scholarly journals RBTT-11. NRG ONCOLOGY NRG-BN006: A PHASE II/III RANDOMIZED, OPEN-LABEL STUDY OF TOCA 511 AND TOCA FC WITH STANDARD OF CARE COMPARED TO STANDARD OF CARE IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi220-vi221
Author(s):  
Manmeet Ahluwalia ◽  
Stephanie Pugh ◽  
Benjamin Ellingson ◽  
Rupesh Kotecha ◽  
Timothy Cloughesy ◽  
...  
Keyword(s):  
Objective Response ◽  
Experimental Treatment ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
High Grade Glioma ◽  
Immune Monitoring ◽  
Newly Diagnosed ◽  
Open Label ◽  
Presumptive Diagnosis ◽  
Newly Diagnosed Glioblastoma

Abstract The standard of care (SOC) in newly diagnosed glioblastoma (nGBM) includes resection and chemoradiotherapy. With a median overall survival (OS) of only 16–18 months for well-selected patients in clinical trials, better therapeutic options are needed. Toca 511 (vocimagene amiretrorepvec) is a retroviral replicating vector encoding a codon optimized, heat stabilized cytosine deaminase that converts Toca FC (extended-release 5- fluorocytosine,5-FC) into 5-fluorouracil. Preclinical evidence demonstrates that Toca 511 & 5-FC kill cancer cells and immunosuppressive myeloid cells in the tumor microenvironment, leading to durable antitumor immune responses. Three phase (P) 1 studies in patients with recurrent high grade glioma have demonstrated tolerable safety profile and encouraging efficacy. NRG-BN006 is a randomized P2/3 trial of Toca 511 & Toca FC with SOC versus SOC for patients with nGBM. Optune use is allowed on the SOC arm, but not on the experimental arm. Patients will be stratified by age and KPS score for 1:1 randomization. The primary endpoint is progression-free survival for P2 and OS for P3. The secondary endpoints include objective response rate in patients with measurable disease and safety. Key inclusion criteria include presumptive diagnosis of glioblastoma with anticipated 80% resection, unifocal tumor, and KPS≥70. Immune monitoring and molecular profiling will be performed. P2 has 90% power to detect a hazard ratio (HR)=0.67 in 250 nGBM patients. P3 has 85% power to detect a HR=0.75 in 720 nGBM patients. Since patients are enrolled prior to surgery and confirmatory diagnosis of GBM, approximately 900 patients will be enrolled, and two interim analyses are planned for OS. In addition, two interim safety analyses will be conducted for the experimental treatment, with the first 15 and 30 eligible and analyzable patients randomized to the experimental arm. NRG-BN006 is anticipated to start enrollment in Q4 2019. Supported by grants U10CA180868, U10CA180822 from NCI and Tocagen.

Study Protocol: Early Stereotactic Gamma Knife Radiosurgery to Residual Tumor After Surgery of Newly Diagnosed Glioblastoma (Gamma-GBM)

Neurosurgery ◽  
2018 ◽  
Vol 84 (5) ◽  
pp. 1133-1137
Author(s):  
Stefanie Brehmer ◽  
Mario Alexander Grimm ◽  
Alex Förster ◽  
Marcel Seiz-Rosenhagen ◽  
Grit Welzel ◽  
...  
Keyword(s):  
External Beam Radiotherapy ◽  
Gamma Knife Radiosurgery ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Residual Tumor ◽  
Extent Of Resection ◽  
Subtotal Resection ◽  
Newly Diagnosed ◽  
Open Label ◽  
Newly Diagnosed Glioblastoma

Abstract BACKGROUND Glioblastoma (GBM) is the most common malignant brain tumor in adult patients. Tumor recurrence commonly occurs around the resection cavity, especially after subtotal resection (STR). Consequently, the extent of resection correlates with overall survival (OS), suggesting that depletion of postoperative tumor remnants will improve outcome. OBJECTIVE To assess safety and efficacy of adding stereotactic radiosurgery (SRS) to the standard treatment of GBM in patients with postoperative residual tumor. METHODS Gamma-GBM is a single center, open-label, prospective, single arm, phase II study that includes patients with newly diagnosed GBM (intraoperative via frozen sections) who underwent STR (residual tumor will be identified by native and contrast enhanced T1-weighted magnetic resonance imaging scans). All patients will receive SRS with 15 Gy (prescribed to the 50% isodose enclosing all areas of residual tumor) early (within 24-72 h) after surgery. Thereafter, all patients undergo standard-of-care therapy for GBM (radiochemotherapy with 60 Gy external beam radiotherapy [EBRT] plus concomitant temozolomide and 6 cycles of adjuvant temozolomide chemotherapy). The primary outcome is median progression-free survival, secondary outcomes are median OS, occurrence of radiation induced acute (<3 wk), early delayed (<3 mo), and late (>3 mo post-SRS) neurotoxicity and incidence of symptomatic radionecrosis. EXPECTED OUTCOMES We expect to detect efficacy and safety signals by the immediate application of SRS to standard-of-care therapy in newly diagnosed GBM. DISCUSSION Early postoperative SRS to areas of residual tumor could bridge the therapeutic gap between surgery and adjuvant therapies.

scholarly journals P14.124 EORTC 1709/CCTG CE.8: A phase III trial of marizomib in combination with standard temozolomide-based radiochemotherapy versus standard temozolomide-based radiochemotherapy alone in patients with newly diagnosed glioblastoma

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii98-iii98 ◽  
Author(s):  
P Roth ◽  
J Reijneveld ◽  
T Gorlia ◽  
F Dhermain ◽  
F De Vos ◽  
...  
Keyword(s):  
Performance Status ◽  
Treatment Strategies ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Primary Objective ◽  
Recurrent Glioblastoma ◽  
Phase Iii ◽  
Newly Diagnosed ◽  
Open Label ◽  
Newly Diagnosed Glioblastoma

Abstract BACKGROUND The standard of care for patients with newly diagnosed glioblastoma includes maximal debulking surgery followed by radiotherapy (RT), and concomitant as well as maintenance therapy with the alkylating agent, temozolomide (TMZ). However, the prognosis remains poor and novel treatment strategies are urgently needed. Targeting the proteasome has been considered a promising anti-cancer approach for several years. Marizomib is a novel, irreversible and pan-proteasome inhibitor, which crosses the blood-brain barrier and has been assessed in phase I trials in patients with newly diagnosed or recurrent glioblastoma. MATERIAL AND METHODS EORTC 1709/CCTG CE.8 is a randomized, controlled, open label phase III superiority trial. Patients with histologically confirmed newly diagnosed glioblastoma and a performance status >70 are eligible. Patients are randomized in a 1:1 ratio to receive standard of care (TMZ/RT→TMZ) alone or TMZ/RT→TMZ plus marizomib. The study aims at enrolling 750 patients. Stratification factors include study site, age, performance status and extent of resection. The primary objective of this trial is to compare overall survival in patients receiving marizomib in addition to standard of care with those receiving standard treatment only. The testing strategy specifies the determination of this objective in the intent-to-treat population as well as the subgroup of patients with MGMT-unmethylated tumors. Secondary endpoints include progression-free survival, safety, neurocognitive function and quality of life. A translational research program has been set up. The study will be activated at approximately 50 EORTC sites across Europe, 25 sites in Canada and additional sites in the US. Patient recruitment started in June 2018 and as of April 29, 2019, a total of 164 patients have been randomized. An update on the enrolment status will be provided at the EANO meeting. ClinicalTrials.gov Identifier: NCT03345095

scholarly journals Safety and tolerability of asunercept plus standard radiotherapy/temozolomide in Asian patients with newly-diagnosed glioblastoma: a phase I study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kuo-Chen Wei ◽  
Peng-Wei Hsu ◽  
Hong-Chieh Tsai ◽  
Ya-Jui Lin ◽  
Ko-Ting Chen ◽  
...  
Keyword(s):  
Phase I ◽  
Phase I Study ◽  
Progression Free Survival ◽  
Multicenter Trial ◽  
Newly Diagnosed ◽  
Open Label ◽  
Free Survival ◽  
Asian Patients ◽  
Newly Diagnosed Glioblastoma ◽  
Secondary Endpoints

AbstractAsunercept (company code APG101 [Apogenix AG]; company code CAN008 [CANbridge Pharmaceuticals]) is a novel glycosylated fusion protein that has shown promising effectiveness in glioblastoma. This Phase I study was initiated to evaluate the tolerability and safety of asunercept in combination with standard radiotherapy and temozolomide (RT/TMZ) in Asian patients with newly diagnosed glioblastoma. This was the Phase I portion of a Phase I/II open label, multicenter trial of asunercept plus standard RT/TMZ. Adults with newly-diagnosed glioblastoma received surgical resection followed by standard RT/TMZ plus asunercept 200 mg/week (Cohort 1) or 400 mg/week (Cohort 2) by 30-min IV infusion. The primary endpoint was the safety and tolerability of asunercept during concurrent asunercept and RT/TMZ; dose-limiting toxicities were observed for each dose. Secondary endpoints included pharmacokinetics (PK) and 6-month progression-free survival (PFS6). All patients (Cohort 1, n = 3; Cohort 2, n = 7) completed ≥ 7 weeks of asunercept treatment. No DLTs were experienced. Only one possibly treatment-related treatment emergent adverse event (TEAE), Grade 1 gingival swelling, was observed. No Grade > 3 TEAEs were reported and no TEAE led to treatment discontinuation. Systemic asunercept exposure increased proportionally with dose and showed low inter-patient variability. The PFS6 rate was 33.3% and 57.1% for patients in Cohort 1 and 2, respectively. Patients in Cohort 2 maintained a PFS rate of 57.1% at Month 12. Adding asunercept to standard RT/TMZ was safe and well tolerated in patients with newly-diagnosed glioblastoma and 400 mg/week resulted in encouraging efficacy.Trial registration NCT02853565, August 3, 2016.

Final results of PEANUT: Pembrolizumab and nanoparticle albumin-bound paclitaxel (nab-paclitaxel) as salvage therapy for metastatic urothelial carcinoma (UC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5017-5017
Author(s):  
Patrizia Giannatempo ◽  
Giuseppina Calareso ◽  
Marco Bandini ◽  
Laura Marandino ◽  
Daniele Raggi ◽  
...  
Keyword(s):  
Performance Status ◽  
Objective Response ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Open Label ◽  
Ecog Performance Status ◽  
Repair Gene ◽  
Good Tolerability ◽  
Blood Samples ◽  
Disease Response

5017 Background: Pembrolizumab (pembro) is a new standard of care in chemotherapy (CT) pre-treated patients (pts) with metastatic UC. Nab-paclitaxel demonstrated preliminary activity in advanced UC. In the PEANUT study (NCT03464734) we investigated their combination in advanced UC after CT failure. Methods: In an open-label, single-arm, phase 2 trial, pts received 200 mg pembro, intravenously (IV), on D1 and 125 mg/m2 IV nab-paclitaxel on D1 and D8, every 3 weeks, until disease progression (PD) or unacceptable toxicity. Inclusion criteria were: predominant UC histology, failure of ≤2 platinum-based CT for metastatic disease. Response was evaluated by RECIST v.1.1 criteria every 2 cycles. Biomarkers included PD-L1 combined positive score (CPS) and comprehensive genomic profiling on tumor and blood samples (FoundationONE and FoundationACT assay). The primary endpoint was the progression-free survival (PFS). The target was to detect an improvement in the median PFS from ≤3.0 months (H0) to ≥5.0 months (H1). Results: Between 01 and 12/2019, PEANUT study enrolled 65 pts: 24% were female, median age was 69 yrs (IQR: 61-73); 25% had failed > 1 prior systemic therapies; 35% had ECOG-performance status 1; 33% had liver metastases. The median TMB was 6.9 mut/Mb. After median follow-up (FUP) of 5.5 months, 34 pts have relapsed (52.3%). The median PFS was 5 months (95%CI: 3-not reached). The 3-month PFS was 60.7% (95%CI: 49.8-74.1). The confirmed objective response-rate (ORR) was 47.7% (95%CI: 35.2-60.4): 22 partial responses and 9 complete responses (13.8%). The median duration of response was not reached, and 4 pts (6.1%) are long-term responders ( > 12 months). Grade 3 treatment-related adverse events (TRAE) were seen in 20 pts (30.7%). Most common any-grade TRAE included alopecia (76%), neutropenia (33.3%) and asthenia (33%). Neither TMB nor CPS were significantly associated with PFS on univariable analyses. In matched tumor/blood samples, objective responses were seen in 8/10 pts with PI3KCA mutations (80%); 6/10 pts with RB1 alterations (60%); 5/12 pts with DNA damage repair gene alterations (41.7%). Conclusions: Pembro-nab-paclitaxel, the first salvage CT-immunotherapy combination in UC, demonstrated a good tolerability, promising PFS and a clinically meaningful ORR in II-III line setting of advanced UC. As more mature data on biomarker selection emerges, this combination warrants additional studies in either second-line or earlier disease settings. Clinical trial information: NCT03464734 .

ELOQUENT-1: A phase III, randomized, open-label trial of lenalidomide/dexamethasone with or without elotuzumab in subjects with previously untreated multiple myeloma (CA204-006).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS8113-TPS8113 ◽  
Author(s):  
Meletios A. Dimopoulos ◽  
Thierry Facon ◽  
Paul Gerard Guy Richardson ◽  
Robert Z. Orlowski ◽  
Jesùs F. San-Miguel ◽  
...  
Keyword(s):  
Objective Response ◽  
Progression Free Survival ◽  
Response Duration ◽  
Surface Glycoprotein ◽  
Phase Iii ◽  
Cell Transplant ◽  
Newly Diagnosed ◽  
Open Label ◽  
Cell Surface Glycoprotein ◽  
Prior Therapy

TPS8113 Background: Elotuzumab (Elo) is a humanized monoclonal IgG1 antibody targeting the cell surface glycoprotein CS1, which is highly expressed on >95% of MM cells. In a MM xenograft mouse model, the combination of Elo + lenalidomide (Len) significantly reduced tumor volume in a synergistic manner compared with either agent alone. In a phase 2 study (N=73) of Elo (10 or 20 mg/kg) in combination with Len and low-dose-dexamethasone (Dex) in pts with RR MM, the 10 mg/kg dose group (n=36) demonstrated objective response rates (ORR) of 92% in all pts, and 100% in pts who had received only 1 prior therapy (n=16). The higher response rate in pts with fewer prior lines of therapy provides a rationale for investigating this combination earlier in the disease course. This randomized, open-label, phase 3 trial will determine if the addition of Elo to Len/Dex improves progression-free survival (PFS) in pts with newly diagnosed, untreated MM. Methods: Pts (N=750) with newly diagnosed symptomatic MM ineligible for stem cell transplant will be randomized in a 1:1 ratio to receive 28-day cycles of Len 25 mg PO (days1-21) and Dex 40 mg PO (days 1, 8, 15 and 22) with or without Elo. Elo dose and schedule is 10 mg/kg IV on days 1, 8, 15, 22 in the first 2 cycles and on days 1 and 15 of cycles 3-18 followed by 20 mg/kg on day 1 of cycle 19 onward. Dex 8 mg IV + 28 mg PO is used during the weeks with Elo. Treatment will continue until disease progression, death, or withdrawal of consent. Pts will be followed up for response every 4 weeks until progressive disease and for survival every 16 weeks. The primary endpoint is PFS (90% power for a hazard ratio [experimental to control arm] of 0.74) and the secondary endpoints are ORR and overall survival. Exploratory endpoints are safety, time to response, duration of response, time to subsequent therapy, health-related quality of life, and pharmacokinetics and immunogenicity of Elo. Potential biomarkers will also be assessed. As of January 1, 2012, 13 pts were enrolled and 9 pts were treated. NCT01335399.

FIGHT-205: Phase II study of first-line pemigatinib (PEMI) plus pembrolizumab (PEMBRO) versus PEMI alone versus standard of care (SOC) for cisplatin (CIS)—Ineligible urothelial carcinoma (UC) with FGFR3 mutation or rearrangement.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. TPS592-TPS592
Author(s):  
Matt D. Galsky ◽  
Thomas Powles ◽  
Robert Dreicer ◽  
Hiroshi Kitamura ◽  
Ekatherine Asatiani ◽  
...  
Keyword(s):  
Objective Response ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Cell Receptor ◽  
Target Lesion ◽  
Ectopic Calcification ◽  
Phase 2 ◽  
Open Label ◽  
Fgfr3 Mutation

TPS592 Background: Fibroblast growth factor receptor (FGFR) 3 gene alterations (GAs) are involved in UC pathogenesis. Pts with metastatic UC and FGFR3 GAs express low programmed cell death ligand 1 (PD-L1) levels; combination with FGFR inhibitors may confer added benefit via tumor-direct and immunomodulatory effects. Preliminary data from a phase 2 monotherapy trial of PEMI (INCB054828), a selective, potent, oral FGFR1–3 inhibitor, confirmed efficacy in previously treated relapsed/refractory pts with UC and FGFR3 GAs (NCT02872714). FIGHT-205, a randomized, open-label, phase 2 study, will assess efficacy and safety of PEMI + PEMBRO vs PEMI alone vs SOC (carboplatin [CARB] + gemcitabine [GEM] or PEMBRO alone) in CIS-ineligible metastatic/unresectable UC with FGFR3 mutation/rearrangement (NCT04003610). Methods: Eligible pts are adults with confirmed metastatic/unresectable UC; ≥1 measurable target lesion (per RECIST v1.1); platinum (PT)/CIS-ineligible; centrally confirmed FGFR3 mutation/rearrangement; ECOG PS ≤2. Exclusions include prior selective FGFR inhibitor, anti-PD-1/PD-L1/2, or co-inhibitory T-cell receptor directed agent; chemotherapy (except adjuvant, neoadjuvant); clinically significant corneal/retinal disorder; Ca/PO4 homeostasis disorder/systemic mineral imbalance with ectopic calcification; untreated CNS metastases. Pts will be randomized (1:1:1) to 3 groups: PEMI 13.5 mg QD (continuous, 21-d cycle) + PEMBRO 200 mg Q3W, PEMI alone (same dose), or SOC (GEM [1000 mg/m2 on D1 + D8] + CARB [AUC 5 (or 4.5) on D1 or D2] Q3W or PEMBRO [same dose] if PD-L1 score high/PT-ineligible). PEMI titration to 18 mg starting at cycle 2 is required for pts without hyperphosphatemia (serum PO4 >5.5 mg/dL) and grade ≥2 treatment-related AEs during cycle 1. Hyperphosphatemia will be managed by diet modifications, PO4 binders, diuretics, or dose adjustments. PEMI will continue until progression/unacceptable toxicity. Primary endpoint is progression-free survival. Secondary endpoints are overall survival, objective response rate, duration of response, safety, and quality of life. Clinical trial information: NCT04003610.

scholarly journals PC3 - 151 Toca 5: A Phase 2/3 Randomized, Open-Label Study of Toca 511, a Retroviral Replicating Vector, Combined with Toca FC versus Standard of Care in Patients Undergoing Planned Resection for Recurrent Glioblastoma (GBM) or Anaplastic Astrocytoma (AA) (NCT02414165)

2016 ◽  
Vol 43 (S4) ◽  
pp. S17-S17
Author(s):  
G. Zadeh ◽  
D. Bota ◽  
D. Cachia ◽  
J. Landolfi ◽  
D. Schiff ◽  
...  
Keyword(s):  
Phase 1 ◽  
Objective Response ◽  
Unmet Need ◽  
Suppressor Cells ◽  
Standard Of Care ◽  
Immune Monitoring ◽  
Recurrent Glioblastoma ◽  
Phase 2 ◽  
Open Label ◽  
Dismal Prognosis

Recurrent GBM and AA have a dismal prognosis and a high unmet need for effective therapies. Toca 511 (vocimagene amiretrorepvec) is an investigational retroviral replicating vector that encodes the transgene cytosine deaminase (CD). Toca 511 selectively infects, persists and spreads in tumor. Subsequent oral administration of 5-fluorocytosine (Toca FC) produces 5-fluorouracil (5-FU) by CD within infected cells. 5-FU kills cancer cells and myeloid derived suppressor cells, inducing robust antitumor immune responses in animal models. Clinical data from phase 1 trials are consistent with this mechanism of action, and show extended survival compared to historical controls. Toca 5 is a multicenter, randomized, open-label Phase 2/3 trial of Toca 511 and Toca FC versus standard of care administered to patients undergoing resection for first or second recurrence of GBM or AA. Phase 2 will enroll 170 patients. Primary endpoint is overall survival (OS). Key secondary endpoints are safety, objective response rate, clinical benefit rate, progression-free survival, and landmark OS. Key inclusion criteria are age 18-75 years, histologically proven GBM or AA, measurable disease preoperatively of less than 5cm, candidate for equal or greater 80% resection of enhancing tumor based on pre-operative evaluation, and KPS equal or greater to 70. Assays for immune monitoring will be performed and molecular profiling of resected tumor samples will be correlated efficacy.

RTID-05. THE MULTI-ARM GLIOBLASTOMA AUSTRALASIA (MAGMA) TRIAL

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi193-vi194
Author(s):  
Benjamin Kong ◽  
Hao-Wen Sim ◽  
Eng-Siew Koh ◽  
Hui Gan ◽  
Elizabeth H Barnes ◽  
...  
Keyword(s):  
Data Collection ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Phase Iii ◽  
Low Grade ◽  
Newly Diagnosed ◽  
Current Standard ◽  
Future Design ◽  
Multiple Treatment ◽  
Newly Diagnosed Glioblastoma

Abstract BACKGROUND Survival outcomes for patients with newly diagnosed glioblastoma have not changed significantly since the introduction of concurrent temozolomide with post-surgical radiation followed by adjuvant temozolomide. METHODS Multi-Arm Glioblastoma Australasia (MAGMA) is a recently initiated phase III multi-arm, multi-centre randomized trial for patients with newly diagnosed glioblastoma, led by the Australian Cooperative Trials Group for Neuro-Oncology (COGNO), that will concurrently test multiple treatment questions. Initially, a partial factorial design will be implemented to compare the current standard of care with either or both of (1) neoadjuvant temozolomide and (2) aduvant temozolomide continued beyond six months until progression. MAGMA will transition to a multi-arm multi-stage (MAMS) design as additional tratment question are introduced. Treatment allocation to each question will be balanced (1:1) using minimisation over several stratification factors, including study site, age, IDH-mutation status, surgical extent and randomization to the prior treatment question(s). The primary outcome is overall survival. Secondary outcomes include progression-free survival (measured by mRANO), time to first non-temozolomide systemic treatment, clinically significant toxicity as measured by Grade 2/4 adverse events, and health-related quality of life measures. Parsimonious data collection and a streamlined assessment schedule have been incorporated to mitigate the burden of data collection (such as low grade toxicity from temozolomide), and to encourage participation in regional and rural settings. A consortium model has been adopted to foster neuro-oncology expertise and infrastructure and share academic credit and future design opportunities. PROGRESS Recruitment commenced in September 2020. To date, 60 patients have been recruited from an initial sample size target of 250 patients for each of these initial two treatment questions. Of these 60 patients, 45 have been randomized in Question 1 (neoadjuvant chemotherapy) whilst 50 randomized in Question 2 (prolonged adjuvant chemotherapy). To date, 14 of the 27 intended sites are open to recruitment.

Sunitinib (SU) in combination with docetaxel (D) versus D alone for the first-line treatment of advanced breast cancer (ABC).

2010 ◽  
Vol 28 (18_suppl) ◽  
pp. LBA1010-LBA1010 ◽  
Author(s):  
J. Bergh ◽  
R. Greil ◽  
N. Voytko ◽  
A. Makhson ◽  
J. Cortes ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Kinase Inhibitor ◽  
Single Agent ◽  
Objective Response ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Newly Diagnosed ◽  
Open Label ◽  
Recommended Treatment

LBA1010 Background: Taxane-based chemotherapy (CT) improves progression-free survival (PFS) in patients (pts) with newly diagnosed HER2-negative metastatic BC (MBC). SU, an oral multitargeted tyrosine kinase inhibitor (MTKI), demonstrated antitumor activity in combination with D in a phase I/II study in pts with MBC. A randomized, open-label, multicenter phase III trial in pts with newly diagnosed ABC tested the hypothesis that addition of a MTKI to D improves PFS vs. D alone. Methods: Eligible pts (female; ≥18 yrs) had an ECOG PS ≤1, and newly diagnosed HER2-negative MBC or ABC. If (neo)adjuvant therapy included a taxane, relapse must have occurred ≥12 mos after CT. Pts were randomized (1:1) to treatment (tx) with D 75 mg/m2 iv on day 1 and SU 37.5 mg/day po from day 2–15 q3w (Schedule 2/1; Arm A), or to D 100 mg/m2 iv 1-hr infusion q3w (Arm B) that could be given until progression. If D was discontinued in Arm A for reasons other than progressive disease (PD), single-agent SU 37.5 mg daily was permitted until PD. Median, independently assessed, PFS (primary endpoint) was compared between tx arms using stratified and unstratified log-rank tests. Overall objective response rate (ORR), overall survival (OS), pt-reported outcomes, and safety were secondary endpoints. Results: As of the data cutoff (February 1, 2010), the ITT population comprised 593 pts (SU+D, n=296; D, n=297). The trial did not meet its primary endpoint of prolonging PFS based on the independent radiologic assessment or in prolonging OS. Baseline characteristics were well balanced. Median relative dose intensity (RDI) was 94.2% and 92.4% for SU+D, and 92.6% for D arms, respectively. Median PFS was 8.6 mos (95% CI 8.2–10.3) in the SU+D arm vs 8.3 mos (95% CI 7.7–9.6) for the D arm (HR 0.922). Median OS was 24.8 mos (95% CI 21.5–33.1) in SU+D arm vs 25.5 mos (95% CI 22.8–27.8) for D arm (HR 1.207). ORR was significantly better for SU+D (51%) vs. D (39%) (p=0.0018). Frequent all causality grade 3/4 adverse events (≥10%) were neutropenia (46%), hand–foot syndrome (17%), and fatigue (12%) in the SU+D arm and neutropenia (44%) in the D arm. Conclusions: Based on these data, SU+D is not a recommended treatment option for patients with newly diagnosed ABC. Strategies using antiangiogenic TKIs that increase RR but not OS may need to be revisited. [Table: see text]

A randomized, open-label phase II study of nanoliposomal irinotecan (nal-IRI)-containing regimens versus nab-paclitaxel plus gemcitabine in patients with previously untreated metastatic pancreatic adenocarcinoma (mPAC).

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. TPS482-TPS482 ◽  
Author(s):  
Andrew Dean ◽  
Li-Tzong Chen ◽  
Ramesh K. Ramanathan ◽  
Sarah Blanchette ◽  
Bruce Belanger ◽  
...  
Keyword(s):  
Objective Response ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Primary Objective ◽  
Clinical Activity ◽  
First Line ◽  
Open Label ◽  
Free Survival ◽  
Open Label Phase ◽  
Secondary Endpoints

TPS482 Background: Two combination chemotherapy regimens have emerged as standard of care options for first-line treatment of mPAC: 5-fluorouracil (5-FU)/leucovorin (LV) + irinotecan + oxaliplatin (FOLFIRINOX), and nab-paclitaxel + gemcitabine. Nal-IRI (MM-398) is a nanoliposomal formulation of irinotecan. In a randomized phase 3 study (NAPOLI-1), of patients with mPAC who had been previously treated with gemcitabine-based therapy, nal-IRI + 5-FU/LV demonstrated its safety and significant clinical activity, increasing overall survival (OS) and progression-free survival (PFS) relative to 5-FU/LV. The goal of this current study is to determine the preliminary safety and efficacy of nal-IRI+ + 5-FU/LV with or without oxaliplatin as compared to nab-paclitaxel + gemcitabine in previously untreated patients with mPAC. Methods: This open-label, phase 2 comparative study will be conducted in two parts. Part 1 is a safety run-in of a nal-IRI+5-FU/LV + oxaliplatin regimen. The safety run-in will enroll small cohorts of patients following a traditional 3 + 3 dose escalation design to confirm the target dose of oxaliplatin (n = ~6-18). The primary objective of Part 1 is the safety and tolerability of nal-IRI + 5FU/LV + oxaliplatin. Part 2 is a randomized, efficacy study of a nal-IRI + 5-FU/LV + oxaliplatin regimen (Arm 1), the nal-IRI + 5-FU/LV combination that previously demonstrated efficacy in the NAPOLI-1 trial (Arm 2), versus a nab-paclitaxel + gemcitabine control arm (Arm 3) (n = ~156-168). The primary objective of Part 2 is to assess the efficacy of nal-IRI-containing regimens in first-line mPAC patients compared to nab-paclitaxel + gemcitabine using the progression-free survival (PFS) rate at 24 weeks as the primary endpoint. Secondary of part 1 is a PK study and Part 2 secondary endpoints will include OS, PFS, objective response rate (per RECIST, v1.1), decrease in CA19-9 levels and quality of life assessments. Clinical trial information: NCT02551991.

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