Statistical modeling of CALGB 80405 (Alliance) to identify influential factors in metastatic colorectal cancer (CRC) dependent on primary (1o) tumor side.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 3528-3528 ◽  
Author(s):  
Leon Furchtgott ◽  
David Swanson ◽  
Boris Hayete ◽  
Iya Khalil ◽  
Diane Wuest ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Protein Level ◽  
Performance Status ◽  
Influential Factors ◽  
Phase Iii ◽  
Reference Level ◽  
Learning Approaches ◽  
Urine Protein ◽  
Ecog Performance Status ◽  
Key Variables

3528 Background: CALGB 80405 is a phase III clinical trial of FOLFOX and FOLFIRI w/ randomly assigned cetuximab or bevacizumab. Novel machine learning approaches to the study dataset provide valuable insights into CRC prognosis and management of CRC progression. Methods: Using a Monte Carlo Bayesian Generalized Linear Model analytical platform, we built an ensemble of models for overall survival (OS). We used 99 baseline and demographic variables, including 1904 patients w/ 1o side and 949 w/ KRAS wild-type status. Building an ensemble of predictive models reduces risk of overfitting, estimates model uncertainty and identifies key variables by model consensus as measured by ensemble frequency (freq). We fit gender and 1o side (L vs R) stratum-specific models to examine differences in drivers of disease in those strata. Results: 1o side (avg Cox hazard ratio = 0.89, R side reference), ECOG performance status (1.30, reference level 0), AST concentration (1.01), peripheral neutrophil percentage (1.01) and local primary and abdominal site of disease indicators (1.22; 1.26) were key variables predictive of OS ( > 75% freq). In 1o side stratum-specific models, urine protein level (1.61), treatment intent (0.75, nonpalliative as reference) and hemoglobin concentration (0.85) were more associated w/ L side progression (freq > 85% in L stratum model, < 20% in R), while liver and lung sites of disease (2.3; 1.09) were more associated w/ R side progression (freq > 65% in R stratum model, < 20% in L). Predictors of 1o left-sidedness included age (avg log odds ratio = 0.02), hemoglobin (0.41), and abdominal (3.79) and liver (0.68) sites of disease. Modest differences in disease prognostic factors existed between genders: women more influenced by metastatic status, age, liver site of disease and creatinine level; men more influenced by urine protein level and prior diabetes. Conclusions: 1o side plays a central role in potentially explaining both variation in OS and differences in drivers of OS. Availability of these measures at baseline enables better sense of disease course at initiation of treatment. Support: U10CA180821, U10CA180882, Eli Lilly & Co., Genentech, Pfizer Clinical trial information: NCT00265850.

Update results from ALTER-C-001: Efficacy and safety of anlotinib plus XELOX regimen as first-line treatment followed by maintenance monotherapy of anlotinib for patients with mCRC-A single-arm, multicenter, phase Ⅱ clinical trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15550-e15550
Author(s):  
Jin Yan ◽  
Yunwei Han ◽  
Li Zhang ◽  
Yongdong Jin ◽  
Hao Sun
Keyword(s):  
Clinical Trial ◽  
Adverse Events ◽  
Performance Status ◽  
Phase Iii ◽  
Line Treatment ◽  
First Line ◽  
Open Label ◽  
Ecog Performance Status ◽  
Multicenter Phase ◽  
First Line Treatment

e15550 Background: The combination of anti-VEGF or anti-EGFR targeted drugs with chemotherapy is the standard first-line therapy for metastatic colorectal cancer (mCRC), and the followed maintenance treatment is an optional approach to balance the efficacy and toxicity. However, studies regarding the maintenance strategies based on antiangiogenic TKIs are limited currently. Anlotinib, a novel oral multi-target TKI which can inhibit both tumor angiogenesis and tumor cell proliferation simultaneously, substantially prolonged the PFS with manageable toxicity for refractory mCRC in the phase III ALTER0703 clinical trial. Here we report an update on the effectiveness and safety of anlotinib plus XELOX as first-line treatment followed by anlotinib monotherapy for mCRC. Methods: In this open label, single-arm, multicenter phase II clinical trial, 53 mCRC patients without prior systemic treated, aged 18-75 and an ECOG performance status of 0 or 1 were planned to recruit. Eligible patients received capecitabine (1000 mg/m2, po, d1-14, q3w) and oxaliplatin (130 mg/m2, iv, d1, q3w) plus anlotinib (10mg, po, d1̃14, q3w) treatment for 6 cycles. After 6 cycles of inducing therapy, patients would receive anlotinib (12mg, po, d1̃14, q3w) as maintenance therapy until disease progression or intolerable adverse events (AEs). The primary endpoint was PFS; Secondary endpoints included ORR, DCR, DOR and safety. Results: By the data analysis cutoff date of January 22, 2021, a total of 18 patients were enrolled, of which 12 patients were available for efficacy assessment. In best overall response assessment, there were 50.0% PR (6/12), 33.3% SD (4/12) and 16.7% PD (2/12). The ORR was 50.0% (95% CI, 21.1-78.9%) and DCR was 83.3% (95% CI, 51.5-97.9%). The longest duration of treatment was 8.8 months and the response was still ongoing. The median PFS was not reached. The most common treatment related adverse events (TRAEs) of any grade (≥20%) were leukopenia, hypertension, neutropenia, diarrhea, fatigue, hypertriglyceridemia. Grade 3/4 TRAEs included hypertension (22.2%), hypertriglyceridemia (11.1%), lipase elevated (11.1%) and neutropenia (5.6%). No grade 5 AEs occurred. Conclusions: The update results suggested that anlotinib combined with XELOX as first line regimen followed by anlotinib monotherapy showed promising anti-tumor activity and manageable safety for patients with mCRC. And the conclusions needed to be confirmed in trials continued subsequently. Clinical trial information: ChiCTR1900028417.

scholarly journals TROG 18.01 phase III randomised clinical trial of the Novel Integration of New prostate radiation schedules with adJuvant Androgen deprivation: NINJA study protocol

BMJ Open ◽  
2019 ◽  
Vol 9 (8) ◽  
pp. e030731 ◽  
Author(s):  
Jarad Martin ◽  
Paul Keall ◽  
Shankar Siva ◽  
Peter Greer ◽  
David Christie ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Controlled Trial ◽  
Performance Status ◽  
Androgen Deprivation ◽  
Phase Iii ◽  
High Dose ◽  
The Novel ◽  
Ecog Performance Status ◽  
Initial Portion ◽  
The Impact

IntroductionStereotactic body radiotherapy (SBRT) is a non-invasive alternative to surgery for the treatment of non-metastatic prostate cancer (PC). The objectives of the Novel Integration ofNew prostate radiation schedules with adJuvant Androgen deprivation (NINJA) clinical trial are to compare two emerging SBRT regimens for efficacy with technical substudies focussing on MRI only planning and the use of knowledge-based planning (KBP) to assess radiotherapy plan quality.Methods and analysisEligible patients must have biopsy-proven unfavourable intermediate or favourable high-risk PC, have an Eastern Collaborative Oncology Group (ECOG) performance status 0-1 and provide written informed consent. All patients will receive 6 months in total of androgen deprivation therapy. Patients will be randomised to one of two SBRT regimens. The first will be 40 Gy in five fractions given on alternating days (SBRT monotherapy). The second will be 20 Gy in two fractions given 1 week apart followed 2 weeks later by 36 Gy in 12 fractions given five times per week (virtual high-dose rate boost (HDRB)). The primary efficacy outcome will be biochemical clinical control at 5 years. Secondary endpoints for the initial portion of NINJA look at the transition of centres towards MRI only planning and the impact of KBP on real-time (RT) plan assessment. The first 150 men will demonstrate accrual feasibility as well as addressing the KBP and MRI planning aims, prior to proceeding with total accrual to 472 patients as a phase III randomised controlled trial.Ethics and disseminationNINJA is a multicentre cooperative clinical trial comparing two SBRT regimens for men with PC. It builds on promising results from several single-armed studies, and explores radiation dose escalation in the Virtual HDRB arm. The initial component includes novel technical elements, and will form an important platform set for a definitive phase III study.Trial registration numberANZCTN 12615000223538.

DREAMseq (Doublet, Randomized Evaluation in Advanced Melanoma Sequencing): A phase III trial—ECOG-ACRIN EA6134.

2021 ◽  
Vol 39 (36_suppl) ◽  
pp. 356154-356154
Author(s):  
Michael B. Atkins ◽  
Sandra J. Lee ◽  
Bartosz Chmielowski ◽  
Antoni Ribas ◽  
Ahmad A. Tarhini ◽  
...  
Keyword(s):  
Checkpoint Inhibitors ◽  
Performance Status ◽  
Initial Therapy ◽  
Phase Iii ◽  
Treatment Sequence ◽  
Ecog Performance Status ◽  
Randomized Evaluation ◽  
Alternate Therapy ◽  
Treatment Naïve ◽  
Grade 3

356154 Background: Combinations of immune checkpoint inhibitors (CPI) blocking PD-1 and CTLA-4 or BRAF/MEK inhibitors have both shown significant antitumor efficacy and overall survival (OS) benefit in patients (pts) with BRAFV600-mutant metastatic melanoma (MM), leading to broad regulatory approval. Little prospective data exists to guide the choice of one over the other as initial therapy or the preferred treatment sequence in this population. The DREAMseq Trial was designed to compare the efficacy and toxicity of the sequence of nivolumab/ipilimumab (N/I) followed by dabrafenib/trametinib (D/T) to the converse sequence. Methods: Eligible pts with treatment-naive BRAFV600-mutant MM were stratified by ECOG Performance Status (PS) 0 or 1 and LDH level and randomized 1:1 to receive Step 1 with either N/I (Arm A) or D/T (Arm B) and at disease progression (PD) were enrolled in Step 2 receiving the alternate therapy, D/T (Arm C) or N/I (Arm D), respectively. Pts received N (1mg/kg)/I (3 mg/kg) q3 wks x 4 doses followed by N 240 IV q2 wks for up to 72 wks (Arms A and D) or D 150 mg po BID and T 2 mg po qD until PD (Arms B and C). In 2019, investigators were given the option to use alternate induction dosing of N (3mg/kg)/I (1 mg/kg) q3 wks x 4 doses for Arms A and D. Cycles were every 6 wks and imaging was obtained at baseline and q12 wks on each arm. Primary endpoint was 2-year OS. At the 4th Interim Analysis with 59% of pts being 2 yrs from enrollment, the DSMC and NCI CTEP recommended halting accrual and releasing the data. Results: Beginning 7/2015, 265 out of a proposed 300 pts were enrolled (133 Arm A and 132 Arm B). Median age was 61 (25-85) and 63% were male. Demographics for Arm A and B were balanced with 67% PS 0 and 60% with normal LDH. As of 7/16/21, at a median follow-up of 27.7 mos, 27 pts had switched to Arm C and 46 to Arm D. Overall Grade 3+ toxicity was 60% in Arm A and 52% in Arm B. Grade 5 treatment-related AEs included 2 on Arm A and 1 on Arm C. ORR to date is: Arm A 46% (52/113), Arm B 43% (49/114), Arm C 48% (11/23) and Arm D 30% (8/27). 37/42 assessed pts in Arm A and 19/37 in Arm B remain in response. Median DOR: Arm A- Not reached; Arm B-12.7 mos (95% CI: 8.2, -) (p <0.001). There were 100 deaths (Arm A to C- 38/Arm B to D- 62). 2-yr OS rate for those starting with Arm A was 72% (95% CI: 62-81%) and for Arm B 52% (95% CI: 42-62%) (log-rank p= 0.0095). PFS showed a trend in favor of Arm A (log-rank p=0.054). Both the PFS and OS curves show a biphasic pattern with Arm B being above Arm A until 6 and 10 mos, respectively. For the 115 pts with documented progression on Step 1 (Arm A-44/Arm B-71), 60 (52%) had registered for Step 2. The principal reason for not enrolling on Step 2 was death from PD within 6 mos (Arm A:15/23; Arm B: 25/32). Conclusions: For pts with advanced BRAFV600-mutant MM, the treatment sequence beginning with the CPI combination of N/I resulted in superior OS, which became evident at 10 mos, with longer Step 1 DOR and more ongoing responses than the treatment sequence beginning with D/T. Clinical trial information: NCT02224781.

scholarly journals Phase III Randomized, Placebo-Controlled Trial of Docetaxel With or Without Gefitinib in Recurrent or Metastatic Head and Neck Cancer: An Eastern Cooperative Oncology Group Trial

2013 ◽  
Vol 31 (11) ◽  
pp. 1405-1414 ◽  
Author(s):  
Athanassios Argiris ◽  
Musie Ghebremichael ◽  
Jill Gilbert ◽  
Ju-Whei Lee ◽  
Kamakshi Sachidanandam ◽  
...  
Keyword(s):  
Head And Neck ◽  
Disease Progression ◽  
Kinase Inhibitor ◽  
Performance Status ◽  
Single Agent ◽  
Eastern Cooperative Oncology Group ◽  
Phase Iii ◽  
Oncology Group ◽  
Ecog Performance Status ◽  
Grade 3

Purpose We hypothesized that the addition of gefitinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, to docetaxel would enhance therapeutic efficacy in squamous cell carcinoma of the head and neck (SCCHN). Patients and Methods Patients with recurrent or metastatic SCCHN with Eastern Cooperative Oncology Group (ECOG) performance status of 2, or patients with ECOG performance status of 0 to 2 but were previously treated with chemotherapy, were randomly assigned to receive weekly docetaxel plus either placebo (arm A) or gefitinib 250 mg/d, orally (arm B) until disease progression. At the time of progression, patients in the placebo arm could receive single-agent gefitinib. EGFR, c-MET, and KRAS mutations and polymorphisms in drug metabolizing enzymes and transporters were evaluated by pyrosequencing. Results Two hundred seventy patients were enrolled before the study was closed early at interim analysis (arm A, n = 136; arm B, n = 134). Median overall survival was 6.0 months in arm A versus 7.3 months in arm B (hazard ratio, 0.93; 95% CI, 0.72 to 1.21; P = .60). An unplanned subset analysis showed that gefitinib improved survival in patients younger than 65 years (median 7.6 v 5.2 months; P = .04). Also, there was a trend for improved survival in patients with c-MET wild-type (5.7 v 3.6 months; P = .09) regardless of treatment. Grade 3/4 toxicities were comparable between the two arms except that grade 3/4 diarrhea was more common with docetaxel/gefitinib. Of 18 eligible patients who received gefitinib after disease progression in arm A, one patient had a partial response. Conclusion The addition of gefitinib to docetaxel was well tolerated but did not improve outcomes in poor prognosis but otherwise unselected patients with SCCHN.

scholarly journals Prognostic Significance of p16INK4A and Human Papillomavirus in Patients With Oropharyngeal Cancer Treated on TROG 02.02 Phase III Trial

2010 ◽  
Vol 28 (27) ◽  
pp. 4142-4148 ◽  
Author(s):  
Danny Rischin ◽  
Richard J. Young ◽  
Richard Fisher ◽  
Stephen B. Fox ◽  
Quynh-Thu Le ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Oropharyngeal Cancer ◽  
Performance Status ◽  
Cell Cancer ◽  
Eastern Cooperative Oncology Group ◽  
Prognostic Significance ◽  
Multivariable Analysis ◽  
Phase Iii ◽  
Significant Prognostic Factor ◽  
Ecog Performance Status

Purpose To determine the prognostic importance of p16 and human papillomavirus (HPV) in patients with oropharyngeal cancer treated on a phase III concurrent chemoradiotherapy trial. Patients and Methods Patients with stage III or IV head and neck squamous cell cancer were randomly assigned to concurrent radiotherapy and cisplatin with or without tirapazamine. In this substudy, analyses were restricted to patients with oropharyngeal cancer. p16 was detected by immunohistochemistry, and HPV was detected by in situ hybridization and polymerase chain reaction. Results Slides were available for p16 assay in 206 of 465 patients, of which 185 were eligible, and p16 and HPV were evaluable in 172 patients. One hundred six (57%) of 185 were p16-positive, and in patients evaluable for both p16 and HPV, 88 (86%) of 102 p16-positive patients were also HPV-positive. Patients who were p16-positive had lower T and higher N categories and better Eastern Cooperative Oncology Group (ECOG) performance status. p16-positive tumors compared with p16-negative tumors were associated with better 2-year overall survival (91% v 74%; hazard ratio [HR], 0.36; 95% CI, 0.17 to 0.74; P = .004) and failure-free survival (87% v 72%; HR, 0.39; 95% CI, 0.20 to 0.74; P = .003). p16 was a significant prognostic factor on multivariable analysis (HR, 0.45; 95% CI, 0.21 to 0.96; P = .04). p16-positive patients had lower rates of locoregional failure and deaths due to other causes. There was a trend favoring the tirapazamine arm for improved locoregional control in p16-negative patients (HR, 0.33; 95% CI, 0.09 to 1.24; P = .13). Conclusion HPV-associated oropharyngeal cancer is a distinct entity with a favorable prognosis compared with HPV-negative oropharyngeal cancer when treated with cisplatin-based chemoradiotherapy.

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.

A randomized comparison of carboplatin/vinorelbine versus carboplatin/gemcitabine in advanced non-small cell lung cancer (NSCLC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7033-7033
Author(s):  
N. Helbekkmo ◽  
S. H. Sundtroem ◽  
U. Aaseboe ◽  
P. F. Brunsvig ◽  
C. L. Von Plessen ◽  
...  
Keyword(s):  
Overall Survival ◽  
Performance Status ◽  
Stage Iiib ◽  
Phase Iii ◽  
Ecog Performance Status ◽  
Intention To Treat ◽  
Primary Endpoints ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
One Year

7033 Background: Carboplatin/vinorelbine (CV) and carboplatin/gemcitabine (CG) are novel 2-drug combinations in the treatment of NSCLC. In a randomized national multicenter phase III study in stage IIIB and IV patients (pts), we compared these regimens with respect to efficacy, toxicity and quality of life (QoL). Methods: Chemonaive pts with histologically or cytologically proven NSCLC, stage IIIB or IV and ECOG performance status (PS) 0–2 were eligible. There was no upper age limit. Pts received vinorelbine 25 mg/m2 or gemcitabine 1000 mg/m2, both administered on day 1 and 8, in combination with carboplatin (Chatelut AUC 4) at day 1. Three courses were administered in 3-week cycles. QoL questionnaires were completed at baseline, before each cycle and then every 8 weeks up to one year. Primary endpoints were survival and QoL and secondary endpoints toxicity and time to progression (TTP). Stratification was done for age, stage and PS, and the planned sample size per arm was minimum 200. The analyses were performed on an intention-to-treat basis Results: From Oct 2003 through Dec 2004, 433 pts from 33 institutions were randomized to CV (n=218) or CG (n=215). Follow-up was minimum one year. There was no difference in overall survival between the two arms (p=0.89). Median survival was 7.3 vs. 6.5 months and 1-year survival 28% and 31% in the CV and CG arm respectively. TTP was significantly longer in the CG arm (p=0.006) with median TTP 4.2 vs. 3.9 months. There was significantly more grade 3–4 anemia and thrombocytopenia in the CG arm (p<0.001) and more grade 3–4 leucopenia in the CV arm (p= 0.001). More pts in the CG arm needed transfusions of blood (p=0.003) or platelets (p=0.001). There was no difference between the arms with respect to neutropenic infections (p=0.87). QoL data are still being analyzed and will be presented at ASCO. Conclusions: Overall survival was similar in the two treatment arms. In the CG arm, the median TTP was longer, but grade 3–4 toxicity requiring interventions, was more frequent when compared to the VC arm. No significant financial relationships to disclose.

Validation of the Functional Assessment of Cancer Therapy-Ovarian (FACT-O) Symptom Index (FOSI) in a phase II clinical trial of pertuzumab in patients with advanced ovarian cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 16021-16021 ◽  
Author(s):  
J. Beaumont ◽  
S. Yount ◽  
D. Lalla ◽  
D. Lubeck ◽  
M. Derynck ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Clinical Trial ◽  
Phase Ii ◽  
Performance Status ◽  
Advanced Ovarian Cancer ◽  
Phase Ii Clinical Trial ◽  
Response To Treatment ◽  
Ecog Performance Status ◽  
Symptom Index ◽  
Cross Sectional

16021 Background: The FOSI is a very brief(8-item) index derived from the FACT-O to measure symptom response to treatment for ovarian cancer(OC). We evaluated its performance in a single arm Phase II clinical trial. Methods: The FOSI was administered to patients with advanced OC participating in a single arm Ph II clinical trial of pertuzumab(Gordon et al, JCO (2006) v24:4324;2006)). Pertuzumab, a humanized HER2 antibody is the first in a new class of investigational agents known as HER dimerization inhibitors(HDIs). Patients completed the FOSI at D1 of each 3 week cycle, up to 17 cycles. Validation analyses focused on data from the first 4 cycles and included Cronbach's alpha coefficients plus cross-sectional and longitudinal comparisons of groups defined by ECOG performance status (PS). Results: 62 patients completed the FOSI at baseline (B), 54 at cycle 2, 44 at cycle 3 and 27 at cycle 4. The FOSI showed acceptable internal consistency reliability with alphas of 0.73 to 0.80. The FOSI differentiated patients with PS 0 from those with PS =1 at each cycle (Table). There was a difference in FOSI scores in patients with worsened PS from those whose PS improved or was unchanged at cycle 2 only (p<0.001). The ES (mean change/ SD of change scores) for the group with worsened PS was -0.77. The minimally important difference was estimated to be 2–3 points. Conclusions: The FOSI is a valid symptom measure in this population of OC patients, demonstrating acceptable reliability, validity and responsiveness to clinical change. [Table: see text] No significant financial relationships to disclose.

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]

A randomized phase III study of gemcitabine (G) versus GV1001 in sequential combination with G in patients with unresectable and metastatic pancreatic cancer (PC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4601-4601 ◽  
Author(s):  
T. Buanes ◽  
J. Maurel ◽  
W. Liauw ◽  
M. Hebbar ◽  
J. Nemunaitis
Keyword(s):  
Overall Survival ◽  
Performance Status ◽  
Locally Advanced ◽  
Peptide Vaccine ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Ecog Performance Status ◽  
Delayed Treatment ◽  
Sequential Combination ◽  
The Impact

4601 Background: A phase I/II study with GV1001, a telomerase peptide vaccine, showed a median overall survival (OS) of 8.6 months in non-resectable PC (Bernhardt SL et al, Br J Cancer. 2006;95:1474–1482). This phase III trial was conducted to determine the impact on overall survival of G monotherapy vs. GV1001 in sequential combination with G in unresectable and metastatic PC. Methods: Eligible patients (pts) had chemotherapy-naive, advanced PC and ECOG performance status 0–1. Pts were randomized 1:1 to receive arm A: G (1,000 mg/m2 30 min i.v.) weekly for 7 weeks (w), 1w off and then 3w during 4-weekly cycles, or arm B: GV1001 0.56 mg s.c. plus GM-CSF as immune adjuvant on days 1, 3, 5, 8, 15, 22, 36, then every 4 weeks. Patients who progressed clinically or radiologically during GV1001 continued on GV1001 and concomitant gemcitabine. CT scans were performed every 8 weeks. The primary end-point was OS. A sample size of 520 patients allowed the detection of a hazard ratio (HR) of 0.73 (B/A), with 2α = 0.05 and 90% power. Results: Between June 2006 and May 2008, 365 pts were enrolled (A / B; 182 / 183). The study was stopped prematurely due to a preliminary analysis with 178 events showing no survival benefit of GV1001. Pts were well balanced for baseline characteristics: male 59.3% / 62.8%; median age 61y / 61y; ECOG PS 0 34.3% / 36.7%; locally advanced 22.4% / 20.7%. As of August 2008, 238 pts (A / B : 114 / 124) had died. Median OS was 7.3 / 5.9 months (HR 0.8; 95% CI 0.6–1.0). Median progression-free survival (PFS) was 3.7 / 1.9 months (HR 0.5; 95%CI 0.4–0.7). Grade 3–4 AEs: gastrointestinal 6% / 8%, infection 5% / 5%, vascular disorders 2% / 3%, neutropenia 6% / 3%. Conclusions: GV1001 did not show efficacy in sequential combination with G in advanced PC. The advantage of G monotherapy over the sequential combination may be due to the delayed treatment with G in arm B. [Table: see text]

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