scholarly journals CTNI-46. A PHASE II TRIAL OF TUMOR TREATING FIELDS (TTFIELDS) CONCOMITANT WITH RADIOSURGERY FOR THE TREATMENT OF RECURRENT, BEVACIZUMAB-NAÏVE GLIOBLASTOMA

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii52-ii53
Author(s):  
Maciej Harat ◽  
Maciej Blok ◽  
Magda Adamczak-Sobczak ◽  
Pawel Szymanski ◽  
Iza Miechowicz ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Methylation Status ◽  
Historical Control ◽  
Phase Iii ◽  
Maximum Diameter ◽  
Target Area ◽  
Open Label ◽  
Fet Pet ◽  
One Year

Abstract BACKGROUND Almost all GBM patients experience recurrent disease, and median survival after recurrence is 6 months. A phase III trial conducted to test safety and efficacy of TTFields alone versus chemotherapy (including bevacizumab) in recurrent GBM showed improved PFS at six months and one-year survival was 20% in both treatment arms. Stereotactic radiosurgery (SRS), another treatment option recommended at recurrence, has limitations due to the invasive nature of glioblastoma. TTFields may decrease the tumor aggressiveness outside the target area potentially by multiple pathways, including immunogenic cell death and DNA repair inhibition sensitizing to radiation. We hypothesize that combined SRS and TTFields will be complementary, improving outcomes with minimal toxicity. METHODS In this open-label, phase II trial 40 participants with recurrence will be treated with SRS and TTFields, starting in 2020. Recurrence will be defined on FET-PET or MRI using RANO criteria. At least 6 months between the end of the first course of radiotherapy and SRS is mandatory with recurrent tumor visible on FET-PET and/or MRI, with the maximum diameter < 5 cm by either technique. SRS must be delivered within 7 days of TTFields start. A 5-day SRS regimen is allowed. TTFields should be interrupted only during SRS. The sample size of the study was calculated for the comparison of survival against a historical control. With 40 patients followed until death, there is at least an 80% ability to detect a 19% difference in one-year survival rate and 17% difference in ORR (p=0.05) compared to the EF-11 clinical trial. The one-year survival and ORR rate were seen in 20% and 14% of TTFields patients in the historical control. Overall survival will be stratified by volume, PET-based treatment, SVZ invasion, MGMT methylation status, time to first progression, and TTFields compliance. Estimated study primary completion date is July 2023.

scholarly journals Regorafenib for the Treatment of Advanced Gastric Cancer (INTEGRATE): A Multinational Placebo-Controlled Phase II Trial

2016 ◽  
Vol 34 (23) ◽  
pp. 2728-2735 ◽  
Author(s):  
Nick Pavlakis ◽  
Katrin M. Sjoquist ◽  
Andrew J. Martin ◽  
Eric Tsobanis ◽  
Sonia Yip ◽  
...  
Keyword(s):  
New Zealand ◽  
South Korea ◽  
Disease Progression ◽  
Gastric Adenocarcinoma ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Phase Iii ◽  
Open Label ◽  
Multikinase Inhibitor ◽  
Advanced Gastric Adenocarcinoma

Purpose We evaluated the activity of regorafenib, an oral multikinase inhibitor, in advanced gastric adenocarcinoma. Patients and Methods We conducted an international (Australia and New Zealand, South Korea, and Canada) randomized phase II trial in which patients were randomly assigned at a two-to-one ratio and stratified by lines of prior chemotherapy for advanced disease (one v two) and region. Eligible patients received best supportive care plus regorafenib 160 mg or matching placebo orally on days 1 to 21 of each 28-day cycle until disease progression or prohibitive adverse events occurred. The primary end point was progression-free survival (PFS). Final analysis included data to December 31, 2014. Results A total of 152 patients were randomly assigned from November 7, 2012, to February 25, 2014, yielding 147 evaluable patients (regorafenib, n = 97; placebo, n = 50). Baseline characteristics were balanced. Median PFS significantly differed between groups (regorafenib, 2.6 months; 95% CI, 1.8 to 3.1 and placebo, 0.9 months; 95% CI, 0.9 to 0.9; hazard ratio [HR], 0.40; 95% CI, 0.28 to 0.59; P < .001). The effect was greater in South Korea than in Australia, New Zealand, and Canada combined (HR, 0.12 v 0.61; interaction P < .001) but consistent across age, neutrophil-to-lymphocyte ratio, primary site, lines of chemotherapy, peritoneal metastasis presence, number of metastatic sites, and plasma vascular endothelial growth factor A. A survival trend in favor of regorafenib was seen (median, 5.8 months; 95% CI, 4.4 to 6.8 v 4.5 months; 95% CI, 3.4 to 5.2; HR, 0.74; P = .147). Twenty-nine patients assigned to placebo received open-label regorafenib after disease progression. Regorafenib toxicity was similar to that previously reported. Conclusion In this phase II trial, regorafenib was effective in prolonging PFS in refractory advanced gastric adenocarcinoma. Regional differences were found, but regorafenib was effective in both regional groups. A phase III trial is planned.

FOLFIRI.3 (CPT-11 plus folinic acid plus 5-FU) alternating with gemcitabine or gemcitabine (G) alone in patients (pts) with previously untreated metastatic pancreatic adenocarcinoma (MPA): Results of the randomized multicenter AGEO phase II trial FIRGEM.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4018-4018 ◽  
Author(s):  
Isabelle Trouilloud ◽  
Anne Claire Dupont-Gossard ◽  
Pascal Artru ◽  
Thierry Lecomte ◽  
Mélanie Gauthier ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Good Condition ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Fixed Dose ◽  
New Strategy ◽  
And Performance ◽  
One Year

4018 Background: CPT-11 showed modest activity and tolerability in MPA. We developed a new strategy to improve efficacy and tolerability of CPT-11 based regimen in MPA pts. Methods: Chemotherapy-naive pts with histologically proven MPA, bilirubin levels < 1.5 ULN and performance status (PS) 0-1 were randomized in a phase II trial to receive either FOLFIRI.3 (CPT-11 90 mg/m2 as a 60-min infusion on day (D) 1, leucovorin 400 mg/m2 as a 2-hr infusion on day 1, followed by 5-FU 2000 mg/m2 as a 46-hr infusion and CPT-11 90 mg/m2, repeated on D3, at the end of the 5-FU infusion, every 2 weeks) for 2 months alternarting with G (1000 mg/m² at a fixed dose rate of 10 mg/m²/min on D1, D8, D15, D29, D36 and D43) for 2 months (arm A) or G alone (arm B). Using Fleming design the primary end point was rate of progression free survival (PFS) at 6 months from (H0) 25% over (H1) 45% needing to include 49 pts/arm. Results: Between 2007 and 2011, 98 pts were enrolled (males: 59, median age: 62 years, PS 0: 32%). Median follow-up was 23 months. Grade 3-4 toxicities per pts (%) in arm A/B were diarrhea 13/0, nausea-vomiting 11/4, neutropenia 51/25 and febrile neutropenia 4/0. No toxic death occurred. Response rate were 40 and 11% as disease control rate (CR+PR+SD) were 73 and 52% in arm A and B, respectively. The primary endpoint of the trial was met with rate of PFS at 6 months of 48% (95% CI: 33-63) in arm A while in arm B PFS was 30% (95% CI: 17 - 44). One year PFS was 23% (95%CI: 11.5-36) and 11% (95%CI: 4-21), respectively. Conclusions: FIRGEM strategy is feasible and efficient with a manageable toxicity profile in good condition pts with MPA. A phase III trial comparing this strategy with the FOLFIRINOX triplet therapy focusing on quality of life should now be performed.

A multicenter, randomized, open-label, phase II trial of erlotinib versus etoposide plus cisplatin with concurrent radiotherapy in unresectable stage III non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) activating mutation.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 8531-8531 ◽  
Author(s):  
Ligang Xing ◽  
Gang Wu ◽  
Lvhua Wang ◽  
Jian-Cheng Li ◽  
Jianhua Wang ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Phase Iii ◽  
Stage Iii ◽  
Stage Iiia ◽  
Open Label ◽  
Concurrent Radiotherapy ◽  
Unresectable Stage ◽  
Open Label Phase ◽  
Egfr Mutant

8531 Background: Concurrent chemoradiotherapy is the standard treatment for patients(pts) with unresectable stage IIIA/IIIB NSCLC. In EGFR mutant pts, tyrosine kinase inhibitor(TKI) exhibits clinical benefits over chemotherapy regimens in terms of efficacy and safety as well as specific enhancement of radiation effects. This multicenter, randomized, open-label, phase II trial aimed to compare the erlotinib and etoposide/cisplatin with concurrent radiotherapy (RT) in pts with EGFR-mutant. Methods: Histopathology/cytology confirmed stage IIIA/B unresectable NSCLC pts (age 18-75) with ECOG PS 0-1 and EGFR exon 19 or 21 mutation were included and randomized (1:1) into two arms: erlotinib (E) and etoposide/cisplatin (EP). E arm was treated with oral erlotinib (150mg/day for 2 years or till either disease progression or intolerable toxicities) and RT (200cGy/day, 5 days/week for 6 weeks from first day erlotinib). EP arm was treated with sequential etoposide (50 mg/m2 IV days 1-5, 29-33) and cisplatin (50mg/m2IV day 1,8, 29,36) and RT (from first day drug). Primary endpoint is progress free survival (PFS). Secondary endpoints are objective response rate(ORR), local control rate(LCR), overall survival(OS), quality of life(QoL) and safety. Results: 252 pts were screened, and 41 were enrolled into E(n=20) and EP(n=21) arms. Characteristics of age, sex, histologic type, N2, EGFR 19 and 21 mutation were well balanced in each arm. Comparing with EP, median PFS of E arm was significantly improved (27.86 vs 6.41 months; HR 0.053, 95% CI: 0.006-0.463; P<0.001). ORR and DCR were 60.0% vs. 38.1%( P=0.217), and 65% vs. 47.6%( P=0.350), respectively. Two arms had same incidence of adverse effects (CTCAE Grade≥1, 86.7%[13/15]), and most common sAE(Grade≥3) was rash (20%, 3/15) and hematological toxicity(26.7%, 4/15), respectively. Conclusions: In unresectable stage III EGFR mutant NSCLC pts, concurrent erlotinib/RT provides a statistically significant PFS improvement with well tolerability. These results warrant a phase III study to confirm. (RECEL, NCT01714908). Clinical trial information: NCT01714908.

scholarly journals Safety and efficacy of N-acetylcysteine in hospitalized patients with HIV-associated tuberculosis: An open-label, randomized, phase II trial (RIPENACTB Study)

PLoS ONE ◽  
2020 ◽  
Vol 15 (6) ◽  
pp. e0235381 ◽  
Author(s):  
Izabella Picinin Safe ◽  
Marcus Vinícius Guimarães Lacerda ◽  
Vitoria Silva Printes ◽  
Adriana Ferreira Praia Marins ◽  
Amanda Lia Rebelo Rabelo ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Hospitalized Patients ◽  
Open Label ◽  
Safety And Efficacy ◽  
Randomized Phase Ii

scholarly journals An open-label, single-arm, phase II trial of buparlisib in patients with melanoma brain metastases not eligible for surgery or radiosurgery—the BUMPER study

2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Teresa Amaral ◽  
Heike Niessner ◽  
Tobias Sinnberg ◽  
Ioannis Thomas ◽  
Andreas Meiwes ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Local Therapy ◽  
Progression Free Survival ◽  
Pi3k Inhibitor ◽  
Open Label ◽  
Preclinical Data ◽  
Overall Response ◽  
Intracranial Disease ◽  
Dismal Prognosis

Abstract Background Patients with melanoma brain metastasis (MBM) still carry a dismal prognosis. Preclinical data originated in xenograft models showed that buparlisib therapy was highly effective in therapy-naïve MBM. Patients and Methods In this open-label, phase II trial, we investigate the safety and efficacy of monotherapy with buparlisib, a PI3K inhibitor, in patients with asymptomatic MBM who were not candidates for local therapy. These patients had also progressed under immunotherapy if BRAF wild-type or under targeted therapy with BRAF/MEK inhibitors if carrying a BRAFV600E/K mutation. The primary endpoint was the intracranial disease control rate assessed by the investigators. The secondary endpoints were overall response rate, duration of response (DOR) of intracranial disease, overall response, progression-free survival (PFS), overall survival (OS), safety, and tolerability of buparlisib. Results A total of 20 patients were screened and 17 patients were treated with buparlisib. Twelve patients had progressed under more than 2 systemic therapy lines and 17 had received at least 1 previous local therapy. There were no intracranial responses. Three patients achieved intracranial stable disease; the median DOR was 117 days. The median PFS was 42 days (95% confidence interval [CI]: 23–61 days) and the median OS was 5.0 months (95% CI: 2.24–7.76 months). No new safety signs were observed. Conclusions Buparlisib was well tolerated but no intracranial responses were observed. These results might be explained in part by the inclusion of only heavily pretreated patients. However, preclinical data strongly support the rationale to explore PI3K inhibitor-based combinations in patients with MBM displaying hyperactivation of the PI3K–AKT pathway.

A randomised, open-label phase II trial of afatinib versus cetuximab in patients with metastatic colorectal cancer

2014 ◽  
Vol 50 (18) ◽  
pp. 3136-3144 ◽  
Author(s):  
Tamas Hickish ◽  
Jim Cassidy ◽  
David Propper ◽  
Ian Chau ◽  
Stephen Falk ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Open Label ◽  
Open Label Phase
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