Phase I trial using toxicity severity weights for dose finding of gemcitabine combined with radiation therapy and subsequent surgery for patients with extremity and trunk soft tissue sarcomas

2004 ◽  
Vol 22 (14_suppl) ◽  
pp. 9008-9008 ◽  
Author(s):  
P. W. Pisters ◽  
M. T. Ballo ◽  
N. Bekele ◽  
P. F. Thall ◽  
B. W. Feig ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Soft Tissue ◽  
Phase I ◽  
Phase I Trial ◽  
Soft Tissue Sarcomas ◽  
Dose Finding

Phase I study of neoadjuvant gemcitabine combined with radiation therapy for patients with high-risk extremity and trunk soft tissue sarcomas.

2014 ◽  
Vol 32 (15_suppl) ◽  
pp. 10571-10571
Author(s):  
William W. Tseng ◽  
Shouhao Zhou ◽  
Peter F. Thall ◽  
Alexander J. F. Lazar ◽  
Raphael E. Pollock ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
High Risk ◽  
Soft Tissue ◽  
Phase I ◽  
Phase I Study ◽  
Soft Tissue Sarcomas

Phase I Trial of Preoperative Doxorubicin-Based Concurrent Chemoradiation and Surgical Resection for Localized Extremity and Body Wall Soft Tissue Sarcomas

2004 ◽  
Vol 22 (16) ◽  
pp. 3375-3380 ◽  
Author(s):  
Peter W.T. Pisters ◽  
Shreyaskumar R. Patel ◽  
Victor G. Prieto ◽  
Peter F. Thall ◽  
Valerae O. Lewis ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Phase I ◽  
Continuous Infusion ◽  
Surgical Resection ◽  
Phase I Trial ◽  
Body Wall ◽  
Soft Tissue Sarcomas ◽  
Maximum Tolerated Dose ◽  
External Beam Radiation ◽  
Preoperative Radiation

Purpose The primary objective of this phase I trial was to define the maximum-tolerated dose of continuous-infusion doxorubicin administered with standard preoperative radiation for patients with localized, potentially resectable soft tissue sarcomas of the extremities or body wall. Patients and Methods Twenty-seven patients with radiographically resectable intermediate- or high-grade soft tissue sarcomas were treated. Preoperative external-beam radiation was administered in 25 2-Gy fractions (total dose, 50 Gy). Concurrent continuous-infusion doxorubicin was administered by an initial bolus (4 mg/m2) and subsequent 4-day continuous infusion (12.5, 15.0, 17.5, or 20.0 mg/m2/wk). Radiographic restaging was performed 4 to 7 weeks after chemoradiation, and patients with localized disease underwent surgical resection. Results Chemoradiation was completed as an outpatient procedure in 25 patients (93%). The maximum-tolerated dose of continuous-infusion doxorubicin combined with standard preoperative radiation was 17.5 mg/m2/wk; at this dose level, seven (30%) of 23 patients had grade 3 dermatologic toxicity. Macroscopically complete resection (R0 or R1) was performed in all 26 patients who underwent surgery. Among 22 patients who were treated with doxorubicin 17.5/mg/m2/wk with concurrent radiation and subsequent surgery, 11 patients (50%) had 90% or greater tumor necrosis, including two patients who had complete pathologic responses. Conclusion Preoperative doxorubicin-based chemoradiation appears safe and feasible. The maximum-tolerated dose of continuous-infusion doxorubicin with standard preoperative radiation was 17.5 mg/m2/wk. Pathologic response rates with this regimen are encouraging.

scholarly journals Phase I trial of concurrent sunitinib and radiation therapy as preoperative treatment for soft tissue sarcoma

BMJ Open ◽  
2013 ◽  
Vol 3 (9) ◽  
pp. e003626 ◽  
Author(s):  
Jens Jakob ◽  
Geraldine Rauch ◽  
Frederik Wenz ◽  
Peter Hohenberger
Keyword(s):  
Radiation Therapy ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Phase I ◽  
Phase I Trial ◽  
Preoperative Treatment

scholarly journals A phase I trial of hyperthermia-induced interleukin-12 gene therapy in spontaneously arising feline soft tissue sarcomas

2007 ◽  
Vol 6 (1) ◽  
pp. 380-389 ◽  
Author(s):  
Farzan Siddiqui ◽  
Chuan-Yuan Li ◽  
Susan M. LaRue ◽  
Jean M. Poulson ◽  
Paul R. Avery ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Soft Tissue ◽  
Phase I ◽  
Phase I Trial ◽  
Soft Tissue Sarcomas ◽  
Interleukin 12

Results of the dose-finding phase of ARST 1321 from the Children's Oncology Group and NRG Oncology: Neoadjuvant chemoradiation or radiation therapy +/- pazopanib in non-rhabdomyosarcoma soft tissue sarcomas.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 11070-11070
Author(s):  
Yen-Lin Chen ◽  
Aaron R. Weiss ◽  
Thomas Scharschmidt ◽  
Yueh-Yun Chi ◽  
Jennifer M. Black ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Soft Tissue ◽  
Dose Level ◽  
Primary Tumor ◽  
Soft Tissue Sarcomas ◽  
Neoadjuvant Chemoradiation ◽  
Dose Finding ◽  
Oncology Group ◽  
Level 1 ◽  
Grade 3

11070 Background: Pazopanib is a tyrosine kinase inhibitor approved globally for advanced soft tissue sarcomas. The dose finding phase of this cooperative group trial assessed the dose limiting toxicities (DLT) and the maximally tolerated dose (MTD) of adding pazopanib to neoadjuvant chemoradiation or radiation therapy in children and adults with unresected intermediate/high-risk trunk and extremity non-rhabdomyosarcoma soft tissue sarcomas (NRSTS). Methods: ARST1321, a jointly designed intergroup study lead by Children's Oncology Group and NRG Oncology opened for enrollment in July 2014. Eligible adult and pediatric patients with newly diagnosed, unresected trunk/extremity NRSTS with plans for primary tumor resection were enrolled into either the Chemotherapy Cohort (those with chemosensitive NRSTS > 5 cm, grade 3, including all synovial sarcoma) or the Non-Chemotherapy Cohort (those with chemotherapy insensitive NRSTS of any size, grade 2/3, or any chemosensitive NRSTS for whom no chemotherapy was planned per discretion of patients and treatment teams). In the Chemotherapy Cohort, pazopanib was given with ifosfamide (7.5 grams/m2) and doxorubicin (75 mg/m2) plus 45 Gy preoperative RT starting after cycle 2. Primary tumor was resected at week 13, followed by chemotherapy and pazopanib to week 25. In the Non-Chemotherapy Cohort, pazopanib was given with 50 Gy preoperative RT, primary tumor was resected at week 10, and pazopanib continued to week 25. Feasibility was assessed through week 6 of therapy to determine pazopanib dose escalation/de-escalation based on DLT, total doses of pazopanib, and overall adverse event profile. Results: In the Chemotherapy Cohort, MTD was reached at Dose Level 1 (350 mg/m2 peds; 600 mg adults) with two DLTs (1 grade 3 ALT rise, 1 intolerability to therapy) in 10 patients. In the Non-Chemotherapy Cohort, 11 patients enrolled at Dose Level 1 (350 mg/m2 peds; 600 mg adults) without any observed DLTs and all received ≥75% of prescribed total pazopanib dose; MTD was reached at Dose Level 2 (450 mg/m2 peds; 800 mg adults) with 2 DLTs in ten patients enrolled (1 grade 3 dermatitis and 1 intolerability to therapy) and 9/10 receiving ≥75% of full dose. Conclusions: Pazopanib in combination with chemoradiation or radiation therapy alone was found to be safe in children and adults with NRSTS. Following this finding, ARST1321 opened in both arms using the newly determined pazopanib MTDs. Clinical trial information: NCT02180867.

scholarly journals A Bayesian dose-finding design for outcomes evaluated with uncertainty

2021 ◽  
pp. 174077452110015
Author(s):  
Matthew J Schipper ◽  
Ying Yuan ◽  
Jeremy MG Taylor ◽  
Randall K Ten Haken ◽  
Christina Tsien ◽  
...  
Keyword(s):  
Phase I ◽  
Phase I Trial ◽  
Data Augmentation ◽  
Maximum Tolerated Dose ◽  
Dose Finding ◽  
Continual Reassessment Method ◽  
Number Of Patients ◽  
Continual Reassessment ◽  
Partially Observed ◽  
Dose Limiting Toxicity

Introduction: In some phase I trial settings, there is uncertainty in assessing whether a given patient meets the criteria for dose-limiting toxicity. Methods: We present a design which accommodates dose-limiting toxicity outcomes that are assessed with uncertainty for some patients. Our approach could be utilized in many available phase I trial designs, but we focus on the continual reassessment method due to its popularity. We assume that for some patients, instead of the usual binary dose-limiting toxicity outcome, we observe a physician-assessed probability of dose-limiting toxicity specific to a given patient. Data augmentation is used to estimate the posterior probabilities of dose-limiting toxicity at each dose level based on both the fully observed and partially observed patient outcomes. A simulation study is used to assess the performance of the design relative to using the continual reassessment method on the true dose-limiting toxicity outcomes (available in simulation setting only) and relative to simple thresholding approaches. Results: Among the designs utilizing the partially observed outcomes, our proposed design has the best overall performance in terms of probability of selecting correct maximum tolerated dose and number of patients treated at the maximum tolerated dose. Conclusion: Incorporating uncertainty in dose-limiting toxicity assessment can improve the performance of the continual reassessment method design.

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