A randomized phase II trial of second-line treatment for advanced soft tissue sarcoma comparing trabectedin, eribulin and pazopanib (2ND-STEP, JCOG1802).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS11580-TPS11580
Author(s):  
Makoto Endo ◽  
Kazuhiro Tanaka ◽  
Yoshihiro Matsumoto ◽  
Hiroaki Hiraga ◽  
Shintaro Iwata ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Phase Ii Trial ◽  
Phase Iii ◽  
Line Treatment ◽  
Second Line ◽  
Oncology Group ◽  
First Line ◽  
Phase Iii Trial ◽  
Randomized Phase Ii ◽  
Line Chemotherapy

TPS11580 Background: Soft tissue sarcomas (STS) are a rare type of malignancy, which comprises of a variety of histologies. Chemotherapy is the standard treatment for patients with advanced STS. Doxorubicin alone or in combination with ifosfamide is widely accepted as the first-line chemotherapy for advanced STS. While a combination with gemcitabine and docetaxel is regarded as a standard regimen of the second-line chemotherapy after failure of doxorubicin-based first-line regimen, the efficacy is not sufficient. Trabectedin, eribulin, and pazopanib are the candidates of the second-line chemotherapy for advanced STS, although there is no clear evidence showing which is better among those agents. The purpose of this clinical trial conducted by Bone and Soft Tissue Tumor Study Group of Japan Clinical Oncology Group (JCOG) is to determine the most promising regimen among trabectedin, eribulin and pazopanib as the test arm regimen in the future phase III trial of the second-line treatment for patients with advanced STS. Methods: The study, JCOG1802, is a multicenter, selection design, randomized phase II trial comparing trabectedin (1.2 mg/m2 IV, every 3 weeks), eribulin (1.4 mg/m2 IV, days 1 and 8, every 3 weeks) and pazopanib (800 mg PO, everyday) for patients with unresectable or metastatic STS refractory to doxorubicin-based first-line chemotherapy. Eligibility criteria include 16 year-old or older, unresectable and/or metastatic STS, an exacerbation within 6 months prior to registration, histological diagnosis of STS other than Ewing sarcoma, well-differentiated liposarcoma and myxoid liposarcoma, a history of chemotherapy for STS other than doxorubicin-based regimen, ECOG (Eastern Cooperative Oncology Group) performance status 0 to 2, and sufficient organ function. Primary endpoint is progression-free survival (PFS), and secondary endpoints include overall survival, disease-control rate, response rate, and adverse events. To select the most promising regimen in median PFS (3 months in the worst regimen and 4 months in the best regimen) with a probability of at least 80%, a total of 120 patients will be enrolled from 37 institutions in Japan. After JCOG1802, a subsequent phase III trial comparing the winner of this study and a combination of gemcitabine and docetaxel will be planned. The study was activated at December 5, 2019 and 22 of planned 120 patients have been enrolled as of February 15, 2021. Clinical trial information: jRCTs031190152.

A phase II trial combining tumor-targeting TP53 gene therapy with gemcitabine/nab-paclitaxel as a second-line treatment for metastatic pancreatic cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4139-4139
Author(s):  
Chris Poki Leung ◽  
Minal A. Barve ◽  
Ming-Shiang Wu ◽  
Kathleen F. Pirollo ◽  
James F. Strauss ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Objective Response ◽  
Tp53 Gene ◽  
Phase Iii ◽  
Published Data ◽  
Line Treatment ◽  
Second Line ◽  
First Line

4139 Background: Nearly all stage IV pancreatic adenocarcinoma (PAC) patients progress after first-line treatment, and second-line options are limited. SGT-53 is an investigational product for tumor-targeted TP53 gene therapy that has completed phase Ia/Ib trials [Senser et al (2013), Mol Ther 21:1096; Pirollo et al (2016) Mol Ther 24:1697]. Methods: Here we provide an interim analysis of a Phase II trial (SGT53-02-1; NCT02340117) combining SGT-53 with gemcitabine/nab-paclitaxel (GEM/ABX). Eligible were first-line patients or those who had progressed after FOLFIRINOX (FFX) and/or gemcitabine-based therapy (second-line). In a 7-week treatment cycle, SGT-53 (3.6 mg DNA) was given once or twice weekly with GEM/ABX (1000 mg/m2/wk and 125 mg/m2/wk, respectively, for 3 of 4 weeks). Progression-free survival (PFS) and objective response rate (ORR) are primary endpoints.Overall survival (OS) and PFS are estimated by Kaplan-Meier analysis. Results: Of all evaluable patients (n=20), best response in 7 patients was determined to be partial response (PR) and 13 had stable disease (SD); none had progressive disease. In the second-line patients (n=11) there were 5 PR and 6 SD after 9 had failed FFX treatment, 3 had failed gemcitabine-based treatment and 1 had failed both. For patients with elevated CA19-9, SGT-53 + GEM/ABX resulted in marked reductions in the tumor marker. Published data for patients with PAC after therapy failure [Mita et al (2019) J Clin Med 8: 761; Portal et al (2015) Br J Cancer 113:989; Wang-Gillam et al (2016) Lancet 387:545] are shown for comparison. Notably, mPFS in our second-line patients was 7.4 months versus 3.1 months for the approved second-line therapy [Wang-Gillam et al (2016)]. This improvement in PFS exceeds the benchmark proposed to predict a clinically meaningful Phase III trial [Rahib et al (2016) Lancet Oncol 2:1209]. Conclusions: Our data suggest a clinically meaningful benefit of adding SGT-53 to GEM/ABX particularly for second-line PAC patients, most of whom had failed prior FFX treatment. Clinical trial information: NCT02340117. [Table: see text]

Irinotecan in the Treatment of Colorectal Cancer: Clinical Overview

2001 ◽  
Vol 19 (5) ◽  
pp. 1501-1518 ◽  
Author(s):  
Udo Vanhoefer ◽  
Andreas Harstrick ◽  
Wolf Achterrath ◽  
Shousong Cao ◽  
Siegfried Seeber ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Topoisomerase I ◽  
Clinical Status ◽  
Phase Iii ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Phase Iii Trials ◽  
Line Chemotherapy

PURPOSE AND METHODS: For more than three decades, the therapeutic options for patients with advanced colorectal cancer have almost exclusively been based on fluoropyrimidines. With the recognition that topoisomerase-I (TOP-I) is an important therapeutic target in cancer therapy, irinotecan, a semisynthetic TOP-I–interactive camptothecin derivative, has been clinically established in the treatment of colorectal cancer. RESULTS: Irinotecan was investigated as second-line chemotherapy after prior treatment with fluorouracil (FU)-based regimens in two large randomized phase III trials comparing irinotecan with either best supportive care or an infusional FU/leucovorin (LV) regimen. The outcomes of these trials established irinotecan as the standard therapy in the second-line treatment of colorectal cancer. The therapeutic value of irinotecan in the first-line treatment of metastatic colorectal cancer was investigated in two large randomized phase III trials comparing the combination of irinotecan and FU/LV with FU/LV alone. Both trials demonstrated significant superior efficacy for the combination of irinotecan and FU/LV in terms of response rate, median time to disease progression, and median survival time. Consequently, the combination of irinotecan and FU/LV has been approved as first-line chemotherapy for patients with metastatic colorectal cancer and constitutes the reference therapy against which other treatment options must be tested in the future. CONCLUSION: In this review, the clinical rationale and update of the present clinical status of irinotecan in the treatment of colorectal cancer and future prospects of irinotecan-based combinations are discussed.

Nonstandard first-line therapy and survival in patients (pts) with recurrent/metastatic head and neck cancer (RMHNSCC): Experience of 194 pts in a single institution.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e16036-e16036
Author(s):  
Jerome Fayette ◽  
Valentine Polivka ◽  
Sylvie Chabaud ◽  
Bertrand Favier ◽  
Severine Racadot ◽  
...  
Keyword(s):  
Overall Survival ◽  
Median Overall Survival ◽  
Alternative Therapy ◽  
Phase Iii ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
First Line Therapy ◽  
Phase Iii Studies ◽  
Line Chemotherapy

e16036 Background: With the standard first line association platinum 5FU and cetuximab, median overall survival (OS) for RMHNSCC was 10.1 months (95% CI [8.6 – 11.2]) (N Engl J Med. 359:1116). Due to the toxicity of this treatment we often offer alternative therapy to our pts. This work aimed to evaluate impact of different 1st line treatment on OS. Methods: With the standard first line association platinum 5FU and cetuximab, median overall survival (OS) for RMHNSCC was 10.1 months (95% CI [8.6 – 11.2]) (N Engl J Med. 359:1116). Due to the toxicity of this treatment we often offer alternative therapy to our pts. This work aimed to evaluate impact of different 1st line treatment on OS. Results: At initiation of palliative chemotherapy, median age was 62 [29-87]; PS was 0, 1, 2, 3 in 13%, 59%, 16% and 11% of pts, respectively. First line chemotherapy consists in combination cisplatin+taxanes (CIST) 24%, caboplatin+taxanes (CART) 33%, cisplatin or carboplatin without taxanes (NOT) 15% or others (OTH) 28%. Median OS was estimated to 9.6 months CI95%=[8.1-11.4], with 39% of pts; CI95%=[32-47] still alive at 1-year. Second line of treatment has been initiated in 61% of pts. Some of them have even been able to have up to 3, 4 or more than 4 lines of treatment in 19%, 11% and 4% of pts, respectively. In the subgroup analysis, which represents a population similar to those included in [ref1], first line chemotherapy was CIST, CART, NOT or OTH in 30%, 30%, 18% and 22%, respectively. Median OS was 13.0 months, CI95%=[11.2-17.7] reaching up to 15.3 months for CIST subgroup. Second line of treatment was initiated in 73% of pts, with 20%, 15% and 5% of pts having a third, a fourth, and a fifth line, respectively. Conclusions: We can reach for unselected pts the best OS published in phase III studies. The use in first line of combination of platinum and taxanes, followed by monotherapies with cetuximab, capecitabine and methotrexate allows reaching OS of 13 months.

Efficacy of S-1 compared to modified FOLFIRINOX as second-line chemotherapy regimens after gemcitabine plus nab-paclitaxel for patients with metastatic pancreatic cancer.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 449-449 ◽  
Author(s):  
Gen Kimura ◽  
Hideaki Takahashi ◽  
Kumiko Umemoto ◽  
Kazuo Watanabe ◽  
Mitsuhito Sasaki ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Chemotherapy Regimen ◽  
Phase Iii ◽  
Metastatic Pancreatic Cancer ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Second Line Chemotherapy ◽  
Clinical Records ◽  
Line Chemotherapy

449 Background: Recently, gemcitabine (GEM) plus nab-paclitaxel (nab-PTX) has been frequently used as a first-line chemotherapy regimen for the treatment of metastatic pancreatic cancer (mPC) in Japan. Nanoliposomal irinotecan combined with 5-fluorouracil and leucovorin (MM-398 plus 5FU/LV) has not yet been approved in Japan. Under these circumstances, a modified FOLFIRINOX (mFFX) regimen or S-1 is commonly used as a second-line chemotherapy regimen for patients with mPC after GEM plus nab-PTX has failed. Methods: Between December 2014 and March 2016, 45 patients with mPC received second-line chemotherapy after the failure of GEM plus nab-PTX (standard dose regimen) at the National Cancer Center Hospital East. Twenty-two patients received mFFX (irinotecan, 150 mg/m2; bolus of 5FU was eliminated), 19 received S-1 (80 mg/m2/d; d1-28, q6w or d1-14, q3w), and 4 received other chemotherapy regimens. The clinical records of the patients were reviewed retrospectively. Results: At baseline, S-1 group had a more severe disease status than the mFFX group (performance status of 0: 21% vs. 68%, P = 0.003; median CA19-9 level: 1832 vs. 577 U/mL, P = 0.30). No significant difference in the response rate (S-1, 5.3% vs. mFFX, 9.1%, P = 0.56) or the disease control rate (S-1, 42% vs. mFFX, 36%, P = 0.71) was seen between the two groups. The progression free survival (PFS) (median: S-1 vs. mFFX: 2.7 vs. 2.4 months (m), P = 0.77), the overall survival (OS) from the second-line treatment (median: 6.1 vs. 6.4m, P = 0.87) and the OS from the first-line treatment (median: 10.9 vs. 12.4m, P = 0.77) were not significantly different between the two groups. These results were similar to those observed for MM-398 plus 5FU/LV (PFS, 3.1m; OS, 6.1m) in a pivotal Phase III study (NAPOLI-1). The incidences of peripheral neuropathy (5.3% vs. 32%, P = 0.04), fatigue (11% vs. 50%, P = 0.007), and neutropenia (11% vs. 64%, P = 0.001) were significantly lower in the S-1 group. Conclusions: S-1 was less toxic than mFFX and exerted a similar anti-tumor effect in the present study. S-1 could be a treatment option for patients with mPC refractory to GEM plus nab-PTX.

scholarly journals The relationship between peripheral neuropathy and efficacy in second-line chemotherapy for unresectable advanced gastric cancer: a prospective observational multicenter study protocol (IVY)

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Hiroaki Tanioka ◽  
Takeshi Nagasaka ◽  
Futoshi Uno ◽  
Masafumi Inoue ◽  
Hiroyuki Okita ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Peripheral Neuropathy ◽  
Advanced Gastric Cancer ◽  
Primary Adenocarcinoma ◽  
Line Treatment ◽  
Second Line ◽  
Oncology Group ◽  
First Line ◽  
Second Line Chemotherapy ◽  
Line Chemotherapy

Abstract Background Paclitaxel is used in second-line conventional chemotherapies to manage patients with unresectable advanced gastric cancer (GC). Paclitaxel-induced peripheral neuropathy is a known adverse event leading to treatment discontinuation. Additionally, oxaliplatin which causes irreversible peripheral neuropathy is now commonly used in first-line chemotherapy for advanced GC in Japan. Thus, examining the incidence of peripheral neuropathy with paclitaxel after oxaliplatin is necessary to improve the quality of life and outcomes of patients with advanced GC in the second-line treatment setting. Methods This prospective observational multicenter study, (which we named IVY study), will evaluate the degree of chemotherapy-induced peripheral neuropathy (CIPN) and the efficacy of second-line chemotherapy for unresectable advanced GC. A patient neurotoxicity questionnaire (PNQ) and the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) will be used to assess CIPN during the second-line treatment. The key eligibility criteria are as follows: 1) unresectable or recurrent GC histologically confirmed to be primary adenocarcinoma of the stomach, 2) age over 20 years, 3) Eastern Cooperative Oncology Group performance status score of 0–2, 4) written informed consent following full study information is provided to the patient, 5) progression or intolerance for first-line chemotherapy comprising fluorinated pyrimidine and platinum anticancer drugs (cisplatin or oxaliplatin) for advanced GC. 6) presence of evaluable lesions as confirmed using a computed tomography (CT) or magnetic resonance imaging. A total of 200 patients is considered to be appropriate for inclusion in this study. Discussion The results of this study will provide some information on CIPN with the sequential usage of oxaliplatin as first-line chemotherapy to paclitaxel as second-line chemotherapy in clinical practice. Trial registration This trial is registered in the University Hospital Medical Information Network’s Clinical Trials Registry with the registration number UMIN000033376 (Registered 11 July 2018).

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