Phase II double-blind placebo-controlled study of armodafinil for brain radiation induced fatigue.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 9505-9505 ◽  
Author(s):  
Edward G. Shaw ◽  
Doug Case ◽  
David Bryant ◽  
David Grisell ◽  
Glenn Lesser ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Phase Ii ◽  
Concurrent Chemotherapy ◽  
Phase Iii ◽  
Controlled Study ◽  
Low Grade ◽  
Eligibility Criteria ◽  
Double Blind ◽  
Phase Iii Study ◽  
Brain Radiation

9505 Background: Armodafinil (ARM), the R-enantiomer of modafinil, is FDA approved for narcolepsy, shift work disorder, and treated sleep-apnea, and has also been shown to reduce fatigue/improve cognitive function in cancer patients. This phase II study estimated the efficacy and toxicity of ARM in primary brain tumor (PBT) patients receiving brain radiation therapy (RT) to determine whether a larger phase III study would be warranted. Methods: Eligibility criteria – adult, PBT, total RT dose >45Gy, KPS>60, no severe headaches, and concurrent chemotherapy allowed. Patients were assessed at baseline, end of RT, then 4 weeks after end RT with the Brief Fatigue Inventory (BFI), Epworth Sleep Scale (ESS), FACT, and FACT brain and FACIT fatigue subscales. Patients were randomized to receive ARM 150mg/day during RT and for 4 weeks after RT or placebo (PLAC). Results: 54 patients enrolled between 9/10-12/12; 26 to ARM, 28 to placebo PLAC. Median age 59; 59% female; 95% White; 41% KPS 90-100, 59% KPS 60-80; 74% malignant glioma, 26% low-grade glioma/benign histology. 83% patients had concurrent chemotherapy. For all randomized patients, there were no statistically significant differences in outcome between ARM and PLAC groups at end-RT vs. baseline or 4 weeks post RT vs. baseline. For patients who had more baseline fatigue (fatigue subscale score <median), ARM-treated patients had significantly/suggestively better outcomes at end-RT vs. baseline compared to PLAC-treated patients: less fatigue (BFI p=0.056, fatigue subscale p=0.0295), less sleepiness (ESS p=0.1034), and better QOL (FACT p=0.0001). Incidence of grade 2/3 toxicities was the same between the two treatment groups: 7% anxiety, 7% nausea, 18% headaches, and 20% insomnia. There were no grade 4 or 5 toxicities. Conclusions: In irradiated PBT patients, fatigue, sleepiness, and reduced QOL occurring at the end of brain RT was less with ARM in those patients who were more fatigued at baseline. Toxicity was minimal. These data support conducting a larger phase III study. Analysis of cognitive function data is ongoing. Support - NIH/NCI grant 2U10 CA 81851 and Teva Pharmaceuticals. Clinical trial information: 95709.

Results of the X-PECT study: A phase III randomized double-blind, placebo-controlled study of perifosine plus capecitabine (P-CAP) versus placebo plus capecitabine (CAP) in patients (pts) with refractory metastatic colorectal cancer (mCRC).

2012 ◽  
Vol 30 (18_suppl) ◽  
pp. LBA3501-LBA3501 ◽  
Author(s):  
Johanna C. Bendell ◽  
Thomas J. Ervin ◽  
Neil N. Senzer ◽  
Donald A. Richards ◽  
Irfan Firdaus ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Phase Ii ◽  
Median Overall Survival ◽  
Phase Iii ◽  
Controlled Study ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Randomized Phase Ii ◽  
Phase Iii Study

LBA3501 Background: Perifosine (P) is an oral, synthetic alkylphospholipid that inhibits or modifies signal transduction pathways including AKT, NFkB and JNK. A randomized phase II study examined P-CAP vs. CAP in pts with 2nd or 3rd line mCRC. This study showed improvement in mTTP (HR 0.254 [0.117, 0.555]) and mOS (HR 0.370 [0.180,0.763]). Based on these results, a randomized phase III study of P-CAP vs. CAP with a primary endpoint of overall survival (OS) in pts with refractory mCRC was initiated. Methods: The study was a prospective, randomized, double-blind, placebo-controlled randomized phase III trial. Eligible pts had mCRC which was refractory to all standard therapies. Pts randomized 1:1 to Arm A = P-CAP (P 50 mg PO QD + CAP 1000 mg/m2PO BID d1-14) or Arm B = CAP (placebo + CAP 1000 mg/m2 PO BID d 1-14). Cycles were 21 days. Baseline tumor block collection and a biomarker cohort of pts with pre- and on-treatment tumor and blood samples were performed. Results: Between 3/31/10 and 8/12/11, 468 pts were randomized, 234 pts were in each arm. Baseline demographics were balanced between the arms: age < 65y (A: 65%, B: 58.5%), male (A: 57.7%, B: 53.0%), ECOG PS 0 (A: 39.7%, B: 39.7%), K-ras mutant (A: 50.4%, B: 51.3%), and median number of prior therapies (A: 4, B: 4). As of 3/19/12, median follow up was 6.6 months. Median overall survival: Arm A = 6.4 mo, Arm B = 6.8 mo, HR 1.111 [0.905,1.365], p = 0.315. Median overall survival for K-ras WT pts: Arm A = 6.6 mo, Arm B = 6.8 mo, HR 1.020 [0.763,1.365], p = 0.894; K-ras mutant pts: Arm A = 5.4 mo, Arm B = 6.9 mo HR 1.192 [0.890,1.596], p = 0.238. Conclusions: Despite promising randomized phase II data, this phase III study shows no benefit in overall survival adding perifosine to capecitabine in the refractory colorectal cancer setting. Response rate, progression free survival, and safety data will be presented. Biomarker analysis is pending to see if subgroups of patients may have potential benefit.

INTEGRATE: A randomized phase II double-blind placebo-controlled study of regorafenib in refractory advanced oesophagogastric cancer (AOGC)—A study by the Australasian Gastrointestinal Trials Group (AGITG), first results.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 9-9 ◽  
Author(s):  
Nick Pavlakis ◽  
Katrin Marie Sjoquist ◽  
Eric Tsobanis ◽  
Andrew Martin ◽  
Yoon-Koo Kang ◽  
...  
Keyword(s):  
Phase Ii ◽  
Kinase Inhibitor ◽  
Secondary Analysis ◽  
Progression Free Survival ◽  
Best Supportive Care ◽  
Phase Iii ◽  
Prognostic Indicators ◽  
Controlled Study ◽  
Primary Analysis ◽  
Double Blind

9 Background: Advanced Oesophago-Gastric Carcinoma (AOGC) has limited options following failure of first or second line chemotherapy (CT). Regorafenib (REG) is an oral multi-kinase inhibitor of kinases involved in angiogenesis, tumor microenvironment, and oncogenesis. This study examined whether REG has sufficient activity and safety for further evaluation. Methods: International (Australia & New Zealand (ANZ), Korea, Canada (NCIC CTG)) randomised phase II trial with 2:1 randomisation and stratification by: (1) Lines of prior CT for advanced disease (1 vs. 2) and (2) Region. Eligible patients received best supportive care plus 160mg REG or matching PBO orally on days 1-21 each 28-day cycle until disease progression or prohibitive adverse events. Primary endpoint was progression free survival (PFS) in the REG arm, assuming median 8 weeks (wks) in PBO arm, aiming for 13.2 wks with REG to be of interest. Results: From Nov 2012 to Feb 2014, 152 patients were enrolled, 147 evaluable [pre-specified primary analysis population]: (REG n=97: PBO n=50); well matched for key baseline prognostic indicators; male:female (118:29); primary location: OG Junction (56), stomach (85); lines of prior therapy: 1 (63), 2 (84); ECOG 0 (62): 1 (85). Time on treatment: Median: 7.9 (REG) v 4 (PBO) wks. In the evaluable population median PFS was 11.1 wks (95% CI: 7.7 - 12.3) (REG) and 3.9 wks (95% CI: 3.7 - 4.0) (PBO), log-rank p <0.0001; HR 0.41 (95% CI: 0.28 to 0.59). PFS results were maintained for secondary analysis including all randomized patients (n = 152). REG was well tolerated, with the spectrum of toxicity in keeping with previous reports. Conclusions: PFS was clearly significantly longer with REG than PBO, though PBO PFS was less than anticipated. The pre-specified exploratory comparisons provide compelling evidence that REG has sufficient activity with acceptable tolerability in refractory AOGC to warrant phase III evaluation. Mature OS results will be presented at the meeting. Clinical trial information: 12612000239864.

scholarly journals Randomized, Double-Blind, Placebo-Controlled Phase III Study of Tasquinimod in Men With Metastatic Castration-Resistant Prostate Cancer

2016 ◽  
Vol 34 (22) ◽  
pp. 2636-2643 ◽  
Author(s):  
Cora Sternberg ◽  
Andrew Armstrong ◽  
Roberto Pili ◽  
Siobhan Ng ◽  
Robert Huddart ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Phase Ii ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Double Blind ◽  
End Point ◽  
Castration Resistant ◽  
Phase Iii Study

Purpose Tasquinimod, a novel oral therapy targeting the tumor microenvironment, significantly improved progression-free survival (PFS) in a randomized, placebo-controlled phase II trial in men with metastatic castration-resistant prostate cancer (mCRPC). This phase III study was conducted to confirm the phase II results and to detect an overall survival (OS) benefit. Patients and Methods Men with chemotherapy-naïve mCRPC and evidence of bone metastases were assigned (2:1) to receive tasquinimod once per day or placebo until progression or toxicity. The primary end point was radiographic PFS (rPFS; time from random assignment to radiologic progression or death) per Prostate Cancer Working Group 2 criteria and RECIST 1.1. The study had 99.9% power to detect an rPFS hazard ratio (HR) of 0.6 with a two-sided alpha error of .05 and 80% power to detect a target HR of 0.8 for OS, the key secondary end point. Results In all, 1,245 patients were randomly assigned to either tasquinimod (n = 832) or placebo (n = 413) between March 2011 and December 2012 at 241 sites in 37 countries. Baseline characteristics were balanced between groups: median age, 71 years; Karnofsky performance status ≥ 90%, 77.3%; and visceral metastases, 21.1%. Estimated median rPFS by central review was 7.0 months (95% CI, 5.8 to 8.2 months) with tasquinimod and 4.4 months (95% CI, 3.5 to 5.5 months) with placebo (HR, 0.64; 95% CI, 0.54 to 0.75; P < .001). Median OS was 21.3 months (95% CI, 19.5 to 23.0 months) with tasquinimod and 24.0 months (95% CI, 21.4 to 26.9 months) with placebo (HR, 1.10; 95% CI, 0.94 to 1.28; P = .25). Grade ≥ 3 adverse events were more frequent with tasquinimod (42.8% v 33.6%), the most common being anemia, fatigue, and cancer pain. Conclusion In chemotherapy-naïve men with mCRPC, tasquinimod significantly improved rPFS compared with placebo. However, no OS benefit was observed.

KEYNOTE-355: Randomized, double-blind, phase III study of pembrolizumab (pembro) + chemotherapy (chemo) vs placebo (PBO) + chemo for previously untreated, locally recurrent, inoperable or metastatic triple-negative breast cancer (mTNBC).

2018 ◽  
Vol 36 (5_suppl) ◽  
pp. TPS18-TPS18 ◽  
Author(s):  
Javier Cortés ◽  
Zifang Guo ◽  
Vassiliki Karantza ◽  
Gursel Aktan
Keyword(s):  
Antitumor Activity ◽  
Disease Recurrence ◽  
Phase Iii ◽  
Controlled Study ◽  
Adjuvant Setting ◽  
Open Label ◽  
Double Blind ◽  
End Points ◽  
Phase Iii Study ◽  
Locally Recurrent

TPS18 Background: In the phase Ib KEYNOTE-012 study, the anti–PD-1 antibody pembro demonstrated promising antitumor activity and acceptable safety as monotherapy in pretreated patients (pts) with PD-L1+ mTNBC. Adding pembro to chemo may enhance antitumor activity. KEYNOTE-355 (NCT02819518) is a global phase III study of pembro+chemo vs PBO+chemo in pts with previously untreated, locally recurrent, inoperable TNBC/mTNBC. Methods: Eligible pts are ≥18 y and have centrally confirmed, locally recurrent, inoperable TNBC or mTNBC not previously treated with chemo (prior chemo in [neo]adjuvant setting is allowed); measurable disease per RECIST v1.1; ECOG PS 0-1; ≥6 mo between definitive surgery or last dose of adjuvant chemo, whichever was last; and first disease recurrence (≥12 mo if prior treatment with same-class agent). Part 1 is an open-label, unblinded safety run-in of ~30 pts in 3 arms (pembro+nab-paclitaxel, pembro+paclitaxel, pembro+gemcitabine/carboplatin). Part 2 is a double-blind, PBO-controlled study of ~828 pts randomized 2:1 to pembro 200 mg every 3 weeks + chemo (nab-paclitaxel 100 mg/m2 on d 1, 8, and 15 every 28 d; paclitaxel 90 mg/m2 on d 1, 8, and 15 every 28 d; or gemcitabine 1000 mg/m2+ carboplatin AUC 2 on d 1 and 8 every 21 d) or PBO+chemo. Crossover is not allowed. Stratification factors are study chemo (taxane vs gemcitabine/carboplatin), tumor PD-L1 expression (+/-), and prior therapy with same-class agent in the (neo)adjuvant setting (yes/no). Treatment will occur for ≤35 administrations (pembro/PBO only) or until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or decision to discontinue. Primary end points are safety in part 1 and PFS (by RECIST v1.1, central radiology review) and OS in part 2; secondary end points include ORR (by RECIST v1.1, central radiology review) and duration of response. AEs will be graded per NCI CTCAE v4.0. Response will be assessed at wk 8, 16, 24, then at 9-wk intervals up to 1 y, and at 12-wk intervals thereafter. Interim safety analysis will occur after pts complete 1 treatment cycle in part 1. Clinical trial information: NCT02819518.

scholarly journals A randomised, double-blind, placebo-controlled, 24-week, phase II, proof-of-concept study of romilkimab (SAR156597) in early diffuse cutaneous systemic sclerosis

2020 ◽  
Vol 79 (12) ◽  
pp. 1600-1607 ◽  
Author(s):  
Yannick Allanore ◽  
Peter Wung ◽  
Christina Soubrane ◽  
Corinne Esperet ◽  
Frederic Marrache ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Phase Ii ◽  
Phase Iii ◽  
Scleroderma Renal Crisis ◽  
Proof Of Concept ◽  
Double Blind ◽  
Immunoglobulin G4 ◽  
Background Therapy ◽  
Registration Number ◽  
Phase Iii Study

ObjectivesRecent advances in systemic sclerosis (SSc) show that it involves a T-helper type-2-oriented immune response with interleukin (IL)-4 and IL-13. Romilkimab is an engineered, humanised, bispecific immunoglobulin-G4 antibody that binds and neutralises IL-4/IL-13 making it ideal for exploration in fibrosis.MethodsPatients aged ≥18 years diagnosed with diffuse cutaneous SSc (dcSSc), and with or without immunosuppressive background therapy, were randomised (1:1) to subcutaneous romilkimab 200 mg or placebo one time per week for 24 weeks in this double-blind, proof-of-concept, phase II study. The primary endpoint was change in modified Rodnan skin score (mRSS) from baseline to week 24.ResultsNinety-seven patients were randomised to romilkimab (n=48) or placebo (n=49) for 24 weeks. Least-squares mean (SE) change in mRSS was –4.76 (0.86) for romilkimab versus –2.45 (0.85) for placebo yielding a mean (SE) (90% CI) difference of –2.31 (1.21) (–4.32 to –0.31; p=0.0291, one-sided). Treatment-emergent AEs were balanced between placebo (n=41; 84%) and romilkimab (n=40; 80%). Most were mild-to-moderate and discontinuations were low (three overall). There were two deaths (one scleroderma renal crisis (romilkimab) and one cardiomyopathy (placebo)), neither were considered treatment related. Two patients in the placebo group had a cardiovascular treatment-emergent SAE (one cardiac failure, one cardiomyopathy), but there were no cardiac safety signals with romilkimab.ConclusionThis study demonstrated significant effects on skin changes with romilkimab in early dcSSc that require confirmation with a longer and more comprehensive phase III study to determine clinical relevance.Trial registration numberNCT02921971.

Randomised, double-blind multicentre phase III study of bevacizumab in combination with cisplatin and gemcitabine in chemotherapy-naïve patients with advanced or recurrent non-squamous non-small cell lung cancer (NSCLC): BO17704

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. LBA7514-LBA7514 ◽  
Author(s):  
C. Manegold ◽  
J. von Pawel ◽  
P. Zatloukal ◽  
R. Ramlau ◽  
V. Gorbounova ◽  
...  
Keyword(s):  
Overall Survival ◽  
Phase Iii ◽  
Primary Analysis ◽  
Eligibility Criteria ◽  
Logrank Test ◽  
Double Blind ◽  
Phase Iii Trial ◽  
Multicentre Phase ◽  
Number Of Patients ◽  
Phase Iii Study

LBA7514 Background: The ECOG 4599 phase III trial demonstrated that the addition of bevacizumab (B) to carboplatin/paclitaxel improved overall and progression-free survival (PFS) in patients (pts) with advanced NSCLC [Sandler et al. NEJM 2006]. Cisplatin/gemcitabine (CG) is a common combination in regions outside of the US. Methods: This randomised, placebo-controlled phase III study compared two doses of B plus CG versus CG plus placebo. The primary endpoint was PFS; secondary endpoints include overall survival, response rate (RR) and safety. Eligibility criteria: histologically or cytologically documented previously untreated advanced or recurrent non- squamous NSCLC; ECOG PS 0–1; no brain metastases. Between 2/05 and 8/06 1,043 pts were randomised to: C 80mg/m2 on d1 and G 1,250mg/m2 on d1 and d8 every 3 wks for up to 6 cycles plus B continued to progression at 7.5mg/kg every 3 wks, or 15mg/kg every 3 wks or placebo. The study was designed to include the number of patients required to observe a 30% reduction in the risk of a PFS event in the B arms compared with control using a two-sided logrank test (a=2.5%) with 80% power. Results: PFS was significantly prolonged as analysed both in a primary analysis (without censoring for non-protocol anti-neoplastic therapy [NPT] prior to progression) and in a prespecified analysis with censoring for NPT. The RR and response duration were also increased. Overall survival is immature due to short duration of follow up. Conclusions: Both doses of B significantly improved PFS and RR, consistent with the results of the earlier phase III trial E4599. No unexpected safety signals were detected. [Table: see text] [Table: see text]

INTEGRATE: A randomized phase II double-blind placebo-controlled study of regorafenib in refractory advanced esophagogastric cancer (AOGC)—A study by the Australasian Gastrointestinal Trials Group (AGITG).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. TPS4157-TPS4157 ◽  
Author(s):  
Nick Pavlakis ◽  
David Goldstein ◽  
Katrin Marie Sjoquist ◽  
Andrew Martin ◽  
Eric Tsobanis ◽  
...  
Keyword(s):  
Phase Ii ◽  
Advanced Disease ◽  
Locally Advanced ◽  
Tissue Growth ◽  
Phase Iii ◽  
Controlled Study ◽  
Second Line ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Esophagogastric Cancer

TPS4157 Background: Advanced Oesophago-Gastric Carcinoma (AOGC) has a poor prognosis, and there is no established standard treatment following failure of first or second line chemotherapy (CT). Regorafenib (BAY 73-4506)(REG) is an oral multi-kinase inhibitor which targets kinases involved in angiogenesis (VEGFR1-3, TIE-2), tumor microenvironment (PDGFR-β, FGFR), and oncogenesis (RAF, RET and KIT), and has shown activity in other solid tumours. Following promising results in colon cancer and GIST, this study will determine if regorafenib has sufficient activity and safety to warrant further evaluation in a phase III trial as a second or third line therapy for AOGC. Methods: International (Australia & New Zealand (ANZ); Canada (NCIC CTG), Korea) randomised phase II, double-blind, placebo-controlled trial with 2:1 (REG:placebo) randomisation and stratification by: (1) Lines of prior chemotherapy for advanced disease (1 vs. 2). (2) Geographic region. Eligible patients with histological confirmation of OGC, with measurable metastatic or locally advanced disease that is refractory to, or relapsed following, first or second line CT, will receive best supportive care plus 160mg REG or matching placebo orally on days 1-21 of each 28 day treatment cycle until disease progression or prohibitive adverse events. Primary endpoint is progression free survival (PFS). Secondary endpoints: PFS by baseline VEGF, response rate, overall survival, safety, quality of life and exploratory plasma angiogenesis and tissue growth factor biomarkers. 150 patients will be randomized in a 2:1 (REG:PBO) ratio. This will provide 90% power to detect a PFS rate at 2 months in the REG arm ≥ 66% versus < 50%. If 16 of 33 (evaluable) REG participants have progressed by 2 months, then the study will be reassessed or stopped. Results: As of January 2013, 19 of 29 planned ANZ sites are open, with 10 patients enrolled. Regulatory approval has been received for 16 sites in Canada and 7 sites in Korea. 4 Korean sites have received ethics approval with recruitment expected to commence in early April 2013. Clinical trial information: ACTRN12612000239864.

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