A randomized phase II study of individualized stereotactic body radiation therapy (SBRT) versus transarterial chemoembolization (TACE) as a bridge to transplant in hepatocellular carcinoma (HCC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15677-e15677 ◽  
Author(s):  
Francis Warren Nugent ◽  
Krishna Gunturu ◽  
Keith E. Stuart ◽  
Sebastian Flacke ◽  
Chris Molgaard ◽  
...  
Keyword(s):  
Locally Advanced ◽  
Local Treatment ◽  
Milan Criteria ◽  
Bridge To Transplant ◽  
Class A ◽  
Randomized Phase Ii ◽  
Median Total Dose ◽  
Secondary Endpoints ◽  
Prescription Dose ◽  
Previously Treated

e15677 Background: For HCC pts undergoing LT, local treatment as a "bridge" is standard to decrease likelihood of tumor progression. The most common treatment is TACE, but the safest and most effective bridging modality is unclear. Recently, SBRT has been shown to be both safe and effective when used in pts with locally advanced HCC. We prospectively compare SBRT to TACE as a bridge for HCC pts undergoing LT. Methods: 60 pts are planned for accrual. Pts with C-P < 9 and HCC within Milan Criteria were randomized between two arms. TACE pts received 2 treatments one month apart using DEBDOX beads. TACE pts were hospitalized after each treatment. Pts randomized to SBRT, after fiducial placement, received a median total dose of 45 Gy delivered over 5 fractions. Mean liver dose, Veff, and NTCP were utilized to determine the prescription dose. Pts were assessed by imaging using mRECIST criteria at 2 months and every 3 months thereafter until LT or death. Toxicity and quality of life (QOL) were assessed before treatment, during treatment, 2 weeks post-treatment, and then every 3 months using the PIQ-6 Pain Impact Questionnaire and the SF-36v2 Health Survey. Primary endpoint was need for retreatment of the previously treated lesion(s). Secondary endpoints include toxicity, pathologic response, radiologic response, QOL, and cost. Results: From 9/2014-1/17, 33 pts within Milan Criteria with C-P Class A/B cirrhosis were randomized to TACE (n = 18) vs. SBRT (15). Data on evaluable pts is summarized in the table below. Conclusions: For HCC patients with C-P Class A/B liver cirrhosis, SBRT appears at least equally effective as TACE as a bridge to liver transplantation. SBRT may engender less toxicity, better maintain QOL, and eliminate the need for hospitalization. An update along with a full cost analysis will be presented in June. Clinical trial information: nct02182687. [Table: see text]

A randomized phase II study of individualized stereotactic body radiation therapy (SBRT) versus transarterial chemoembolization (TACE) with DEBDOX beads as a bridge to transplant in hepatocellular carcinoma (HCC).

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 223-223 ◽  
Author(s):  
Francis W. Nugent ◽  
Amir Qamar ◽  
Keith E. Stuart ◽  
Kari Galuski ◽  
Sebastian Flacke ◽  
...  
Keyword(s):  
Stereotactic Body Radiation Therapy ◽  
Locally Advanced ◽  
Bridge To Transplant ◽  
Class A ◽  
Randomized Phase Ii ◽  
Median Total Dose ◽  
Secondary Endpoints ◽  
Prescription Dose ◽  
Clinical Trial Information

223 Background: For HCC pts undergoing LT, local regional treatment as a "bridge" is standard to decrease tumor progression. The most common treatment is TACE, but the best bridging modality is unclear. Recently, SBRT has been shown to be both safe and effective when used in pts with locally advanced HCC. We prospectively compare SBRT to TACE as a bridge for HCC pts undergoing LT. Methods: 60 pts planned for accrual. From 9/2014-9/2016, 29 pts within Milan Criteria with C-P Class A/B cirrhosis were randomized to TACE vs. SBRT. TACE pts received 2 treatments one month apart utilizing DEBDOX beads (n = 15). TACE pts were hospitalized after each TACE. Pts receiving SBRT (n = 12) received a median total dose of 45Gy delivered over 5 fractions using fiducials. Mean liver dose, Veff, and NTCP were utilized to determine the prescription dose. Pts were assessed by imaging using mRECIST criteria at 2 months and every 3 months thereafter until LT or death. Toxicity and quality of life were assessed before treatment, during treatment, two weeks post-treatment, and then every three months using the PIQ-6 Pain Impact Questionnaire and the SF-36v2 Health Survey. Primary endpoint was time to retreatment of treated lesion(s). Secondary endpoints include toxicity, pathologic response, radiologic response, number of subsequent treatments, cost, and QOL. Results: A. Demographics/Toxicity. Conclusions: For HCC patients with C-P Class A/B liver cirrhosis, SBRT appears equally effective to TACE as a bridge to liver transplantation, may engender less toxicity, and eliminates hospitalizations. Clinical trial information: NCT02182687. [Table: see text][Table: see text]

A randomized phase II feasibility study of individualized stereotactic body radiation therapy (SBRT) versus transarterial chemoembolization (TACE) with DEBDOX beads as a bridge to transplant in hepatocellular carcinoma (HCC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4586-4586 ◽  
Author(s):  
Francis W. Nugent ◽  
Klaudia Hunter ◽  
Chris Molgaard ◽  
Amir Qamar ◽  
Krishna Gunturu ◽  
...  
Keyword(s):  
Stereotactic Body Radiation Therapy ◽  
Early Stage ◽  
Bridge To Transplant ◽  
Class A ◽  
Randomized Phase Ii ◽  
Median Total Dose ◽  
Secondary Endpoints ◽  
Prescription Dose ◽  
To Receive ◽  
Clinical Trial Information

4586 Background: For HCC pts undergoing LT, loco-regional treatment as a "bridge" is standard. The best bridging modality is unclear. SBRT is safe and effective when used in pts with advanced HCC. We prospectively compared SBRT to TACE as a bridge for HCC pts undergoing LT. Methods: From 9/2014-10/2019, 60 pts within Milan Criteria with CTP Class A/B8 cirrhosis were consented. 54 pts were randomized to TACE vs. SBRT. TACE pts (n =30) were scheduled to receive 2 treatments one month apart utilizing DEBDOX beads. TACE pts were hospitalized after each TACE. Pts receiving SBRT (n =24) received a median total dose of 45Gy delivered over 5 fractions using fiducials. Mean liver dose, Veff, and NTCP determined prescription dose. Pts were assessed by using mRECIST criteria at 2 months and every 3 months thereafter until LT or death. Toxicity and QOL were assessed before treatment, during treatment, two weeks post-treatment, and then every three months using the PIQ-6 Pain Impact Questionnaire and the SF-36v2 Health Survey. The 1° endpoint was time to recurrent or residual dz. Secondary endpoints were toxicity, pathologic response, radiologic response, number of subsequent treatments, cost, and QOL. 50 pts are evaluable for review. Results: See table. Conclusions: For early stage HCC patients with CTP Class A/B liver cirrhosis, SBRT appears as effective as TACE at controlling HCC prior to LT, may engender less toxicity, and eliminates the need for hospitalization. A larger multi-center trial is ongoing. Clinical trial information: NCT02182687. [Table: see text]

Multicenter randomized phase II study of chemoradiation (CRT) followed by surgery (S) and chemotherapy (CT) versus induction CT followed by CRT and S in high-risk rectal cancer: GCR-3 final efficacy and safety results

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4103-4103
Author(s):  
C. Fernandez-Martos ◽  
J. Aparicio ◽  
A. Salud ◽  
V. Alonso ◽  
B. Massuti ◽  
...  
Keyword(s):  
High Risk ◽  
Locally Advanced ◽  
Dose Intensity ◽  
Treatment Compliance ◽  
Complete Response ◽  
R0 Resection ◽  
Randomized Phase Ii ◽  
Secondary Endpoints ◽  
Therapeutic Sequence ◽  
Intent To Treat

4103 Background: In locally advanced RC the optimal therapeutic sequence remains an important clinical question. Induction CT prior to CRT and S may be associated with better efficacy and compliance. Methods: Eligible pts had medium or distal high risk RC defined by MRI and/or US: Tumors within 2mm of mesorectal fascia, distal T3 at/below levators, resectable T4 and T3N+. Pts, stratified by center, were randomized assigned to receive either Arm A : capecitabine (Cap) 825 mg/m2 BID 5 d/w, oxaliplatin (Ox) 50 mg/m2 IV weekly x 5 and concomitant RT: 50.4 Gy in 28 fractions. S was planned 5–6 w after CRT. Post-op four cycles of Cap 1,000 mg/m2 bid days 1 to 14; Ox 130 mg/m2 day 1 or Arm B: Induction CapOx followed by CRT and S. Two parallel, Simon 2-stage designs: α=0.05 β=0.1; 24 evaluable pts/arm 1st stage and 54 pts/arm for 2nd stage. Primary endpoint: pathological complete response (pCR). Secondary endpoints included toxicity and treatment compliance. Results: 108 Pts were randomly assigned (arm A/B, 52/56), and 103 were assessable (49/54) from 14 sites. Median age 62/60 years, Male 65/70%. During treatment period 6 pts died A/B: 2 vascular, 1 suicide/ 3 post-op. Pts with any grade ¾ toxicity during CRT were arm A/B: 29% (14/49) and 23% (12/53). Any grade ¾ toxicity during adjuvant/induction CT were 51% (19/37) and 17% (9/54); χ2,p= 0.0004. On an intent-to-treat basis the pCR for Arm A/B was achieved in seven (13.5%; 95% CI, 5.6%-25.8%) and eight (14.3%; 95% CI, 6.4%-26.2%). R0 resections were achieved in 92% (45/49) and 88% (48/54). 51% (25/49) and 93% (50/54) received all four cycles of adjuvant/induction CT (χ2;p<0.0001). Relative Median Dose intensity of adjuvant /induction CT was 0.74/0.96 (Wilcoxon; p<0.0001) for Cap and 0.75/1.0 (Wilcoxon; p<0.0001) for Ox. Conclusions: Induction CT prior to CRT has more favorable compliance and toxicity profiles. Furthermore, there is no compromise in pCR and R0 resection rates. Larger trials evaluating this strategy are justified. [Table: see text]

SPIRITT (study 20060141): A randomized phase II study of FOLFIRI with either panitumumab (pmab) or bevacizumab (bev) as second-line treatment (tx) in patients (pts) with wild-type (WT) KRAS metastatic colorectal cancer (mCRC).

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 454-454 ◽  
Author(s):  
J. Randolph Hecht ◽  
Allen Lee Cohn ◽  
Shaker R. Dakhil ◽  
Mansoor N. Saleh ◽  
Bilal Piperdi ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Eligibility Criteria ◽  
Grade 5 ◽  
Randomized Phase Ii ◽  
Secondary Endpoints ◽  
Previously Treated

454 Background: Pmab has demonstrated significant improvement in progression-free survival (PFS) in pts with WT KRAS mCRC as 2nd-line tx in a phase III trial comparing pmab + FOLFIRI vs FOLFIRI alone. Here, we describe the results of SPIRITT, a multicenter, randomized phase II study evaluating pmab + FOLFIRI and bev + FOLFIRI in pts with WT KRAS mCRC previously treated with a 1st-line bev + oxaliplatin (Ox)-based chemotherapy regimen. Methods: Pts were randomized 1:1 to pmab 6.0 mg/kg + FOLFIRI Q2W or to bev 5.0 or 10.0 mg/kg + FOLFIRI Q2W. Eligibility criteria included: WT KRAS mCRC, ECOG ≤ 1, no prior irinotecan or anti-EGFR tx, and tx failure of prior 1st-line bev + Ox-based therapy (≥ 4 cycles). The primary endpoint was PFS; secondary endpoints included overall survival (OS), objective response rate (ORR), and safety. No formal hypothesis was tested. Results: 182 pts with WT KRAS mCRC were randomized. All pts received tx. Efficacy results are shown (table). Worst grade of 3/4 adverse events (AE) occurred in 78% of pts in the pmab + FOLFIRI arm and 65% in the bev + FOLFIRI arm. Grade 5 AEs occurred in 7% of pts in the pmab + FOLFIRI arm and 7% in the bev + FOLFIRI arm. Tx discontinuation due to any AE was 29% in the pmab + FOLFIRI arm and 25% in the bev + FOLFIRI arm. Conclusions: In this estimation study of pts with WT KRAS mCRC that previously received bev + Ox-based tx, the PFS hazard ratio (HR) was 1.01 (95% CI: 0.68 - 1.50). The OS HR was 1.06 (95% CI: 0.75 - 1.49). The observed ORR was higher in the pmab + FOLFIRI arm. 54% of bev + FOLFIRI pts received subsequent anti-EGFR tx. The safety profile for both arms was similar to previously reported studies. Tx discontinuation rates due to AEs were similar between the arms. Clinical trial information: NCT00418938. [Table: see text]

A randomized phase II study of nivolumab or nivolumab combined with ipilimumab in patients (pts) with melanoma brain metastases (mets): The Anti-PD1 Brain Collaboration (ABC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9508-9508 ◽  
Author(s):  
Georgina V. Long ◽  
Victoria Atkinson ◽  
Alexander M. Menzies ◽  
Serigne Lo ◽  
Alexander David Guminski ◽  
...  
Keyword(s):  
Antitumour Activity ◽  
Braf Inhibitor ◽  
Local Therapy ◽  
Progression Free Survival ◽  
Leptomeningeal Disease ◽  
Open Label ◽  
Randomized Phase Ii ◽  
Treatment Naïve ◽  
Secondary Endpoints ◽  
Previously Treated

9508 Background: Nivolumab (nivo) and the combination of nivo + ipilimumab (ipi) improve response rates (RR) and progression-free survival (PFS) compared with ipi alone in clinical trials of metastatic melanoma pts, but pts with untreated brain mets were excluded. Brain mets are a major cause of morbidity and mortality in melanoma and their management is critical. We sought to determine the antitumour activity and safety of nivo and nivo+ipi in pts with active melanoma brain mets (NCT02374242). Methods: This open-label, ph II trial enrolled 3 cohorts of pts naïve to anti-PD1/PDL1/PDL2/CTLA4 from Nov 2014 - Feb 2017. Pts with asymptomatic melanoma brain mets with no prior local brain therapy were randomised to cohort A (nivo 1mg/kg + ipi 3mg/kg, Q3W x4, then nivo 3mg/kg Q2W) or cohort B (nivo 3mg/kg Q2W). Cohort C (nivo 3mg/kg Q2W) had brain mets 1) that failed local therapy (new +/- progressed in previously treated met), 2) were neurologically symptomatic and/or 3) with leptomeningeal disease. Prior BRAF inhibitor (BRAFi) was allowed. The primary endpoint was best intracranial response (ICR) ≥ wk12. Secondary endpoints were best extracranial response (ECR), best overall response (OR), IC PFS, EC PFS, overall PFS, OS, and safety. Results: A total of 66 pts (med f/u 14 mo) were included in this analysis of total 76 planned; median age 60y, 77% male. For cohorts A, B and C: elevated LDH 48%, 58% and 19%; V600BRAF 44%, 56% and 81%; prior BRAFi 24%, 24%, 75%. Table shows RR, PFS and OS. ICR in cohort A treatment naïve vs prior BRAFi was 53% vs 16%. Treatment-related gd 3/4 toxicity in cohorts A, B and C were 68%, 40% and 56%, respectively. There were no treatment-related deaths. Conclusions:Nivo monotherapy and ipi+nivo and are active in melanoma brain mets. Ipi+nivo had reduced activity in pts who progressed on BRAFi. Pts with symptomatic brain mets, leptomeningeal mets or previous local therapy responded poorly to nivo alone. Clinical trial information: NCT02374242. [Table: see text]

SPIRITT (study 20060141): A randomized phase II study of FOLFIRI with either panitumumab (pmab) or bevacizumab (bev) as second-line treatment (tx) in patients (pts) with wild-type (WT) KRAS metastatic colorectal cancer (mCRC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3616-3616 ◽  
Author(s):  
Allen Lee Cohn ◽  
J. Randolph Hecht ◽  
Shaker Dakhil ◽  
Mansoor N. Saleh ◽  
Bilal Piperdi ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Eligibility Criteria ◽  
Grade 5 ◽  
Randomized Phase Ii ◽  
Secondary Endpoints ◽  
Previously Treated

3616 Background: Pmab has demonstrated significant improvement in progression-free survival (PFS) in pts with WT KRAS mCRC as 2nd-line tx in a phase III trial comparing pmab + FOLFIRI vs FOLFIRI alone. Here, we describe the results of SPIRITT, a multicenter, randomized phase II study evaluating pmab + FOLFIRI and bev + FOLFIRI in pts with WT KRAS mCRC previously treated with a 1st-line bev + oxaliplatin (Ox)-based chemotherapy regimen. Methods: Pts were randomized 1:1 to pmab 6.0 mg/kg + FOLFIRI Q2W or to bev 5.0 or 10.0 mg/kg + FOLFIRI Q2W. Eligibility criteria included: WT KRAS mCRC, ECOG ≤ 1, no prior irinotecan or anti-EGFR tx, and tx failure of prior 1st-line bev + Ox-based therapy (≥ 4 cycles). The primary endpoint was PFS; secondary endpoints included overall survival (OS), objective response rate (ORR), and safety. No formal hypothesis was tested. Results: 182 pts with WT KRAS mCRC were randomized. All pts received tx. Efficacy results are shown (Table). Worst grade of 3/4 adverse events (AE) occurred in 78% of pts in the pmab + FOLFIRI arm and 65% in the bev + FOLFIRI arm. Grade 5 AEs occurred in 7% of pts in the pmab + FOLFIRI arm and 7% in the bev + FOLFIRI arm. Tx discontinuation due to any AE was 29% in the pmab + FOLFIRI arm and 25% in the bev + FOLFIRI arm. Conclusions: In this estimation study of pts with WT KRAS mCRC that previously received bev + Ox-based tx, the PFS hazard ratio (HR) was 1.01 (95% CI: 0.68 - 1.50). The OS HR was 1.06 (95% CI: 0.75 - 1.49). The observed ORR was higher in the pmab + FOLFIRI arm. 54% of bev + FOLFIRI pts received subsequent anti-EGFR tx. The safety profile for both arms was similar to previously reported studies. Tx discontinuation rates due to AEs were similar between the arms. Clinical trial information: NCT00418938. [Table: see text]

Prospective randomized phase II study of FOLFIRI versus FOLFOX7 in advanced gastric adenocarcinoma: A Chinese Western Cooperative Gastrointestinal Oncology Group study.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 1-1 ◽  
Author(s):  
Feng Bi ◽  
Qiu Li ◽  
Feng Wen ◽  
Chengya Zhou ◽  
Meng Qiu ◽  
...  
Keyword(s):  
Gastric Adenocarcinoma ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Randomized Phase Ii ◽  
Significant Difference ◽  
Evaluable Population ◽  
Secondary Endpoints ◽  
Advanced Gastric Adenocarcinoma

1 Background: The purpose was to compare mFOLFIRI (arm A) with mFOLFOX7 (arm B) as first-line treatments in patients (pts) with locally advanced gastric adenocarcinoma in an open, randomized, phase II study. Methods: Previously untreated metastatic or recurrent gastric adenocarcinoma pts with measurable disease received mFOLFIRI (arm A) or mFOLFOX7 (arm B) every 2 weeks. The second-line treatment was mFOLFOX7 for arm A and mFOLFIRI for arm B. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were overall survival (OS), disease control rate (DCR) and toxicity. Results: In total, 200 pts were included. The evaluable population consisted of 128 pts (54 in arm A; 74 in arm B). The median PFS of arm A was 2.9 months (m) (1.9 to 4.1 m) versus 4.1 m (3.2 to 4.8 m) for arm B(p0.109). The median OS was 9.9 months (6.0 to 13.5 m) for arm A versus 12.0 m for arm B (10.3 to 13.7m; p= 0.431). The DCRs for arm A and arm B were 59.3% and 66.3%, respectively (p = 0.850). In subgroup analysis of the pts who completed both treatment lines per protocol, the median OS was 11.0 m (5.1 to 16.9 m) for the mFOLFIRI/mFOLFOX7 group and 20.2 m (13.4 to 26.6 m) for the mFOLFOX7/mFOLFIRI group ( p= 0.030). Both regimens were well-tolerated with acceptable and manageable toxicities. Grade ¾ adverse events were 53.2% and 55.4% in arm A and arm B, respectively. Conclusions: There was no significant difference in the PFS or DCR. However, mFOLFOX7 followed by mFOLFIRI might have a better OS. Clinical trial information: ChiCTR-TRC-08000167. [Table: see text]

scholarly journals Randomized phase II trial of avelumab alone or in combination with cetuximab for patients with previously treated, locally advanced, or metastatic squamous cell anal carcinoma: the CARACAS study

2021 ◽  
Vol 9 (11) ◽  
pp. e002996
Author(s):  
Sara Lonardi ◽  
Alessandra Anna Prete ◽  
Federica Morano ◽  
Marco Messina ◽  
Vincenzo Formica ◽  
...  
Keyword(s):  
Phase Ii ◽  
Squamous Cell ◽  
Primary Endpoint ◽  
Phase Ii Trial ◽  
Locally Advanced ◽  
Anal Carcinoma ◽  
Open Label ◽  
Egfr Inhibition ◽  
Randomized Phase Ii ◽  
Previously Treated

BackgroundNo standard therapies beyond first line are established for advanced squamous cell anal carcinoma (aSCAC). Earlier preliminary data suggest activity of epidermal growth factor receptor (EGFR) inhibition and programmed cell death ligand (PD-(L))1 blockade in patients with previously treated disease. Aim of this study was to explore activity and safety of avelumab with/without cetuximab in patients with aSCAC.MethodsIn this open-label, non-comparative, ‘pick the winner’, multicenter randomized phase II trial (NCT03944252), patients with aSCAC progressing after one or more lines of treatment were randomized 1:1 to the anti-PD-L1 agent avelumab alone (arm A) or combined with cetuximab (arm B). Overall response rate (ORR) was the primary endpoint. With one-sided α error set at 0.05 and power of 80%, at least 4 responses out of 27 patients per arm had to be observed to declare the study positive. Secondary endpoints were progression free survival (PFS), overall survival (OS), and safety.ResultsThirty patients per arm were enrolled. Three patients in arm A and five in arm B achieved partial response: primary endpoint was reached in combination arm. ORR was 10% (95% CI 2.1 to 26.5) and 17% (95% CI 5.6 to 34.7) in arms A and B; disease control rate was 50% (95% CI 31.3 to 68.7) in arm A and 57 (95% CI 37.4–74.5) in arm B. At a median follow-up of 26.7 months (IQR 26.5–26.9), median PFS was 2.0 months (95% CI 1.8 to 4.0) in arm A and 3.9 (95% CI 2.1 to 5.6) in arm B. Median OS was 13.9 months (95% CI 7.7 to 19.4) in arm A and 7.8 (95% CI 6.2 to 11.2) in arm B. Acceptable safety profile was observed in both arms.ConclusionsCARACAS study met its primary endpoint in arm B, documenting promising activity of dual EGFR and PD-L1 blockade in aSCAC.

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