Open-label study of pemetrexed alone for chemonaive patients and pre-treated patients with malignant pleural mesothelioma: Outcomes of the International Expanded Access Program (EAP)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7709-7709
Author(s):  
P. Taylor ◽  
J. von Pawel ◽  
B. Castagneto ◽  
G. Dark ◽  
M. Marangolo ◽  
...  
Keyword(s):  
Median Survival ◽  
Phase Ii ◽  
Malignant Pleural Mesothelioma ◽  
Survival Data ◽  
Single Agent ◽  
Safety Data ◽  
Phase Iii ◽  
Pleural Mesothelioma ◽  
Open Label ◽  
Pretreated Group

7709 Background: In a previous phase II study of chemonaive malignant pleural mesothelioma (MPM) patients (pts), single-agent pemetrexed (P) resulted in a 14.1% response rate (RR) and median survival of 10.7 mos (95% CI 7.7–14.5) (Scagliotti 2003). Likewise, the P arm in a phase III study of pre-treated MPM pts yielded an 18.7% RR (40.7% with stable disease, SD) and median survival of 8.4 mos (95% CI 6.2–10.5) (Jassem 2006). The EAP provided 3311 MPM pts with access to P alone, P plus cisplatin, or P plus carboplatin in 13 countries. In this abstract we report on the safety and efficacy data of those MPM pts treated with P alone. Methods: Eligible pts had histologic or cytologic diagnosis of MPM and were either chemonaïve or previously treated with =1 line(s) of chemotherapy. Pts pre-treated with P were allowed if they had experienced clinical benefit from the prior P. Treatment consisted of P (500 mg/m2) once (day 1) every 21 days with standard pre-medication of vitamin B12, folic acid, and dexamethasone. Investigator-determined response (RR) and survival data (with censoring) were recorded at the end of study participation. Myelosuppression data (CTC) were also collected. Results: 812 MPM pts (319 chemonaïve; 493 pre-treated) received =1 dose of P and were evaluated for safety, and 643 pts (247 chemonaïve; 396 pre-treated) were evaluated for efficacy (RR and survival). In chemonaïve pts with MPM, the median age was 69 yrs (range: 39–87 yrs), 78.1% were male, and 71.6% had a KPS ≥80 (of the 93% who had PS evaluated). In pre-treated pts with MPM, the median age was 63 yrs (range: 31–85 yrs), 75.9% were male, and 74.5% had a KPS ≥80 (of the 95% who had PS evaluated). Both groups received a median of 4 cycles (chemonaive group range 1–18; pretreated group range 1–23). See the table for efficacy and safety data. Conclusions: Results of the EAP confirm earlier phase II and phase III studies. No significant financial relationships to disclose. [Table: see text]

Phase II Study of Vinflunine in Malignant Pleural Mesothelioma

2007 ◽  
Vol 25 (30) ◽  
pp. 4751-4756 ◽  
Author(s):  
Denis C. Talbot ◽  
Jacques Margery ◽  
Gérard Dabouis ◽  
Graham Dark ◽  
Henry Taylor ◽  
...  
Keyword(s):  
Median Survival ◽  
Phase Ii ◽  
Malignant Pleural Mesothelioma ◽  
Response Rate ◽  
Single Agent ◽  
Dose Intensity ◽  
High Dose ◽  
Pleural Mesothelioma ◽  
Multiple Testing Procedure ◽  
Microtubule Inhibitor

Purpose Malignant pleural mesothelioma (MPM) is a disease of increasing incidence for which treatment options are limited. This study reports the clinical efficacy data for vinflunine, a novel microtubule inhibitor, in MPM. Patients and Methods Patients with a histologically confirmed diagnosis of MPM were eligible for enrollment onto this multicenter phase II trial if they had not received prior chemotherapy or radiotherapy and had measurable lesions by Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Vinflunine 320 mg/m2 by 10-minute intravenous infusion was administered on day 1 of 21-day cycles. Modifications of dose and schedule were made according to National Cancer Institute Common Toxicity Criteria version 2.0. Efficacy was assessed by an external, independent radiologist. The one-sample multiple testing procedure of Fleming was applied at the predetermined recruitment stages of 20 and 40 assessable patients. Results Sixty-seven patients were enrolled. Five patients were not assessable for tumor response. The response rate was 13.8% (95% CI, 6.5% to 24.7%). The median survival was 10.8 months (95% CI, 7.8 to 12.0 months). The most common adverse events were anemia, neutropenia, fatigue, constipation, and nausea. Of grade 3 and 4 toxicities, neutropenia and constipation were the most common (45% and 9% of patients, respectively). Conclusion Vinflunine can be delivered with high-dose intensity in patients with MPM. The response rate and median survival are encouraging for a single agent. These data suggest that vinflunine should be further evaluated in the management of MPM.

Survival of patients (pts) with metastatic melanoma treated with the anti-CTLA4 monoclonal antibody (mAb) CP-675,206 in a phase I/II study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8524-8524 ◽  
Author(s):  
J. Gomez-Navarro ◽  
S. Antonia ◽  
J. Sosman ◽  
J. M. Kirkwood ◽  
B. Redman ◽  
...  
Keyword(s):  
Phase I ◽  
Metastatic Melanoma ◽  
Median Survival ◽  
Phase Ii ◽  
Survival Data ◽  
Phase I Study ◽  
Objective Response ◽  
Phase Iii ◽  
Open Label ◽  
Expansion Cohort

8524 Background: The fully human anti-CTLA4 mAb CP-675,206 has demonstrated clinical activity in pts with metastatic melanoma. Prolonged survival was observed in a prior single-dose phase I study, even in pts who did not achieve objective tumor responses. Methods: A multidose phase I/II trial was conducted in pts (N = 119) with histologically confirmed stage IIIc (unresectable) or stage IV recurrent metastatic melanoma and ECOG PS = 1. The study consisted of a phase I, open-label, multidose study (3, 6, and 10 mg/kg) and a phase I expansion cohort for HLA-A2.1+ pts (10 mg/kg monthly [Q1M]), followed by a phase II open-label study of 2 dosing regimens: 10 mg/kg Q1M and 15 mg/kg every 3 months (Q3M). The primary endpoint was safety in phase I, immune monitoring in the expansion cohort, and response in phase II. Survival was analyzed as a secondary endpoint. Results: In the phase I study, Kaplan-Meier estimates of median overall survival were 17.6 months for all dose groups combined (n = 28). In the phase II study, median survival was 10.3 months in the 10 mg/kg arm and 11.0 months in the 15 mg/kg arm. Survival outcomes were favorable, compared with historical median survival of 7 months, independent of whether pts achieved an objective response. Updated survival data will be presented. Conclusions: Patients participating in a multiple dose study of CP-675,206 showed a survival time that was greater than expected on historic controls. These observations support the endpoints of an ongoing randomized phase III study in melanoma to further evaluate survival in the frontline setting. [Table: see text] [Table: see text]

scholarly journals 462 A randomised open-label phase I/II study adding ONCOS-102 to pemetrexed/cisplatin in patients with unresectable malignant pleural mesothelioma – 24 month survival data

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A491-A491
Author(s):  
Magnus Jaderberg ◽  
Luis Paz-Ares ◽  
Susana Cedres ◽  
Charles Ricordel ◽  
Nicolas Isambert ◽  
...  
Keyword(s):  
Survival Rate ◽  
Malignant Pleural Mesothelioma ◽  
Survival Data ◽  
Phase Iii ◽  
Control Group ◽  
Pleural Mesothelioma ◽  
List Type ◽  
Open Label ◽  
Open Label Phase ◽  
Experimental Group

BackgroundMalignant pleural mesothelioma (MPM) is an aggressive malignancy without curative treatment. Standard of care (SOC) include pemetrexed/cisplatin and nivolumab/ipilimumab with median overall survival in unresectable disease of 12.1 months and 18.1 months respectively.1 2 ONCOS-102 is a granulocyte-macrophage colony stimulating factor (GM-CSF) expressing oncolytic adenovirus (Ad5/3-D24-GMCSF) with a unique ability to both prime and boost immune responses. The aim of the study was to assess efficacy and safety of ONCOS-102 in combination with SOC chemotherapy in 1st and 2nd line unresectable MPM.MethodsTwenty patients (experimental arm) were allocated to receive ONCOS-102 given intratumorally under CT or US guidance at a dose of 3 x 1011 VP on Day 1, 4, 8, 36, 78 and 120 plus six cycles of SOC starting on Day 22. Eleven patients (control group) received SOC. Imaging was done at baseline, Day 43–64 and 127–148 with regular monitoring of blood and biopsy based immune markers. Primary objective was safety and tolerability. Secondary objectives were ORR, PFS and OS as well as immunological activation. An analysis of 24 month survival data compared randomised only patients excluding six patients in the single-arm safety lead-in.Results24-month survival rate for 1st line pts was 50% in the experimental group and 0% in the control group with mOS of 25.0 months and 13.5 months respectively (N.S). Based on censoring, mOS in the experimental group will be within 21.9 – 25.0 months range. mOS across both 1st and 2nd line was 19.3 and 18.3 months for experimental and control patients (N.S). mPFS was 9.8 months in the experimental group and 7.6 in the control group (N.S.).ConclusionsThe survival rate of patients receiving ONCOS-102 in combination with SOC was seen to be numerically higher than previously reported for SOC or nivolumab/ipilimumab. Improved survival was associated with ONCOS-102 induced immune activation with a favourable TME modulation providing scientific rationale for combination with check point inhibition.Trial RegistrationClinicalTrials.gov NCT02879669ReferencesVogelzang, et al, Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol 2003;21: 2636–44.Baas P, et al, First-line nivolumab plus ipilimumab in unresectable pleural mesothelioma (CheckMate 743): a multicentre, randomised, open-label, phase 3 trial. The Lancet 2021; 397: 375–386.Ethics ApprovalThis study was approved by the IRBs of all the participating sites in Madrid, Barcelona, Rennes and Poitiers.

Tolerability and Efficacy of Bortezomib Added to CVP-R for Previously Untreated Advanced Stage Follicular Lymphoma: Interim Analysis of a Phase II Study by the NCIC Clinical Trials Group.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1576-1576 ◽  
Author(s):  
Laurie H Sehn ◽  
David A Macdonald ◽  
Sheldon H. Rubin ◽  
Morel Rubinger ◽  
Kevin R Imrie ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Phase Ii ◽  
Interim Analysis ◽  
Standard Dose ◽  
Single Agent ◽  
Acceptable Level ◽  
Phase Iii ◽  
Hematologic Toxicity ◽  
Open Label ◽  
Grade 3

Abstract Background: Despite recent improvements in therapy, follicular lymphoma (FL) remains incurable with standard treatment, warranting investigation of new approaches. Bortezomib, the first-in-class proteasome inhibitor has demonstrated promising efficacy as a single agent in heavily pretreated patients (pts) with FL. This is the first study to evaluate the safety and efficacy of the addition of bortezomib to cyclophosphamide, vincristine, prednisone and rituximab (CVP-R). Methods: This is a phase II multi-center open-label trial adding bortezomib (1.3 mg/m2 day 1&8) to standard dose C(750 mg/m2) V(1.4 mg/m2, capped at 2 mg) P(40 mg/m2 × 5) –R(375 mg/m2) for up to 8 cycles in pts with newly diagnosed stage III/IV FL requiring therapy. Planned accrual is 90 patients. A two-stage design was employed with a planned interim analysis of the first 28 patients to ensure an acceptable level of neurotoxicity (defined as less than 5/28 patients with grade 3/4 neurotoxicity after the first 4 cycles) and meaningful response rate (more than 12/28 patients with a complete response following 8 cycles), prior to enrolling remaining patients. Results: Median age of the first 28 patients was 55 years (range, 30–73). Fifty percent were male and 79% had stage IV disease. FLIPI score at study entry: low 14%, intermediate 43%, high 43%. Overall, the combination of bortezomib and CVP-R was extremely well tolerated. To date, no pts have developed grade 4 neurotoxicity and only 1/28 (4%) has developed grade 3 neurotoxicity within the first 4 cycles (neuropathic pain which resolved without need for treatment modification). The incidence of grade 1 and 2 neurotoxicity was 54% and 25% respectively. Only 3 pts discontinued therapy prematurely (2 pt refusal, 1 progressive disease). Ninety-four percent of planned bortezomib treatments in the first four cycles and 93% of vincristine doses were administered without dose reduction. Hematologic toxicity was mild, with no pts experiencing grade 3/4 anemia or thrombocytopenia. Only 2 episodes of febrile neutropenia occurred and no grade 3/4 infections were noted. Although it is too early to report on efficacy in this ongoing trial, response objectives for stage I have been met, and enrollment to stage 2 is underway. Conclusions: The addition of bortezomib to standard dose CVP-R is very well tolerated, with an acceptable level of neurotoxicity, without compromising the delivery of bortezomib or vincristine. This ongoing study will provide toxicity and efficacy data to facilitate the development of a planned phase III trial.

Randomized phase II trial of two dose schedules of carboplatin/paclitaxel/cetuximab in stage IIIB/IV non-small cell lung cancer (NSCLC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7586-7586 ◽  
Author(s):  
M. N. Saleh ◽  
M. A. Socinski ◽  
D. Trent ◽  
T. Dobbs ◽  
L. M. Zehngebot ◽  
...  
Keyword(s):  
Phase Ii ◽  
Survival Data ◽  
Single Agent ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Stage Iiib ◽  
Open Label ◽  
Randomized Phase Ii ◽  
Igg1 Monoclonal Antibody ◽  
Epidermal Growth

7586 Background: Cetuximab, an IgG1 monoclonal antibody targeting the epidermal growth factor receptor (EGFR) on both normal and tumor cells, has been investigated in advanced NSCLC as a single agent and in combination with chemotherapy. This ongoing randomized phase II open-label trial evaluates cetuximab in combination with carboplatin (Cb) and paclitaxel (Pac) when given in two dose schedules to patients (pts) with previously untreated stage IIIB/IV NSCLC. Methods: Eligible pts were randomized to 1 of 2 treatment arms. Cetuximab treatment was identical in both arms: 400 mg/m2 IV on day 1 and 250 mg/m2 weekly thereafter. Beginning on day 8, a schedule of Cb AUC=6 IV and Pac 225 mg/m2 IV given on a 3-week cycle was compared with a schedule of Cb AUC=6 IV q4 weeks and Pac 100 mg/m2 IV given weekly for 3 weeks of each 4-week cycle. Pts who achieve CR, PR, or SD after 4 cycles may continue weekly cetuximab monotherapy until disease progression or unacceptable toxicity. The primary objectives were to estimate median progression-free survival (PFS) and the PFS rate at 6 months. Secondary objectives included response rate. Results: The study has completed accrual, with 168 pts randomized and 165 treated. Data are available for 164 pts and confirmed responses for 155 pts. Conclusions: Cetuximab combined with Cb and Pac in both dose schedules demonstrated activity and an acceptable toxicity profile in pts with NSCLC. Final PFS and overall survival data are pending. No significant financial relationships to disclose. [Table: see text]

A randomized phase III trial of active symptom control (ASC) with or without chemotherapy in the treatment of patients with malignant pleural mesothelioma: First results of the Medical Research Council (MRC) / British Thoracic Society (BTS) MS01 trial

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. LBA7525-LBA7525 ◽  
Author(s):  
M. Muers ◽  
P. Fisher ◽  
M. Snee ◽  
E. Lowry ◽  
M. O'Brien ◽  
...  
Keyword(s):  
Randomized Trial ◽  
Median Survival ◽  
Malignant Pleural Mesothelioma ◽  
Survival Benefit ◽  
Phase Iii ◽  
Pleural Mesothelioma ◽  
Significant Survival Benefit ◽  
Significant Survival ◽  
Symptom Palliation ◽  
Weekly Cycles

LBA7525 Background: Although chemotherapy is widely used in the treatment of mesothelioma it has never been compared in a randomized trial with ASC alone. Two chemotherapy regimens that had shown good symptom palliation in phase II studies were chosen for investigation. Methods: Patients with malignant pleural mesothelioma were randomized to ASC alone (regular follow-up in a specialist clinic, and treatment could include steroids, analgesics, bronchodilators, palliative radiotherapy, etc), ASC+MVP (4 × 3-weekly cycles of mitomycin 6g/m2, vinblastine 6mg/m2, and cisplatin 50mg/m2), or ASC+N (12 weekly injections of vinorelbine 30mg/m2). 420 patients were required to detect a 3-month improvement in median survival with ASC+CT (both chemotherapy arms combined). Quality of Life (QL) was assessed using the EORTC QLQ-C30. Results: 409 patients were accrued (136 ASC, 137 ASC+MVP, 136 ASC+N). Median age: 65 years, male: 91%, Performance status 0: 23%, Epithelial histology: 73%, Stage III: 33%, Stage IV: 48%. In the ASC+MVP group 61% received all 4 cycles, and in the ASC+N group 49% received at least 10 weekly cycles. Good symptom palliation (defined as prevention, control or improvement) was achieved in all 3 groups, and no between-group differences were observed in 4 pre-defined QL subscales (physical functioning, dyspnoea, pain and global QL). A small (not conventionally significant) survival benefit was seen for ASC+CT (349 deaths, HR 0.89, 95%CI 0.72, 1.12, p=0.32). Median survival: ASC: 7.6 months, ASC+CT: 8.5 months. Exploratory analyses suggested a survival advantage for vinorelbine compared to ASC alone (HR 0.81, 95%CI 0.63, 1.05, p=0.11), with a median survival of 9.4 months, but no evidence of a benefit with MVP (HR 0.98, 95%CI 0.76, 1.28), p=0.91). Conclusions: This is the 2nd largest ever randomized trial in mesothelioma and the first to compare ASC with or without chemotherapy. Although the addition of chemotherapy to ASC did not result in a conventionally significant survival benefit, there was an indication that vinorelbine should be investigated further, and that MVP probably has no role in this disease. [Table: see text]

ICORG 06-41: A phase II trial of single-agent sorafenib in the treatment of platinum-pretreated relapsed gastroesophageal adenocarcinoma (GECa).

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 88-88 ◽  
Author(s):  
Louise Catherine Connell ◽  
Seamus O'Reilly ◽  
Glenn Webb ◽  
Brian Moulton ◽  
Imelda Parker ◽  
...  
Keyword(s):  
Phase Ii ◽  
Kinase Inhibitor ◽  
Single Agent ◽  
Locally Advanced ◽  
Safety Data ◽  
Primary Objective ◽  
Open Label ◽  
Oncology Research ◽  
Translational Studies ◽  
Gastroesophageal Adenocarcinoma

88 Background: Over 1 million individuals worldwide annually are diagnosed with GECa. The majority of patients(pts) present with inoperable locally advanced or metastatic disease(dx). Even with resectable dx 5 year survival is low at ~40% with current best treatment (tx). Following initial platinum based therapy there is no established standard 2nd line tx. Besides HER2-directed therapy there has been little progress with targeted biologic agents. ICORG, the all-Ireland Cooperative Oncology Research Group investigated the utility of the tyrosine kinase inhibitor sorafenib in a multicentre trial. Methods: A prospective Phase II, nonrandomised, open label, one arm study of single agent sorafenib in the tx of platinum pre-treated relapsed GECa was conducted. Primary objective was dx control rate (DCR) post 4 months of tx. Secondary endpoints were OS, PFS, TTP, ORR, tolerability/toxicity and biomarkers of tx response/resistance. The protocol allowed for an interim analysis to be performed if clinically indicated. A sample size of 54 pts was identified using the single stage Fleming design approach to test whether the proportion responding, P, is ≤ 0.35 or ≥ 0.50. Pts received Sorafenib 400mg bid p.o. continuously q28days until dx progression or intolerable toxicity. Response by RECIST was evaluated by CT q8weeks. For pts with sufficient tumour samples translational studies were done. Results: An interim review performed in Nov 2012 (35 months post study opening) indicated that 33/41 evaluable pts recruited to date had progressed before completing 4 months of tx. Therefore, the number of evaluable pts with dx control could not reach the pre-specified figure of 22, & the hypothesis P >= 0.50 was rejected. Fifteen pts had just 1 cycle of tx, 5 of whom completed ≤ 2 weeks. A further 14 pts had 2 cycles. Median survival time to progression was 56 days (95% CI 53 – 59 days).Median OS was 120 days (95% CI 91 – 149 days). Safety data analyses and translational studies are ongoing and will be available for presentation at the meeting. Conclusions: Sorafenib as monotherapy is inactive in platinum pretreated pts with relapsed GECa. A significant unmet clinical need for novel effective therapies remains. Clinical trial information: 2008-005062-31.

scholarly journals Prophylactic Irradiation of Tracts in Patients With Malignant Pleural Mesothelioma: An Open-Label, Multicenter, Phase III Randomized Trial

2019 ◽  
Vol 37 (14) ◽  
pp. 1200-1208 ◽  
Author(s):  
Neil Bayman ◽  
Wiebke Appel ◽  
Linda Ashcroft ◽  
David R. Baldwin ◽  
Andrew Bates ◽  
...  
Keyword(s):  
Chest Wall ◽  
Malignant Pleural Mesothelioma ◽  
Phase Iii ◽  
Radiation Dermatitis ◽  
Pleural Mesothelioma ◽  
Open Label ◽  
Significant Difference ◽  
Prophylactic Irradiation ◽  
Prophylactic Radiotherapy ◽  
To Receive

PURPOSE Prophylactic irradiation to the chest wall after diagnostic or therapeutic procedures in patients with malignant pleural mesothelioma (MPM) has been a widespread practice across Europe, although the efficacy of this treatment is uncertain. In this study, we aimed to determine the efficacy of prophylactic radiotherapy in reducing the incidence of chest wall metastases (CWM) after a procedure in MPM. METHODS After undergoing a chest wall procedure, patients with MPM were randomly assigned to receive prophylactic radiotherapy (within 42 days of the procedure) or no radiotherapy. Open thoracotomies, needle biopsies, and indwelling pleural catheters were excluded. Prophylactic radiotherapy was delivered at a dose of 21 Gy in three fractions over three consecutive working days, using a single electron field adapted to maximize coverage of the tract from skin surface to pleura. The primary outcome was the incidence of CWM within 6 months from random assignment, assessed in the intention-to-treat population. Stratification factors included epithelioid histology and intention to give chemotherapy. RESULTS Between July 30, 2012, and December 12, 2015, 375 patients were recruited from 54 centers and randomly assigned to receive prophylactic radiotherapy (n = 186) or no prophylactic radiotherapy (n = 189). Participants were well matched at baseline. No significant difference was seen in the incidence of CWM at 6 months between the prophylactic radiotherapy and no radiotherapy groups (no. [%]: 6 [3.2] v 10 [5.3], respectively; odds ratio, 0.60; 95% CI, 0.17 to 1.86; P = .44). Skin toxicity was the most common radiotherapy-related adverse event in the prophylactic radiotherapy group, with 96 patients (51.6%) receiving grade 1; 19 (10.2%), grade 2; and 1 (0.5%) grade 3 radiation dermatitis (Common Terminology Criteria for Adverse Events, version 4.0). CONCLUSION There is no role for the routine use of prophylactic irradiation to chest wall procedure sites in patients with MPM.

scholarly journals A phase II study of nivolumab: a multicenter, open-label, single arm study in malignant pleural mesothelioma (MERIT)

2018 ◽  
Vol 29 ◽  
pp. vii52
Author(s):  
Keisuke Aoe ◽  
Morihito Okada ◽  
Takashi Kijima ◽  
Terufumi Kato ◽  
Nobukazu Fujimoto ◽  
...  
Keyword(s):  
Phase Ii ◽  
Malignant Pleural Mesothelioma ◽  
Phase Ii Study ◽  
Pleural Mesothelioma ◽  
Open Label
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