Efficacy and safety of gemcitabine in combination with TH-302 compared with gemcitabine in combination with placebo in previously untreated patients with metastatic or locally advanced unresectable pancreatic adenocarcinoma: The MAESTRO trial.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. TPS4148-TPS4148 ◽  
Author(s):  
Eric Van Cutsem ◽  
Robert J. Fram ◽  
Michael Schlichting ◽  
David P. Ryan
Keyword(s):  
Pancreatic Adenocarcinoma ◽  
Controlled Trial ◽  
Performance Status ◽  
Objective Response ◽  
Locally Advanced ◽  
Predictive Biomarkers ◽  
Treatment Discontinuation ◽  
Phase Iii ◽  
Ecog Performance Status ◽  
Double Blind

TPS4148 Background: Tumors often consist of highly hypoxic subregions that are resistant to chemotherapy and radiotherapy. The investigational hypoxia-targeted drug TH-302 is reduced at its nitroimidazole group, and under hypoxic conditions releases the DNA alkylator bromo-isophosphoramide mustard (Br-IPM). A randomized Phase IIb trial of TH-302 in pts with metastatic or locally advanced unresectable pancreatic adenocarcinoma (PDAC) confirmed a significant PFS improvement (p=0.008) in pts treated with TH-302 at 340 mg/m2+ gemcitabine compared with gemcitabine alone (Borad et al, ESMO 2012). Skin and mucosal toxicities, mainly Grade 1/2, and myelosuppression (thrombocytopenia, neutropenia and anemia) were the most common AEs related to TH-302 and did not lead to increases in treatment discontinuation. Grade 3/4 myelosuppression was more frequent in the TH-302 + gemcitabine arm. AEs leading to treatment discontinuation as well as non-hematological serious AEs were balanced across arms. Methods: This is a Phase III, randomized, double-blind, placebo-controlled trial (NCT01746979) of gemcitabine + TH-302 compared with gemcitabine + placebo in pts with locally advanced unresectable or metastatic PDAC. The study is designed to detect a 25% risk reduction of death with 90% power and two-sided alpha of 5%. A total of 660 pts are planned to be randomized 1:1. Key eligibility criteria include histologically or cytologically confirmed disease, no prior chemotherapy or systemic therapy (except as specified in the protocol), ECOG performance status 0 – 1, and bilirubin ≤ 1.5x upper limit of normal. Randomized pts receive TH-302 + gemcitabine or gemcitabine + placebo in 4-week cycles until progressive disease, intolerable toxicity, or pt withdrawal. The primary objective is to evaluate OS. Secondary objectives include PFS, objective response, and disease control; safety and tolerability; pt-reported QoL and pain; CA 19-9 levels and PK of TH-302; exploratory pharmacogenomic markers and potential predictive biomarkers. Enrollment to the study is ongoing. Clinical trial information: NCT01746979.

Randomized phase III trial of regorafenib in patients (pts) with metastatic and/or unresectable gastrointestinal stromal tumor (GIST) progressing despite prior treatment with at least imatinib (IM) and sunitinib (SU): GRID trial.

2012 ◽  
Vol 30 (18_suppl) ◽  
pp. LBA10008-LBA10008 ◽  
Author(s):  
George D. Demetri ◽  
Peter Reichardt ◽  
Yoon-Koo Kang ◽  
Jean-Yves Blay ◽  
Heikki Joensuu ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Controlled Trial ◽  
Performance Status ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Double Blind Study ◽  
Open Label ◽  
Ecog Performance Status ◽  
Double Blind ◽  
Multikinase Inhibitor

LBA10008 Background: Oral multikinase inhibitor regorafenib (REG) demonstrated substantial activity in a phase II trial in pts with GIST after failure of both IM and SU (J Clin Oncol. 2011; 29:606s; abstr 10007). This phase III, randomized, double-blind, placebo-controlled trial evaluated the efficacy and safety of REG for this unmet clinical need. Methods: Eligible pts had metastatic and/or unresectable GIST, objective failure of both prior IM and SU (progressive disease [PD] on, or intolerance to, IM and PD on SU), ≥1 measurable lesion, ECOG performance status 0 or 1. Pts were randomized 2:1 to receive best supportive care plus either REG 160 mg po once daily (3 wks on/1 wk off) or placebo (PL). The primary endpoint was progression-free survival (PFS) (modified RECIST 1.1, independent central review). Secondary endpoints included overall survival (OS), disease control rate (DCR, defined as rate of partial response [PR] plus stable disease [SD] lasting for ≥12 wks), response rate and duration, safety and correlative genotype analyses. At time of PD, pts were eligible for unblinding and crossover to open-label REG. Results: Between Jan and Aug of 2011, 234 pts were screened; 199 were randomized (REG: 133, PL: 66). Pts were stratified at randomization according to number of prior systemic therapies and geographical region. Baseline characteristics were balanced between the two arms. The primary endpoint was met: median PFS was 4.8 months for REG vs. 0.9 months for PL. Hazard ratio for PFS was 0.27 (95% CI, 0.18-0.39), p<0.0001. PFS rates at 3 and 6 months were 60% and 38% for REG vs. 11% and 0% for PL. DCR was 53% (REG) vs. 9% (PL).The HR for OS was 0.77 (p=0.20) with 85% PL pts having crossed over to REG. The most common > grade 3 treatment-emergent AEs in the REG arm during double-blind study were hypertension (28%), hand-foot skin reaction (21%), and diarrhea (8%). Conclusions: This randomized trial demonstrated that REG significantly improved PFS and DCR in pts with advanced GIST after failure of at least prior IM and SU. REG was well tolerated, with AEs as expected for this class and manageable with dose modifications.

RILOMET-1: An international phase III multicenter, randomized, double-blind, placebo-controlled trial of rilotumumab plus epirubicin, cisplatin, and capecitabine (ECX) as first-line therapy in patients with advanced MET-positive gastric or gastroesophageal junction (G/GEJ) adenocarcinoma.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. TPS4153-TPS4153 ◽  
Author(s):  
David Cunningham ◽  
Salah-Eddin Al-Batran ◽  
Irina Davidenko ◽  
David H. Ilson ◽  
André M. Murad ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Human Monoclonal Antibody ◽  
Gastroesophageal Junction ◽  
Objective Response ◽  
Locally Advanced ◽  
Eastern Cooperative Oncology Group ◽  
Data Monitoring Committee ◽  
Phase Iii ◽  
Double Blind ◽  
Disease Extent

TPS4153 Background: Rilotumumab is an investigational, fully human monoclonal antibody to hepatocyte growth factor/scatter factor that inhibits signaling through the MET receptor. In a randomized phase II study in patients with advanced G/GEJ adenocarcinoma, addition of rilotumumab every 3 weeks (Q3W) to ECX showed trends toward improved overall survival (OS) and progression-free survival (PFS) compared with ECX alone. In patients with high tumor MET expression and high rilotumumab exposure, the treatment effect of rilotumumab combined with ECX was significantly enhanced. Methods: In this phase III study, patients (planned N=450) are randomized 1:1 to ECX (intravenous [IV] epirubicin 50 mg/m2 on day 1, IV cisplatin 60 mg/m2 on day 1, and oral capecitabine 625 mg/m2 twice daily on days 1−21) plus double-blind rilotumumab 15 mg/kg or placebo IV Q3W. Randomization is stratified by disease extent (locally advanced vs metastatic) and Eastern Cooperative Oncology Group (ECOG) score (0 vs 1). Key eligibility criteria include previously untreated, pathologically confirmed unresectable locally advanced or metastatic G/GEJ adenocarcinoma; ECOG score 0 or 1; ≥18 years old; MET-positive by centralized immunohistochemistry; HER2-negative; adequate organ function; and ≥6 months since neoadjuvant/adjuvant therapy. The primary endpoint is OS. Key secondary endpoints include PFS, 12-month survival rate, objective response, OS in MET expression tertiles, safety, and pharmacokinetics. An exploratory objective is to assess associations between outcomes and tumor and circulating biomarkers. Enrollment began in November 2012, and the trial continues to accrue. An independent data monitoring committee will conduct planned interim reviews for safety and efficacy. Status: recruiting participants. Sponsored by Amgen Inc. Clinical trial information: NCT01697072.

Phase III LEAP-010 study: first-line pembrolizumab with or without lenvatinib in recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS6589-TPS6589 ◽  
Author(s):  
Lillian L. Siu ◽  
Barbara Burtness ◽  
Ezra E.W. Cohen ◽  
Kevin Joseph Harrington ◽  
Lisa F. Licitra ◽  
...  
Keyword(s):  
Disease Progression ◽  
Tumor Imaging ◽  
Performance Status ◽  
Objective Response ◽  
Phase Iii ◽  
First Line ◽  
Ecog Performance Status ◽  
Double Blind ◽  
Multikinase Inhibitor ◽  
End Points

TPS6589 Background: The PD-1 inhibitor pembrolizumab is currently approved as first-line monotherapy for patients with R/M HNSCC whose tumors express PD-L1 combined positive score (CPS) ≥1. In a phase 1b/2 trial (NCT02501096) of pembrolizumab plus lenvatinib (multikinase inhibitor of VEGFR 1-3, FGFR 1-4, PDGFRa, RET, and KIT) in solid tumors, the combination demonstrated promising antitumor activity and a manageable safety profile in patients with HNSCC. LEAP-010 (NCT04199104) is a randomized, double-blind, placebo-controlled, phase 3 study that will evaluate the efficacy and safety of first-line pembrolizumab with or without lenvatinib in patients with PD-L1–positive R/M HNSCC. Methods: Key eligibility criteria include histologically confirmed R/M HNSCC incurable by local therapies, PD-L1–positive tumor (CPS ≥1) as determined by central laboratory, measurable disease as assessed by blinded independent central review (BICR) per RECIST v1.1, and ECOG performance status (PS) 0 or 1. Patients will be randomly assigned 1:1 to pembrolizumab plus lenvatinib or pembrolizumab plus placebo. Randomization will be stratified by PD-L1 status defined by tumor proportion score ( < 50% vs ≥50%), human papillomavirus status for oropharynx cancer (positive vs negative), and ECOG PS (0 or 1). Patients will receive intravenous pembrolizumab 200 mg every 3 weeks for 35 cycles (~2 years) and oral lenvatinib 20 mg or placebo once daily; patients may continue to receive lenvatinib or placebo after pembrolizumab treatment is complete. Treatment will continue until BICR-verified disease progression or unacceptable toxicity. Pembrolizumab retreatment (second course) for 17 additional cycles will be allowed for eligible patients who stop pembrolizumab and subsequently experience BICR-verified disease progression. These patients could have stopped treatment with stable disease, partial response, or complete response or after 35 cycles of pembrolizumab for reasons other than disease progression or toxicity. Tumor imaging assessment will be performed at week 6, then every 6 weeks until 1 year, and thereafter every 9 weeks. Primary end points are objective response rate and progression-free survival, assessed by BICR per RECIST v1.1, and overall survival. Secondary end points are duration of response and safety and tolerability. Recruitment is ongoing; planned enrollment is ~500 patients. Clinical trial information: NCT04199104 .

A multicenter phase III randomized double-blind placebo controlled trial of pravastatin added to first-line standard chemotherapy in patients with small cell lung cancer (SCLC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 7595-7595 ◽  
Author(s):  
Michael Seckl ◽  
Christian Ottensmeier ◽  
Michael H. Cullen ◽  
Peter Schmid ◽  
Lindsay E. James ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Performance Status ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
Cell Types ◽  
Phase Iii ◽  
Standard Chemotherapy ◽  
Ecog Performance Status ◽  
Double Blind ◽  
The Uk

7595 Background: Most SCLC patients initially respond to chemotherapy but then relapse and die so new therapies are urgently required. Pre-clinical data shows statins induce growth arrest and apoptosis in SCLC and several other tumour cell types and are additive with chemotherapy. This may in part be due to impaired Ras superfamily function as statins deplete mevalonate, reducing geranylgeranylation and farnesylation of these proteins. We therefore undertook this large pragmatic phase III trial in order to determine if overall survival (OS) was affected by the addition of pravastatin in SCLC. Methods: Patients with limited (LD) or extensive (ED) stage SCLC were randomised to pravastatin 40mg OD or placebo for up to 2 years and given standard chemotherapy according to local practice recommended as either cisplatin 60mg/m2 iv or carboplatin AUC 5 or 6 and etoposide 120 mg/m2iv d1 to 3 or 100 mg BD po d2 & 3; max 6 cycles plus radiotherapy as usually given. Patients were excluded if they had used statins within 12 months prior to randomisation. Stratification was: LD vs ED and ECOG 0,1 vs 2,3. Endpoints were: primary - OS; secondary - progression free survival (PFS), local PFS (local control), response rates (RR) and toxicity. Results: Between 2007 and 2012, 846 patients were randomised, 422 (49.9.%) received pravastatin and 424 (50.1%) placebo in 93 participating sites in the UK. The median age was 64 years (range 54-69); ECOG performance status: 0: 23%; 1: 54%; 2: 17% and 3: 6%; weight 72.6 kg; LD, 357 (42.2%); ED, 479 (56.6%); 211 (24.9%) had ipsilateral effusion and 201 (23.8%) had ipsilateral SCF lymph nodes; Relative Dose intensity of cisplatin/carboplatin and etoposide was 91.6% (range 80.8 to 99.7), and 94.7% (range 85.7 to 100); 83.4% vs 86.3% completed > 4 cycles of chemotherapy on the pravastatin and placebo arms respectively. Most patients completed 6 cycles of chemotherapy: 263 (62.3%) vs 265 (62.5%) in the pravastatin vs. placebo groups. Updated results showing OS, PFS, local PFS and toxicity will be presented. Conclusions: This trial will report on whether pravastatin 40 mg OD added to standard therapy alters the outcome for SCLC patients. Clinical trial information: ISRCTN56306957.

TRICC-c: BIBF 1120 versus placebo in patients receiving oxaliplatin plus fluorouracil and leucovorin (mFOLFOX6) for advanced, chemorefractory metastatic colorectal cancer (mCRC)—A multicenter, randomized phase II trial in progress.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS3636-TPS3636
Author(s):  
Andreas Berger ◽  
Thomas Ettrich ◽  
Angela Marten ◽  
Thomas Seufferlein
Keyword(s):  
Colorectal Cancer ◽  
Growth Factor ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Objective Response ◽  
Predictive Biomarkers ◽  
Survival Duration ◽  
Ecog Performance Status ◽  
Double Blind

TPS3636 Background: Colorectal cancer (CRC) is the second leading cause of cancer-related death in western countries. With advances in the treatment of metastatic CRC (mCRC) in the last decade using combination chemotherapy and bevacizumab, a monoclonal antibody against the vascular endothelial growth factor (VEGF), progression free survival (PFS) in first and second line setting was substantially improved. Tumour angiogenesis is also driven by other factors but VEGF including Platelet Derived Growth Factor (PDGF) and Fibroblast Growth Factor (FGF). BIBF1120 is a potent, orally available triple angiokinase inhibitor that blocks the receptor tyrosine kinase activity of human VEGFR1-3, FGFR1 and -3 and PDGFRα and -β. Thus, BIBF1120 could be an exciting addition to the treatment of patients with chemorefractory CRC. Methods: Randomized, double-blind, placebo-controlled, multicentre, phase II trial of BIBF1120 (orally, 200 mg, bid, d1-d14, Arm A) vs. placebo (Arm B) in patients receiving mFOLFOX6 (oxaliplatin, 85 mg/m2, fluorouracil, 400 mg/m2 bolus and 2400 mg/m2 over 46 h, leucovorin, 200 mg/m2) q14 d for patients (ECOG performance status 0-1) with chemorefractory mCRC who received one prior line of chemotherapy. Scheduled are 90 patients per treatment arm. Primary endpoint: PFS, Secondary endpoints: objective response, overall survival, duration of overall response, safety. Additionally there will be an explorative analysis of predictive biomarkers for BIBF1120. 4 of planned 180 patients have been enrolled. We expect the last patient out in June 2013. (Trial identifier: NCT01362361.)

Phase III randomized, placebo-controlled trial of carboplatin (C) and paclitaxel (P) with/without veliparib (ABT-888) in HER2- BRCA-associated locally advanced or metastatic breast cancer (BC).

2015 ◽  
Vol 33 (28_suppl) ◽  
pp. 155-155 ◽  
Author(s):  
Shannon Leigh Huggins-Puhalla ◽  
Hyo S. Han ◽  
Véronique Diéras ◽  
Michael Friedlander ◽  
George Somlo ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Phase 1 ◽  
Single Agent ◽  
Objective Response ◽  
Locally Advanced ◽  
Metastatic Breast ◽  
Primary Objective ◽  
Receptor Expression ◽  
Phase Iii ◽  
Double Blind

155 Background: BRCA-mutated tumors are more susceptible to platinum therapy and PARP inhibitors due to underlying defects in homologous recombination repair of DNA damage. In preclinical models the potent oral PARP1/2 inhibitor veliparib was shown to enhance sensitivity to C and to have single-agent activity in BRCA+ cell lines. Phase 1 trials suggest promising antitumor activity and acceptable toxicity of veliparib plus C/P in triple-negative BC (Puhalla et al. Cancer Res 2012;72:PD09-06) and single-agent activity of veliparib in BRCA+ BC (Somlo et al. J Clin Oncol 2014;32:abstr. 1021). This phase III trial assesses efficacy and toxicity of veliparib plus C/P vs C/P alone in patients with HER2− BRCA-associated locally advanced or metastatic BC (NCT02163694). Methods: Phase III randomized, double-blind, placebo-controlled, multicenter trial. Eligible patients (female or male; ≥ 18 years) have HER2−metastatic/locally advanced unresectable BC with (suspected) deleterious BRCA1/2 germline mutations and received 2 or fewer prior lines of DNA-damaging chemotherapy for metastatic BC. In addition, patients must have received ≤ 1 prior line of platinum therapy (any setting) without progression within 12 months of completing treatment. Patients are randomized 2:1 to C/P with veliparib or C/P with placebo, stratified by estrogen and/or progesterone receptor expression, prior platinum therapy, and central nervous system metastases. Veliparib (120 mg p.o. BID) or placebo will be given on Days −2 to 5, C (AUC 6 mg/mL/min i.v.) on Day 1, and P (80 mg/m2i.v.) on Days 1, 8, and 15 (21-day cycles). Treatment continues until unacceptable toxicity or progressive disease (PD). Patients in the placebo arm who discontinue due to PD are eligible for crossover to veliparib monotherapy. The primary objective is to assess if the addition of veliparib to C/P increases progression-free survival; additional objectives include evaluation of overall survival, clinical benefit rate, objective response rate, quality of life, and safety. Enrollment began in July 2014 with a planned sample size of 270 patients. Clinical trial information: NCT02163694.

BOLERO-1: A randomized, phase III, double-blind, placebo-controlled multicenter trial of everolimus in combination with trastuzumab and paclitaxel as first-line therapy in women with HER2-positive (HER2+), locally advanced or metastatic breast cancer (BC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS648-TPS648 ◽  
Author(s):  
Sara A. Hurvitz ◽  
Fabrice Andre ◽  
Howard A. Burris ◽  
Masakazu Toi ◽  
Marc E. Buyse ◽  
...  
Keyword(s):  
Standard Therapy ◽  
Performance Status ◽  
Objective Response ◽  
Locally Advanced ◽  
Metastatic Breast ◽  
Phase Iii ◽  
Trastuzumab Resistance ◽  
First Line ◽  
Double Blind ◽  
Good Tolerability

TPS648 Background: Up to 25% of BCs overexpress human epidermal growth factor receptor 2 (HER2). Patients with HER2+ disease have a higher rate of relapse and shorter overall survival (OS). Trastuzumab, a monoclonal antibody targeting HER2, is the standard of care and improves OS for HER2+ BC, but acquired resistance is common. The combination of trastuzumab and paclitaxel has shown good tolerability and excellent objective response rates (ORR) in up to 84% of patients with HER2+ metastatic BC (MBC) (Gasparini G, et al. BCRT. 2007;101:355-65). Everolimus is an orally bioavailable inhibitor of mammalian target of rapamycin (mTOR), a protein kinase central to multiple protein synthesis pathways and implicated in trastuzumab resistance. Everolimus-containing regimens have shown promising results in patients with ER+, HER2– advanced BC in phase II/III trials; everolimus plus trastuzumab/paclitaxel or vinorelbine has shown encouraging ORR with an acceptable safety profile in phase I/II trials in patients with HER2+ MBC. The present phase III study was undertaken to assess the effectiveness of adding everolimus to first-line standard therapy in HER2+ advanced BC. Methods: Women with HER2+, locally advanced or metastatic BC who have received no prior systemic therapy (except endocrine) are eligible. Local disease must not be amenable to resection with curative intent. Women with a history of central nervous system metastasis are excluded. Patients are randomized 2:1 (everolimus vs control) to receive standard therapy (paclitaxel and trastuzumab) plus everolimus (10 mg daily) or placebo. The primary endpoint is progression-free survival. Secondary endpoints include OS, ORR, and clinical benefit rate. Additional endpoints are safety, performance status, and biomarkers. This trial is sponsored by Novartis Pharmaceuticals and is registered (ClinicalTrials.gov: NCT00876395). Enrollment began September 2009, with a planned accrual of 717. The current accrual is 719, and the estimated primary completion date is October 2012.

Integrate II: A randomised phase 3 double-blind placebo-controlled study of regorafenib in refractory advanced gastro-oesophageal cancer (AGOC)—An international study organized by the Australasian Gastrointestinal Trials Group (AGITG).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS4136-TPS4136 ◽  
Author(s):  
Katrin Marie Sjoquist ◽  
Nick Pavlakis ◽  
Andrew James Martin ◽  
Eric Tsobanis ◽  
Sonia Yip ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Controlled Trial ◽  
Locally Advanced ◽  
Predictive Biomarkers ◽  
Phase Iii ◽  
Controlled Study ◽  
Phase 3 ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Geographical Regions

TPS4136 Background: AGOC has a poor prognosis with no established standard treatment following failure of chemotherapy (CT). Regorafenib (BAY 73-4506)(REG) is an oral multi-kinase inhibitor targeting kinases involved in angiogenesis (VEGFR1-3, TIE-2), tumor microenvironment (PDGFR-β, FGFR), and oncogenesis (RAF, RET and KIT). INTEGRATE (phase 2) demonstrated REG was highly effective in prolonging PFS across a range of AGOC pts, with a positive OS trend. Regional differences were found in magnitude of effect, but REG was effective in all regions/subgroups. The phase 3 INTEGRATE II will explore whether REG is effective in prolonging survival in patients overall, and in the Asian sub-population. Methods: International (Australia/New Zealand (NHMRC CTC); Canada (CCTG), Korea, Japan, Taiwan, USA (ACCRU)) randomised phase III, double-blind, placebo-controlled trial with 2:1 (REG:placebo)(PBO) randomisation and stratification by: Location of tumour, Geographic region, prior VEGF inhibitors. Eligible patients (histologically confirmed AGOC), with evaluable metastatic or locally advanced disease refractory to, or relapsed following second line CT, will receive best supportive care plus 160mg REG or matched placebo orally on days 1-21 of each 28 day cycle until disease progression or prohibitive adverse events. Primary endpoint is OS. Secondary endpoints: PFS, response rate, quality of life, safety, identification of prognostic/predictive biomarkers for study endpoints, and REG PK across geographical regions. 350 patients (50% from Asia) randomized in a 2:1 ratio will provide 90% power to detect a hazard ratio (HR) for OS of 0.67 with a 2-sided α of 0.05 assuming PBO median survival is 4.5 mos. The sample size accommodates 2 interim analyses undertaken at 1/3 and 2/3 of required events. As of January 2017, 12 of 28 planned ANZ sites are open, with 4 patients enrolled. Regulatory approval has been received for 12 Canadian sites, and 12 Korean sites. Korean recruitment is expected to commence in February 2017. Regulatory submissions are pending in Taiwan, Japan, and the USA. Clinical trial information: NCT02773524.

Brivanib in Patients With Advanced Hepatocellular Carcinoma Who Were Intolerant to Sorafenib or for Whom Sorafenib Failed: Results From the Randomized Phase III BRISK-PS Study

2013 ◽  
Vol 31 (28) ◽  
pp. 3509-3516 ◽  
Author(s):  
Josep M. Llovet ◽  
Thomas Decaens ◽  
Jean-Luc Raoul ◽  
Eveline Boucher ◽  
Masatoshi Kudo ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Growth Factor ◽  
Controlled Trial ◽  
Objective Response ◽  
Phase Iii ◽  
Advanced Hepatocellular Carcinoma ◽  
Time To Progression ◽  
Fibroblast Growth Factor Receptors ◽  
Double Blind ◽  
Dual Inhibitor

Purpose Brivanib is a selective dual inhibitor of vascular endothelial growth factor and fibroblast growth factor receptors implicated in tumorigenesis and angiogenesis in hepatocellular carcinoma (HCC). An unmet medical need persists for patients with HCC whose tumors do not respond to sorafenib or who cannot tolerate it. This multicenter, double-blind, randomized, placebo-controlled trial assessed brivanib in patients with HCC who had been treated with sorafenib. Patients and Methods In all, 395 patients with advanced HCC who progressed on/after or were intolerant to sorafenib were randomly assigned (2:1) to receive brivanib 800 mg orally once per day plus best supportive care (BSC) or placebo plus BSC. The primary end point was overall survival (OS). Secondary end points included time to progression (TTP), objective response rate (ORR), and disease control rate based on modified Response Evaluation Criteria in Solid Tumors (mRECIST) and safety. Results Median OS was 9.4 months for brivanib and 8.2 months for placebo (hazard ratio [HR], 0.89; 95.8% CI, 0.69 to 1.15; P = .3307). Adjusting treatment effect for baseline prognostic factors yielded an OS HR of 0.81 (95% CI, 0.63 to 1.04; P = .1044). Exploratory analyses showed a median time to progression of 4.2 months for brivanib and 2.7 months for placebo (HR, 0.56; 95% CI, 0.42 to 0.76; P < .001), and an mRECIST ORR of 10% for brivanib and 2% for placebo (odds ratio, 5.72). Study discontinuation due to treatment-related adverse events (AEs) occurred in 61 brivanib patients (23%) and nine placebo patients (7%). The most frequent treatment-related grade 3 to 4 AEs for brivanib included hypertension (17%), fatigue (13%), hyponatremia (11%), and decreased appetite (10%). Conclusion In patients with HCC who had been treated with sorafenib, brivanib did not significantly improve OS. The observed benefit in the secondary outcomes of TTP and ORR warrants further investigation.

scholarly journals TROG 18.01 phase III randomised clinical trial of the Novel Integration of New prostate radiation schedules with adJuvant Androgen deprivation: NINJA study protocol

BMJ Open ◽  
2019 ◽  
Vol 9 (8) ◽  
pp. e030731 ◽  
Author(s):  
Jarad Martin ◽  
Paul Keall ◽  
Shankar Siva ◽  
Peter Greer ◽  
David Christie ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Controlled Trial ◽  
Performance Status ◽  
Androgen Deprivation ◽  
Phase Iii ◽  
High Dose ◽  
The Novel ◽  
Ecog Performance Status ◽  
Initial Portion ◽  
The Impact

IntroductionStereotactic body radiotherapy (SBRT) is a non-invasive alternative to surgery for the treatment of non-metastatic prostate cancer (PC). The objectives of the Novel Integration ofNew prostate radiation schedules with adJuvant Androgen deprivation (NINJA) clinical trial are to compare two emerging SBRT regimens for efficacy with technical substudies focussing on MRI only planning and the use of knowledge-based planning (KBP) to assess radiotherapy plan quality.Methods and analysisEligible patients must have biopsy-proven unfavourable intermediate or favourable high-risk PC, have an Eastern Collaborative Oncology Group (ECOG) performance status 0-1 and provide written informed consent. All patients will receive 6 months in total of androgen deprivation therapy. Patients will be randomised to one of two SBRT regimens. The first will be 40 Gy in five fractions given on alternating days (SBRT monotherapy). The second will be 20 Gy in two fractions given 1 week apart followed 2 weeks later by 36 Gy in 12 fractions given five times per week (virtual high-dose rate boost (HDRB)). The primary efficacy outcome will be biochemical clinical control at 5 years. Secondary endpoints for the initial portion of NINJA look at the transition of centres towards MRI only planning and the impact of KBP on real-time (RT) plan assessment. The first 150 men will demonstrate accrual feasibility as well as addressing the KBP and MRI planning aims, prior to proceeding with total accrual to 472 patients as a phase III randomised controlled trial.Ethics and disseminationNINJA is a multicentre cooperative clinical trial comparing two SBRT regimens for men with PC. It builds on promising results from several single-armed studies, and explores radiation dose escalation in the Virtual HDRB arm. The initial component includes novel technical elements, and will form an important platform set for a definitive phase III study.Trial registration numberANZCTN 12615000223538.

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