Conservative treatment of intraocular retinoblastoma: A prospective phase II randomized trial of neoadjuvant chemotherapy followed by local treatments and chemothermotherapy.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 9538-9538
Author(s):  
Isabelle Aerts ◽  
Livia Lumbroso-Le Rouic ◽  
David Hajage ◽  
Christine Levy-Gabriel ◽  
Alexia Savignoni ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Phase Ii ◽  
Laser Diode ◽  
Tumour Size ◽  
Randomized Study ◽  
Single Agent ◽  
Local Treatment ◽  
New Treatment ◽  
Intraocular Retinoblastoma ◽  
Number Of Cycles

9538 Background: intraocular retinoblastoma treatments often associate chemotherapy and focal treatments. The protocols vary and may combine two or three drugs, and different number of cycles associated to the local adjuvant treatments. A first prospective protocol of conservative treatments in our institution showed the efficacy of the use of two courses of chemoreduction with etoposide and carboplatin, followed by chemothermotherapy using carboplatin, as a single agent. In order to decrease the possible long term toxicity of chemotherapy due to etoposide, a prospective randomized phase II chemo reduction protocol was conducted, using vincristine and carboplatin vs. etoposide carboplatin. Methods: the study was proposed when initial tumour size or location did not allow the use of front-line local treatments. The phase II randomized study of reduction chemotherapy used vincristin carboplatin or etoposide carboplatin, followed by local treatment including chemothermotherapy using the combination carboplatin and laser diode hyperthermia. Primary endpoint was the need for secondary enucleation or EBRT not exceeding 40% at 2 years. The new treatment was considered sufficiently effective if 10 events or less were observed among 33 eyes. Results: 55 children, 65 eyes were included in the study (May 2004- August 2009).32 eyes (27 children) were treated conservatively in the arm etoposide-carboplatin and 33 (28 children) eyes in the arm vincristin carboplatin.At two years after treatment 23/33 (69.7%) eyes were treated and salvaged without EBRT or enucleation in the arm vincristin-carboplatin and 26/32 (81.3%) in the arm etoposide and carboplatin. Conclusions: neoadjuvant chemotherapy by two cycles of vincristine and carboplatin followed by chemothermotherapy (using the combination carboplatin, as a single drug, and laser diode hyperthermia) does not seem to offer an optimal local control.

A phase II trial of gemcitabine and docetaxel in hormone-refractory metastatic prostate cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14501-14501 ◽  
Author(s):  
S. Thakkar ◽  
T. Hutson ◽  
J. Garcia ◽  
J. Rothaermal ◽  
M. Bart ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Antitumor Activity ◽  
Phase Ii ◽  
Metastatic Prostate Cancer ◽  
Single Agent ◽  
Significant Activity ◽  
Hormone Refractory ◽  
Gi Bleed ◽  
Number Of Cycles ◽  
Ecog Ps

14501 Background: Docetaxel is a microtubule stabilizing agent with demonstrated ability to improve survival in patients (pts) with hormone refractory metastatic prostate cancer (HRMPC). Gemcitabine is a nucleoside analogue that exhibits broad antitumor activity, although as a single agent has modest activity in advanced prostate cancer. The combination of docetaxel and gemcitabine has demonstrated significant activity in a variety of chemotherapy resistant neoplasms. We performed a phase II study of this combination to assess its safety and antitumor activity in chemotherapy naïve patients with HRMPC. Methods: Eligible pts had HRMPC with radiologic and/or biochemical evidence of progression following antiandrogen withdrawal with castrate testosterone levels, ECOG PS 0–2 and adequate organ function; no prior chemotherapy was permitted. Gemcitabine (800 mg/m2) was administered on days 1 and 8 and docetaxel (75mg/m2) on day 8 every 21 days for a maximum of 6 cycles. Results: Twenty-nine pts have been enrolled to date with 22 currently evaluable for response, all are evaluable for toxicity. The median age was 68. The average number of cycles completed was 4.9. Nine pts have experienced grade 4 neutropenia (1 neutropenic fever admission). Twelve of 29 pts have required dose delays secondary to wbc or platelets, two pts have required dose modification. Non-hematologic grade 3/4 toxicities include 1 pt with a PE, 1 grade 4 dyspnea, 1 grade 4 GI bleed. Four pts (18%) achieved measurable disease + PSA, partial response (PR), 7 (32%) additional pts had >50% decline in PSA, for a composite overall response rate of 50%. Conclusions: The combination of gemcitabine and docetaxel is moderately toxic primarily impacting bone marrow reserve. Although there is evidence of significant antitumor activity, the ulitmiate utility of this doublet remains undefined. Accrual to this study is ongoing. [Table: see text]

Phase II study of single agent perifosine in patients with hepatocellular carcinoma (HCC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15505-e15505 ◽  
Author(s):  
L. T. Campos ◽  
J. Nemunaitis ◽  
J. Stephenson ◽  
D. Richards ◽  
M. Barve ◽  
...  
Keyword(s):  
Median Time ◽  
Phase Ii ◽  
Randomized Study ◽  
Single Agent ◽  
Phase Iii ◽  
Weekly Dose ◽  
Dismal Prognosis ◽  
Systemic Treatments ◽  
Elevated Liver Enzymes ◽  
Daily Dose

e15505 Background: Perifosine (Peri) is a novel oral alkylphospholipid with effects on multiple signal transduction pathways including Akt, MAPK and JNK. Unresectable HCC continues to have dismal prognosis. In a phase III randomized study, sorafenib demonstrated a 2% partial response (PR) rate with a median time to symptomatic progression of 4.1 months (mos) and radiologic progression of 5.5 mos, however patients (pts) had not received prior systemic treatment. Hence, additional therapies are needed. Peri was evaluated in a phase II multi-disease trial where 558 pts were randomized to daily vs. weekly schedules of Peri (50/100 mg daily or 900/1,200 mg weekly) with 42 of the pts having HCC. The following are the efficacy and safety results of this sub-group. Methods: Pts with advanced measurable HCC, up to 3 prior systemic treatments allowed. Normal organ / marrow function required. Primary outcome analyses included median time to progression (TTP) and disease control rate (DCR; CR+PR+SD > 12 weeks). Results: Of the 42 HCC pts treated, the median age was 71 (range 26–83), 22 were male and 48% had received > 1 prior systemic therapy. Child-Pugh status not available. As of 12/08, 32/42 pts were evaluable for efficacy (5 withdrew consent < 30 days, 4 toxicity < 30 days, 1 lost to follow up). One patient achieved a PR (3%) and 15 (47%) had stable disease > 12 weeks; overall DCR of 50%. Median TTP was 14 wks (range 2–86). As of 12/08, one patient remains active at 12 mos. The daily dose was well tolerated. The weekly dose was significantly more toxic (3 of the 4 who came off treatment < 30 days due to toxicity were on weekly). Most common grade 1/2 toxicities were GI related and fatigue. Grade 3/4 drug-related toxicities > 10% included: abdominal pain (12%), elevated liver enzymes (10%) and fatigue (10%). Conclusions: Perifosine was well tolerated at the daily dose and overall demonstrates clinical benefit in patients with advanced HCC as reflected by an encouraging TTP. A combination study with sorafenib is ongoing and future randomized studies are under consideration. [Table: see text]

A randomized phase II study of cediranib (CED) alone versus CED plus dasatinib (DAS) in patients (pts) with castration-resistant prostate cancer (CRPC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 5039-5039
Author(s):  
Anna Spreafico ◽  
Kim N. Chi ◽  
Srikala S. Sridhar ◽  
David C Smith ◽  
Michael Anthony Carducci ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Targeted Therapy ◽  
Phase Ii ◽  
Kinase Inhibitors ◽  
Randomized Study ◽  
Single Agent ◽  
Castration Resistant Prostate Cancer ◽  
Retroperitoneal Hemorrhage ◽  
Phase Ii Studies ◽  
Patient Reported

5039 Background: Activation of the Vascular Endothelial Growth Factor Receptor (VEGFR) and the oncogenic Src pathway has been implicated in the development of CRPC in preclinical models. CED and DAS are multi-kinase inhibitors targeting VEGFR and Src respectively. Phase II studies of CED (Karakunnel et al ASCO 2009) and DAS (Yu et al Urology 2011) in CRPC have shown single agent activity. Methods: Docetaxel-preteated CRPC pts were randomized to arm A: CED alone (20 mg/day) vs arm B: CED (20 mg/day) plus DAS (100 mg/day) given orally on 4-week cycles. Primary endpoint was 12 week progression-free survival (PFS) as per the Prostate Cancer Clinical Trials Working Group (PCWG2). Patient reported outcomes were evaluated using Functional Assessment of Cancer Therapy-Prostate (FACT-P) and Present Pain Intensity (PPI) scales. Correlative studies of bone turnover markers (BTM), including bone alkaline phosphate (BAP) and serum beta-C telopeptide (B-CTx) were serially assayed. Results: 22 patients, 11 per arm, were enrolled. Baseline demographics were similar in both arms. Median number of cycles = 4 in arm A (range 1-12) and 2 in arm B (range 1-9). Twelve-week PFS was 73 % in arm A vs 18 % in arm B (p = 0.03). Median PFS in months (arm A vs B) was: 5.2 vs 2.6 (95% CI: 1.9-6.5 vs 1.4-not reached). Most common grade 3 toxicities were hypertension, anemia and thrombocytopenia in arm A and hypertension, diarrhea and fatigue in arm B. One treatment-related death (retroperitoneal hemorrhage) was seen in arm A. FACT-P and PPI scores did not significantly change in either arm. No correlation between BTM and PFS was seen in both arms A and B. Conclusions: Although limited by small numbers, this randomized study showed that the combination of VEGFR and Src targeted therapy did not result in improved efficacy and may be associated with a worse outcome than VEGFR targeted therapy alone in pts with CRPC. Clinical trial information: NCT01260688.

Phase II trial evaluating the efficacy and safety of the anti-CD20 monoclonal antibody obinutuzumab in patients with marginal zone lymphoma

2020 ◽  
Vol 16 (13) ◽  
pp. 817-825
Author(s):  
Alexander Grunenberg ◽  
Lisa M Kaiser ◽  
Stephanie Woelfle ◽  
Birgit Schmelzle ◽  
Andreas Viardot ◽  
...  
Keyword(s):  
Phase Ii ◽  
Marginal Zone ◽  
De Novo ◽  
Phase Ii Trial ◽  
Single Agent ◽  
Local Treatment ◽  
Marginal Zone Lymphoma ◽  
Efficacy And Safety ◽  
Anti Cd20 ◽  
Hodgkin's Lymphomas

Marginal zone lymphoma (MZL) belongs to the group of indolent B-cell non-Hodgkin’s lymphomas, which is characterized by an indolent course. In this mostly elderly patient population, the development of chemotherapy-free approaches is of particular interest. In this situation, single-agent treatment with the next-generation anti-CD20 antibody obinutuzumab is an attractive approach, which promises high efficacy without major toxicity. We describe here an open-label, multicentric Phase II trial evaluating the efficacy and safety of obinutuzumab in de novo MZL patients, who are treatment naive for systemic therapy and not eligible for or failed local treatment. ClinicalTrials.gov identifier NCT03322865

ENGINE: Phase III randomized study of enzastaurin/R-CHOP versus placebo/R-CHOP in frontline high-risk diffuse large B-cell lymphoma patients with novel genomic biomarker DGM1.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS7569-TPS7569
Author(s):  
Stephen Smith ◽  
Jun Zhu ◽  
Owen A. O'Connor ◽  
Wen Luo ◽  
Ronald L. Shazer ◽  
...  
Keyword(s):  
High Risk ◽  
Phase Ii ◽  
Randomized Study ◽  
Single Agent ◽  
B Cell Lymphoma ◽  
Response Assessment ◽  
Phase Iii ◽  
Genome Wide ◽  
Phosphoinositide 3 Kinase ◽  
A Prospective Study

TPS7569 Background: Progress in genome technology allows analysis of previously completed trials to identify patients subgroups potentially benefiting from therapy. Enzastaurin is a potent inhibitor of protein kinase C beta (PKC- b) and suppresses the phosphoinositide 3-kinase (PI3K)/AKT pathway. The safety and efficacy of Enzastaurin has been tested in more than 60 clinical trials including 2 major studies in DLBCL: (1) PRELUDE (A phase III maintenance trial of Enzastaurin vs Placebo, N=758) ( Crump, 2016), and (2) S028 (A randomized phase II study of Enzastaurin/R-CHOP vs R-CHOP in frontline intermediate/high-risk DLBCL, N=101) ( Hainsworth, 2016). DNA samples extracted from blood of patients from PRELUDE were retrospectively genotyped using whole genome SNP arrays. From the genome wide screening a novel genetic biomarker, DGM1, was identified showing high correlation with response to Enzastaurin treatment ( Luo, ASH 2018). Importantly, these findings were replicated in the phase II S028 study. In the S028 study the hazard ratio (HR) for OS in high-risk (IPI ≥ 3) DGM1 positive (+) patients who received Enzastaurin/R-CHOP was 0.28 (0.1-0.81) when compared to subjects who received R-CHOP, a benefit favoring Enzastaurin (p=0.018). These data suggest that addition of Enzastaurin to R-CHOP may significantly improve outcome in frontline high-risk DGM1 (+) DLBCL. The ENGINE study was initiated to validate this finding in a prospective study. Methods: Adult patients must have untreated CD20+ DLBCL, IPI ≥ 3. Patients are randomized 1:1 to Enzastaurin/R-CHOP or Placebo/R-CHOP for 6 cycles during combination phase. Each subject’s treatment assignment will be unblinded after response assessment at the end of the combination phase. Subjects randomized to the investigational arm who have a complete or partial response will have the option to continue in the single agent phase to receive Enzastaurin for up to 2 additional years. The study intends to enroll approximately 235 patients with primary endpoint of OS in DGM1 (+) patients. The study is ongoing with 51 sites open in the US and China. As of 22 Jan 2019, 70 patients have been randomized. Clinical trial information: NCT03263026.

scholarly journals Phase II Study of Sorafenib in Patients With Metastatic or Recurrent Sarcomas

2009 ◽  
Vol 27 (19) ◽  
pp. 3133-3140 ◽  
Author(s):  
Robert G. Maki ◽  
David R. D'Adamo ◽  
Mary L. Keohan ◽  
Michael Saulle ◽  
Scott M. Schuetze ◽  
...  
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Study ◽  
Single Agent ◽  
Evaluation Criteria ◽  
Progression Free Survival ◽  
Median Number ◽  
Nerve Sheath Tumor ◽  
Extracellular Signal ◽  
Number Of Cycles

PurposeSince activity of sorafenib was observed in sarcoma patients in a phase I study, we performed a multicenter phase II study of daily oral sorafenib in patients with recurrent or metastatic sarcoma.Patients and MethodsWe employed a multiarm study design, each representing a sarcoma subtype with its own Simon optimal two-stage design. In each arm, 12 patients who received 0 to 1 prior lines of therapy were treated (0 to 3 for angiosarcoma and malignant peripheral-nerve sheath tumor). If at least one Response Evaluation Criteria in Solid Tumors (RECIST) was observed, 25 further patients with that sarcoma subtype were accrued.ResultsBetween October 2005 and November 2007, 145 patients were treated; 144 were eligible for toxicity and 122 for response. Median age was 55 years; female-male ratio was 1.8:1. The median number of cycles was 3. Five of 37 patients with angiosarcoma had a partial response (response rate, 14%). This was the only arm to meet the RECIST response rate primary end point. Median progression-free survival was 3.2 months; median overall survival was 14.3 months. Adverse events (typically dermatological) necessitated dose reduction for 61% of patients. Statistical modeling in this limited patient cohort indicated sorafenib toxicity was correlated inversely to patient height. There was no correlation between phosphorylated extracellular signal regulated kinase expression and response in six patients with angiosarcoma with paired pre- and post-therapy biopsies.ConclusionAs a single agent, sorafenib has activity against angiosarcoma and minimal activity against other sarcomas. Further evaluation of sorafenib in these and possibly other sarcoma subtypes appears warranted, presumably in combination with cytotoxic or kinase-specific agents.

Phase II trial assessing niraparib with or without dostarlimab (anti-PD-1) in recurrent endometrial carcinoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5574-5574
Author(s):  
Ainhoa Madariaga ◽  
Swati Garg ◽  
Nairi Tchrakian ◽  
Neesha C. Dhani ◽  
Waldo Jimenez ◽  
...  
Keyword(s):  
Endometrial Carcinoma ◽  
Phase Ii ◽  
Clinical Benefit ◽  
Phase Ii Trial ◽  
Treatment Options ◽  
Single Agent ◽  
Median Number ◽  
Toxicity Assessment ◽  
Clinical Benefit Rate ◽  
Number Of Cycles

5574 Background: Treatment options in recurrent endometrial carcinoma (EC) are limited. Endometrioid EC shows alterations in PTEN, a possible biomarker of response to PARP inhibitors (PARPi). Similarly, homologous recombination deficiency (HRd), a biomarker of response to PARPi in ovarian cancer, is associated with serous EC harbouring TP53 mutations. Preclinical EC models have shown synergy between combining a PARPi and immune checkpoint inhibitor (ICI). Methods: A pilot multi-centre, non-randomized, phase II trial enrolled patients (pts) with recurrent serous or endometrioid EC in two consecutive cohorts (NCT03016338). In the first cohort (C1) pts received niraparib 200 or 300 mg qd, based on baseline body weight and platelet count, in 4 week (w) cycles. In the second cohort (C2) niraparib was given with dostarlimab 500 mg q 3 w for 4 cycles, followed by 1000 mg q 6 w thereafter. There was no limit on prior lines of therapy. Prior ICI was not allowed in C2. Primary endpoint was clinical benefit rate (CBR; complete, partial response or stable disease ≥16w). Secondary endpoints included toxicity assessment and ORR. CT scans were performed q 8 w. Potential biomarkers were assessed in archival tissue by IHC (PTEN, p53, MMR, PDL-1 [threshold 1%]) and a NGS panel (including TP53, PTEN, POLE and other HRd genes). Tumour mutational burden-high (TMBh) was defined as top 20% mutation load. Results: In C1, 25 pts were enrolled (23 evaluable for response). Median age was 69 years old, 64% had serous EC, 72% were platinum resistant (PlatR) and median prior therapies was 2 (range 1-4). Median number of cycles was 3. The CBR was 20% (95% CI: 9-39) and median clinical benefit (CB) duration was 5.3 (1.8-7.2) months. The ORR was 1/23 (4%; 0-20). Related grade (g) ≥3 AEs ≥10% were anemia (24%), fatigue (16%) and thrombocytopenia (16%). In C2, 22 pts were enrolled (all evaluable) and two continue on-treatment. Median age was 64 years old, 46% had serous EC, 68% were PlatR and median prior therapies was 2 (1-6). Three pts had MMR deficient (MMRd) tumors (14%) and one pt a POLE mutation (5%). Median number of cycles was 3. The CBR was 31.8% (16-53) and median CB duration was 6.8 months (3.7-9.5). The ORR was 3/22 (14%; 3-35), out of the three responders one had MMRd and one a POLE mutation. Related g≥3 AEs ≥10% were anemia (27%) and neutropenia (14%). No significant correlation was detected between CB and IHC markers (PTEN, p53, MMR, PDL-1), or NGS ( PTEN, TP53, HRd TMBh) in C1 and C2. Conclusions: Niraparib as single agent for treatment in a PlatR enriched recurrent EC population showed modest activity with clinical benefit rate at 16w of 20%. The combination of niraparib and dostarlimab showed a clinical benefit rate at 16w of 31.8% in a predominantly PlatR recurrent EC. PTEN loss by IHC or NGS, and alterations in HRd genes did not correlate with clinical benefit. Clinical trial information: NCT03016338.

Updated Results from a Phase II Study of Galiximab (Anti-CD80) in Combination with Rituximab for Relapsed or Refractory, Follicular NHL.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2435-2435 ◽  
Author(s):  
Jonathan W. Friedberg ◽  
John P. Leonard ◽  
Anas Younes ◽  
David C. Fisher ◽  
Leo I. Gordon ◽  
...  
Keyword(s):  
Phase Ii ◽  
Randomized Study ◽  
Univariate Analysis ◽  
Single Agent ◽  
Costimulatory Molecule ◽  
Phase Iii ◽  
Clinical Activity ◽  
Monotherapy Group ◽  
Variable Regions ◽  
Baseline Characteristics

Abstract Galiximab is a PRIMATIZED®, anti-CD80, monoclonal antibody with human IgG1 constant regions and macaque variable regions. CD80 is an immune costimulatory molecule that is constitutively expressed on the surface of follicular lymphomas. Modest single-agent clinical activity was demonstrated in a Phase I study in relapsed or refractory, follicular NHL (ORR=11%). Preclinical data show that galiximab + rituximab may be more effective than either antibody alone. Here we report updated results from the Phase II part of a multicenter study (Study 114–21) evaluating galiximab + rituximab for relapsed or refractory, follicular NHL. Patients (pts) were administered galiximab (500 mg/m2 qwk x 4) concurrently with a standard course of rituximab (375 mg/m2 qwk x 4). Rituximab-refractory pts (no response or a response with TTP&lt;6 months) were excluded. Study objectives were to evaluate safety, PK, and efficacy. Sixty-four pts received treatment. The median follow up is 14.5 months. Mean age at study entry was 59 yrs. The majority of pts (88%) were Stage III/IV, and FLIPI risk groups were distributed as good (27%), intermediate (39%), or poor (34%). All pts had received at least 1 prior lymphoma therapy; 42% were rituximab naïve. Galiximab infusions were delivered over 1 hr and were well tolerated. No DLTs were reported. Sixty-one (95%) pts experienced study-related AEs; the most common were lymphopenia (44%), leucopenia (38%), fatigue (38%), neutropenia (23%), and chills (23%). IWRC was used to evaluate response. An ORR of 64% was demonstrated: 17% CR, 14% CRu, and 33% PR. The median PFS was 12.1 months. Univariate analysis showed no correlation between response and baseline characteristics, although there was a trend for fewer responses in pts with elevated LDH, poor FLIPI score, and Grade III follicular histology. Cmax and AUC values were dose-proportional, with a mean serum half-life of 13 to 24 days. These results were retrospectively compared with 3 historical Biogen Idec studies of follicular NHL pts treated with a standard course of rituximab monotherapy. Baseline characteristics were similar; however, there was a higher incidence of rituximab-naïve pts in the rituximab monotherapy group (77%) compared with galiximab + rituximab (42%). The toxicity profiles for the 2 groups were similar. The median PFS was longer in the galiximab + rituximab group (12.1 mo.) than in the historical rituximab monotherapy group (9.4 mo.). These results suggest that galiximab can be safely combined with a standard course of rituximab and produce promising response rates and PFS. The toxicity profile and PFS with this combination compared favorably with historical rituximab monotherapy studies. A Phase III, randomized study is planned.

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