Phase Ib study of concurrent durvalumab and radiation therapy (DUART) followed by adjuvant durvalumab in patients with urothelial cancer of the bladder: BTCRC-GU15-023 study.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 455-455 ◽  
Author(s):  
Monika Joshi ◽  
Leonard Tuanquin ◽  
Matthew Kaag ◽  
Yousef Zakharia ◽  
Jason Liao ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Human Monoclonal Antibody ◽  
Locally Advanced ◽  
Safety Data ◽  
Stage Iv ◽  
Phase Ib ◽  
Cancer Of The Bladder ◽  
Platinum Refractory ◽  
Grade 3 ◽  
Clinical Trial Information

455 Background: There is a significant variation in the treatment of locally advanced unresectable (T2-4 N0-2 M0) or cisplatin-ineligible (non-cis) bladder cancer (BC) patients (pts). The advent of immunotherapy (IO) in non-cis stage IV BC has been promising (response rate [RR] 23%; median survival 16 mo) but we are still in need of novel combinations for locally advanced unresectable BC. Durvalumab (Durva) is a human monoclonal antibody that inhibits the binding of PD-L1 to PD-1 on T-cell receptors. It has shown efficacy in platinum refractory BC with RR of 17%. Radiation (RT) is also effective in BC and can upregulate pro-inflammatory signals allowing for improved antitumor activity of IO. We report the safety data from phase Ib trial of combining RT with Durva (DurvaRT) in locally advanced BC. Methods: Treatment (Rx) naïve or post neoadjuvant chemotherapy pts with T3-4, N0-2, M0 who were either unresectable or unfit for surgery were treated with DurvaRT followed by Durva. Rx naïve locally advanced non-cis pts were also included in the study. DurvaRT: Durva 1500mg D1, D28 plus concurrent RT, 64.8Gy given in 36 fractions over 7weeks starting D1. These patients then started adjuvant Q4 weekly Durva after 4 weeks for 12 months. Primary end point for Ph Ib was safety of combining Durva with RT during 7-weeks period. Results: We enrolled 6 pts on phase Ib. 5/6 pts had completed the DurvaRT phase and none of them had any dose limiting toxicity. The table below summarizes the treatment related adverse events (TRAE). Post DurvaRT 3/4 pts have ongoing ORR; 1 pt. had progression; Rx response evaluation in 2 pts is ongoing. Clinical trial information: NCT02891161. Conclusions: DurvaRT was tolerable in pts with locally advanced unresectable BC, where there is a dearth for good Rx options. No grade 3 immune related AEs were observed during DurvaRT. Further investigation with DurvaRT is ongoing to evaluate the efficacy in this subset of pts (Clinical trial # NCT02891161).[Table: see text]

Interim results of a randomized phase II study of PEGPH20 added to nab-paclitaxel/gemcitabine in patients with stage IV previously untreated pancreatic cancer.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 439-439 ◽  
Author(s):  
Sunil R. Hingorani ◽  
William Proctor Harris ◽  
Tara Elisabeth Seery ◽  
Lei Zheng ◽  
Darren Sigal ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Clinical Trial ◽  
Phase Ii ◽  
Randomized Study ◽  
Safety Data ◽  
Stage Iv ◽  
Phase Iii ◽  
Clinical Hold ◽  
Stage 1 ◽  
Clinical Trial Information

439 Background: Poor outcome in pancreatic cancer (PDA) is associated partly with stromal hyaluronan (HA) accumulation, which compromises chemotherapy perfusion. PEGPH20, PEGylated recombinant human hyaluronidase, potentiates chemotherapy by depleting HA in tumors. Methods: In an ongoing, phase II, open-label, randomized study of PEGPH20+nab-paclitaxel (Nab)+Gemcitabine (Gem) (PAG) vs Nab+Gem (AG) in previously untreated stage IV PDA, pts receive PEGPH20 3 µg/kg twice weekly (C1), then weekly (C2+) with standard AG dosing. HA status was tested retrospectively. After a temporary clinical hold (Apr-Jul 2014) for an imbalance in thromboembolic (TE) events (29% PAG vs 15% AG), the protocol was amended to exclude high-TE-risk pts and add enoxaparin (LMWH) prophylaxis. Endpoints are PFS and TE events (primary); PFS and ORR by HA level and OS (secondary). Efficacy and safety data through Dec 2014 are for pts enrolled up to clinical hold (Stage 1); TE data are through Sep 2015 (Stage 2). Results: 135 pts were treated (74 PAG, 61 AG). PFS results are shown below (median follow-up 7 mo). In HA-high pts receiving PAG vs AG, ORR was 52% (1 CR) vs 24% (P=.038); ORR was 37% vs 38% in HA-low pts. OS was 12 mo vs 9 mo (HR=0.62) despite 12/23 PAG pts discontinuing PEGPH20 at clinical hold. Common ADRs (PAG vs AG) included peripheral edema (58% vs 31%), muscle spasms (55% vs 1.6%), and neutropenia (32% vs 18%). TE events were: Stage 1 42% vs 25% (no LMWH); Stage 2 (with LMWH; 40 mg/d or 40 mg/d increased to 1 mg/kg/d) 28% vs 29%; (1 mg/kg/d) 5% vs 6%; overall (40 mg/d or 1 mg/kg/d) 13% each arm (to be updated). Conclusions: Pts with HA-high tumors receiving PAG, vs AG, showed significant improvements in PFS and ORR and a trend toward improved OS. PAG was well tolerated, with TE events reduced with LMWH prophylaxis. A global phase III trial of PAG will initiate Q1 2016. Clinical Trial Information: NCT01839487. Clinical trial information: NCT01839487. [Table: see text]

Safety and disease control achieved with the addition of nivolumab (Nivo) to chemoradiotherapy (CRT) for intermediate (IR) and high-risk (HR) local-regionally advanced head and neck squamous cell carcinoma (HNSCC): RTOG Foundation 3504.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 6073-6073 ◽  
Author(s):  
Maura L. Gillison ◽  
Robert L. Ferris ◽  
Jonathan Harris ◽  
A. Dimitrios Colevas ◽  
Loren K. Mell ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Performance Status ◽  
High Dose ◽  
Newly Diagnosed ◽  
Programmed Death ◽  
Platinum Refractory ◽  
Programmed Death 1 ◽  
Grade 3 ◽  
Clinical Trial Information

6073 Background: Nivo, which inhibits the programmed death-1 (PD-1) receptor, improved survival for pts with platinum-refractory recurrent/metastatic HNSCC. A clinical trial evaluated the safety of adding nivo to 4 standard intensity modulated (chemo) radiotherapy (RT) regimens (see table) for pts with newly diagnosed IR/HR HNSCC. Primary endpoint was safety and feasibility. Methods: Eligibility included IR (p16+ oropharynx [op], T1-2N2b-N3/T3-4N0-3, >10 pack-years [pys], or T4N0-N3/T1-3N3, ≤10 pys) & HR HNSCC (oral cavity, larynx, hypopharynx, p16- op, T1-2N2a-N3/T3-4N0-3). 10 pts/arm (8 evaluable; 0-2/8 DLTs acceptable). Nivo (dose & schedule varied per arm) started 2 wks pre-RT & continued 3 months post-RT. Feasibility of adjuvant nivo months 3-12 post-RT defined as ≥4 of 8 pts/arm received 7 doses. Arm 4 limited to age ≥70, Zubrod performance status (PS) 2, CrCl <50 ml/min, grade ≥2 hearing loss or ≥ grade 3 neuropathy. Results: Characteristics of 39/40 treated pts: median age 62, 79% male, 49% PS0, 38% HR, 67% >10 pys, 62% p16+ op, 72% T3-4, 85% N2-3. Grade ≥3 nivo-related AEs: adrenal insufficiency, diarrhea-3, anemia, fatigue-2, mucositis-3, nausea, vomiting, lipase increase-6, amylase increase-2, lymphocyte/neutrophil/WBC decrease-4, hyponatremia-3, anorexia, maculo-papular rash. SAE in 4/10, 4/9, 5/10 & 4/10. DLTs, adjuvant chemo feasibility, median follow-up (mo), progression or death events per arm shown in table. Conclusions: Nivo concomitant with all (chemo)RT regimens was safe for patients with newly diagnosed IR/HR HNSCC but adjuvant nivo was infeasible after high-dose cisplatin or in cisplatin-ineligible patients ( NCT02764593 ). Preliminary data on progression/death is provided. Acknowledgements: Support for this study was provided by Bristol-Myers Squibb Company. Clinical trial information: NCT02764593. [Table: see text]

A phase Ib dose escalation study of vantictumab (VAN) in combination with nab-paclitaxel (Nab-P) and gemcitabine (G) in patients with previously untreated stage IV pancreatic cancer.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 249-249 ◽  
Author(s):  
S. Lindsey Davis ◽  
Dana Backlund Cardin ◽  
Safi Shahda ◽  
Heinz-Josef Lenz ◽  
Efrat Dotan ◽  
...  
Keyword(s):  
Human Monoclonal Antibody ◽  
Stage Iv ◽  
Pathologic Fracture ◽  
Fragility Fractures ◽  
Therapeutic Index ◽  
Maximum Tolerated Dose ◽  
Dose Escalation Study ◽  
Phase Ib ◽  
Safety Parameters ◽  
Grade 3

249 Background: Vantictumab is a fully human monoclonal antibody that inhibits Wnt pathway signaling through binding FZD1, 2, 5, 7, and 8 receptors. A phase Ib study of VAN in combination with Nab-P and G was performed in patients with untreated stage IV pancreatic adenocarcinoma. Methods: Patients received VAN at escalating doses (3-7 mg/kg) in combination with standard dosing of Nab-P and G according to a 3+3 design. Due to fragility fractures occurring in this and other related clinical trials, dosing on an every 2 week schedule in cohorts 1 and 2 was transitioned to every 4 week dosing for cohorts 3 through 5. In these later cohorts, a minimum of six patients were treated at each dose level and additional criteria for maximum tolerated dose (MTD) integrating bone safety parameters were added. The bone safety plan was also revised for these cohorts. Sequential dosing of VAN followed by Nab-P and G was explored in cohort 5. Results: Thirty-one patients (52% male, 48% female) were enrolled and treated in 5 dosing cohorts. Median age was 66. Most common study-treatment related adverse events were nausea (68%) and fatigue (52%). One dose limiting toxicity (DLT) event occurred in the study population—grade 3 dehydration in 1 of 9 patients in cohort 4 (5 mg/kg q4w). Fragility fractures attributed to VAN occurred in two patients in cohort 2 (7 mg/kg q2w). Once the dosing schedule was revised to every 4 weeks, the maximum administered VAN dose was 5 mg/kg. No fragility fractures attributed to VAN occurred in these cohorts; pathologic fracture not attributed to VAN was documented in 2 patients. The study was terminated due to lack of an acceptable therapeutic index. Partial response was documented in 13 patients (42%) and stable disease in 11 (36%). Conclusions: The MTD of VAN plus Nab-P and G was not determined, but the maximum administered dose (MAD) of VAN, 7 mg/kg every 2 weeks, was considered unsafe related to bone toxicity, a known effect of WNT inhibition. After the study was revised, the MAD was 5 mg/kg every 4 weeks, with no protocol-specified bone toxicity observed (n = 16). Clinical trial information: NCT02005315.

Efficacy and safety of patritumab deruxtecan (HER3-DXd) in EGFR inhibitor-resistant, EGFR-mutated (EGFRm) non-small cell lung cancer (NSCLC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9007-9007
Author(s):  
Pasi A. Janne ◽  
Christina S Baik ◽  
Wu-Chou Su ◽  
Melissa Lynne Johnson ◽  
Hidetoshi Hayashi ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Topoisomerase I ◽  
Human Monoclonal Antibody ◽  
Locally Advanced ◽  
Safety Data ◽  
Platinum Based Chemotherapy ◽  
Tki Resistance ◽  
Grade 3 ◽  
Egfr Tki

9007 Background: Patients (pts) with advanced EGFRm NSCLC have limited treatment options after failure of EGFR TKI and platinum-based chemotherapy (PBC). HER3-DXd is an antibody drug conjugate consisting of a fully human monoclonal antibody to HER3 attached to a topoisomerase I inhibitor payload via a tetrapeptide-based cleavable linker. We previously presented efficacy/safety data (median follow-up, 5.4 mo) from an ongoing study of HER3-DXd in EGFRm NSCLC after failure of EGFR TKI therapy. We now present extended follow-up of pts receiving the recommended dose for expansion (5.6 mg/kg IV Q3W). Methods: This Ph 1 dose-escalation/expansion study included pts with locally advanced or metastatic EGFRm NSCLC with prior EGFR TKI therapy (NCT03260491). Pts with stable brain metastases (BM) were allowed. The primary endpoint was confirmed ORR by blinded independent central review (BICR) per RECIST v1.1; secondary endpoints included DOR, PFS and safety. Results: At data cutoff (Sept 24, 2020), 57 pts were treated with HER3-DXd 5.6 mg/kg IV Q3W; median follow-up, 10.2 mo (range, 5.2-19.9 mo). Median number of prior anticancer regimens was 4 (range, 1-10). 100% had prior EGFR TKI (86% prior osimertinib [OSI]) and 91% had prior PBC. 47% had a history of BM. Median treatment duration was 5.5 mo (range, 0.7-18.6 mo); treatment was ongoing in 18 pts (32%). Confirmed ORR by BICR was 39% (22/57; 95% CI, 26.0%-52.4%; 1 CR, 21 PR, 19 SD) with 14/22 responses occurring within 3 mo of starting HER3-DXd. DCR was 72% (95% CI, 58.5%-83.0%). Median DOR was 6.9 mo (95% CI, 3.1 mo-NE), and median PFS was 8.2 mo (95% CI, 4.4-8.3 mo). Antitumor activity was observed across diverse mechanisms of EGFR TKI resistance, including those not directly related to HER3 ( EGFR C797S, MET or HER2 amp, and BRAF fusion). Among pts with prior PBC, ORR was 37% (19/52; 95% CI, 23.6%-51.0%); in pts with prior OSI and PBC, ORR was 39% (17/44; 95% CI, 24.4%-54.5%). Among 43 pts evaluable for HER3 expression, nearly all expressed HER3; median membrane H-score by IHC was 180 (range, 2-280). Median H-score (range; N) was 195 (92-268; 15) in pts with CR/PR, 180 (4-280; 15) with SD, 126.5 (2-251; 6) with PD, and 180 (36-180; 7) in pts unevaluable for best overall response. The most common grade ≥3 adverse events (AEs) were thrombocytopenia (30%), neutropenia (19%), and fatigue (14%). Drug-related interstitial lung disease by central adjudication occurred in 4 pts (7%; 1 grade ≥3 [2%]; no grade 5). 6/57 pts (11%) had AEs associated with treatment discontinuation (none were due to thrombocytopenia). Conclusions: HER3-DXd 5.6 mg/kg IV Q3W demonstrated antitumor activity across various EGFR TKI resistance mechanisms in heavily pretreated metastatic/locally advanced EGFRm NSCLC. The safety profile was consistent with previous reports. A Ph 2 study of HER3-DXd in pts with EGFRm NSCLC after failure of EGFR TKI and PBC has been initiated (NCT04619004). Clinical trial information: NCT03260491.

Overall survival (OS) analysis from an expanded access program (EAP) of nivolumab (NIVO) in combination with ipilimumab (IPI) in patients with advanced melanoma (MEL).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9522-9522 ◽  
Author(s):  
David Hogg ◽  
Paul B. Chapman ◽  
Mario Sznol ◽  
Christopher D. Lao ◽  
Rene Gonzalez ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Phase Ii ◽  
Safety Data ◽  
Stage Iv ◽  
Clinical Trial Data ◽  
Induction Phase ◽  
Drug Induced ◽  
Metastatic Setting ◽  
Treatment Naïve ◽  
Grade 3

9522 Background: NIVO (anti-PD-1) and IPI (anti-CTLA-4), alone and in combination, are approved for the treatment of MEL. Phase II and III trials showed improved efficacy for NIVO+IPI versus IPI alone, but with a higher frequency of adverse events (AEs). In the phase II CheckMate 069 trial, the 2-year OS rate was 63.8% for all patients (pts) in the NIVO+IPI group. We report the first OS analysis, as well as updated safety data, from a North American EAP of NIVO+IPI in pts with MEL (CheckMate 218; NCT02186249). Methods: CheckMate 218 included pts with MEL who could have progressed on other therapies, but were anti-CTLA-4 and anti-PD-1 treatment-naive. Pts received NIVO 1 mg/kg + IPI 3 mg/kg Q3W x 4, followed by NIVO 3 mg/kg Q2W until disease progression or a maximum of 48 weeks from the first monotherapy dose. We assessed OS in the US cohort (n = 580) and safety in all pts (n = 732). Pts were followed for a minimum of 1 year in the USA and 6 months in Canada. Results: Of 732 pts, 43% had a BRAFmutation, 84% stage IV MEL, 51% M1c disease, 31% LDH > ULN (9% LDH > 2x ULN), and 13% received ≥1 prior systemic therapy in the metastatic setting. All pts received a median of 3 doses each for NIVO (range: 1–4) and IPI (range: 0–4) in the induction phase; 34% of pts received at least 1 dose of NIVO maintenance. The 1- and 2-year OS rates were 78.6% (95% CI: 74.2–82.4) and 65.3% (95% CI: 56.1–73.0), respectively. AEs of any grade occurred in 717 pts (98%), with grade 3/4 AEs in 470 pts (64%). Immune-modulating medications were used to manage any grade AEs, including grade 1/2 skin and gastrointestinal AEs, in 538 of 717 pts (75%), and to manage grade 3/4 AEs in 279 of 470 pts (59%). The most common treatment-related AEs of any grade were diarrhea (39%), pruritus (26%), and an increase in aspartate aminotransferase level (23%). Treatment-related deaths in 2 pts were reported as drug-induced liver injury and myocardial infarction. Conclusions: In this EAP, which included pts who had received prior systemic therapies for MEL and pts with poor prognostic factors generally not included in clinical trials, NIVO+IPI treatment demonstrated survival outcomes and a safety profile consistent with clinical trial data. Clinical trial information: NCT02186249.

Combining radiation therapy with anti-PD-1 for patients with advanced hepatocellular carcinoma: An open-label, single-center, single-arm clinical study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16117-e16117
Author(s):  
Jian-Xu Li ◽  
Ting-Shi Su ◽  
Xiao-Feng Lin ◽  
Yi-Tian Chen ◽  
Shi-Xiong Liang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Clinical Trial ◽  
Radiation Therapy ◽  
Clinical Study ◽  
Cancer Staging ◽  
Advanced Hepatocellular Carcinoma ◽  
Single Center ◽  
Open Label ◽  
Grade 3 ◽  
Clinical Trial Information

e16117 Combining radiation therapy with anti-PD-1 for patients with advanced hepatocellular carcinoma: an open-label, single-center, single-arm clinical study Jian-Xu Li, Ting-Shi Su, Xiao-Feng Lin, Yi-Tian Chen, Shi-Xiong Liang, Bang-De Xiang; Guangxi Medical University Cancer Hospital, Nanning, China Abstract Research Funding: Jiangsu Hengrui Pharmaceuticals Co., Ltd., Shanghai, China. Guangxi Medical and Health Appropriate Technology Development and Application Project (No. S2019039), Guangxi, China. Background: Based on the results of recent studies, the PD-1 monoclonal antibodies have been approved to treat the patients with advanced hepatocellular carcinoma (HCC) by the FDA. Radiation therapy (RT) can enhance responsiveness to PD-1 monoclonal antibody by potential mechanisms. A phase Ⅱa study was conducted to assess the safety and the efficacy of combining RT with anti-PD-1 for patients with advanced hepatocellular carcinoma. Methods: Patients with advanced HCC were eligible. Stereotactic body radiation therapy (SBRT) were adopted, and the dose of radiation were Dt-PGTV 30-50 Gy/10fractions. Camrelizumab (200mg) were given intravenously every 3 weeks since the first day of RT until disease progression, or intolerable toxicity. Adverse events (AEs) and objective response rate (ORR) were summarized to assess the safety and efficacy. Results: From April 2020 to November 2020, 17 patients were enrolled (median age 54, range 32-69). 15 (88%) patients were male. 14 (82%) had ECOG performance score of 0. All the patients had Child-Pugh score A. 16 patients staged as Barcelona Clinic Liver Cancer staging C or China Liver Cancer staging Ⅲ. Extrahepatic metastases were identified in 11 (65%) patients. 13 (77%) patients were Hepatitis B virus infected. 15 (88%) patients had previously 2 lines or more chemotherapy. 9 (53%) patients had Alpha-fetoprotein level≥400 ng/ml. The ORR was 47%. The best response assessed by RECIST 1.1 was partial response (8 patients). Four patients had grade 3 immune-related adverse events (irAEs), including increased aspartate aminotransferase and alanine transaminase (n =1)，decreased hemoglobin (n =1)，decreased platelet count (n =1)，decreased neutrophil count (n =1). All grade 3 irAEs were mitigated with proper treatment. None treatment-related deaths occurred. Conclusions: In this study, RT combined with anti-PD-1 had an acceptable safety profile and indicated an effective treatment option in patients with unresectable HCC. Clinical trial information: NCT04193696. Clinical trial information: NCT04193696.

A phase Ⅰ open-label dose-escalation study of AL2846 in combination with gemcitabine in patients with locally advanced or metastatic pancreatic adenocarcinoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16210-e16210
Author(s):  
Rui Liu ◽  
Ting Deng ◽  
Ming Bai ◽  
Le Zhang ◽  
Tao Ning ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Dose Level ◽  
Standard Dose ◽  
Locally Advanced ◽  
Maximum Tolerated Dose ◽  
Ductal Adenocarcinoma ◽  
Efficacy Evaluation ◽  
Dose Escalation Study ◽  
Grade 3 ◽  
Dose Levels

e16210 Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with a 5-year survival rate of 10%. Overexpression of c-Met is associated with the poor prognosis in patients with PDAC and it was noted that phosphorylation of c-Met is increased in gemcitabine-resistant PDAC. AL2846 is an oral c-Met inhibitor, which targets multiple receptor tyrosine kinases (RTK’s) primarily including c-Met, VEGFR1, KIT, Axl and RET. The combination of AL2846 with chemotherapy may improve the clinical efficacy of PDAC. Based on these consideration, a phase Ⅰ clinical trial was initiated to determine the maximum tolerated dose (MTD) of AL2846 in combination with gemcitabine in patients with advanced PDAC and to clarify the potential anti-tumor activity. Methods: Patients with untreated locally advanced or metastatic PDAC were enrolled to receive oral AL2846 once daily in a fasted state in combination with gemcitabine intravenous infusion over 30 min on days 1, 8, and 15 every 28 days. The starting dose level is AL2846 40 mg and gemcitabine 1000 mg/m2. Primary endpoint was the maximum tolerated dose (MTD), defined as the highest dose level at which ≤33 % of patients incurred a dose-limiting toxicity (DLT), and RP2D. Secondary endpoints included response rate (ORR), progression-free survival (PFS) and overall survival (OS). Results: As of January 1, 2021, a total of 15 patients with PDAC were enrolled and received 4 dose-levels of AL2846 (40 mg: n = 1; 60 mg: n = 6; 90 mg: n = 3; 120 mg: n = 5) treatment. DLTs occurred in 1 patient who experienced grade 3 abnormal liver function. The most common grade 3 or above drug-related adverse events were neutropenia (n = 7, 46.7%), thrombocytopenia (n = 5, 33.3%), leukopenia (n = 4, 26.7%), GGT increased (n = 4, 26.7%), hyperbilirubinemia (n = 3, 20.0%) and alkaline phosphatase increased (n = 3, 20.0%). Among the 15 patients available for efficacy evaluation, 1 patient (6.6%) achieved partial response who was at the dose levels of 90mg. There were 4 patients whose PFS was more than 5 months. Although there were no more than 2 DLT events, we chose 90 and 120 mg as the target dose for RP2D according to the dose reduction and proportion of gemcitabine. Conclusions: The RP2D of AL2846 in combination with standard dose of gemcitabine were 90 and 120 mg QD continuously. The results demonstrated that AL2846 in combination with gemcitabine was well tolerated at doses up to 120 mg. Further clinical studies about the efficacy of AL2846 in pancreatic cancer are in progress. Clinical trial information: CTR20201021.

Treatment of advanced carcinoma of the vulva with chemoradiotherapy — can exenterative surgery be avoided?

1994 ◽  
Vol 4 (3) ◽  
pp. 150-155 ◽  
Author(s):  
D. J. Sebag-Montefiore ◽  
C. Mclean ◽  
S. J. Arnott ◽  
P. Blake ◽  
P. Van Dam ◽  
...  
Keyword(s):  
Locally Advanced ◽  
Stage Iv ◽  
Complete Response ◽  
Figo Stage ◽  
Who Grade ◽  
Low Toxicity ◽  
Venous Infusion ◽  
Grade 3 ◽  
Extent Of Disease ◽  
Disease Free

Thirty-seven patients with advanced FIGO stage (17 stage III, 20 stage IV) carcinoma of the vulva whose extent of disease would have required extenterative surgery were treated with chemoradiotherapy (CRT). Radiotherapy was given as a split course (2500 cGy mid-plane dose in 10 daily fractions, repeated 1 month later) to the first seven patients. Subsequently radiotherapy was given as a continuous course (4500 cGy mid-plane dose in 20–25 daily fractions). Chemotherapy included mitomycin c as an intravenous bolus and 5 fluorouracil as a continuous intra-venous infusion over 4–5 days, with variations in timing and dose according to the type of radiotherapy course. Fifteen (47%) complete and 11 (34%) partial responses were seen at 3 months after completion of treatment. Of the 15 patients with complete response, 10 remained disease-free for a median of 24 months (range 6–36 months). The median sur-vival for complete and partial responding patients was 15 and 11 months, respectively (range 2–37 months). Acute toxicity included moist perineal desquamation, diarrhea and myelosupression. One death secondary to neutropaenic sepsis occurred in the split course group. WHO grade 3 radiation enteritis occurred in one patient (14%) in the split course and two patients (6%) in the continuous CRT groups. Using CRT, very high response rates have been obtained with relatively low toxicity. There is a useful role for CRT in the treatment of patients with locally advanced recurrent disease although its place in the management of extensive primary disease requires further evaluation.

Cisplatin(P)-including triplets versus P-free doublets in the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC): SICOG 0101 randomized trial

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7103-7103 ◽  
Author(s):  
P. Comella ◽  
S. Palmeri ◽  
G. De Cataldis ◽  
G. Filippelli ◽  
R. Cioffi ◽  
...  
Keyword(s):  
Advanced Nsclc ◽  
Locally Advanced ◽  
Stage Iv ◽  
Standard Of Care ◽  
Rank Test ◽  
Stage Iiia ◽  
Log Rank Test ◽  
Grade 3 ◽  
Metastatic Sites ◽  
Nsclc Patients

7103 Background: We previously reported that triplets with P-gemcitabine (G) plus vinorelbine (V) (PGV) or paclitaxel (T) (PGT) prolonged the survival (S) of advanced NSCLC patients (pts) in comparison with P-based doublets (PG or PV). Aims of the present study were: (1) to compare (log-rank test) the S of P-based triplets vs P-free doublets, and (2) to compare (Fisher test) safety and response rate (RR) of T- and V-regimens. Methods: A 2x2 factorial design was adopted. Pts aged ≤ 70 years, with PS (ECOG) < 2, inoperable stage IIIA, IIIB, or IV NSCLC were randomly treated with: GV = G 1,000 mg/m2 + V 25 mg/m2 on day (D) 1 and 8; GT = G 1,000 mg/m2 + T 125 mg/m2 on D 1 and 8; PGV = P 50 mg/m2 on D 1 and 8 + GV; PGT = P 50 mg/m2 on D 1 and 8 + GT. In all arms, cycles were repeated Q 3 weeks. Only responder pts after 3 cycles received further chemotherapy (CT). Thoracic RT was delivered after CT to pts with intra-thoracic disease. 330 events were required to have a 90% power to demonstrate (two-sided P < 0.05) a 30% reduction of hazard of death. Results: From April 2001 to December 2005, 431 pts were recruited in the 4 arms. Characteristics in % were well balanced in P-based triplets and P-free doublets: males, 84/91; PS 0, 25/23; squamous cell carcinoma, 38/42; weight loss, 22/29; stage IV, 66/65; CNS metastases, 5/8; ≥ 2 metastatic sites, 29/30. So far, 411 pts were assessed for response: RR of triplets vs doublets was 88/204 (43%) vs 68/207 (33%) (P = 0.020), and of T-based vs V-based regimens was 40% vs 36% (P = 0.218). To date, 313 deaths were registered: median and 1-year S were 10.6 mo. and 41% for pts treated with triplets, and 10.4 mo. and 39% for pts treated with doublets (P = 0.786). Over initial 3 courses, occurrence of grade ≥ 3 toxicity (T vs V, % pts) was: neutropenia, 18% vs 30% (P < 0.004); febrile neutropenia, 4% vs 7%; platelets, 7% vs 12% (P = 0.056); anemia, 5% vs 7%; vomiting, 1% vs 2%; diarrhea, 6% vs 3%; stomatitis, 3% vs 0.5%. Grade ≥ 2 neurotoxicity occurred in 1% of both groups. Conclusions: Activity was significantly higher with P-based triplets, but they did not affect the OS. T-based regimens were equally active and less toxic than V-based regimens. Therefore, the GT regimen may represent a new standard of care for advanced NSCLC pts. No significant financial relationships to disclose.

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