Phase I/II study of percutaneous vertebroplasty (PVP) for painful malignant vertebral compression fracture(PMVCF): JIVROSG- 0202

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 9118-9118
Author(s):  
Y. Arai ◽  
K. Kobayashi ◽  
Y. Takeuchi ◽  
Y. Nakajima ◽  
Y. Shioyama ◽  
...  
Keyword(s):  
Phase I ◽  
Treatment Modality ◽  
Response Rate ◽  
Bone Biopsy ◽  
Performance Status ◽  
Compression Fracture ◽  
Phase Iii ◽  
Increase Response Rate ◽  
Ecog Performance Status ◽  
Safety And Efficacy

9118 Backgrounds: This multi-center prospective study was conducted to evaluate the safety and efficacy of PVP, a new treatment modality for PMVCF, using techniques of interventional radiology. Methods: Enrolled patients (pts) had PMVCF by primary or metastatic tumor; restricted activities by PMVCF; tumor not exposed into spinal canal; adequate hematologic, hepatic, renal and cardiac functions; 0–3 ECOG performance status (PS); estimated prognosis over 4 weeks; and written consent. In phase I, 9 pts were enrolled; in phase II, 24 pts. Safety and efficacy were evaluated by NCI-CTC Ver. 2 and Visual Analogue Scale (VAS) at week 1 after PVP, respectively. By VAS score decreases, efficacy was classified into significantly effective (SE: =5 or reached 0–2), moderately effective (ME: 2–4), or not effective (NE: <2 or increase). Response rate was the ratio of pts with SE or ME in total pts. PVP was performed by insertion of 14–16 G bone biopsy needle into fractured vertebral body (FVB) using fluoroscopy or CT guidance, injection of bone cement (BC) under real time imaging observation, and discontinuation of BC injection at its distribution to adequate area of FVB or into extra bone space. Results: Procedures were completed in all 33 patients with 42 PMVCF. PS of pts was 0 in 1, 1 in 7, 2 in 12 and 3 in 13. In 30 days after PVP, 2 patients died of primary disease progression, but no major adverse reaction (>Grade 2) was observed. Response rate was 73% (56–85% in 95% CI) (61% (n=20) with SE; 12% (n=4) with ME; 27% (n=9) with NE), and increased to 83% at week 4. Median to PVP effect was 1 day (mean: 2.4). Median pain controlled survival was 73 days. Conclusion: For PMVCF, PVP is a safe and effective treatment modality with immediate responses. A phase III trial comparing PVP and standard radiation therapy is planned to evaluate PVP as the front line treatment. No significant financial relationships to disclose.

Hematologic Response To Oral Azacitidine (CC-486) In Subjects With WHO-Defined RAEB-1 Or RAEB-2 Myelodysplastic Syndromes (MDS)

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1554-1554 ◽  
Author(s):  
Guillermo Garcia -Manero ◽  
Michael Savona ◽  
Steven D. Gore ◽  
Christopher R. Cogle ◽  
Paul Conkling ◽  
...  
Keyword(s):  
Phase I ◽  
Lower Risk ◽  
Research Funding ◽  
Performance Status ◽  
Phase Iii ◽  
Cell Transplant ◽  
Ecog Performance Status ◽  
Overall Response ◽  
Hematologic Response ◽  
Oncology Research

Abstract Background Subcutaneous (SC) azacitidine prolongs overall survival in subjects with higher-risk MDS (Fenaux, JCO, 2009). Previous Phase I and II studies have shown extended oral azacitidine dosing schedules to be safe and effective in subjects with IPSS-defined lower-risk MDS (Garcia-Manero et al, ASH 2010 and ASH 2012). Objective To assess the efficacy and safety of extended oral azacitidine dosing schedules in subjects with WHO-defined RAEB-1 or RAEB-2 MDS. Methods The subset of subjects with WHO-defined RAEB-1 or RAEB-2 MDS from two ongoing Phase I/II studies was included in this ad hoc analysis. Subjects received oral azacitidine 300mg QD or 200mg BID for 14 or 21 days of repeated 28-day cycles. For purposes of this analysis, subject data were analyzed collectively. Hematologic responses were defined by International Working Group (IWG) 2006 criteria. Overall Response was calculated as any response of complete or partial remission (CR or PR), RBC or platelet transfusion independence (TI), and/or any hematologic improvement (HI). Marrow complete remission (mCR) was not included in Overall Response. Serious treatment-emergent adverse events (STEAEs) that occurred in 2 or more subjects are reported. Results Of 23 subjects in all, 20 received 300mg QD oral azacitidine x 14 or 21 days/28-day cycle and 3 received oral azacitidine 200mg BID x 14 days/28-day cycle. Subjects had median age of 71 (range: 36 - 90) years and were predominantly male (61%). Fourteen subjects (61%) had a diagnosis of RAEB-1 and 9 (39%) had RAEB-2, median time from diagnosis was 2.1 (0.1 - 33.2) months, and ECOG performance status scores were 0 (n=4, 17%), 1 (n=15, 65%), or 2 (n=4, 17%). Five subjects had received prior MDS treatments (azacitidine injection; erythropoiesis stimulating agent [ESA]; thalidomide; azacitidine injection and decitabine; G-CSF, anti-thymocyte globulin, methylprednisolone, cyclosporine, and ESA). Median number of oral azacitidine treatment cycles was 3 (1 - 29). Overall Response was achieved by 11/22 subjects (50%) (Table). Four subjects achieved mCR only and are not included in the Overall Response category. RBC TI was achieved by 5/12 subjects (42%) and platelet TI was achieved by 2/5 subjects (40%). Two subjects were able to consolidate remission and proceed to allogeneic stem cell transplant and 1 subject progressed to AML on-study. Oral azacitidine was generally well tolerated. Three subjects discontinued treatment due to an AE. STEAEs were consistent with the known safety profile of SC azacitidine. Of 8 subjects who had an STEAE of febrile neutropenia, pneumonia, and/or septic shock, 3 were severely neutropenic (ANC <0.5 x 109/L) at baseline. Other STEAEs were diarrhea, nausea, and vomiting (n=2 subjects each). Conclusions This analysis in subjects with RAEB-1 and RAEB-2 is the first to assess extended oral azacitidine dosing schedules in higher-risk MDS. One-half of treated subjects achieved a hematologic response to oral azacitidine, which is easy to administer and was generally well-tolerated. Two Phase III studies of extended oral azacitidine dosing (in lower-risk MDS and as maintenance therapy in older patients with AML) are ongoing. Results of these large studies will better elucidate the use of extended oral azacitidine dosing schedules in treating hematologic malignancies. Disclosures: Gore: Celgene Corporation: Consultancy. Cogle:Celgene Corporation: Honoraria, Research Funding. Conkling:US Oncology: Research Funding. Beach:Celgene Corporation: Employment. Hetzer:Celgene Corporation: Employment. Dong:Celgene Corporation: Employment. Skikne:Celgene Corporation: Employment.

Randomized phase III study of irinotecan and 5-FU/FA with or without cetuximab in the first-line treatment of patients with metastatic colorectal cancer (mCRC): The CRYSTAL trial

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4000-4000 ◽  
Author(s):  
E. Van Cutsem ◽  
M. Nowacki ◽  
I. Lang ◽  
S. Cascinu ◽  
I. Shchepotin ◽  
...  
Keyword(s):  
Response Rate ◽  
Performance Status ◽  
Phase Iii ◽  
Line Treatment ◽  
First Line ◽  
Ecog Performance Status ◽  
Skin Reactions ◽  
Group A ◽  
Group B ◽  
First Line Treatment

4000 Background: Cetuximab in combination with irinotecan-based regimens has proven activity in previously-treated patients (pts) with mCRC. The present trial investigated the effectiveness of cetuximab in combination with standard FOLFIRI compared with FOLFIRI alone in the first-line treatment of pts with epidermal growth factor receptor (EGFR)-expressing mCRC. Methods: Pts were randomized 1:1 to receive either cetuximab (400 mg/m2 initial dose then 250 mg/m2/week [w]) plus FOLFIRI q 2 w (irinotecan 180 mg/m2, FA 400 mg/m2, 5-FU bolus 400 mg/m2, 5-FU infusion 2,400 mg/m2 over 46 hours) (Group A) or FOLFIRI alone (Group B). The primary endpoint was progression-free survival (PFS), with secondary endpoints of overall survival (OS), response rate (RR), disease control rate and safety. 633 events were required to statistically differentiate PFS between groups with 80% power. Results: Between August 2004 and October 2005, 1,217 pts were randomized, 608 to Group A and 609 to Group B (60% male, median age 61 [19–84], ECOG performance status: 0=54%; 1=43.5%; 2=3.5%). Median PFS was significantly longer for Group A compared to Group B (8,9 months [8 - 9,5] for Group A vs. 8 months [7.6 - 9] for Group B, p=0.036). Response Rate was also significantly increased by cetuximab (46.9% vs. 38.7%, p=0.005). Treatment was generally well tolerated with neutropenia (26.7% Group A, 23.3% Group B), diarrhea (15.2% and 10.5% respectively) and skin reactions (18.7% and 0.2% respectively) being the most common grade 3/4 adverse events. Conclusions: Cetuximab in combination with FOLFIRI significantly increases response rate and significantly prolongs PFS in the first-line treatment of pts with mCRC, reducing the relative risk of progression by approximately 15%. Treatment-related side effects of cetuximab in combination with FOLFIRI were as expected, with diarrhea being moderately and skin reactions significantly more frequent as compared to FOLFIRI alone. [Table: see text]

FOLFOXIRI plus bevacizumab (bev) versus FOLFIRI plus bev as first-line treatment of metastatic colorectal cancer (mCRC): Updated survival results of the phase III TRIBE trial by the GONO group.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 657-657 ◽  
Author(s):  
Chiara Cremolini ◽  
Fotios Loupakis ◽  
Gianluca Masi ◽  
Vittorina Zagonel ◽  
Francesca Bergamo ◽  
...  
Keyword(s):  
Treatment Effect ◽  
Primary Tumor ◽  
Response Rate ◽  
Performance Status ◽  
Survival Rates ◽  
Phase Iii ◽  
First Line ◽  
Ecog Performance Status ◽  
Term Survival

657 Background: The phase III TRIBE trial met its primary endpoint, by demonstrating that first-line FOLFOXIRI plus bev significantly prolongs PFS, as compared to FOLFIRI plus bev. Also RECIST response rate, early response rate and deepness of response were significantly increased. At the first statistical analysis, with a median follow-up of 32.2 months, OS results were considered preliminary. Methods: Between July 2008 and May 2011, 508 patients were randomized to either FOLFIRI plus bev (arm A, n=256) or FOLFOXIRI plus bev (arm B, n=252). Both treatments were administered for a maximum of 12 cycles followed by 5FU/bev until progression. Results: At a median follow-up of 48.1 months, 374 deaths were recorded (Arm A=200 vs. Arm B=174). Median OS for Arm B vs. Arm A was 29.8 vs. 25.8 months (HR=0.80, 95% CI, 0.65-0.98, p=0.030). Long-term survival rates are reported in Table 1. Treatment effect was consistent across all analyzed subgroups. Among clinical variables, ECOG performance status of 1 or 2, right-sided primary tumor, synchronous metastases, disease not confined to the liver, unresected primary tumor, high Kohne score negatively affected prognosis at univariate analyses. At an exploratory model accounting for these variables, adjusted HR for treatment effect on OS was 0.77 (95% CI, 0.61-0.96, p=0.020). Conclusions: FOLFOXIRI plus bev improves survival of mCRC patients, as compared to FOLFIRI plus bev. The estimated 5-years OS rate of patients treated with FOLFOXIRI plus bev was equal to 24.9%, with an absolute benefit of 12.5% compared to controls. FOLFOXIRI plus bev represents a valuable option for the upfront treatment of mCRC. Clinical trial information: NCT00719797. [Table: see text]

Comparative trial of BBR 2778 (pixantrone) + rituximab vs single agent rituximab in the treatment of relapsed/refractory indolent non-Hodgkin’s lymphoma (NHL)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7578-7578 ◽  
Author(s):  
A. Santoro ◽  
J. Voglova ◽  
N. Gabrail ◽  
T. Ciuleanu ◽  
M. Liberati ◽  
...  
Keyword(s):  
Adverse Events ◽  
Response Rate ◽  
International Workshop ◽  
Performance Status ◽  
Single Agent ◽  
Phase Iii ◽  
Time To Progression ◽  
Open Label ◽  
Ecog Performance Status ◽  
Serious Adverse Events

7578 Background: BBR 2778 is a novel aza-anthracenedione that shows structural similarities to the anthracyclines, demonstrates single agent activity in patients with NHL, and does not exhibit cardiotoxic effects in animal models. This phase III open-label study was designed to compare the efficacy and tolerability of combination rituximab and BBR 2778, with that of single agent rituximab, in patients (pts) with relapsed or refractory indolent NHL. Methods: Pts were randomly assigned to receive both rituximab and BBR 2778 (experimental arm), or rituximab alone (control arm). In the experimental arm, pts received 375 mg/m2 rituximab IV on days 1 and 8 of cycles 1 and 2 only, and 90 mg/m2 BBR 2778 IV on days 2 and 8 of cycle 1, and on days 1 and 8 of all subsequent cycles. Pts could receive six 21-day cycles of BBR 2778. In the control arm, pts received 375 mg/m2 rituximab IV on days 1, 8 and 15 of cycle 1 and day 1 of cycle 2 only. Disease response was assessed every other cycle according to International Workshop to Standardize Response Criteria for NHL. Toxicities were assessed throughout the study using NCI-CTC criteria. Study was closed early due to poor enrollment. Results: 38 pts (20 experimental, 18 control) were enrolled. Mean age was 66 and 59 years in the experimental and control arm, respectively. Most patients were males and most had ECOG performance status 0 or 1. Efficacy is summarized in the table. Response rate (75 vs 33%) and time to progression (13.2 vs 8.1 months) were better in the BBR 2778 arm. Only pts in the experimental arm had study drug related serious adverse events (2 febrile neutropenia, 1 pneumonia, 1 neutropenia) and adverse events resulting in withdrawal (6 vs 0). Conclusions: Combination of BBR 2778 and rituximab is superior to rituximab alone with regard to time to progression and overall response rate. BBR 2778 combined with rituximab appeared to be a generally well tolerated regimen in patients with relapsed/refractory indolent NHL. [Table: see text] [Table: see text]

scholarly journals Phase I/II trial of dose-reduced capecitabine in elderly patients with advanced colorectal cancer

2017 ◽  
Vol 24 (4) ◽  
pp. 261 ◽  
Author(s):  
M.D. Vincent ◽  
D. Breader ◽  
M.C. Cripps ◽  
D.J. Jonker ◽  
P. Klimo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Phase I ◽  
Advanced Colorectal Cancer ◽  
Response Rate ◽  
Performance Status ◽  
Objective Response ◽  
Eastern Cooperative Oncology Group ◽  
Survival Duration ◽  
Ecog Performance Status ◽  
Pelvic Radiation

BackgroundCombination chemotherapy is associated with improved outcomes in trials of selected fit patients with advanced colorectal cancer (acrc). For older or less-fit patients, combination chemotherapy is associated with greater toxicity and less benefit. Capecitabine monotherapy is a reasonable option for those patients, but the optimal dose remains controversial.MethodsA multicentre phase i/ii trial of reduced-dose capecitabine (2000 mg/m2, days 1–14 every 21 days) was conducted in 221 patients representing one or more of the following subsets: age greater than 65 years (n = 167), Eastern Cooperative Oncology Group (ecog) performance status of 1 or greater (n = 139), elevated lactate dehydrogenase (ldh) (n = 105), or prior pelvic radiation (n = 54). Based on phase i results, patients with prior pelvic radiation received capecitabine 750 mg/m2 twice daily. The goal was to ascertain efficacy in a design that was unlikely to cause high levels of toxicity.Results Median age in the patient cohort was 72 years. A median of 5 and a mean of 8 capecitabine cycles were given (range: 0–50 cycles). Grade 3 or 4 toxicity occurred in 25% of patients during the first 3 cycles (8.1% hand–foot syndrome, 7.7% diarrhea). The response rate was 13.6%, with a 69.7% disease control rate. Median progression-free survival (pfs) was 5.6 months. Post progression, 56 patients received further capecitabine monotherapy (median of 4 additional cycles). Median overall survival duration for the patients was 14.3 months. Median survival was significantly higher for those who, at baseline, had an ecog performance status of 0 (compared with 1 or more) and normal ldh (compared with elevated ldh).Conclusions Toxicity is less with dose-reduced capecitabine than with historical full-dose capecitabine, with only a small trade-off in efficacy, seen as a lower objective response rate. The improved tolerability could lead to an increased number of cycles of therapy, and pfs appears to be consistently higher at the lower dose. Those observations should, in the absence of a head-to-head clinical trial, be viewed as compelling evidence that 1000 mg/m2, or even 750 mg/m2, twice daily is an appropriate dose in elderly or frail patients with acrc.

Phase I/II study of GM-CSF gene-transduced allogeneic prostate cancer cellular immunotherapy (GVAX IT) in advanced prostate cancer patients made lymphopenic by chemotherapy and infused with autologous peripheral blood mononuclear cells (MC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14635-14635 ◽  
Author(s):  
B. D. Curti ◽  
I. Assman ◽  
T. Moudgil ◽  
T. Ratzow ◽  
D. Haley ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Phase I ◽  
Mononuclear Cells ◽  
Performance Status ◽  
Study Groups ◽  
Phase Iii ◽  
Cellular Immunotherapy ◽  
Ecog Performance Status ◽  
Peripheral Blood Mononuclear ◽  
Pre Treatment

14635 Background: GVAX IT has been tested in phase I/ II and is currently being tested in phase III clinical trials of patients (pts) with androgen-independent prostate carcinoma (AIPC). Immunological and PSA responses have been described in men receiving GVAX IT. Preclinical studies have shown that antitumor immune responses induced by GVAX IT could be augmented further by making animals lymphopenic and reconstituting with lymphocytes prior to vaccination. A clinical trial was designed to study the effects of lymphopenic reconstitution in pts with AIPC. Methods: All pts had MC collection by leukapheresis pre-treatment. Study groups were as follows: Arm A - GVAX IT given every two weeks for 6 months; Arm B - Cyclophosphamide (350 mg/m2 IV on days 1–3), MC infusion on day 6, GVAX IT on day 7, then every 2 weeks for 6 months; Arm C - Cyclophosphamide (350 mg/m2 IV on days 1–3) and fludarabine (20 mg/m2 IV on days 1–3), MC infusion on day 6, GVAX IT on day 7, then every 2 weeks for 6 months. Results: Seven pts have been treated thus far and completed at least 2 GVAX IT treatments. Pts had ECOG performance status ≤ 1, castrate testosterone levels, ≤ 1 prior chemotherapy regimen and measurable or evaluable metastatic AIPC. Lymphopenia was induced in all pts enrolled in Arms B and C, with recovery of total granulocytes and lymphocytes within 4 weeks following treatment. Monitoring of humoral and cellular immunological responses is underway and shall be presented. Conclusions: GVAX IT and lymphopenic reconstitution is feasible in men with AIPC. Analysis of clinical and immune response is ongoing. Supported by DAMD grant PC020094 and generous support of Mr. Tom Denhart, the Chiles Foundation and the Murdock Trust. [Table: see text]

Impact of age on safety and efficacy of first-line FOLFOXIRI/bevacizumab in mCRC: A pooled analysis of TRIBE and TRIBE2 studies.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 3536-3536
Author(s):  
Federica Marmorino ◽  
Daniele Rossini ◽  
Giuseppe Aprile ◽  
Mariaelena Casagrande ◽  
Sara Lonardi ◽  
...  
Keyword(s):  
Febrile Neutropenia ◽  
Performance Status ◽  
Primary Prophylaxis ◽  
Pooled Analysis ◽  
Relative Increase ◽  
Phase Iii ◽  
First Line ◽  
Ecog Performance Status ◽  
Safety And Efficacy ◽  
Ecog Ps

3536 Background: FOLFOXIRI/bevacizumab is a valuable upfront option in mCRC based on results of phase III TRIBE and TRIBE2 studies: 1187 pts aged 18–70 years with ECOG performance status (PS) ≤ 2 or between 71–75 years with an ECOG PS of 0 were randomized to receive first-line FOLFOXIRI/bevacizumab or a doublet (FOLFIRI in TRIBE and mFOLFOX6 in TRIBE2)/bevacizumab. Here, we aimed at assessing the effect of the intensification of the upfront chemotherapy (triplet versus doublet) in terms of safety and efficacy in pts aged < 70 versus 70-75. Methods: Subgroup analyses for ORR, PFS, G3/4 overall adverse events (AEs), chemo-related and bevacizumab-related AEs were performed according to baseline age. Results: 182 (15%) out of 1187 pts were 70-75 years old (97 in the FOLFOXIRI/bevacizumab and 85 in the doublets/bevacizumab arms). The benefit provided by the intensification of the upfront chemotherapy was independent of the age subgroup in terms of both ORR (p for interaction = 0.684) and PFS (p for interaction = 0.634). The risk of overall and chemo-related G3/4 AEs was increased with the triplet independently of age (p for interaction = 0.736 and 0.790), while no difference in bevacizumab-related AEs was observed in both subgroups (p for interaction = 0.566). In the overall population, as compared to younger pts, those aged 70-75 were more susceptible to overall G3/4 AEs (70% vs 57%, p = 0.001). In the FOLFOXIRI/bevacizumab arm a higher incidence of G3/4 diarrhea (27% vs 17%, p = 0.016) and febrile neutropenia (16% vs 6% p = 0.001) and a lower incidence of all grade nausea (51% vs 65%, p = 0.009) and vomiting (26% vs 44% p = 0.001) were reported among elderly pts. Conclusions: The activity and efficacy of FOLFOXIRI/bevacizumab are confirmed among selected pts between 70 and 75 years old, with a relative increase in the risk of chemo-related AEs similar to that of younger pts. However, elderly pts are more susceptible to experience AEs independently of the treatment arm. Considering the increased incidence of febrile neutropenia and diarrhea with FOLFOXIRI/bevacizumab, the use of G-CSF as primary prophylaxis or an initial dose reduction of irinotecan and 5-fluorouracil might be considered in this population.

A Phase I Study of OMN54 (Aneustat™) in Patients with Advanced Malignancies

2020 ◽  
Vol 7 (2) ◽  
pp. 125-132
Author(s):  
Karen A. Gelmon ◽  
Christian Kollmannsberger ◽  
Stephen Chia ◽  
Anna V. Tinker ◽  
Teresa Mitchell ◽  
...  
Keyword(s):  
Phase I ◽  
Salvia Miltiorrhiza ◽  
Performance Status ◽  
Parent Drug ◽  
Maximum Tolerated Dose ◽  
Ecog Performance Status ◽  
Advanced Malignancies ◽  
Gi Toxicity ◽  
Adequate Organ Function ◽  
Recommended Phase Ii Dose

Background/Objective: With the increasing interest in natural products, a phase I openlabel study of OMN54 (Aneustat™) in patients with advanced malignancies was initiated to determine toxicity, maximum tolerated dose (MTD), dose limiting toxicities (DLT), and pharmacokinetics (PK). OMN54 is a multitargeted agent, combining three Chinese botanicals; Ganoderma lucidium, Salvia miltiorrhiza and Scutellaria barbata. Methods: Eligible patients (pts) were >18 years of age with advanced solid tumors, able to swallow oral capsules, ECOG performance status < 2, measurable disease as defined by RECIST 1.1 and adequate organ function. Results: Twenty-two patients were enrolled in 6 dose levels, 2 with daily dosing and 4 with twicedaily dosing ranging from 1 to 5 grams daily. All were evaluated for toxicity and 20 for response. No treatment-related dose-limiting toxicities (DLTs) were reported and the recommended phase II dose (RP2D) was determined to be 2.5 g twice daily. Seven adverse events in 5 patients were reported as possibly drug-related; 6 were GI toxicity and 1 was a skin disorder. All were grade 1 except one grade 2 vomiting. No RECIST responses were seen. Six pts were treated with > 2 cycles; one for 8 cycles. Four patients had reductions in TGF –β and EGF, exploratory biomarkers possibly suggestive of a drug effect. Plasma half-lives of 1 -2 hours were noted for all parent drug chemical markers with no accumulation over time. Conclusion: OMN54 was well tolerated, with no DLTs observed. Further studies at the RP2D will assess the biological activity.

Safety and efficacy of apatinib as third or later line treatment for advanced gastric cancer or gastroesophageal junction adenocarcinoma: A post-marketing phase IV study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16034-e16034
Author(s):  
Jin Li ◽  
Shukui Qin ◽  
Lu Wen ◽  
Junsheng Wang ◽  
Wenying Deng ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Performance Status ◽  
Gastroesophageal Junction ◽  
Line Treatment ◽  
Ecog Performance Status ◽  
Safety And Efficacy ◽  
Gastroesophageal Junction Adenocarcinoma ◽  
Grade 3 ◽  
Phase Iv

e16034 Background: Apatinib, a small molecule multi-target tyrosine kinase inhibitor with high selectivity for VEGFR-2, has been approved for the treatment of advanced gastric cancer or gastroesophageal adenocarcinoma in China by significantly improving progression-free survival (PFS) and overall survival (OS). Here, we report safety and efficacy data from an open-label, single-arm, multicenter, phase IV trial of apatinib as a third-line or later line treatment for advanced gastric cancer. Methods: Eligible patients had histologically or cytologically confirmed advanced gastric cancer or gastroesophageal junction adenocarcinoma; and an Eastern Cooperative Oncology Group (ECOG) performance status of 0–2; and adequate haematological and hepatic function; and failure of at least two lines of chemotherapy. Patients received oral apatinib until disease progression, death or unacceptable toxicity. The primary endpoint was safety, and secondary endpoints included PFS and OS. Results: The intention-to-treat population (ITT) included 2004 patients. At baseline, the median age was 59 (range, 19-85) years, ECOG performance status of 0/1/2 (%) was 15.4/68.8/15.1, and stage III/IV was 3.5/96.4; 98.8% had metastases, and among which metastatic foci≤2/ > 2 was 64.5/34.2 (%), respectively. 89.6% of the patients were given apatinib 500mg as the initial does and the median treatment duration was 56 days. After a median follow-up of 126.5 days, adverse events (AEs) occurred in 95.1% of the patients and 70.3% were grade ≥3. 87.9% of the patients experienced treatment-related AEs (TRAEs), of which 51% had grade ≥3, 12.3% and 16.8% reduced dose and discontinued the treatment, respectively. 57 (2.9%) TRAEs-related deaths were reported, mainly because of gastrointestinal bleeding (16 cases), upper gastrointestinal haemorrhage (7), cerebral haemorrhage (2), and gastric perforation (1). The incidence of TRAEs of special interest was 74.3%; 38.1% of patients developed grade≥3, mainly including hypertension (26.3%), bleeding (5.1%), proteinuria (4.5%), and hand-foot syndrome (3.1%). In an ITT population, median PFS was 2.7 months (95%CI 2.23-2.79) and median OS was 5.8 months (95% CI 5.42-6.11). Conclusions: This study confirms that apatinib has a well-established and manageable safety profile and survival benefit as third or later line therapy for patients with advanced gastric cancer or gastroesophageal junction adenocarcinoma. Clinical trial information: NCT02426034.

scholarly journals 418 Phase 1b/2 KEYNOTE-365 cohort I: platinum-containing chemotherapy alone or in combination with pembrolizumab for treatment-emergent neuroendocrine prostate carcinoma

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A448-A448
Author(s):  
Johann De Bono ◽  
Neal Shore ◽  
Gero Kramer ◽  
Anthony Joshua ◽  
Xin Tong Li ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostate Carcinoma ◽  
Response Rate ◽  
Performance Status ◽  
Ecog Performance Status ◽  
End Points ◽  
Status Score ◽  
Modified Recist ◽  
Phase 1B ◽  
Performance Status Score

BackgroundTreatment-emergent neuroendocrine prostate carcinoma (t-NE) can occur de novo or after diagnosis of prostate adenocarcinoma. Treatment often includes platinum-containing chemotherapy because of t-NE’s histologic similarity to small cell lung cancer. The PD-1 inhibitor pembrolizumab has shown promising efficacy and acceptable safety when combined with olaparib, docetaxel, or enzalutamide for treatment of metastatic castration-resistant prostate cancer (mCRPC) in the multicohort phase 1b/2 KEYNOTE-365 study (NCT02861573). Cohort I will be used to compare platinum-containing chemotherapy alone with chemotherapy + pembrolizumab as treatment for t-NE.MethodsPatients who have t-NE (≥1% neuroendocrine cells in a recent biopsy specimen confirmed by central histology review); experienced progression within 6 months of starting a next-generation hormonal agent (NHA) for mCRPC or hormone-sensitive prostate cancer and experienced progression within 6 cycles of docetaxel treatment for mCRPC; and have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 are eligible. Prior therapy with ≤2 NHAs and 1 other chemotherapy for mCRPC is permitted. Patients will be randomly assigned 1:1 to receive pembrolizumab 200 mg IV on day 1 of each cycle every 3 weeks + carboplatin AUC of 5 IV on day 1 + etoposide 100 mg/m2 IV on days 1, 2, and 3 of each 21-day cycle for 4 cycles (arm 1) or the same chemotherapy regimen without pembrolizumab (arm 2); in each arm 40–100 patients will be enrolled. Pembrolizumab treatment will continue up to 2 years until disease progression, unacceptable toxicity, or withdrawal of consent. Patients will be stratified by ECOG performance status score (0 or 1). Computed tomography or magnetic resonance imaging will be performed every 9 weeks through week 54 and every 12 weeks thereafter. Primary end points are safety and tolerability, prostate-specific antigen (PSA) response rate, and objective response rate (ORR) per RECIST v1.1 by blinded independent central review (BICR). Secondary end points are time to PSA progression; ORR and radiographic progression-free survival (PFS) per PCWG3-modified RECIST v1.1 by BICR; duration of response and disease control rate per RECIST v1.1 by BICR and PCWG3-modified RECIST v1.1 by BICR; and overall survival. End points will be summarized for each arm without formal hypothesis testing.AcknowledgementsMedical writing and/or editorial assistance was provided by Matthew Grzywacz, PhD, of ApotheCom (Yardley, PA, USA). This assistance was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Funding for this research was provided by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.Trial RegistrationClinicaltrials.gov, NCT02861573Ethics ApprovalThe study and the protocol were approved by the Institutional Review Board or ethics committee at each site.

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