Abstract 4531: SWATH-MS profiling identifies prognostic factors for progression-free survival (PFS) In INTEGRATE - A randomized phase II double-blind placebo-controlled study of regorafenib in refractory advanced oesophagogastric cancer (AOGC) - A study by the Australasian Gastrointestinal Trials Group (AGITG)

2019 ◽  
Author(s):  
Sarah A. Hayes ◽  
Andrew Martin ◽  
Sonia Yip ◽  
Viive M. Howell ◽  
Katrin M. Sjoquist ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Phase Ii ◽  
Progression Free Survival ◽  
Controlled Study ◽  
Double Blind ◽  
Free Survival ◽  
Double Blind Placebo ◽  
Randomized Phase Ii ◽  
Oesophagogastric Cancer

Results of the X-PECT study: A phase III randomized double-blind, placebo-controlled study of perifosine plus capecitabine (P-CAP) versus placebo plus capecitabine (CAP) in patients (pts) with refractory metastatic colorectal cancer (mCRC).

2012 ◽  
Vol 30 (18_suppl) ◽  
pp. LBA3501-LBA3501 ◽  
Author(s):  
Johanna C. Bendell ◽  
Thomas J. Ervin ◽  
Neil N. Senzer ◽  
Donald A. Richards ◽  
Irfan Firdaus ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Phase Ii ◽  
Median Overall Survival ◽  
Phase Iii ◽  
Controlled Study ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Randomized Phase Ii ◽  
Phase Iii Study

LBA3501 Background: Perifosine (P) is an oral, synthetic alkylphospholipid that inhibits or modifies signal transduction pathways including AKT, NFkB and JNK. A randomized phase II study examined P-CAP vs. CAP in pts with 2nd or 3rd line mCRC. This study showed improvement in mTTP (HR 0.254 [0.117, 0.555]) and mOS (HR 0.370 [0.180,0.763]). Based on these results, a randomized phase III study of P-CAP vs. CAP with a primary endpoint of overall survival (OS) in pts with refractory mCRC was initiated. Methods: The study was a prospective, randomized, double-blind, placebo-controlled randomized phase III trial. Eligible pts had mCRC which was refractory to all standard therapies. Pts randomized 1:1 to Arm A = P-CAP (P 50 mg PO QD + CAP 1000 mg/m2PO BID d1-14) or Arm B = CAP (placebo + CAP 1000 mg/m2 PO BID d 1-14). Cycles were 21 days. Baseline tumor block collection and a biomarker cohort of pts with pre- and on-treatment tumor and blood samples were performed. Results: Between 3/31/10 and 8/12/11, 468 pts were randomized, 234 pts were in each arm. Baseline demographics were balanced between the arms: age < 65y (A: 65%, B: 58.5%), male (A: 57.7%, B: 53.0%), ECOG PS 0 (A: 39.7%, B: 39.7%), K-ras mutant (A: 50.4%, B: 51.3%), and median number of prior therapies (A: 4, B: 4). As of 3/19/12, median follow up was 6.6 months. Median overall survival: Arm A = 6.4 mo, Arm B = 6.8 mo, HR 1.111 [0.905,1.365], p = 0.315. Median overall survival for K-ras WT pts: Arm A = 6.6 mo, Arm B = 6.8 mo, HR 1.020 [0.763,1.365], p = 0.894; K-ras mutant pts: Arm A = 5.4 mo, Arm B = 6.9 mo HR 1.192 [0.890,1.596], p = 0.238. Conclusions: Despite promising randomized phase II data, this phase III study shows no benefit in overall survival adding perifosine to capecitabine in the refractory colorectal cancer setting. Response rate, progression free survival, and safety data will be presented. Biomarker analysis is pending to see if subgroups of patients may have potential benefit.

Final analysis of a multi-center, double-blind, placebo-controlled, randomized phase II trial of gemcitabine/cisplatin (GC) plus bevacizumab (B) or placebo (P) in patients (pts) with malignant mesothelioma (MM)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7526-7526 ◽  
Author(s):  
T. Karrison ◽  
H. L. Kindler ◽  
D. R. Gandara ◽  
C. Lu ◽  
T. L. Guterz ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Phase Ii Trials ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Randomized Phase Ii ◽  
Major Vessel ◽  
Grade 3

7526 Background: In phase II trials in MM, GC on a 21-day (D) schedule has response rates of 16%–26% and median overall survival (OS) of 9.6–13 months (mo). Since VEGF has a key role in MM biology, we added anti-VEGF antibody B to GC in a multi-center, double- blind, placebo-controlled randomized phase II trial. Methods: Eligible pts had unresectable MM; no prior chemotherapy; PS 0–1; no thrombosis, bleeding, or major vessel invasion. Primary endpoint: progression-free survival (PFS). Statistics: 90% power to detect HR 0.57. Stratification: PS (0/1), histology (epithelial/other). G 1,250 mg/m2 D 1, 8 Q21D, C 75 mg/m2 D1 Q21D, and B 15 mg/kg or P D1 Q21D was given × 6 cycles, then B or P Q21D until progression. Baseline plasma VEGF was measured. 115 pts enrolled 12/01- 07/05 at 11 sites, 108 (GCB/GCP) 53/55 were evaluable. Male 74%/84%; median age 62/65 (range 44–78/20–84); PS 1 55%/47%; epithelial 74%/67%; pleural 93%/91%; thrombocytosis 40%/40%. Results: Cycles: total 458/424, median 7/6, range 1–42/2–39. Statistically significantly different (SSD) toxicity (p <0.05), any grade: alopecia 60%/38%; epistaxis 62%/24%; hypertension 45%/22%; non-neutropenic infection 15%/4%; proteinuria 62%/47%; stomatitis 23%/7%. There were no SSD toxicities = grade 3. Median PFS 6.9/6.0 mo (HR 0.93, p=0.88). Median OS 15.6/14.7 mo (p=0.91). 1-year survival 59%/57%. Partial response 25%/22%; stable disease 51%/60%. Median VEGF (N=56) 131/154 pg/ml (range 31–1760/5–1786). Higher VEGF was associated with shorter PFS (p=0.02) and OS (p=0.0066). In pts with VEGF = the median, PFS (p=0.043) and OS (p=0.028) were significantly greater for GCB than GCP; in high VEGF strata this was not SSD. Conclusion: Adding B to GC in MM pts does not yield statistically significant differences in PFS, OS, response, or grade ¾ toxicity. GCB-treated pts with low VEGF levels had longer PFS and OS. Supported by NCI grant N01-CM-17102. No significant financial relationships to disclose.

Double-Blind Randomized Phase II Study of the Combination of Sorafenib and Dacarbazine in Patients With Advanced Melanoma: A Report From the 11715 Study Group

2008 ◽  
Vol 26 (13) ◽  
pp. 2178-2185 ◽  
Author(s):  
David F. McDermott ◽  
Jeffrey A. Sosman ◽  
Rene Gonzalez ◽  
F. Stephen Hodi ◽  
Gerald P. Linette ◽  
...  
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Advanced Melanoma ◽  
Time To Progression ◽  
Double Blind ◽  
Free Survival ◽  
Randomized Phase Ii ◽  
Independent Assessment

PurposeThis phase II study evaluated the efficacy and safety of sorafenib plus dacarbazine in patients with advanced melanoma.Patients and MethodsThis randomized, double-blind, placebo-controlled, multicenter study enrolled chemotherapy-naïve patients with stage III (unresectable) or IV melanoma. A total of 101 patients received placebo plus dacarbazine (n = 50) or sorafenib plus dacarbazine (n = 51). On day 1 of a 21-day cycle, patients received intravenous dacarbazine 1,000 mg/m2for a maximum of 16 cycles. Oral sorafenib 400 mg or placebo was administered twice a day continuously. The primary end point was progression-free survival (PFS) by independent assessment. Secondary and tertiary end points included time to progression (TTP), response rate, and overall survival (OS).ResultsMedian PFS in the sorafenib plus dacarbazine arm was 21.1 weeks versus 11.7 weeks in the placebo plus dacarbazine arm (hazard ratio [HR], 0.665; P = .068). There were statistically significant improvements in PFS rates at 6 and 9 months, and in TTP (median, 21.1 v 11.7 weeks; HR, 0.619) in favor of the sorafenib plus dacarbazine arm. No difference in OS was observed (median, 51.3 v 45.6 weeks in the placebo plus dacarbazine and sorafenib plus dacarbazine arms, respectively; HR, 1.022). The regimen was well tolerated and had a manageable toxicity profile.ConclusionSorafenib plus dacarbazine was well tolerated in patients with advanced melanoma and yielded an encouraging improvement in PFS. Based on these findings, additional studies with the combination are warranted in this patient population.

Evaluation of circulating VEGF based biomarkers in INTEGRATE: A randomized phase II double-blind placebo-controlled study of regorafenib in refractory advanced oesophagogastric cancer (AOGC)—A study by the Australasian Gastrointestinal Trials Group (AGITG).

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 64-64 ◽  
Author(s):  
Sonia Yip ◽  
Rozelle Harvie ◽  
Andrew James Martin ◽  
Katrin Marie Sjoquist ◽  
Eric Tsobanis ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Controlled Study ◽  
Strong Correlations ◽  
Protein Biomarkers ◽  
Double Blind ◽  
Free Survival ◽  
Randomized Phase Ii ◽  
Integrate Study

64 Background: The INTEGRATE study evaluated activity of regorafinib (REG) v placebo (PBO) in 147 eligible patients with refractory AOGC. REG was highly effective in prolonging progression free survival (PFS). Differences between regions (i.e. Australia New Zealand/Canada (ANZ/CAN) vs Korea) were found in the magnitude of effect, but REG was effective across all regions and subgroups. We report on an exploratory analysis of VEGF biomarkers to identify predictive/prognostic markers. Methods: Protein biomarkers IL8, VEGF-A,-B,-C-D, soluble(s)VEGFR-1,-2-3 were analysed in plasma at baseline (BL) by multiplex immunoassays (Bio-Plex,BioRad) or ELISA (Abnova). Spearman statistics were used to quantify correlations between markers. Wilcoxon Rank-Sum tests were used to compare markers across regions. The prognostic and predictive value of markers was determined using cox proportional hazards analysis of PFS. Results: There were moderate-to-strong correlations between BL levels of IL8 and VEGF-C (ρ = 0.68), IL8 and VEGF-D (ρ = 0.66), VEGF-A and VEGF-C (ρ = 0.68), VEGF-A and sVEGFR-1 (ρ = 0.54); and a modest negative correlation between VEGF-D and sVEGRF-1 (ρ = -0.33). The regions differed according to BL levels of: VEGF-A (higher in ANZ/CAN; p = 0.0015), VEGF-B (higher in Korea; p = 0.0003), VEGF-D (higher in Korea; p <.0001), and sVEGFR-1 (higher in ANZ/CAN; p <.0001). Adjusting for treatment group, there were statistically significant negative associations between PFS and BL IL8 (p = 0.047), VEGF-A (p = 0.037) and sVEGFR-1 (p = 0.045). There was no convincing statistical evidence that any BL plasma biomarker modified the effect of REG. The effect of region on effectiveness of REG was maintained when evaluated in conjunction with BL biomarkers individually and in combination. Conclusions: Highplasma IL8, VEGF-A and sVEGFR-1 may be adverse prognostic factors. A predictive VEGF blood based biomarker remains elusive. A broader biomarker study including markers beyond the VEGF axis and tissue based markers is ongoing. Clinical trial information: ACTRN12612000239864.

Phase II Randomized, Double-Blind, Placebo-Controlled Study of Tasquinimod in Men With Minimally Symptomatic Metastatic Castrate-Resistant Prostate Cancer

2011 ◽  
Vol 29 (30) ◽  
pp. 4022-4028 ◽  
Author(s):  
Roberto Pili ◽  
Michael Häggman ◽  
Walter M. Stadler ◽  
Jeffrey R. Gingrich ◽  
Vasileios J. Assikis ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Phase Ii ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Antitumor Agent ◽  
Controlled Study ◽  
Castration Resistant Prostate Cancer ◽  
Double Blind ◽  
Double Blind Placebo ◽  
The Impact

Purpose The activity of the novel antitumor agent tasquinimod (TASQ) with S100A9 as a molecular target was investigated in men with metastatic castration-resistant prostate cancer (CRPC) and minimal symptoms. Patients and Methods We conducted a randomized, double-blind, placebo-controlled phase II trial in men assigned (at a ratio of two to one) to either oral once-daily TASQ 0.25 mg/d escalating to 1.0 mg/d over 4 weeks or placebo. The primary end point was the proportion of patients without disease progression at 6 months, defined by Response Evaluation Criteria in Solid Tumors Group, Prostate Cancer Working Group (PCWG2), or pain criteria, excluding prostate-specific antigen. Results Two hundred one men (134 assigned to TASQ; 67 to placebo) were evaluable, and baseline characteristics were well balanced. Six-month progression-free proportions for TASQ and placebo groups were 69% and 37%, respectively (P < .001), and median progression-free survival (PFS) was 7.6 versus 3.3 months (P = .0042). In PCWG2 CRPC clinical subgroups, PFS in months was as follows: nodal metastases, 6.1 versus 3.1; bone metastases, 8.8 versus 3.4; and visceral metastases, 6.0 versus 3.0 for patients receiving TASQ versus placebo, respectively. Bone alkaline phosphatase levels were stabilized in the TASQ group, whereas the impact on PSA kinetics was less pronounced. Adverse events (AEs) occurring more frequently in the TASQ arm included GI disorders, fatigue, musculoskeletal pains, and elevations of pancreatic and inflammatory biomarkers. Grade 3 to 4 AEs, including asymptomatic elevations of laboratory parameters, were reported in 40% of patients receiving TASQ versus 10% receiving placebo; deep vein thrombosis (4% v 0%) was more common in the TASQ arm. Conclusion TASQ significantly slowed progression and improved PFS in patients with metastatic CRPC with an acceptable AE profile.

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