scholarly journals Oral mTOR Inhibitor Everolimus in Patients With Gemcitabine-Refractory Metastatic Pancreatic Cancer

2009 ◽  
Vol 27 (2) ◽  
pp. 193-198 ◽  
Author(s):  
Brian M. Wolpin ◽  
Aram F. Hezel ◽  
Thomas Abrams ◽  
Lawrence S. Blaszkowsky ◽  
Jeffrey A. Meyerhardt ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Adverse Events ◽  
Single Agent ◽  
Progression Free Survival ◽  
Mtor Inhibitors ◽  
Mtor Pathway ◽  
Metastatic Pancreatic Cancer ◽  
Clinical Activity ◽  
Antitumor Effects ◽  
Gemcitabine Refractory

PurposeThe PI3K/Akt/mTOR pathway is activated in the majority of pancreatic cancers, and inhibition of this pathway has antitumor effects in preclinical studies. We performed a multi-institutional, single-arm, phase II study of RAD001(everolimus), an oral inhibitor of mTOR, in patients who experienced treatment failure on first-line therapy with gemcitabine.Patients and MethodsThirty-three patients with gemcitabine-refractory, metastatic pancreatic cancer were treated continuously with RAD001 at 10 mg daily. Prior treatment with fluorouracil in the perioperative setting was allowed. Patients were observed for toxicity, treatment response, and survival.ResultsTreatment with single-agent RAD001 was well-tolerated; the most common adverse events were mild hyperglycemia and thrombocytopenia. No patients were removed from the study because of drug-related adverse events. No complete or partial treatment responses were noted, and only seven patients (21%) had stable disease at the first restaging scans performed at 2 months. Median progression-free survival and overall survival were 1.8 months and 4.5 months, respectively. One patient (3%) had a biochemical response, defined as ≥ 50% reduction in serum CA19-9.ConclusionAlthough well-tolerated, RAD001 administered as a single-agent had minimal clinical activity in patients with gemcitabine-refractory, metastatic pancreatic cancer. Future studies in metastatic pancreatic cancer should assess the combination of mTOR inhibitors with other agents and/or examine inhibitors of other components of the PI3K/Akt/mTOR pathway.

Safety and efficacy of modified FOLFIRINOX in pancreatic cancer: A retrospective experience.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14614-e14614 ◽  
Author(s):  
Hemchandra Mahaseth ◽  
John S. Kauh ◽  
Edith Brutcher ◽  
Natalyn Nicole Hawk ◽  
Sungjin Kim ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Performance Status ◽  
Single Agent ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Metastatic Pancreatic Cancer ◽  
Clinical Activity ◽  
Ecog Performance Status ◽  
Emory University ◽  
Grade 3

e14614 Background: Conroy et al reported a significant improvement in overall survival of patients with metastatic pancreatic cancer treated with FOLFIRINOX compared to single agent gemcitabine. The regimen was associated with significant grade 3/ 4 toxicities, such as myelosuppression(46%), fatigue(24%), vomiting(15%) and diarrhea (13%). In order to improve the toxicity profile, we have modified FOLFIRINOX (mFOLFIRINOX) regimen by removing the bolus 5-FU and adding the routine use of growth factor prophylaxis. We present our experience with mFOLFIRINOX in patients with locally advanced or metastatic pancreatic cancer. Methods: After obtaining IRB approval, patients with a diagnosis of pancreatic cancer were identified from the Emory University tumor registry. Twenty eight patients who received at least one dose of mFOLFIRINOX (5-FU 2400 mg/m2 CIVI over 46 hours, leucovorin 400 mg/m2, oxaliplatin 85 mg/m2, irinotecan 180 mg/m2 and pegfilgrastim 6 mg every two weeks ) were selected and their charts were retrospectively reviewed for safety, response, and survival. Results: Of 28 patients, 14 (50%) were male, 18 (64%) white, 8 (29%) black and other 2(7%). Median age was 63 (50-75) and ECOG performance status 0-1. Nineteen (68%) patients had primary tumor located in head of pancreas. Eight patients (29%) experienced grade 3/4 toxicities, i.e., nausea/vomiting (11%), diarrhea (11%), fatigue (11%), neuropathy (4%), neutropenia (4%), thrombocytopenia(4%), and sepsis not-related to neutropenia (4%). No grade 3/4 anemia or febrile neutropenia was noted. mFOLFIRINOX controlled the disease in 20 patients (71%) with 2 CR, 4 PR and 14 SD. With a median follow up of 5.5 months, median overall or progression free survival is not reached. Two patients have died and six patients have progressed. Conclusions: Modified FOLFIRINOX is well tolerated in this US population. The clinical activity appears very promising with majority of patients being free of progression.

RX 3117: Activity of an oral antimetabolite nucleoside in subjects with pancreatic cancer–Preliminary results of stage II of the phase Ia/IIb study.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 396-396
Author(s):  
Vincent M. Chung ◽  
Jaime R. Merchan ◽  
Allyson J. Ocean ◽  
Drew W. Rasco ◽  
Hani M. Babiker ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Partial Response ◽  
Primary Endpoint ◽  
Stable Disease ◽  
Single Agent ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Metastatic Pancreatic Cancer ◽  
Cancer Data ◽  
Phase 1B

396 Background: RX-3117 is an oral small-molecule antimetabolite, cyclopentyl pyrimidyl nucleoside that is activated by uridine cytidine kinase 2. RX-3117 has shown efficacy in xenograft models of gemcitabine resistant pancreatic, bladder and colorectal cancer. Data from stage 2 of the Phase 1b/2a clinical study of RX3117 as a single agent in subjects with metastatic pancreatic cancer is described below. Methods: Stage 2 of the Phase 1b/2a study (NCT02030067) is designed to evaluate safety, tolerability and efficacy following treatment with 700 mg administered orally once-daily for 5 consecutive days with 2 days off per week for 3 weeks with 1 week off in each 4 week cycle. Eligible subjects (aged ≥ 18 years) had relapsed/refractory metastatic pancreatic cancer. The primary endpoint is a ≥ 20% rate of progression free survival (PFS) benefit (i.e., proportion of subjects with stable disease for at least 4 months) and/or a 10% of evaluable subjects with a partial response rate or better. Results: As of Sep 2017, 44 subjects have been enrolled (22 females, 22 males). The median age was 68 years, ECOG performance statuses were 0 (13 subjects) and 1 (31 subjects) and 6 subjects had received 4 or more prior therapies. One subject had an unconfirmed partial response and 21 subjects met the primary endpoint of stable disease with a duration of 30-224 days. The most frequent adverse events were mild to moderate anemia (19%), mild to moderate fatigue (15%), mild to moderate diarrhea (11%), and severe anemia (9%). Conclusions: This ongoing trial shows an early efficacy signal where RX-3117 is active against advanced pancreatic cancer. The study continues to enroll subjects with advanced pancreatic cancer into stage 2. A phase 2 study with nab-paclitaxel in first-line patients with advanced pancreatic cancer has been started. Clinical trial information: NCT02030067.

A phase Ib trial of IPI-926, a hedgehog pathway inhibitor, plus gemcitabine in patients with metastatic pancreatic cancer.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 213-213 ◽  
Author(s):  
Donald Anthony Richards ◽  
Joe Stephenson ◽  
Brian M. Wolpin ◽  
Carlos Becerra ◽  
John Turner Hamm ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Single Agent ◽  
Progression Free Survival ◽  
Metastatic Pancreatic Cancer ◽  
Final Report ◽  
Double Blind ◽  
Free Survival ◽  
Phase 1B ◽  
Grade 3 ◽  
Dose Reductions

213 Background: IPI-926 is a novel, natural product-derived small molecule that targets the Hedgehog (Hh) pathway by inhibiting smoothened. In preclinical models of pancreatic cancer, repressing activation of the Hh pathway diminishes tumor-associated desmoplasia and improves chemotherapy delivery. Methods: This is the final report of the Phase 1b portion of a Phase 1b/2 trial evaluating the safety and efficacy of IPI-926 plus gemcitabine. Eligible patients (pts) with untreated metastatic pancreatic cancer and ECOG status 0-1 were administered oral IPI-926 daily (QD) for 28-day cycles, in 3 to 6 pt dose cohorts. Gemcitabine (1,000 mg/m2) was administered IV weekly for 3 weeks with 1 week off. DLTs were evaluated during Cycle 1. Results: 16 pts (median age 69 years; range 58-86) were enrolled at IPI-926 doses of 110, 130 or 160 mg QD (single agent MTD). Pts received a median of 5 cycles (1-13). Two pts remain on trial. No IPI-926-related serious AEs have been observed. One DLT of Grade 3 AST increase was observed (130 mg dose cohort) and was asymptomatic; it resolved with dose interruption, and did not recur with dose reduction. The most common AEs occurring were fatigue (75% total, 6% ≥ Grade 3), thrombocytopenia (63%, 25%), anemia (56%, 13%), nausea (50%, 0%), diarrhea (44%, 0%), vomiting (44%, 0%), peripheral edema (44%, 0%), pyrexia (44%, 0%), and AST increase (44%, 13%). Dose reductions of IPI-926 occurred in 3 (19%) pts. Dose reductions of gemcitabine occurred in 11 (69%) pts, primarily for thrombocytopenia (9 pts). One pt (6%) discontinued due to an AE (microangiopathic hemolytic anemia). Five (31%) radiographic partial responses were observed (1/3 at 110 mg, 2/6 at 130 mg, 2/7 at 160 mg). Median progression-free survival is > 7 months. 74% of pts were alive 6 months after study entry. Conclusions: IPI-926 plus gemcitabine is well tolerated in pts with untreated metastatic pancreatic cancer, with evidence of activity and no unexpected toxicity. Complete Phase 1b data, including final overall survival, will be presented. Clinical evaluation of this combination continues in the randomized, double-blind, placebo-controlled Phase 2 portion of the trial.

Updated single institution outcome data from the first-in-human CEND-1 trial in metastatic pancreatic cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16274-e16274
Author(s):  
Andrew Peter Dean ◽  
Fiona Mulligan ◽  
Geena Kelly ◽  
Emma Shaughnessy ◽  
Kate Wilson
Keyword(s):  
Pancreatic Cancer ◽  
Adverse Events ◽  
Cyclic Peptide ◽  
Day Treatment ◽  
Progression Free Survival ◽  
Outcome Data ◽  
Metastatic Pancreatic Cancer ◽  
Free Survival ◽  
Phase 2 Trial

e16274 Background: In our phase I trial of the first-in-class agent CEND-1 with gemcitabine and nab-paclitaxel in patients with metastatic pancreatic cancer, we reported a preliminary overall RR of 59% in 29 patients across 3 institutions. Our site enrolled 19 of these patients and we present updated outcome data from this institution. CEND-1 is a bifunctional cyclic peptide (a.k.a. iRGD) that homes to tumors via RGD motif interaction with alphav-integrins and then transforms the solid tumor microenvironment into a temporary drug conduit via interaction with neuropilin-1. This leads to an enhanced tumor delivery of co-administered anti-cancer agents. Methods: We reviewed our updated outcome data from the first in human CEND-1 trial in pancreatic cancer. Patients received a combination of CEND-1 with nab-paclitaxel (125 mg/m2) and gemcitabine (1000 mg/m2) on days 1, 8, 15 of a 21-day treatment cycle. Data was analysed to determine response rate, progression free survival and ongoing benefit. Results: Of the 19 patients that were enrolled at this institution; 13 (69%) showed partial response, 5 (26) % had stable disease, and 1 (3.4%) had progressive disease. Median progression free survival for this cohort was 8.8 months. 4 patients (21%) remain on the trial without disease progression to date. Median treatment duration for these patients is 20 months (range 17.1 – 24.6 months). Adverse events were as previously described¹ with no new significant events or toxicities. Conclusions: Ongoing follow-up data from the CEND-1 study at our institution shows ongoing continuing benefit for patients who remain on trial with notable progression free survival. No new safety signals or adverse events have been detected with this prolonged follow-up. The randomised phase 2 trial of this combination will be proceeding later this year. Clinical trial information: ACTRN12618000804280.

A phase Ib study to evaluate the safety and efficacy of AMG 655 in combination with gemcitabine (G) in patients (pts) with metastatic pancreatic cancer (PC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4501-4501 ◽  
Author(s):  
H. L. Kindler ◽  
L. Garbo ◽  
J. Stephenson ◽  
J. Wiezorek ◽  
T. Sabin ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Single Agent ◽  
Objective Response ◽  
Death Receptor ◽  
Progression Free Survival ◽  
Median Number ◽  
Metastatic Pancreatic Cancer ◽  
Death Receptor 5 ◽  
Number Of Cycles ◽  
Ecog Ps

4501 Background: AMG 655 is an investigational, fully human agonist monoclonal antibody (IgG1) that binds human death receptor 5 (DR5), activates caspases, and induces apoptosis in sensitive tumor cells. In preclinical PC models, cooperative activity is observed when G is added to AMG 655. We performed a multi-center phase I trial to evaluate AMG 655 + G in metastatic PC pts. The primary endpoint was dose-limiting toxicity (DLT). Secondary endpoints included toxicity, pharmacokinetics, antibody formation, objective response rate, progression-free survival (PFS), 6-month and overall survival. Methods: Eligible pts had previously untreated metastatic PC and ECOG PS 0 or 1. Pts enrolled into sequential cohorts and received AMG 655 3 or 10 mg/kg IV days (D) 1 and 15 and G 1000 mg/m2 IV D 1, 8, and 15 every 28 D. CT scans were obtained Q8 weeks. Results: 13 pts (3 mg/kg cohort = 6; 10 mg/kg cohort = 7) enrolled from 7/07–11/07. Pt characteristics: females 61%; ECOG PS 1 69%; median age 65 (range 35–81); liver metastases 77%. Median number of cycles: 6 (range 2–12). There were no DLT. Nine (69%) pts had grade 3–4 toxicity, the most common were: thrombocytopenia (4 pts), neutropenia (2 pts), and abdominal pain (2 pts). No anti-AMG 655 antibodies were detected. After one 3 or 10 mg/kg dose of AMG 655 after G, the Cmax and AUC of AMG 655 were similar to those in the first- in-human single-agent study (LoRusso JCO 2007; 25: abstract 3534). Preliminary data indicate no effect of AMG 655 on PK of G. Partial response 31% (4 pts, 2 unconfirmed); stable disease 38%. Median PFS: 5.3 months (95% CI, 3.5, 6.2); 6-month survival rate: 76.2% (95% CI: 42.7%-91.7%). Conclusions: AMG 655 + G is well-tolerated and may have activity in metastatic pancreatic cancer. A randomized phase II trial of G ± AMG 655 at 10-mg/kg is currently enrolling. [Table: see text]

A phase IIb trial of coix seed injection for advanced pancreatic cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15023-e15023 ◽  
Author(s):  
Mary Ann Tagliaferri ◽  
Lee Steven Schwartzberg ◽  
Michael M. Chen ◽  
Luis H. Camacho ◽  
Edward H. Kaplan ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Clinical Trial ◽  
Adverse Events ◽  
Primary Liver Cancer ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Clinical Activity ◽  
Serious Adverse Events ◽  
Coix Seed

e15023 Background: Kanglaite injection (KLTi) is a purified botanical extract injection tested for pancreatic cancer. KLTi is derived from Coix seed of the plant Coix lacrama-jobi. KLTi demonstrated growth inhibitory effects in vitro. In xenograft models with PANC-1 cell lines in BALB/C mice, KLTi combined with gemcitabine had synergistic tumor inhibitory activity greater than gemcitabine alone. KLTi is approved and widely used in China to treat non-small cell lung cancer and primary liver cancer. We report final cohort 1 results from a US phase 2b clinical trial. Methods: Eligible patients with histologically confirmed unresectable pancreatic cancer were randomized to a regimen of either KLTi 30g/day plus a standard course of gemcitabine or a standard course of gemcitabine only. The two groups were compared in efficacy, measure by progression-free survival (PFS), and safety. Results: Forty-one patients were randomized to cohort 1 and 38 patients received treatment: 26 received KLTi plus gemcitabine, 12 received gemcitabine only, and 3 received no treatment. The KLTi plus gemcitabine group had a median PFS of 114 days, significantly longer than the median PFS of 57.5 days in the gemcitabine only group (HR 0.338, 95% CI: 0.145, 0.788, p=0.008). The overall response rates were 15.5% (4/26) and 8.3% (1/12) for KLTi plus gemcitabine and gemcitabine only, respectively. Two serious adverse events were possibly related to KLTi; one subject had a pulmonary embolism and the other experienced transient confusion. The adverse events were similar between the groups and consistent with gemcitabine toxicities. Conclusions: Combined with gemcitabine, KLTi injection showed favorable tolerability and encouraging clinical activity for the treatment of advanced pancreatic cancer. Clinical trial information: NCT00733850.

Concurrent high-dose intensity-modulated radiotherapy and chemotherapy for unresectable locally advanced and metastatic pancreatic cancer: a pilot study

2021 ◽  
pp. 1-6
Author(s):  
Kenichi Matsumoto ◽  
Akihiko Miyamoto ◽  
Tomoya Kawase ◽  
Taro Murai ◽  
Yuta Shibamoto
Keyword(s):  
Pancreatic Cancer ◽  
Locally Advanced ◽  
Intensity Modulated Radiotherapy ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
Concurrent Chemotherapy ◽  
Metastatic Pancreatic Cancer ◽  
High Dose ◽  
Chemotherapy Group ◽  
Intensity Modulated

Abstract Aim: To evaluate the efficacy of concurrent chemotherapy and high-dose (≥55 Gy) intensity-modulated radiotherapy (CCIMRT) in comparison with chemotherapy alone and intensity-modulated radiotherapy (IMRT) alone for unresectable locally advanced or metastatic pancreatic cancer. Methods: Forty-six patients with pancreatic cancer undergoing CCIMRT (n = 17), chemotherapy alone (n = 16) or IMRT alone (n = 13) were analysed. Overall survival (OS), locoregional progression-free survival (LRPFS) and gastrointestinal toxicities were evaluated. The median radiation dose was 60 Gy (range, 55–60) delivered in a median of 25 fractions (range, 24–30). Gemcitabine (GEM) alone, GEM + S-1, S-1 alone, FOLFIRINOX and GEM + nab-paclitaxel were used in CCIMRT and chemo-monotherapy. Results: The 1-year OS rate was 69% in the CCIMRT group, 27% in the chemotherapy group and 38% in the IMRT group (p = 0·12). The 1-year LRPFS rate was 73, 0 and 40% in the 3 groups, respectively (p = 0·012). Acute Grade ≥ 2 gastrointestinal toxicity (nausea, diarrhea) was observed in 12% (2/17) in the CCIMRT group, 25% (4/16) in the chemotherapy group and 7·7% (1/13) in the IMRT group (p = 0·38). Late Grade 3 gastrointestinal bleeding was observed in 6·3% (1/16) in the chemotherapy group. Conclusion: High-dose CCIMRT yielded acceptable toxicity and favorable OS and LRPFS.

Gemcitabine Plus Nab-Paclitaxel as Second-Line Chemotherapy following FOLFIRINOX in Patients with Unresectable Pancreatic Cancer: A Single-Institution, Retrospective Analysis

Chemotherapy ◽  
2021 ◽  
pp. 1-7
Author(s):  
Kotone Hayuka ◽  
Hiroyuki Okuyama ◽  
Akitsu Murakami ◽  
Yoshihiro Okita ◽  
Takamasa Nishiuchi ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Adverse Events ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Unresectable Pancreatic Cancer ◽  
Line Treatment ◽  
Second Line ◽  
Free Survival ◽  
Common Grade ◽  
Grade 3

<b><i>Introduction:</i></b> Patients with advanced pancreatic cancer have a poor prognosis. FOLFIRINOX (FFX) and gemcitabine plus nab-paclitaxel (GnP) have been established as first-line treatment, but they have not been confirmed as second-line treatment after FFX. The aim of this study was to evaluate the safety and efficacy of GnP as second-line therapy after FFX in patients with unresectable pancreatic cancer. <b><i>Methods:</i></b> Twenty-five patients with unresectable pancreatic cancer were enrolled. The patients were treated with GnP after FFX between September 2015 and September 2019. Tumor response, progression-free survival (PFS), overall survival (OS), and incidence of adverse events were evaluated. <b><i>Results:</i></b> The response rate, disease control rate, median PFS, and median OS were 12%, 96%, 5.3 months, and 15.6 months, respectively. The common grade 3 or 4 adverse events were neutropenia (76%) and anemia (16%). <b><i>Conclusions:</i></b> GnP after FOLFIRINOX is expected to be one of the second-line recommendations for patients with unresectable pancreatic cancer.

A phase Ib/II study of selinexor in combination with imatinib in patients with advanced gastrointestinal stromal tumor (GIST): SeliGIST/GEIS-41 trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 11534-11534
Author(s):  
Cesar Serrano ◽  
Claudia Valverde ◽  
Josefina Cruz Jurado ◽  
Javier Martinez-Trufero ◽  
Xavier Guri ◽  
...  
Keyword(s):  
Clinical Benefit ◽  
Nuclear Export ◽  
Single Agent ◽  
Progression Free Survival ◽  
Antitumoral Activity ◽  
Clinical Activity ◽  
Activity Data ◽  
Phase Ib ◽  
Best Response ◽  
Heavily Pretreated

11534 Background: KIT or PDGFRA oncogenic activation drives GIST progression throughout the disease course. Accordingly, currently approved agents in metastatic GIST focus on the therapeutic suppression of these receptors. However, the clinical benefit after imatinib (IM) progression is still modest, suggesting the co-operation of KIT/PDGFRA-independent mechanisms in GIST cell survival. Selinexor is an oral, selective inhibitor of XPO1-mediated nuclear export, and preclinical studies evidenced antitumoral activity in GIST as single agent and in combination with IM in both IM-sensitive and IM-resistant models. Methods: The phase Ib portion studied IM 400 mg daily plus weekly selinexor in patients (pts) with IM-resistant, advanced GIST. Prior intolerance to IM was not allowed. A standard 3+3 dosing schema was utilized to determine the recommended phase II dose (RP2D) of this combination. Investigator-assessed response was evaluated every 8 weeks using RECIST 1.1. Results: At data cutoff of Sep 25, 2020, 12 pts were enrolled and received treatment with IM 400 mg and selinexor once weekly at dose levels (DL) 1 (60 mg), DL2 (80 mg) and DL3 (100 mg). Median age 57 (range 46-77), 42% female, median prior therapies 4 (range 2-7). Although only 1/6 pts developed a dose limiting toxicity (DLT) at DL3, the RP2D was defined at DL2 (IM 400 mg daily and selinexor 80 mg once weekly) based on activity data in the DL2 and the need for dose reductions in 5/6 pts at DL3 after the DLT window. All pts were evaluable for toxicity and response. One DLT occurred at DL3 (G3 nausea). Non-DLT G3/4 toxicities were anemia (1/12 pts), neutropenia (1/12 pts), vomiting (1/12 pts) and fatigue (2/12 pts). Common G1/2 toxicities were nausea (11/12 pts), vomiting (10/12 pts), neutropenia (5/12 pts) and anemia, fatigue, diarrhea, and periorbital edema (4/12 pts each). No unexpected toxicities were observed. Overall response rate in the 12 pts evaluable for response was 67% (95% CI 0.349-0.901), with 2 pts achieving PR (17%) and 6 pts SD (50%) as the best response. Clinical benefit rate (CBR = CR, PR, SD) ≥ 16 weeks was 42% (95% CI 0.157-0.723). Median progression free survival was 3.5 months (95% CI 1.7-7.3). Four pts remain on trial at data cutoff. Conclusions: IM and selinexor combination is well-tolerated and has clinical activity in heavily pretreated GIST pts. The trial is currently exploring selinexor as single agent in the IM-resistant GIST population. Clinical trial information: NCT04138381.

Phase I Trial of Intravenous Administration of PV701, an Oncolytic Virus, in Patients With Advanced Solid Cancers

2002 ◽  
Vol 20 (9) ◽  
pp. 2251-2266 ◽  
Author(s):  
Andrew L. Pecora ◽  
Naiyer Rizvi ◽  
Gary I. Cohen ◽  
Neal J. Meropol ◽  
Daniel Sterman ◽  
...  
Keyword(s):  
Adverse Events ◽  
Phase I ◽  
Intravenous Administration ◽  
Single Agent ◽  
Progression Free Survival ◽  
Maximum Tolerated Dose ◽  
Repeat Dose ◽  
Tumor Cell Membrane ◽  
Dosing Regimens ◽  
Higher Doses

PURPOSE: PV701, a replication-competent strain of Newcastle disease virus, causes regression of tumor xenografts after intravenous administration. This phase I study was designed to define the maximum-tolerated dose (MTD) and safety of single and multiple intravenous doses of PV701 as a single agent in patients with cancer. PATIENTS AND METHODS: Seventy-nine patients with advanced solid cancers that were unresponsive to standard therapy were enrolled. Four PV701 intravenous dosing regimens were evaluated: (1) single dose: one dose every 28 days; (2) repeat dose: three doses in 1 week every 28 days; (3) desensitizing: one lower dose followed by two higher doses in 1 week every 28 days; and (4) two week: one lower dose followed by five higher doses over 2 weeks every 21 days. RESULTS: A 100-fold dose intensification was achieved over 195 cycles. A first-dose MTD of 12 × 109 plaque-forming units (PFU)/m2 was established for outpatient dosing. After an initial dose of 12 × 109 PFU/m2, patients tolerated an MTD for subsequent doses of 120 × 109 PFU/m2. The most common adverse events were flu-like symptoms that occurred principally after the first dose and were decreased in number and severity with each subsequent dose. Tumor site–specific adverse events and acute dosing reactions were also observed but not cumulative toxicity. Objective responses occurred at higher dose levels, and progression-free survival ranged from 4 to 31 months. Tumor tissue from one patient was obtained after 11 months of therapy and showed evidence of PV701 particles budding from the tumor cell membrane by electron microscopy and a pronounced lymphoplasmacytic infiltrate by histologic examination. CONCLUSION: PV701 warrants further study as a novel therapeutic agent for cancer patients.

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