Comparison of melphalan-prednisone-thalidomide (MP-T) to melphalan-prednisone (MP) in patients 75 years of age or older with untreated multiple myeloma (MM). Preliminary results of the randomized, double-blind, placebo controlled IFM 01–01 trial

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8001-8001 ◽  
Author(s):  
C. Hulin ◽  
J. Virion ◽  
X. Leleu ◽  
P. Rodon ◽  
B. Pegourie ◽  
...  
Keyword(s):  
Partial Response ◽  
Progression Free Survival ◽  
Data Safety Monitoring Board ◽  
Response To Treatment ◽  
Rank Test ◽  
Double Blind ◽  
Vte Prophylaxis ◽  
Preliminary Results ◽  
Intent To Treat ◽  
Therapeutic Recommendation

8001 Background: The MP-T combination has been shown to be the standard treatment in newly diagnosed MM patients (pts) aged 65 to 75 years (Facon et al; JCO 2006; 24, A1). However, no specific therapeutic recommendation exists for pts older than 75 years regarding the benefit of adding Thalidomide to MP. Methods: The IFM 01–01 trial was initiated in 04/2002. Patients > 75 years with untreated MM were randomized to receive MP (Melphalan 0.2mg/kg/d + Prednisone 2 mg/kg/d day1–4, 12 courses at 6-weeks intervals) + placebo (MP-placebo) vs MP + daily Thalidomide 100mg/d (MP-T). No anti-VTE prophylaxis was given. The primary end-point was overall survival (OS). Secondary end points were progression-free survival (PFS), response to treatment and toxicity. A first interim analysis was performed after the inclusion of 150 patients and a data safety monitoring board recommended a second analysis after the accrual of 200 patients. We here present the preliminary results of this analysis. Results: At the reference date of November 1, 2006, 232 pts were randomised. In all, 200 pts were analysed (100 per group), with 33.5% of pts >80 years (median age, 78.4 years). There were no differences between the 2 groups regarding baseline characteristics. Data were analysed on an intent-to-treat basis. After the completion of therapy the rates of partial response and very good partial response were 31% and 8% respectively with MP-placebo vs 61% and 22% respectively with MP-T. The median PFS time was 19 months (95%-CI 14.6–21.5) with MP-placebo vs 24.1 months (95%-CI 19.4–29.7) with MP-T (p=0.004 log-rank test). In the MP-T arm, 43/100 pts stopped treatment due to toxicity (10 due to neuropathy) versus 11/100 in the MP-placebo arm. Toxicity (Grade 2–4) included peripheral neuropathy (18%), somnolence (7%) and DVT (7%) with MP-T, vs 6%, 6% and 1% respectively, with MP-placebo. Final results including OS data will be presented at the meeting. Conclusion: MPT is an effective combination with acceptable toxicity in patients with MM = 75 years of age, with a significant improvement in PFS. No significant financial relationships to disclose.

Melphalan-Prednisone-Thalidomide (MP-T) Demonstrates a Significant Survival Advantage in Elderly Patients ≥75 Years with Multiple Myeloma Compared with Melphalan-Prednisone (MP) in a Randomized, Double-Blind, Placebo-Controlled Trial, IFM 01/01.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 75-75 ◽  
Author(s):  
Cyrille Hulin ◽  
Thierry Facon ◽  
Philippe Rodon ◽  
Brigitte Pegourie ◽  
Lotfi Benboubker ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Partial Response ◽  
Elderly Patients ◽  
Controlled Trial ◽  
Response To Treatment ◽  
Rank Test ◽  
Newly Diagnosed ◽  
Very Elderly ◽  
Double Blind ◽  
Vte Prophylaxis

Abstract Background: The MP-T combination has become the standard treatment for newly diagnosed MM patients (pts) aged 65 to 75 years (Facon et al; Lancet 2007 [Epub ahead of print]). However, no specific therapeutic recommendation exists for pts ≥75 years regarding the benefit of adding thalidomide to MP. Patients older than 75 years have frequently been excluded from large clinical trials, although they represent more than 20% of MM pts. Methods: The IFM 01-01 trial was initiated in 4/2002. Pts ≥75 years with untreated MM were randomized to receive MP-placebo (M [0.2mg/kg/d] + P [2 mg/kg/d day1–4]) x 12 courses every 6-weeks + placebo) or MP-T (MP + daily thalidomide [100mg/d]). No anti-VTE prophylaxis was given. The primary end-point was overall survival (OS). Secondary end points were progression-free survival (PFS), response to treatment, and toxicity. Trial enrollment was prospectively planned for 258 patients. Two interim analyses were performed after inclusion of 150 and 200 patients. The IFM board decided to stop enrollment after the second interim analysis. Results: In all, 232 pts were randomized and 3 failed to meet inclusion criteria. In all, 229 pts were analyzed (113 MP-T; 116 MP-placebo) with a median age of 78.5 years (36% ≥80years). No differences between the 2 groups for baseline characteristics were observed except for gender (p=0.03). Data were analysed on an intent-to-treat basis. The median follow-up time was 24 months. The median OS time (se) was 45.3 (1.6) months with MP-T vs 27.7 (2.1) months with MP-placebo, the benefit was significant (p=0.03 log-rank test). The median PFS time (se) was 24.1 (2) months with MP-T vs 19 (1.4) months with MP-placebo (p=0.001). Rates of at least partial response, very good partial response and complete response were 62%, 22% and 7% with MP-T vs 31%, 7% and 1% with MP-placebo, respectively (p<0.001). In the MP-T arm, 42% of pts stopped treatment due to toxicity vs 11% in the MP-placebo arm. The major reasons in the MP-T arm were peripheral neuropathy (12/48), neutropenia (7/48), and DVT (7/48). Some toxicities (Grade 2–4) were significantly increased with MP-T: peripheral neuropathy (20% vs 5%), neutropenia (23% vs 9%) depression (7% vs 2%). There were no significative differences in DVT rates for MP-T (6%) vs MP-placebo (4%) or somnolence (6% vs 3%, respectively). After relapse in the MP-placebo arm, 77% of patients received Thalidomide. Survival time after progression was similar in the 2 groups, 9.8 months after MP-placebo and 9.3 months after MP-T. Conclusion: These results confirm the superiority of MP-T over MP for prolonging OS in elderly patients with newly diagnosed MM. The toxicity was acceptable in this very elderly population ≥ 75 years. A new era of progress is opened for these very elderly patients.

FLC Assay and Multiparameter Flowcytometry Based Clonal Plasma Cell Measurement Are Independent but Complementary in Assessing the Treatment Response in Multiple Myeloma.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2969-2969
Author(s):  
Hiroki Sugihara ◽  
Kenji Tsuda ◽  
Tomotaka Ugai ◽  
Yuki Nishida ◽  
Masayuki Yamakura ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Partial Response ◽  
Plasma Cell ◽  
Cox Regression ◽  
Conflicts Of Interest ◽  
Univariate Analysis ◽  
Response To Treatment ◽  
Rank Test ◽  
Multiparameter Flow Cytometry ◽  
Prognostic Impact

Abstract Abstract 2969 Purpose: Although stringent complete response (sCR) defined by paraprotein negativity on immunofixation and serum free light chain (sFLC) ratio normalization are considered deeper responses in the IMWG criteria, recent report indicated that Multiparameter flow cytometry (MFC)-dased immunophenotypic response (IR) is a more relevant prognostic factor in MM patients. However, data on the prognostic impact of IR and sFLC ratio (sFLCκ/λ) normalization are still scarce. We investigated the prognostic impact of IR and sFLCκ/λ normalization in MM patients treated with novel agents. Patients and Methods: A total of 124 consecutive patients (M:F=68:56; median age, 71 yr) were treated by chemotherapy regimens containing at least one novel agent (thalidomide, bortezomib, lenalidomide)from April 2005 to May 2012. Treatment responses were assessed using the IMWG criteria, and the best response to treatment during the clinical course was assessed by simultaneous serum immunofixation, sFLC measurements, and MFC analysis of bone marrow (BM) plasma cells. Normalization of sFLCκ/λ was defined 2 consecutive normal sFLCκ/λ apart from at least 4 weeks. MFC-defined minimal residual disease (MRD) was evaluated by single-tube 6-color MFC, CD45-CD38 gating strategy, and combination CD19, CD56, and cytoplasmic κ-λ analysis. Clonal plasma cell (PC) negativity by MFC (MFC-negative) was defined as <10−4 neoplastic PCs in BM samples on MFC. Overall survival (OS) and progression-free survival (PFS) were analyzed by the Kaplan–Meier (K-M) method and differences between curves were calculated by two-sided log-rank test. Univariate analysis was used to assess the impacts of factors on sFLCκ/λ normalization and MFC negativity (age, Durie–Salmon stage, ISS stage, LDH, hemoglobin, serum albumin, serum creatinine, FISH at diagnosis). The Cox regression proportional hazard model (stepwise regression) was used to explore the independent effects of these variables on PFS and OS. Results: At a median follow-up of 25.8 months, 3- and 5-year OS of all patients were 61.0% and 42.4%, respectively. CR was obtained in 25% (31/124), very good partial response (VGPR) in 33.5% (41/124), partial response (PR) in 30.5% (38/124), and stable disease or less (SD) in 11% (14/124). Normal sFLCκ/λ was achieved in 81% of CR, 56% of VGPR, 13% of PR, and 0% of SD or less response of patients. K-M estimated 3- and 5-year OS were 100% in CR patients; these were significantly better than in VGPR (75.8% and 43.2%, respectively) and PR patients (63% and 26.7.%, respectively). There were no significant differences in 3- or 5-year OS between VGPR and PR patients. Normal sFLCκ/λ and MFC negativity were achieved in 25 (81%) and 18 (58%) of 31 CR patients, respectively. Among 25 CR patients with normal sFLCκ/λ (stringent CR), 15 (60%) were MFC-negative and 10 (40%) were MFC-positive; three of 6 CR patients (50%)without normal sFLCκ/λ were MFC-positive. Twenty-three of 41 VGPR patients (56%) obtained normal sFLCκ/λ, while only 5 (12%) became MFC-negative; all 5 MFC-negative patients also obtained normal sFLCκ/λ. Among 52 patients with less than PR, only 5 (9.6%) obtained normal sFLCκ/λ and none achieved MFC negativity. Patients with MFC-negative CR showed significantly better PFS than patients with MFC-positive CR (p<0.05). Although patients in stringent CR with MFC-negative showed slightly better PFS compared to patients in stringent CR with MFC-positive, difference between the curves were not significant. Within the group of VGPR, PFS and OS were significantly longer in normal sFLCκ/λ patients than abnormal sFLCκ/λ(P<0.001). Univariate analysis showed that hemoglobin 10.0 g/dl>, age >70 yr, and abnormal LDH had negative prognostic impacts on attaining normal sFLCκ/λ, but none of these factors remained significant on multivariate analysis. Cox analysis showed that sFLCκ/λ normalization was an independent prognostic factor for longer PFS and OS in patients with CR, VGPR and PR (P=0.001). Conclusions: This study confirmed that magnitude of CR and VGPR response defined by IMWG criteria was heterogeneous in terms of sFLCκ/λ normalization and MFC negativity. Although MFC and sFLC analysis frequently gave discrepant results among patients with CR and VGPR, both analyses appeared to give important complementary information for assessing the depth of CR and VGPR category. Disclosures: No relevant conflicts of interest to declare.

An international, randomized, placebo-controlled, double-blind phase III study (MONET1) of motesanib plus carboplatin/paclitaxel (C/P) in patients with advanced nonsquamous non-small cell lung cancer (NSCLC).

2011 ◽  
Vol 29 (18_suppl) ◽  
pp. LBA7512-LBA7512 ◽  
Author(s):  
G. Scagliotti ◽  
I. Vynnychenko ◽  
Y. Ichinose ◽  
K. Park ◽  
K. Kubota ◽  
...  
Keyword(s):  
Cox Model ◽  
Objective Response ◽  
Stage Iv ◽  
Progression Free Survival ◽  
High Rate ◽  
Phase Iii ◽  
Rank Test ◽  
Double Blind ◽  
Grade 3 ◽  
Nonsquamous Nsclc

LBA7512 Background: This study evaluated whether motesanib (a selective oral inhibitor of VEGFR 1, 2 and 3; PDGFR and Kit) plus C/P improved overall survival (OS) compared with placebo + C/P in patients (pts) with nonsquamous NSCLC and in a subset of pts with adenocarcinoma. Methods: Pts had stage IIIB/IV or recurrent nonsquamous NSCLC and no prior systemic therapy for advanced NSCLC. The study initially enrolled all histologies but was amended to exclude pts with squamous NSCLC owing to a high rate of hemoptysis. Pts were randomized 1:1 to receive up to six 3-wk cycles of C (AUC 6 mg/mL·min) and P (200 mg/m2) with either motesanib 125 mg QD (Arm A) or placebo QD (Arm B) orally continuously. The primary endpoint was OS; secondary endpoints included progression-free survival (PFS), adverse events (AEs), objective response rate (ORR) and association between placental growth factor (PLGF) change and OS. OS was evaluated using a stratified Cox model and 2-sided log-rank test (α=0.03 for nonsquamous pts and α=0.02 for adenocarcinoma pts). Results: 1090 pts with nonsquamous NSCLC were randomized (Arm A/B, n=541/549); 890 had adenocarcinoma (n=448/442). 61% were men; median age was 60 years (range 21–87); 83% had stage IV disease. At the time of analysis, 753 pts had died (608 pts with adenocarcinoma). Median follow-up was 10.6 mo. OS was not significantly improved in Arm A compared with Arm B (Table). In Arm A, PLGF analysis did not show an association with OS. The incidence of grade ≥3 AEs in Arms A/B was 73/59%. Grade ≥3 AEs occurring more frequently in Arm A than B included neutropenia (22/15%), diarrhea (9/1%), hypertension (7/1%) and cholecystitis (3/0%). The incidence of grade 5 AEs was 14/9% in Arms A/B. Conclusions: In pts with advanced nonsquamous NSCLC, treatment with motesanib + C/P did not significantly improve OS compared with C/P alone. [Table: see text]

Palbociclib plus cetuximab versus placebo plus cetuximab in platinum-resistant, cetuximab-naive, HPV-unrelated head and neck cancer: A double-blind randomized phase II trial (PALATINUS).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 6013-6013 ◽  
Author(s):  
Douglas Adkins ◽  
Jin-Ching Lin ◽  
Assuntina Gesualda Sacco ◽  
Jessica C. Ley ◽  
Peter Oppelt ◽  
...  
Keyword(s):  
Head And Neck ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Rank Test ◽  
Double Blind ◽  
Platinum Resistant ◽  
Randomized Phase Ii

6013 Background: Cetuximab monotherapy results in a median overall survival (OS) of approximately 6 months (mo) in platinum-resistant recurrent/metastatic head and neck squamous cell carcinoma (HNSCC). HNSCC unrelated to human papillomavirus (HPV) is driven by hyperactivation of the CDK4/6 and cyclin D1 (CD1) regulatory complex, resulting in cell cycle progression and tumor growth, suggesting that CDK4/6 inhibition can be a rational therapeutic strategy in this setting. Palbociclib (PAL) is a selective CDK4/6 inhibitor that may reverse cetuximab resistance by countering the actions of deregulated CD1. PAL plus an epidermal growth factor receptor inhibitor synergistically reduced cell viability of HPV-unrelated HNSCC cell lines. In a single-arm, multicenter trial of platinum-resistant, cetuximab-naive, HPV-unrelated HNSCC, PAL in combination with cetuximab resulted in a median OS of 9.5 mo. Methods: In a double-blind randomized phase II trial, patients (pts) with platinum-resistant, cetuximab-naïve, HPV-unrelated HNSCC were treated with cetuximab plus either PAL (arm A) or placebo (arm B). Pts were stratified by performance status (PS) and prior immunotherapy (IT). 120 pts were required for 1:1 randomization to have ≥ 80% power to detect a hazard ratio (HR) of 0.6 (corresponding to a median OS of 10 mo in arm A and 6 mo in arm B) using a 1-sided log-rank test P=0.10). Key secondary endpoints included progression-free survival (PFS), adverse events (AEs), and p16 status. Results: Pts (n=125) were randomized (arm A, 65; arm B, 60). PS and prior IT were balanced between the arms. Median (95% CI) follow-up for OS was 15.9 (15.0–19.4) mo. Median OS was 9.7 (7.3–13.9) mo in arm A and 7.8 (6.7–10.6) mo in Arm B (stratified by PS: HR=0.82 [95% CI, 0.54–1.25], P=0.18). Median PFS was 3.9 mo in arm A and 4.6 mo in arm B (stratified by PS: HR=1.00 [0.7–1.5], P=0.5). Hematologic AEs were more common in arm A. Only 11 pts (9%) received IT after being treated on the trial. Conclusions: Among pts with platinum-resistant, HPV-unrelated HNSCC, PAL plus cetuximab resulted in a trend of prolongation of median OS compared with cetuximab. Clinical trial information: NCT02499120.

ANNOUNCE: A randomized, placebo (PBO)-controlled, double-blind, phase (Ph) III trial of doxorubicin (dox) + olaratumab versus dox + PBO in patients (pts) with advanced soft tissue sarcomas (STS).

2019 ◽  
Vol 37 (18_suppl) ◽  
pp. LBA3-LBA3 ◽  
Author(s):  
William D. Tap ◽  
Andrew J. Wagner ◽  
Zsuzsanna Papai ◽  
Kristen N. Ganjoo ◽  
Chueh-Chuan Yen ◽  
...  
Keyword(s):  
Disease Control ◽  
Locally Advanced ◽  
Soft Tissue Sarcomas ◽  
Progression Free Survival ◽  
Geographic Region ◽  
Double Blind ◽  
Primary Endpoints ◽  
Prior Systemic Therapy ◽  
Intent To Treat ◽  
Ecog Ps

LBA3 Background: Dox is standard therapy in STS. In a Ph 2 trial, olaratumab (a human IgG1 antibody targeting PDGFRα) + dox improved overall survival (OS) and progression-free survival (PFS) vs dox. ANNOUNCE aimed to confirm the OS benefit in advanced STS. Methods: Adult pts with unresectable locally advanced or metastatic STS, anthracycline-naïve, and ECOG PS 0-1 were eligible. Pts were randomized 1:1 to olaratumab (20mg/kg Cycle 1, 15mg/kg subsequent cycles) or PBO on Days 1 and 8 of each 21-day cycle combined with dox (75mg/m2) on Day 1 for up to 8 cycles. After 8 cycles, pts with disease control continued olaratumab or PBO until progression or toxicity. Randomization was stratified by histology, prior systemic therapy, ECOG PS, and geographic region. Dexrazoxane use was allowed to mitigate dox-related cardiotoxicity. Primary endpoints were OS in the intent-to-treat (ITT) population and/or leiomyosarcoma (LMS) subset of the ITT population; the study was designed to be positive if either primary endpoint was met. Secondary endpoints included PFS, response/disease control rates, safety, and pharmacokinetics. Results: 509 pts were randomized: 258 in the investigational and 251 in the control arm. Baseline pt characteristics were well balanced. Dexrazoxane was received by 63.0% vs 65.1% of pts (investigational vs control arm, respectively, for all data). In the ITT population, median OS was 20.4 vs 19.8 months (m) (HR=1.05, 95% CI: 0.84-1.30; p = 0.69) and was 21.6 vs 21.9 m in LMS pts (HR=0.95, 95% CI: 0.69-1.31; p = 0.76). Median PFS was lower in the investigational arm in the ITT population (5.4 vs 6.8 m; HR=1.23, 95% CI: 1.01-1.50; p = 0.04) and in LMS pts (4.3 vs 6.9 m, HR=1.22, 95% CI: 0.92-1.63; p = 0.17). Median dox exposure was 6 vs 7 cycles. Safety was similar between arms. Olaratumab serum concentrations reached levels expected from prior trials. Additional subgroup/biomarker results will be presented. Conclusions: ANNOUNCE did not confirm that olaratumab + dox, followed by olaratumab monotherapy, improves OS over dox in pts with advanced STS. Further analyses are warranted to explore the inconsistent outcomes between the Ph 3 and Ph 2 studies. Clinical trial information: NCT02451943.

Fluorouracil, Doxorubicin, and Streptozocin in the Treatment of Patients With Locally Advanced and Metastatic Pancreatic Endocrine Carcinomas

2004 ◽  
Vol 22 (23) ◽  
pp. 4762-4771 ◽  
Author(s):  
Maria A. Kouvaraki ◽  
Jaffer A. Ajani ◽  
Paulo Hoff ◽  
Robert Wolff ◽  
Douglas B. Evans ◽  
...  
Keyword(s):  
Response Rate ◽  
Objective Response ◽  
Locally Advanced ◽  
Evaluation Criteria ◽  
Progression Free Survival ◽  
Response Duration ◽  
Response To Treatment ◽  
Rank Test ◽  
Median Response ◽  
Log Rank Test

Purpose The role of systemic chemotherapy in the management of pancreatic endocrine carcinoma (islet cell carcinoma; PEC) is an area of considerable controversy. Response rates ranging from 6% to 69% have been reported for streptozocin-based chemotherapy. We retrospectively studied 84 patients with locally advanced or metastatic PEC who had been treated with fluorouracil, doxorubicin, and streptozocin (FAS) to determine the objective response rate, duration of progression-free survival (PFS), and duration of overall survival (OS). Patients and Methods Eligible patients had histologic or cytologic confirmation of their tumor and measurable disease on computed tomography or magnetic resonance imaging scans. Response to treatment was evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors Committee. Results Sixty-one of the patients were male and 23 were female, with a median age of 54 years (range, 24 to 78 years). The response rate (RR) to FAS was 39%, with a median response duration of 9.3 months. The 2-year PFS rate was 41%, and the 2-year OS rate was 74%. The extent of liver metastatic disease correlated with a worse PFS (P = .01 by log-rank test) and a worse OS (P < .0001 by log-rank test). Analyses showed that metastatic replacement of more than 75% of the liver and prior chemotherapy were independently associated with inferior PFS. Conclusion Patients with locally advanced or metastatic PEC who are treated with FAS may have a reasonable RR, and responders may experience longer PFS and OS. The volume of metastases in the liver is the most important predictor of outcome.

A randomized, double-blind, placebo-controlled phase Ib/II study of ralimetinib, a p38 MAPK inhibitor, plus gemcitabine (G) and carboplatin (C) versus GC for women with recurrent platinum-sensitive ovarian cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5537-5537 ◽  
Author(s):  
Ignace Vergote ◽  
Florian Heitz ◽  
Paul Buderath ◽  
Matthew A. Powell ◽  
Jalid Sehouli ◽  
...  
Keyword(s):  
Treatment Phase ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Mitogen Activated Protein Kinase ◽  
Rank Test ◽  
Double Blind ◽  
Peritoneal Cancer ◽  
Platinum Sensitive ◽  
Safety Population ◽  
Grade 3

5537 Background: p38 mitogen-activated protein kinase (MAPK) regulates cytokine production in the tumor microenvironment and enables therapeutic resistance of cancer cells. Ralimetinib (R) is a selective small-molecule inhibitor of p38α and p38β MAPKs. Methods: Main inclusion criteria: ≥18 y; recurrent platinum-sensitive epithelial ovarian, fallopian tube, or primary peritoneal, cancer after first-line treatment. Phase (Ph)1b was to determine the recommended Ph2 dose (RP2D) of R administered 12-hourly (Q12H) on Days 1-10 (21-day cycle [Q21D]) in combination with gemcitabine (G: 1000 mg/m2 on Days 3 and 10) and carboplatin (C: AUC 4 on Day 3) for 6 cycles. In Ph2, patients (pts) were randomized double-blind, 1:1 to RP2D R+GC or placebo (P)+GC, for 6 cycles, followed by R 300 mg Q12H or P on Days 1-14, Q28D until disease progression. The stratified log-rank test compared progression-free survival (PFS; primary endpoint) between treatment groups in Ph2, at a 1-sided α level of 0.2. ClinicalTrials.gov, NCT01663857. Results: 118 pts received ≥1 dose of R or P (safety population); 8 in Ph1b and 110 in Ph2 (R+GC N = 58; P+GC N = 52). The RP2D for R in combination with GC was 200 mg Q12H. The study met its primary objective (median PFS: R+GC 10.3 mo vs P+GC 7.9 mo; HR = 0.773, 2-sided p = 0.246). The secondary objectives of median overall survival (R+GC 29.2 mo vs P+GC 25.1 mo; HR = 0.827, p = 0.469) or overall response rate (R+GC 46.6% vs P+GC 46.2%; p = 0.967) were not statistically significant, and 32.4% vs 25.0% of pts had normalized CA125 at the end of cycle 6. Most pts (safety population) experienced ≥1 Grade 3/4 treatment-emergent adverse event (TEAE: R+GC 63/66 [95.5%]; P+GC 48/52 [92.3%]). Decreased neutrophil count (60.6% vs 76.9%), platelet count (43.9% vs 38.5%), and white blood cell count, (30.3% vs 26.9%), anemia (22.7% vs 25.0%), and increased alanine aminotransferase (ALT) (19.7% vs 3.8%) were the Grade 3/4 TEAEs in ≥10% of pts in the R+GC and P+GC arms, respectively. Conclusions: Addition of ralimetinib to GC resulted in modest improvements in PFS. Grade 3/4 elevated ALT was more common in the ralimetinib arm. Clinical trial information: NCT01663857.

scholarly journals Clinical Relevance of Viable Circulating Tumor Cells in Patients with Metastatic Colorectal Cancer: The COLOSPOT Prospective Study

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2966
Author(s):  
Thibault Mazard ◽  
Laure Cayrefourcq ◽  
Françoise Perriard ◽  
Hélène Senellart ◽  
Benjamin Linot ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Progression Free Survival ◽  
Response To Treatment ◽  
Rank Test ◽  
Functional Assay ◽  
Predictive Values ◽  
Treatment Naïve

Background: Circulating tumor cells (CTCs) allow the real-time monitoring of tumor course and treatment response. This prospective multicenter study evaluates and compares the early predictive value of CTC enumeration with EPISPOT, a functional assay that detects only viable CTCs, and with the CellSearch® system in patients with metastatic colorectal cancer (mCRC). Methods: Treatment-naive patients with mCRC and measurable disease (RECIST criteria 1.1) received FOLFIRI–bevacizumab until progression or unacceptable toxicity. CTCs in peripheral blood were enumerated at D0, D14, D28, D42, and D56 (EPISPOT assay) and at D0 and D28 (CellSearch® system). Progression-free survival (PFS) and overall survival (OS) were assessed with the Kaplan–Meier method and log-rank test. Results: With the EPISPOT assay, at least 1 viable CTC was detected in 21% (D0), 15% (D14), 12% (D28), 10% (D42), and 12% (D56) of 155 patients. PFS and OS were shorter in patients who remained positive, with viable CTCs between D0 and D28 compared with the other patients (PFS = 7.36 vs. 9.43 months, p = 0.0161 and OS = 25.99 vs. 13.83 months, p = 0.0178). The prognostic and predictive values of ≥3 CTCs (CellSearch® system) were confirmed. Conclusion: CTC detection at D28 and the D0–D28 CTC dynamics evaluated with the EPISPOT assay were associated with outcomes and may predict response to treatment.

A Phase 2, Double-Blind, Placebo-Controlled Trial of Rituximab + Galiximab Vs Rituximab + Placebo In Advanced Follicular Non-Hodgkin's Lymphoma (NHL)

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 428-428 ◽  
Author(s):  
Isabelle Bence-Bruckler ◽  
David Macdonald ◽  
Patrick J Stiff ◽  
Byron McKinney ◽  
Katherine L. Ruffner ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Controlled Trial ◽  
Bone Marrow Involvement ◽  
Progression Free Survival ◽  
Complete Response ◽  
Rank Test ◽  
Phase 2 ◽  
Phase 3 ◽  
Double Blind

Abstract Abstract 428 Background: Galiximab is a primatized chimeric monoclonal antibody directed against CD80, an immunoregulatory protein normally expressed on antigen presenting cells and T cells, as well as in B-cell NHL, Hodgkin lymphoma, multiple myeloma, and certain leukemias. Galiximab directly mediates antibody-dependent cell-mediated cytotoxicity against tumor cells in vitro. In ex vivo assays, galiximab can act on non-malignant cells to modulate immune signaling within the tumor microenvironment. Methods: Subjects with relapsed or refractory, Grade I-IIIa, follicular NHL in relapse following treatment with at least 1 chemotherapy regimen, and who were not refractory to rituximab were randomized to rituximab (375 mg/m2) plus galiximab (500 mg/m2; R+G) or rituximab plus placebo (R+P) and treated on Days 1, 8, 15, and 22. Randomization and primary efficacy analyses were stratified by age (≤60 vs >60), rituximab exposure (rituximab naïve vs non-naïve), and baseline tumor bulk (diameter of largest lesion ≤7 cm vs >7 cm). Primary endpoint of progression-free survival (PFS) was analyzed using a stratified log-rank test. Results: This study, originally planned as a Phase 3 confirmatory study, was terminated early due to changes in standard of care and converted to a Phase 2 study. Therefore, interpretation of p-values was focused on assessing the potential of these data to support subsequent Phase 2 and Phase 3 studies. At study termination, 337 subjects were randomized (175 R+G and 162 R+P) with median follow-up of 13.8 months. Demographics and disease characteristics were well balanced across the 2 treatment groups (Table 1). The addition of galiximab to rituximab reduced the hazard for disease progression or death by 26% (hazard ratio [HR] = 0.738; 95% confidence interval [CI] [0.543, 1.002]; p = 0.050) compared to the R+P group. Kaplan-Meier median PFS was 12.0 months (95% CI [9.0, 14.7]) for R+G and 9.0 months (95% CI [8.9, 10.5]) for R+P. Overall response rate was 51% for R+G vs 48% for R+P (p = 0.455) and complete response was 20% for R+G and 15% for R+P (p = 0.251). Consistency in treatment effect was seen across patient subgroups (Figure 1). A trend toward a larger PFS effect was observed in patients who were rituximab-naïve, had bulky tumor (largest lesion >7 cm), had lactate dehydrogenase (LDH) >1 × upper limit of normal, or had bone marrow involvement at study entry. There were 10 deaths in R+G vs 17 deaths in R+P; HR = 0.549 based on a stratified log-rank analysis (95% CI [0.248, 1.217]; p = 0.135). No substantial difference was observed between groups for Grade 3/4 adverse events (AEs) or serious AEs, and there were no treatment-related deaths in either group. Incidence of AEs was ≥3% higher in the R+G vs R+P group for the following: pyrexia (18% vs 11%), headache (13% vs 7%), cough (10% vs 6%), upper respiratory infection (8% vs 4%), insomnia (8% vs 4%), neutropenia (6% vs 3%), muscle spasms (5% vs <1%), and oropharyngeal pain (4% vs 1%). Anti-galiximab antibodies were not detected in 169 subjects treated with galiximab who were tested while on study. Conclusions: Galiximab in combination with rituximab demonstrated a trend toward an improved PFS compared with rituximab alone and was well tolerated in subjects with relapsed or refractory follicular NHL. Disclosure: McKinney: Biogen Idec: Employment. Ruffner:Biogen Idec: Employment. Wilson:Biogen Idec: Employment. Whiteley:Biogen Idec: Employment.

Results of a Phase III, Randomized, Placebo-Controlled Study of Sorafenib in Combination With Carboplatin and Paclitaxel As Second-Line Treatment in Patients With Unresectable Stage III or Stage IV Melanoma

2009 ◽  
Vol 27 (17) ◽  
pp. 2823-2830 ◽  
Author(s):  
Axel Hauschild ◽  
Sanjiv S. Agarwala ◽  
Uwe Trefzer ◽  
David Hogg ◽  
Caroline Robert ◽  
...  
Keyword(s):  
Stage Iv ◽  
Progression Free Survival ◽  
Advanced Melanoma ◽  
Phase Iii ◽  
Controlled Study ◽  
Rank Test ◽  
Line Treatment ◽  
Second Line ◽  
Double Blind ◽  
End Points

PurposeThis phase III, randomized, double-blind, placebo-controlled study was conducted to evaluate the efficacy and safety of sorafenib with carboplatin and paclitaxel (CP) in patients with advanced melanoma who had progressed on a dacarbazine- or temozolomide-containing regimen.Patients and MethodsA total of 270 patients were randomly assigned to receive intravenous paclitaxel 225 mg/m2plus intravenous carboplatin at area under curve 6 (AUC 6) on day 1 of a 21-day cycle followed by either placebo (n = 135) or oral sorafenib 400 mg (n = 135) twice daily on days 2 to 19. The primary efficacy end point was progression-free survival (PFS); secondary and tertiary end points included overall survival and incidence of best response, respectively.ResultsThe median PFS was 17.9 weeks for the placebo plus CP arm and 17.4 weeks for the sorafenib plus CP arm (hazard ratio, 0.91; 99% CI, 0.63 to 1.31; two-sided log-rank test P = .49). Response rate was 11% with placebo versus 12% with sorafenib. Dermatologic events, grade 3 thrombocytopenia, diarrhea, and fatigue were more common in patients treated with sorafenib plus CP versus placebo plus CP.ConclusionIn this study, the addition of sorafenib to CP did not improve any of the end points over placebo plus CP and cannot be recommended in the second-line setting for patients with advanced melanoma. Both regimens had clinically acceptable toxicity profiles with no unexpected adverse events. A trial of similar design for the first-line treatment of patients with advanced melanoma (intergroup trial E2603) is currently ongoing.

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