Phase II study of amrubicin for previously treated patients with malignant pleural mesothelioma.

e21095 Background: Malignant pleural mesothelioma (MPM) is a rare disease with few effective treatments and poor prognosis. Although pemetrexed (PEM) and cisplatin for the first-line treatment, and nivolumab for the second-line are considered as the standard treatment for patients with unresectable disease, these effects are still limited. There are no other effective agents for second-line treatment, although PEM-based regimens, vinorelbine, gemcitabine are recommended by some guidelines. Novel therapeutic strategies for the treatment of MPM are urgently required. Amrubicin (AMR) is a chemically synthesized anthracycline-based anticancer drug that inhibits cell growth by stabilizing the cleavable complex via topoisomerase II. The same anthracycline; adriamycin was one of the key drugs for MPM prior to the appearance of PEM, but its efficacy against MPM has not been revealed. Thus, we planned a phase II study of AMR therapy for previously treated MPM. Methods: Eligibility criteria were previously treated patients with unresectable MPM, performance status 0-2, age≦75, and adequate hematological, hepatic and renal function. Patients were treated with injections of AMR 35 mg/m2 on days 1, 2, and 3. The treatments were repeated every 3-4 weeks. The primary endpoint was the response rate (RR), the secondary endpoints were safety, progression-free survival time (PFS), overall survival time (OS). Results: Although the number of target cases was 32 cases, case registration was delayed and evaluation was performed with 10 cases enrolled. Patients' characteristics were as follows: male/female = 9/1; performance status 0/1/2 = 0/10/0; median age (range) = 67 (49-73); histology epithelial/sarcomatoid/mixed = 4/3/3; stage (IMIG) I/II/III/IV/postoperative recurrence = 0/1/4/4/1. RR was 10.0% (1/10), median PFS was 1.6 months and median OS was 6.6 months. Disease control rate was 50.0% (5/10). Adverse events of Grade 3 or 4 were neutropenia 60.0% (6/10), thrombocytopenia 10.0% (1/10), anemia 10.0% (1/10), febrile neutropenia 10.0% (1/10), and pneumonia 10.0% (1/10). Conclusions: This study demonstrated that AMR therapy for previously treated MPM was tolerable. The efficacy was limited, but may be effective in some cases. Clinical trial information: UMIN000006381 .

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Amrubicin in previously treated patients with malignant pleural mesothelioma: A phase II study

Thoracic Cancer ◽

10.1111/1759-7714.13490 ◽

2020 ◽

Vol 11 (7) ◽

pp. 1972-1978

Author(s):

Takaya Ikeda ◽

Shinnosuke Takemoto ◽

Hiroaki Senju ◽

Hiroshi Gyotoku ◽

Hirokazu Taniguchi ◽

...

Keyword(s):

Phase Ii ◽

Malignant Pleural Mesothelioma ◽

Phase Ii Study ◽

Pleural Mesothelioma ◽

Previously Treated Patients ◽

Previously Treated

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9011 NGR-hTNF, a vascular targeting agent (VTA), in previously treated patients with malignant pleural mesothelioma (MPM): a phase II study

European Journal of Cancer Supplements ◽

10.1016/s1359-6349(09)71724-0 ◽

2009 ◽

Vol 7 (2) ◽

pp. 509 ◽

Cited By ~ 1

Author(s):

V. Gregorc ◽

G.L. Ceresoli ◽

P.A. Zucali ◽

F.G. De Braud ◽

E. Bajetta ◽

...

Keyword(s):

Phase Ii ◽

Malignant Pleural Mesothelioma ◽

Phase Ii Study ◽

Vascular Targeting ◽

Pleural Mesothelioma ◽

Previously Treated Patients ◽

Previously Treated ◽

Vascular Targeting Agent

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1900P RAMES trial: A multicentre, double-blind, randomized, phase II study on gemcitabine plus ramucirumab versus gemcitabine alone as second-line treatment for advanced malignant pleural mesothelioma (MPM)

Annals of Oncology ◽

10.1016/j.annonc.2020.08.1443 ◽

2020 ◽

Vol 31 ◽

pp. S1078

Author(s):

M. Pagano ◽

G.L. Ceresoli ◽

P.A. Zucali ◽

G. Pasello ◽

M.C. Garassino ◽

...

Keyword(s):

Phase Ii ◽

Malignant Pleural Mesothelioma ◽

Phase Ii Study ◽

Pleural Mesothelioma ◽

Line Treatment ◽

Second Line ◽

Double Blind ◽

Randomized Phase Ii

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Phase II Study of Gemcitabine Plus Docetaxel as Second-Line Treatment in Malignant Pleural Mesothelioma

American Journal of Clinical Oncology ◽

10.1097/coc.0b013e3181cae90e ◽

2011 ◽

Vol 34 (1) ◽

pp. 38-42 ◽

Cited By ~ 18

Author(s):

Ioannis Tourkantonis ◽

Nektaria Makrilia ◽

Maria Ralli ◽

Christina Alamara ◽

Ilias Nikolaidis ◽

...

Keyword(s):

Phase Ii ◽

Malignant Pleural Mesothelioma ◽

Phase Ii Study ◽

Pleural Mesothelioma ◽

Line Treatment ◽

Second Line

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A Multicentre Phase II Study of the Aminopeptidase Inhibitor, CHR- 2797, in the Treatment of Elderly and/or Previously Treated patients with Acute Myeloid Leukemia.

Blood ◽

10.1182/blood.v112.11.961.961 ◽

2008 ◽

Vol 112 (11) ◽

pp. 961-961 ◽

Cited By ~ 2

Author(s):

B. Lowenberg ◽

F. Davies ◽

C. Müller-Tidow ◽

Ulrich Dührsen ◽

A. Burnett ◽

...

Keyword(s):

Bone Marrow ◽

Phase Ii ◽

Phase Ii Study ◽

Performance Status ◽

Single Agent ◽

Clinical Activity ◽

Open Label ◽

Elderly Aml ◽

Previously Treated Patients ◽

Previously Treated

Abstract Tosedostat (TSD, CHR-2797) is an aminopeptidase inhibitor that selectively depletes amino acid pools in malignant cells, resulting in anti-proliferative, pro-apoptotic and antiangiogenic effects. In a phase I study, treatment with TSD resulted in complete remission in a number of refractory AML patients. The primary objective of this phase II study was to determine whether TSD was a sufficiently effective therapy to warrant pivotal studies. Methods. This was an open label, single agent, phase II study to assess clinical activity of TSD in elderly and/or previously treated patients with AML/MDS. Patients were treated with once daily oral doses of the maximum acceptable dose (130 mg) of TSD for up to 84 days. Further treatment was allowed if, in the opinion of the investigator, this was considered to be beneficial. Clinical responses were assessed by monthly bone marrow aspirates and weekly hematological assessments. Results. Of the 41 TSD-treated patients with AML (n=38) or MDS (n=3), who were enrolled between March and October 2007, 27 were male, 14 female, with a mean age of 67 years (range 34–82). The median performance status (ECOG) at baseline was 1 (range 0–2). Twelve (31.6%) AML patients and 2 (66.7%) MDS patients were chemotherapy naïve, and 9 (23.7%) AML patients had either secondary disease or adverse cytogenetics. For 16 (39%) patients, treatment with TSD was a second or later salvage attempt. Thirty two patients (30 AML, 2 MDS-RAEB1 and 2) received ≥28 days treatment, and 21 (51.2%) patients completed the formal 84-day study period (19 AML, 2 MDS). Nine (22%) of the patients (7 AML, 2 MDS) continued treatment with TSD after 84 days, and 6 (15%) patients were on TSD in total for more than 6 months (4 AML, 2 MDS). Ten (26.3%) of the AML patients responded to treatment; amongst these, 2 patients received TSD as 2nd/3rd salvage therapy, and a further 2 patients did not show a complete response (CR) after 2 previous induction courses of chemotherapy. Three AML patients achieved a CR (< 5% blasts in bone marrow), of whom 2 were in durable remission (232 days, continuing*; 171 days), and 7 had a partial response (PR, 5–15% blasts) lasting approximately 1–3 months. Two (66.7%) of the MDS patients also responded to treatment with TSD; these patients maintained stable disease for more than 6 months. All responders (CR, PR and SD) were >60 years at the time of the first dose. Median overall survival in AML patients was 130 days (range 8 – 478 days*). The most frequently reported adverse events were: fatigue (61%), thrombocytopenia (49%), pyrexia (39%), peripheral edema (39%) and diarrhea (34%); 9 (22%) patients withdrew due to drug related toxicity. TSD had no effect on hemoglobin or neutrophils. Conclusions. This study in patients with advanced AML/MDS with adverse prognosis demonstrates the anti-leukemic activity of TSD in elderly AML patients, as measured by CR and decreases in leukemic blasts. In addition, 2 relapsed high risk MDS patients achieved disease stabilization. TSD at 130mg qd is also very well tolerated over a long period of exposure (6–10 months). These results support further pivotal studies with TSD in elderly AML and MDS patients.

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Phase II trial of gemcitabine and irinotecan in previously treated patients with small-cell lung cancer

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.7718 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 7718-7718

Author(s):

M. Nishio ◽

F. Ohyanagi ◽

A. Horikike ◽

Y. Okano ◽

Y. Satoh ◽

...

Keyword(s):

Survival Time ◽

Phase Ii ◽

Phase Ii Trial ◽

Performance Status ◽

Single Agent ◽

Refractory Disease ◽

Platinum Based Chemotherapy ◽

Previously Treated Patients ◽

Previously Treated ◽

Grade 3

7718 Background: Gemcitabine and irinotecan has been shown to have an antitumor activity as a single agent against previously treated SCLC. The objective of this study was to assess the efficacy and safety of gemcitabine combined with irinotecan in patients with refractory or relapsed SCLC. Methods: Patients with histologically or cytologically confirmed SCLC, 20 to 74 years in age, performance status 0–2, with a history of receiving one platinum-based chemotherapy were eligible for the study. Treatment consisted of gemcitabine (1,000 mg/m2) and irinotecan (150 mg/m2) on days 1 and 15 of a 28-day cycle.The primary endpoint was the response rate (RR), and planned sample size for this phase II study was 30 patients (Simon's two-stage minimax design). Results: Thirty-one patients were enrolled and 30 patients (24 males/6 females, 10 refractory/20 sensitive, median age, 65 years) receive protocol treatment in this phase II trial. The median treatment cycles were 3 (1–10). The overall response rates was obtained in 39.3% (95% CI: 18.1% to 60.5%) of the patients, including two patients with refractory disease and 9 patients with sensitive disease. The median overall survival time was 14.4 months, and the 1-year survival rate was 51%. The median survival time of the patients with refractory disease was 7.4 months, compared with 14.4 months for patients with sensitive disease. The chief grade 3/4 toxicities included neutropenia (42%), thrombocytopenia (3%), diarrhea (9%), and liver dysfunction (3%). The only grade 4 toxicities were one case of grade 4 neutropenia (3.3%) and one case of grade 4 thrombocytopenia (3.3%). Conclusion: Gemcitabine plus irinotecan is an active regimen that seems to be well- tolerated by patients with previously treated SCLC. No significant financial relationships to disclose.

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