scholarly journals Phase II Trial of Dolastatin-10, a Novel Anti-Tubulin Agent, in Metastatic Soft Tissue Sarcomas

Sarcoma ◽  
2004 ◽  
Vol 8 (4) ◽  
pp. 107-111 ◽  
Author(s):  
M. von Mehren ◽  
S. P. Balcerzak ◽  
A. S. Kraft ◽  
J. H. Edmonson ◽  
S. H. Okuno ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Objective Response ◽  
Soft Tissue Sarcomas ◽  
Hematological Toxicity ◽  
The Novel ◽  
Version 2.0 ◽  
Tumor Measurements ◽  
Dolastatin 10

Patients:Soft tissue sarcomas are uncommon malignancies with few therapeutic options for recurrent or metastatic disease. Dolastatin-10 (Dol-10) is a pentapeptide anti-microtubule agent that binds to tubulin sites distinct from vinca alkaloids. Based on the novel mechanism of action, limited activity of other anti-microtubular agents, and anti-neoplastic activity in pre-clinical screening of Dol-10, this multi-institutional phase II study was conducted to determine the objective response rate of Dol-10 in recurrent or metastatic soft tissue sarcomas that had not been treated with chemotherapy outside of the adjuvant setting.Methods:Dol-10 was given intravenously at a dose of 400 μg/m2and repeated every 21 days. Toxicities were assessed using the Common Toxicity Criteria (version 2.0). Radiographic studies and tumor measurements were repeated every two cycles to assess response [Miller AB, et al.Cancer1981; 47(1): 207].Results:Dol-10 was associated with hematological toxicity and with some vascular toxicities. There was no significant gastrointestinal, hepatic or renal toxicity. There was one death on study due to respiratory failure. There were no objective responses in 12 patients treated with Dol-10.Discussion:Based on this phase II trial, further study of Dol-10 on this schedule is not recommended in advanced or metastatic soft tissue sarcomas.

Phase II trial of carboplatin in the management of malignant mesothelioma.

1990 ◽  
Vol 8 (1) ◽  
pp. 151-154 ◽  
Author(s):  
D Raghavan ◽  
P Gianoutsos ◽  
J Bishop ◽  
J Lee ◽  
I Young ◽  
...  
Keyword(s):  
Phase Ii ◽  
Malignant Mesothelioma ◽  
Phase Ii Trial ◽  
Objective Response ◽  
World Health ◽  
Hematological Toxicity ◽  
Who Grade ◽  
Life Threatening ◽  
Grade 3 ◽  
Health Organization

Thirty-one patients with advanced malignant mesothelioma, previously untreated or having received only one prior cytotoxic regimen, were treated in a prospective, single-arm phase II trial with carboplatin (NSC 241240) at a dose of 150 mg/m2 per day intravenously (IV) for 3 days (450 mg/m2/course). One complete remission and four partial remissions were achieved, yielding an overall objective response rate of 16% (95% confidence interval [CI], 5.4% to 34%). The median duration of remission was 8 months (range, 5 to 17). Nonhematological toxicity was mild (only 12% with World Health Organization [WHO] grade 3 vomiting); 16% suffered WHO grade 3 to 4 hematological toxicity, but there were no life-threatening episodes and no treatment-related deaths. Carboplatin has modest activity against malignant mesothelioma and, because of its low toxicity, has a role in the management of this disease.

scholarly journals Trabectedin with concurrent low-dose of radiation therapy for metastatic soft tissue sarcomas: A phase II trial of Spanish, French and Italian sarcoma groups

2019 ◽  
Vol 30 ◽  
pp. v686-v687
Author(s):  
J Martin Broto ◽  
A. Italiano ◽  
R M Alvarez Alvarez ◽  
I. Rincon ◽  
J. Peinado ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Soft Tissue ◽  
Phase Ii ◽  
Low Dose ◽  
Phase Ii Trial ◽  
Soft Tissue Sarcomas

Continuous daily dosing (CDD) of sunitinib (SU) in patients with metastatic soft tissue sarcomas (STS) other than GIST: Results of a phase II trial

2008 ◽  
Vol 26 (15_suppl) ◽  
pp. 10533-10533 ◽  
Author(s):  
M. L. Keohan ◽  
J. A. Morgan ◽  
D. R. D’Adamo ◽  
D. Harmon ◽  
J. E. Butrynski ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Soft Tissue Sarcomas

A phase II trial of axitinib plus pembrolizumab for patients with advanced alveolar soft part sarcoma (ASPS) and other soft tissue sarcomas (STS).

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. 11547-11547 ◽  
Author(s):  
Breelyn A. Wilky ◽  
Matteo Maria Trucco ◽  
Despina Kolonias ◽  
Eric Wieder ◽  
Ty Subhawong ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Soft Part ◽  
Soft Tissue Sarcomas ◽  
Alveolar Soft Part Sarcoma

PD1 inhibition in soft-tissue sarcomas with tertiary lymphoid structures: A multicenter phase II trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 11507-11507
Author(s):  
Antoine Italiano ◽  
Alban Bessede ◽  
Emmanuelle Bompas ◽  
Sophie Piperno-Neumann ◽  
Christine Chevreau ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Soft Tissue ◽  
Phase Ii ◽  
Progressive Disease ◽  
Objective Response ◽  
Soft Tissue Sarcomas ◽  
Progression Rate ◽  
Multicenter Phase ◽  
Tertiary Lymphoid Structures ◽  
Lymphoid Structures

11507 Background: PD1 inhibition has shown limited activity in all comers clinical trials including patients with advanced soft-tissue sarcomas (STS). In the PEMBROSARC study, objective response rate, progression-free (PFS) and overall survival (OS) were respectively 2.1%, 1.4 and 7.1 months respectively (Toulmonde et al. Jama Oncol 2017). We have recently shown that the presence of tertiary lymphoid structures (TLS) may represent a biomarker to select patients who are more likely to benefit from immunotherapy (PetitPrez et al., Nature 2020). We report here the first clinical trial investigating the efficacy of PD1 inhibition in TLS-positive STS. Methods: PEMBROSARC is an open-label multicenter phase II study of pembrolizumab in combination with low-dose cyclophosphamide in pts with STS selected based on the presence of TLS. TLS status has been assessed centrally has previously described (PetitPrez et al., Nature 2020). Eligible patients received pembrolizumab 200mg IV q21 days and cyclophosphamide 50 mg BID 1week on, 1 week off. All patients had confirmed progressive disease at inclusion based on central review of two imaging performed at less than 6 months interval. The primary efficacy endpoint was 6-month non-progression (as per RECIST evaluation criteria v1.1). Based on the following hypotheses: 15% 6-month non-progression rate (H0), 40% acceptable 6-month non-progression rate (H1), 5% type I error rate, 90% power, a total of 29 assessable patients were necessary and 8 patients or more had to be progression-free at 6 months to reach the first endpoint. Results: 240 patients were screened for TLS status between September 2018 and January 2020 in 7 centers of the French Sarcoma Group. Among them, 48 were found to be TLS+ as per central review and 35 were included in the study. The three most frequent histological subtypes were: well-differentiated/dedifferentiated liposarcoma (n = 13); UPS (n = 6), and leiomyosarcoma (n = 4). 30 patients were eligible for efficacy. Of those, as per central imaging review, 13 patients (43.3%) had tumor shrinkage resulting in partial response in 8 patients (26.7%) and stable disease in 5 cases (16.7%). 10 patients had progressive disease. Twelve patients were progression-free at 6 months (40.0% 95%CI = [22.7 – 59.4]).Median PFS and OS were 4.1 months (95%CI, 1.4-9.6) and 14.5 months (95%CI, 8.5- 18.3 months), respectively. Conclusions: With an objective response and a 6-month non-progression rates of 26.7% and 40% respectively versus 2.1% and 4.2% in all comers, the PEMBROSARC study confirms that selection based on TLS status is an efficient approach to tailor immunotherapy in STS patients. Clinical trial information: NCT02406781.

A randomized phase II trial of cabozantinib combined with PD-1 and CTLA-4 inhibition in metastatic soft tissue sarcoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS11583-TPS11583
Author(s):  
Vanessa Anne Eulo ◽  
Breelyn A. Wilky ◽  
Jingqin Luo ◽  
Angela C. Hirbe ◽  
Mia C. Weiss ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Soft Tissue ◽  
Phase Ii ◽  
Immune Checkpoint ◽  
Response Rate ◽  
Single Agent ◽  
Objective Response ◽  
Soft Tissue Sarcomas ◽  
Randomized Phase Ii ◽  
Metastatic Setting

TPS11583 Background: Soft tissue sarcomas (STS) are rare malignancies with poor prognosis in the metastatic setting. Current standard therapy includes anthracycline based chemotherapy. Cabozantinib is a multikinase inhibitor that has demonstrated efficacy in solid tumors such as renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC). A phase II study of cabozantinib in advanced STS is underway. Cabozantinib in combination with immune checkpoint blockade has shown clinical benefit in several tumor types including HCC, RCC, non-small cell lung cancer, and urothelial carcinoma. Since cabozantinib may alter PD-1 expression in regulatory T-cells and promote an immune permissive environment, we hypothesize that combining cabozantinib with immune checkpoint inhibition is a therapeutic strategy that will be more effective than cabozantinib alone. Additionally, the design of the trial will allow assessment of whether pretreatment with cabozantinib will enhance the efficacy of nivolumab and ipilimumab alone. Methods: This is an open label, multicenter, randomized phase II clinical trial of cabozantinib (60mg orally daily as a single agent, 40mg in combination) with or without combination Ipilimumab (ipi, 1mg/kg IV every 3 weeks for 4 doses) and Nivolumab (nivo, 3mg/kg IV every 3 weeks for four doses, then 480mg IV every 4 weeks) in patients (pts) with unresectable or metastatic STS refractory to up to two lines of chemotherapy. 105 pts with non-translocation driven sarcomas will be enrolled at three US sites and randomized 2:1 to the combination group. Pts will be stratified by prior pazopanib use and balanced for histologies. Patients who progress on arm A will cross over to combination therapy (arm B). The primary efficacy endpoint is objective response rate (ORR) by RECIST 1.1. 35 patients in Cohort A (cabozantinib alone) and 70 patients in Cohort B (cabozantinib plus ipi/nivo) will be required to detect an increase of the ORR from 10% in cohort A to 30% in cohort B with 81% power with a one-sided alpha level of 10%. Key eligibility criteria include: at least 18 years of age, ECOG performance status of 0 or 1, ≤2 prior lines of therapy and measurable disease. Exclusion criteria include: translocation-driven sarcoma except alveolar soft part sarcoma (ASPS), prior immunotherapy, and chronic use of corticosteroids or other immunosuppression. Secondary endpoints are safety, overall and progression free survival, disease control rate, and response rate to ipilimumab and nivolumab after cabozantinib pretreatment. Mandatory tumor biopsies pre-treatment and at 6 weeks will be obtained. Peripheral blood will be collected for circulating immune phenotyping. Enrollment will occur at 3 participating institutions and is expected to be completed in 2022. Clinical trial information: NCT04551430.

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