred gave a HR of 0.44 favoring the standard arm, thus the study was closed to accrual (March 2017). As of August 22, 2017 (n = 111), the estimated median OS in the mFFOX arm was 15.1 mo (95% CI 10.1-15.7) vs 7.6 mo (95% CI 4.6-9.2) in the PEGPH20 arm. Conclusions: OS in the mFFOX control arm (15.1 mo) is longest yet reported. Addition of PEGPH20 to mFFOX is not recommended for further study and appears to be detrimental (HR = 0.48). The impact of PEGPH20 on OS was unexpected and in contrast to favorable results reported for the combination of gemcitabine/nab-paclitaxel + PEGPH20 especially in the HA high cohort (Hingorani S et al. A 4008, ASCO 2017). PEGPH20 with mFFOX caused increased toxicity (mostly GI and TE events) and decreased treatment duration compared to mFFOX alone. Tumor HA content will be analyzed. Funding: NIH/NCI grants CA180888, CA180819; and in part by Halozyme Inc. Clinical trial information: 01959139. [Table: see text]

Phase II study of weekly cisplatin, etoposide and irinotecan (PE/CPT) for refractory relapsed small cell lung cancer (SCLC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7088-7088 ◽  
Author(s):  
Y. Kim ◽  
K. Goto ◽  
Y. Nishiwaki ◽  
K. Kubota ◽  
H. Omatsu ◽  
...  
Keyword(s):  
Phase Ii ◽  
Overall Response Rate ◽  
Phase Ii Study ◽  
Performance Status ◽  
Phase Ii Trials ◽  
Organ Function ◽  
First Line Therapy ◽  
Adequate Organ Function ◽  
Grade 3 ◽  
Weekly Cisplatin

7088 Background: There is no standard treatment for relapsed SCLC. Irinotecan and etoposide has been studied in several phase II trials as active agents for relapsed SCLC. We reported the efficacy and tolerability of irinotecan combined with weekly cisplatin and etoposide (PE) in patients (pts) with sensitive relapsed SCLC (Goto, et al. Br J Cancer 2005). Methods: We conducted a phase II study to evaluate the efficacy and toxicity of PE/CPT regimen in pts with refractory relapsed SCLC, who had relapsed within 8 weeks after completion of first-line therapy. Pts must have measurable or assessable disease, age of 75 years or younger, performance status of 0 to 2 (ECOG), and adequate organ function. PE/CPT regimen consisted of cisplatin 25 mg/m2 on day 1 at one-week intervals for 9 weeks (at least 6 weeks), etoposide 60 mg/m2 on days 1–3 on week 1, 3, 5, 7, 9 (at least on week 1, 3, 5), and irinotecan 90 mg/m2 on day 1 on weeks 2, 4, 6, 8 (at least on week 2, 4, 6). After day 1 on week 2, G-CSF was administered on days when cytotoxic drugs were not given. Results: From May 2000 to January 2005, 30 pts were enrolled in this study. Pt characteristics were median age 64 years (range 44–75); 23 male and 7 female; 3 LD and 27 ED. Prior chemotherapy included PE in 13 pts, cisplatin and irinotecan in 7, carboplatin and etoposide in 5, and others in 5. 23 pts (77%) completed 6 or more weeks of chemotherapy. 2 CR and 19 PR were observed and the overall response rate was 70% (95% CI 50.6–85.3%). Grade 3/4 neutropenia, anemia and thrombocytopenia were observed in 60%, 73% and 47%, respectively. Grade 3/4 diarrhea was observed in only 7%. Coclusions: PE/CPT regimen was active and well tolerated for refractory relapsed SCLC. No significant financial relationships to disclose.

Phase II study of cyclophosphamide, interferon-α and betamethasone (CIB) as induction therapy for patients 60–75 years of age with multiple myeloma stages II and III

2003 ◽  
Vol 4 (4) ◽  
pp. 248-252 ◽  
Author(s):  
Jeanette Lundin ◽  
Anders Österborg ◽  
Magnus Björkholm ◽  
Bo Björkstrand ◽  
Fredrik Celsing ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Phase Ii ◽  
Induction Therapy ◽  
Phase Ii Study ◽  
Interferon Α

Phase II study of docetaxel and cisplatin in advanced non-small-cell lung cancer.

1998 ◽  
Vol 16 (5) ◽  
pp. 1948-1953 ◽  
Author(s):  
J Zalcberg ◽  
M Millward ◽  
J Bishop ◽  
M McKeage ◽  
A Zimet ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Phase Ii ◽  
Advanced Nsclc ◽  
Response Rate ◽  
Phase Ii Study ◽  
Performance Status ◽  
Objective Response ◽  
Small Cell ◽  
Small Cell Lung ◽  
Grade 3

PURPOSE Docetaxel (Taxotere, Rhone-Poulenc Rorer, Antony, France) and cisplatin are two of the most active single agents used in the treatment of non-small-cell lung cancer (NSCLC). A recently reported phase I study of the combination of docetaxel and cisplatin recommended a dose of 75 mg/m2 of both drugs every 3 weeks for subsequent phase II study. PATIENTS AND METHODS Eligible patients were aged 18 to 75 years with a World Health Organization (WHO) performance status < or = 2 and life expectancy > or = 12 weeks, with metastatic and/or locally advanced NSCLC proven histologically or cytologically. Patients were not permitted to have received prior chemotherapy, extensive radiotherapy, or any radiotherapy to the target lesion and must have had measurable disease. Concurrent treatment with colony-stimulating factors (CSFs) or prophylactic antibiotics was not permitted. Docetaxel (75 mg/m2) in 250 mL 5% dextrose was given intravenously (i.v.) over 1 hour immediately before cisplatin (75 mg/m2) in 500 mL normal saline given i.v. over 1 hour in 3-week cycles. Premedication included ondansetron, dexamethasone, promethazine, and standard hyperhydration with magnesium supplementation. RESULTS A total of 47 patients, two thirds of whom had metastatic disease, were entered onto this phase II study. The majority of patients were male (72%) and of good (WHO 0 to 1) performance status (85%). All 47 patients were assessable for toxicity and 36 were for response. Three patients were ineligible and eight (17%) discontinued treatment because of significant toxicity. In assessable patients, the overall objective response rate was 38.9% (95% confidence limits [CL], 23.1% to 56.5%), 36.1% had stable disease, and 25% progressive disease. On an intention-to-treat analysis, the objective response rate was 29.8%. Median survival was 9.6 months and estimated 1-year survival was 33%. Significant (grade 3/4) toxicities included nausea (26%), hypotension (15%), diarrhea (13%), and dyspnea mainly related to chest infection (13%). One patient experienced National Cancer Institute (NCI) grade 3 neurosensory toxicity after eight cycles. Grade 3/4 neutropenia was common and occurred in 87% of patients, but thrombocytopenia > or = grade 3 was rare (one patient). Significant (grade 3/4) abnormalities of magnesium levels were common (24%). Febrile neutropenia occurred in 13% of patients and neutropenic infection in 11%, contributing to two treatment-related deaths. No neutropenic enterocolitis or severe fluid retention was reported. CONCLUSION Compared with other active regimens used in this setting, the combination of docetaxel and cisplatin in advanced NSCLC is an active regimen with a similar toxicity profile to other combination regimens.

NCT04552223: A phase II study of nivolumab plus BMS-986016 (relatlimab) in patients with metastatic uveal melanoma (UM) (CA224-094).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS9590-TPS9590
Author(s):  
Jose Lutzky ◽  
Lynn G. Feun ◽  
Norma Magallanes ◽  
Deukwoo Kwon ◽  
J. William Harbour
Keyword(s):  
T Cells ◽  
Mhc Class Ii ◽  
Uveal Melanoma ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Performance Status ◽  
Objective Response ◽  
Type I ◽  
Tumor Escape ◽  
Potential Candidate

TPS9590 Background: Uveal melanoma (UM) is a rare disease but 50% of patients will eventually develop metastatic disease, for which not effective therapy is available. Liver-directed therapies, immunotherapy, targeted therapy and chemotherapy have limited activity [1]. Lymphocyte activation gene 3(LAG-3) is an immune checkpoint receptor associated with decreased T-cell effector function and tumor escape. Preclinical models have shown that dual inhibition of LAG-3 and PD-1 blockade generates synergistic anti-tumor activity [2]. Recent preclinical data indicates that uveal melanoma CD8+ T cells express the checkpoint receptor LAG3 to a greater extent than PD1 or CTLA4 [3,4]. Therefore, LAG3 is a potential candidate for checkpoint inhibitor immunotherapy in UM. Relatlimab is a human LAG-3-specific antibody isolated from immunized transgenic mice which binds to a defined epitope on LAG-3 with high affinity and specificity and potently blocks the interaction of LAG-3 with its ligand, MHC Class II. Methods: This is an open-label, single arm, single site investigator-initiated phase II study, NCT04552223. Based on Simon two-stage minimax design, 13 patients will be enrolled in Stage 1. If at least one response is noted, the study will proceed to Stage 2 and enroll an additional 14 patients. The null hypothesis will be rejected if 4 or more responses are observed among 27 patients. This design achieves 5% type I error and 80% power when the true ORR is 20%. The trial opened to accrual in December 2020. As of February 15, 2021 four patients had been enrolled the first stage of accrual. Main eligibility criteria include patients with biopsy proven metastatic uveal melanoma, previously untreated with PD-1, CTLA-4 and/or LAG-3 blocking antibodies and in good performance status. Enrolled patients are treated in the outpatient setting. Nivolumab 480 mg is mixed in the same bag with relatlimab 160 mg and administered intravenously over 60 minutes every 4 weeks until disease progression or intolerable toxicity for up to 24 months. The primary endpoint is best objective response rate (ORR). Secondary endpoints include disease control rate (DCR), progression-free survival (PFS), overall survival (OS), median duration of response (mDOR), and adverse events (AEs). Correlative studies will evaluate pre- and post-treatment characteristics of T cells in the tumor microenvironment and blood. Clinical trial information: NCT04552223.

Sign in / Sign up

Export Citation Format

Share Document