Lapatinib in combination with ECF/x in EGFR1 positive first-line metastatic gastric cancer (GC): A phase II randomized placebo controlled trial (EORTC 40071).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS4140-TPS4140
Author(s):  
Markus Hermann Moehler ◽  
Arno Schad ◽  
Murielle E. Mauer ◽  
Michel Praet ◽  
Francisco J. Sapunar ◽  
...  
Keyword(s):  
Phase Ii ◽  
Controlled Trial ◽  
Cohort Analysis ◽  
Progression Free Survival ◽  
Metastatic Gastric Cancer ◽  
Phase Iii ◽  
Her2 Status ◽  
Clinical Activity ◽  
Curative Surgery ◽  
Double Blind

TPS4140 Background: Survival of HER2+ metastatic GC is prolonged by trastuzumab when administered with CF/X (VanCutsem, ASCO 2009). Lapatinib inhibits both EGFR1 and HER2, is active in HER2+ GC lines, and has shown clinical activity in uncontrolled phase II GC trials. A phase III trial of lapatinib with X + oxaliplatin in HER2+ (FISH) GC is closed to recruitment. Additional unaddressed questions include the efficacy and safety of lapatinib with ECF/X (epirubicin + cisplatin + 5-FU or capecitabine (X), which is a preferred chemotherapy (CT) regimen in GC), and its activity in patients (pts) with discordant FISH or IHC HER2 status or EGFR1+. Methods: This is a phase II, randomized, double- blind, placebo controlled, multicenter trial sponsored by the EORTC. About 480 pts with adenocarcinoma of the stomach or esophagogastric junction not amenable to curative surgery and without prior palliative CT are screened centrally for HER2/EGFR1 by FISH and IHC. Patients are enrolled into one of two strata: 1) HER2 FISH- and IHC 2/3+, or 2) HER2 IHC 0/+ and EGFR1 FISH+ or IHC 2/3+. Pts HER2 FISH+/IHC 2/3+ and pts without HER2/EGFR1 by FISH/IHC will be excluded. 168 pts are anticipated to be randomized to lapatinib 1,250 mg cont. until progression or placebo, administered 6 cycles of ECF or ECX (72/96 in stratum 1/2, respectively).The primary endpoint is progression-free survival (PFS) in stratum 2 and 77 events are needed for 80% power to detect an increase in PFS from 4 to 6.5 months with lapatinib (HR=0.615, one-sided alpha 10%). Secondary endpoints include PFS, toxicity, response rate, overall survival, and correlation of HER2/EGFR1 status with response. Currently, half of all screened patients (19/38) have been randomized. So far, 8/38 (21%) pts were HER2+ according TOGA criteria. By FISH or IHC, 14/38 were EGFR1+, with 4/14 pts double HER2/EGFR+. Enrolment continues in 5 centers with about 4-10 patients per month. A safety cohort analysis will be performed in the first 15 pts receiving lapatinib. Conclusions: This is the first trial to analyze prospectively and separately the role of lapatinib combined with chemotherapy in EGFR1+ GC pts stratified by FISH/ IHC.

Randomized, Double-Blind Phase II Trial With Prospective Classification by ATM Protein Level to Evaluate the Efficacy and Tolerability of Olaparib Plus Paclitaxel in Patients With Recurrent or Metastatic Gastric Cancer

2015 ◽  
Vol 33 (33) ◽  
pp. 3858-3865 ◽  
Author(s):  
Yung-Jue Bang ◽  
Seock-Ah Im ◽  
Keun-Wook Lee ◽  
Jae Yong Cho ◽  
Eun-Kee Song ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Phase Ii ◽  
Progression Free Survival ◽  
Metastatic Gastric Cancer ◽  
Phase Iii ◽  
Double Blind Study ◽  
Double Blind ◽  
Gastric Cancer Cell Lines ◽  
Study Population ◽  
Atm Protein

Purpose Gastric cancer cell lines, particularly those with low levels of ataxia telangiectasia mutated (ATM), a key activator of DNA damage response, are sensitive to the poly (ADP-ribose) polymerase inhibitor olaparib. We compared the efficacy of olaparib plus paclitaxel (olaparib/paclitaxel) with paclitaxel alone in patients with recurrent or metastatic gastric cancer and assessed whether low ATM expression is predictive of improved clinical outcome for olaparib/paclitaxel. Patients and Methods In this phase II, double-blind study (Study 39; NCT01063517), patients were randomly assigned to oral olaparib 100 mg twice per day (tablets) plus paclitaxel (80 mg/m2 per day intravenously on days 1, 8, and 15 of every 28-day cycle) or placebo plus paclitaxel (placebo/paclitaxel), followed by maintenance monotherapy with olaparib (200 mg twice per day) or placebo. The study population was enriched to 50% for patients with low or undetectable ATM levels (ATMlow). Primary end point was progression-free survival (PFS). Results One hundred twenty-three of 124 randomly assigned patients received treatment (olaparib/paclitaxel, n = 61; placebo/paclitaxel, n = 62). The screening prevalence of ATMlow patients was 14%. Olaparib/paclitaxel did not lead to a significant improvement in PFS versus placebo/paclitaxel (overall population: hazard ratio [HR], 0.80; median PFS, 3.91 v 3.55 months, respectively; ATMlow population: HR, 0.74; median PFS, 5.29 v 3.68 months, respectively). However, olaparib/paclitaxel significantly improved overall survival (OS) versus placebo/paclitaxel in both the overall population (HR, 0.56; 80% CI, 0.41 to 0.75; P = .005; median OS, 13.1 v 8.3 months, respectively) and the ATMlow population (HR, 0.35; 80% CI, 0.22 to 0.56; P = .002; median OS, not reached v 8.2 months, respectively). Olaparib/paclitaxel was generally well tolerated, with no unexpected safety findings. Conclusion Olaparib/paclitaxel is active in the treatment of patients with metastatic gastric cancer, with a greater OS benefit in ATMlow patients. A phase III trial in this setting is under way.

Lapatinib combined with ECF/x as first-line metastatic gastric cancer (GC) according to HER2 and EGFR status: A randomized placebo controlled phase II (EORTC 40071).

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 80-80 ◽  
Author(s):  
Markus Hermann Moehler ◽  
Arno Schad ◽  
Murielle E. Mauer ◽  
Carlo G. M. Messina ◽  
Jestinah. M. Mahachie John ◽  
...  
Keyword(s):  
Phase Ii ◽  
Statistical Tests ◽  
Progression Free Survival ◽  
Metastatic Gastric Cancer ◽  
Her2 Status ◽  
Double Blind ◽  
Free Survival ◽  
Phase 2 Trial ◽  
Secondary Endpoints ◽  
Clinical Trial Information

80 Background: ECF/X (epirubicin (E) + cisplatin (C) + 5-fluoruracil (F) or capecitabine (X)) is a reference chemotherapy (CT) regimen in metastatic GC. Trastuzumab with CF/X prolonged survival (OS) of metastatic HER2+ gastric or esophagogastric junction cancer (GC) patients (pts). Lapatinib (LAP) inhibits both, EGFR1 and HER2, and showed activity in phase II GC trials. This double-blind Phase II study prospectively addressed efficacy and safety of LAP with ECF/X in GC pts with discordant FISH or IHC HER2 status or EGFR1+. Methods: Pts without prior palliative CT, screened centrally for HER2/EGFR1 (by FISH and IHC) were enrolled into 3 strata: 1) HER2 FISH+ and IHC 2/3+, 2) HER2 FISH- and IHC 2/3+, or 3) HER2 IHC 0/+ and EGFR1 FISH+ or IHC 2/3+. Pts without HER2 + or EGFR1+, by FISH or IHC, were excluded. Pts were randomized to LAP 1250mg (arm 1) or placebo (arm 2), with ECF or ECX (investigator-selected) for 6 cycles. Primary endpoint was progression free survival (PFS). Secondary endpoints were toxicity, response rates, OS, HER2 concordance and correlation of HER2/EGFR. Results: The trial was prematurely closed to patient accrual given the LOGIC trial results at ASCO 2013. A total of 69 pts were tested in central lab of whom 9 (13%), 5 (7.2%) and 25 (36.2%) were in stratum 1, 2 and 3. Of these, 28 patients (6/4/18) were randomized (14 in arm 1, 14 in arm 2) and followed up. Due to the low number of pts accrued, no formal statistical tests were carried out. No safety concerns were found in arm 1. No complete responses were seen. 6 pts had partial responses in arm 1 vs. 3 pts in arm 2. Median PFS was 7.1 months in arm 1 vs. 5.9 months in arm 2 (HR=0.94, 95% CI: 0.41-2.14) for all pts, and 6.2 months in arm 1 vs. 6.3 months in arm 2 (HR=0.99, 95% CI: 0.36-2.75) for stratum 3 pts, respectively. Median overall survival was 13.8 months in arm 1 vs. 10.1 months in arm 2 (HR=0.90, 95% CI: 0.35-2.27) for all pts. Conclusions: Lapatinib with ECF/X did not show appealing activity in EGFR+ metastatic GC patients in this small phase 2 trial. The combination was well tolerated. Clinical trial information: NCT01123473.

Randomized Phase II Placebo-Controlled Trial of Maintenance Therapy Using the Oral Triple Angiokinase Inhibitor BIBF 1120 After Chemotherapy for Relapsed Ovarian Cancer

2011 ◽  
Vol 29 (28) ◽  
pp. 3798-3804 ◽  
Author(s):  
Jonathan A. Ledermann ◽  
Allan Hackshaw ◽  
Stan Kaye ◽  
Gordon Jayson ◽  
Hani Gabra ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Maintenance Therapy ◽  
Phase Ii ◽  
Controlled Trial ◽  
Progression Free Survival ◽  
Early Recurrence ◽  
Phase Iii ◽  
Double Blind ◽  
Grade 3 ◽  
Bibf 1120

Purpose Inhibiting angiogenesis is one of the most promising avenues for new therapies for ovarian cancer. We investigated the efficacy and safety of a novel agent, BIBF 1120, a triple angiokinase inhibitor, after chemotherapy for relapsed disease. Patients and Methods We conducted a randomized, double-blind, controlled phase II trial in 83 patients who had just completed chemotherapy for relapsed ovarian cancer, with evidence of response, but at high risk of further early recurrence. The patients were randomly assigned to receive maintenance therapy using BIBF 1120 250 mg or placebo, twice per day, continuously for 36 weeks. End points were progression-free survival (PFS), toxicity, and overall survival. Results Thirty-six–week PFS rates were 16.3% and 5.0% in the BIBF 1120 and placebo groups, respectively (hazard ratio, 0.65; 95% CI, 0.42 to 1.02; P = .06). Four patients continued on BIBF 1120, including two patients for another year or more. The proportion of patients with any grade 3 or 4 adverse events was similar between the groups (34.9% for BIBF 1120 v 27.5% for placebo; P = .49; mostly grade 3). However, more patients on BIBF 1120 experienced diarrhea, nausea, or vomiting (mainly grade 1 or 2 and no grade 4). There was a higher rate of grade 3 or 4 hepatotoxicity in patients on BIBF 1120 (51.2%) compared with patients on placebo (7.5%; P < .001), but this was rarely of clinical significance, and patients continued with the trial treatment. A single-level dose reduction to 150 mg was made in 15 patients, all on active drug. Conclusion BIBF 1120 is well tolerated and associated with a potential improvement in PFS. The observed treatment effect is sufficient to justify further study within a large phase III trial.

scholarly journals Anti-Angiogenic Agents in Management of Sarcoma Patients: Overview of Published Trials

2020 ◽  
Vol 10 ◽  
Author(s):  
Pierre-Yves Cren ◽  
Loïc Lebellec ◽  
Thomas Ryckewaert ◽  
Nicolas Penel
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Phase Ii ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Phase Ii Trials ◽  
Double Blind ◽  
Multikinase Inhibitors ◽  
Randomized Phase Ii ◽  
Phase Iii Trials

We reviewed all fully published clinical trials assessing anti-angiogenic agents in sarcoma patients (last issue, January 13, 2020). Anti-angiogenic macromolecules (e.g., bevacizumab or ombrabulin) provide disappointing results. Many multikinase inhibitors have been assessed with non-randomized phase II trials with limited samples and without stratification according to histological subtypes, therefore interpretation of such trials is very challenging. On the contrary, pazopanib, regorafenib, and sorafenib have been assessed using double-blind placebo-controlled randomized phase II or phase III trials. Compared to placebo, sorafenib demonstrates activity in desmoid-type fibromatosis patients. Based on results of phase 3 trial, pazopanib had obtained approval for treatment of pretreated non-adipocytic soft tissue sarcoma. Regorafenib is currently assessed in several clinical settings and provides significant improvement of progression-free survival in pre-treated non-adipocytic soft tissue sarcoma and in advanced pretreated osteosarcoma. Multikinase inhibitors are a breakthrough in sarcoma management. Many trials are ongoing. Nevertheless, predictive factors are still missing.

Randomized Multicenter Phase II Trial of a Biweekly Regimen of Fluorouracil and Leucovorin (LV5FU2), LV5FU2 Plus Cisplatin, or LV5FU2 Plus Irinotecan in Patients With Previously Untreated Metastatic Gastric Cancer: A Fédération Francophone de Cancérologie Digestive Group Study—FFCD 9803

2004 ◽  
Vol 22 (21) ◽  
pp. 4319-4328 ◽  
Author(s):  
Olivier Bouché ◽  
Jean Luc Raoul ◽  
Franck Bonnetain ◽  
Marc Giovannini ◽  
Pierre Luc Etienne ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Progression Free Survival ◽  
Metastatic Gastric Cancer ◽  
Phase Iii ◽  
Survival Times ◽  
Multicenter Phase ◽  
Independent Expert ◽  
Phase Iii Study ◽  
Cancérologie Digestive

Purpose To determine the efficacy and safety of a biweekly regimen of leucovorin (LV) plus fluorouracil (FU) alone or in combination with cisplatin or irinotecan in patients with previously untreated metastatic gastric adenocarcinoma and to select the best arm for a phase III study. Patients and Methods One hundred thirty-six patients (two were ineligible) were enrolled onto the randomized multicenter phase II trial. Patients received LV 200 mg/m2 (2-hour infusion) followed by FU 400 mg/m2 (bolus) and FU 600 mg/m2 (22-hour continuous infusion) on days 1 and 2 every 14 days (LV5FU2; arm A), LV5FU2 plus cisplatin 50 mg/m2 (1-hour infusion) on day 1 or 2 (arm B), or LV5FU2 plus irinotecan 180 mg/m2 (2-hour infusion) on day 1 (arm C). Results The overall response rates, which were confirmed by an independent expert panel, were 13% (95% CI, 3.4% to 23.3%), 27% (95% CI, 14.1% to 40.4%), and 40% (95% CI, 25.7% to 54.3%) for arms A, B, and C, respectively. Median progression-free survival and overall survival times were 3.2 months (95% CI, 1.8 to 4.6 months) and 6.8 months (95% CI, 2.6 to 11.1 months) with LV5FU2, respectively; 4.9 months (95% CI, 3.5 to 6.3 months) and 9.5 months (95% CI, 6.9 to 12.2 months) with LV5FU2-cisplatin, respectively; and 6.9 months (95% CI, 5.5 to 8.3 months) and 11.3 months (95% CI, 9.3 to 13.3 months) with LV5FU2-irinotecan, respectively. Conclusion Of the three regimens tested, the combination of LV5FU2-irinotecan is the most promising and will be assessed in a phase III trial.

Randomized, Controlled Trial of Irinotecan Plus Infusional, Bolus, or Oral Fluoropyrimidines in First-Line Treatment of Metastatic Colorectal Cancer: Results From the BICC-C Study

2007 ◽  
Vol 25 (30) ◽  
pp. 4779-4786 ◽  
Author(s):  
Charles S. Fuchs ◽  
John Marshall ◽  
Edith Mitchell ◽  
Rafal Wierzbicki ◽  
Vinod Ganju ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Controlled Trial ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Primary Study ◽  
Line Treatment ◽  
First Line ◽  
Double Blind ◽  
First Line Treatment

PurposeThis phase III study compared the safety and efficacy of the following three different irinotecan-containing regimens in the first-line treatment of metastatic colorectal cancer: irinotecan plus infusional fluorouracil (FU)/leucovorin (LV) (FOLFIRI), irinotecan plus bolus FU/LV (mIFL), and irinotecan plus oral capecitabine (CapeIRI).Patients and MethodsA total of 430 previously untreated metastatic colorectal cancer patients were randomly assigned to receive FOLFIRI (n = 144), mIFL (n = 141), or CapeIRI (n = 145). Patients were concurrently randomly assigned to a double-blind treatment with celecoxib or placebo. After a protocol amendment, an additional 117 patients were randomly assigned to either FOLFIRI plus bevacizumab (FOLFIRI+Bev; n = 57) or mILF plus bevacizumab (mIFL+Bev; n = 60), whereas the CapeIRI arm was discontinued. The primary study end point was progression-free survival (PFS), with secondary end points of overall survival (OS), response rate, and toxicity.ResultsMedian PFS was 7.6 months for FOLFIRI, 5.9 months for mIFL (P = .004 for the comparison with FOLFIRI), and 5.8 months for CapeIRI (P = .015). Median OS was 23.1 months for FOLFIRI, 17.6 months for mIFL (P = .09), and 18.9 months for CapeIRI (P = .27). CapeIRI was associated with higher rates of severe vomiting, diarrhea, and dehydration. After the amendment to add bevacizumab, the median survival time has not yet been reached for FOLFIRI+Bev and was 19.2 months for mIFL+Bev (P = .007). FOLFIRI+Bev was associated with a higher rate of ≥ grade 3 hypertension than mIFL+Bev.ConclusionFOLFIRI and FOLFIRI+Bev offered superior activity to their comparators and were comparably safe. An infusional schedule of FU should be the preferred irinotecan-based regimen in first-line metastatic colorectal cancer.

Phase III, placebo-controlled trial (SUCCEED) evaluating ridaforolimus as maintenance therapy in advanced sarcoma patients following clinical benefit from prior standard cytotoxic chemotherapy: Long-term (≥ 24 months) overall survival results.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10010-10010 ◽  
Author(s):  
Jean-Yves Blay ◽  
Sant P. Chawla ◽  
Isabelle Ray-Coquard ◽  
Axel Le Cesne ◽  
Arthur P. Staddon ◽  
...  
Keyword(s):  
Overall Survival ◽  
Maintenance Therapy ◽  
Controlled Trial ◽  
Mammalian Target Of Rapamycin ◽  
Progression Free Survival ◽  
Mtor Inhibitors ◽  
Phase Iii ◽  
Clinical Activity ◽  
Prior Chemotherapy

10010 Background: The mammalian target of rapamycin (mTOR) regulates cell growth and proliferation and is abnormally activated in many sarcomas. Ridaforolimus, an oral mTOR inhibitor, demonstrated clinical activity in previous nonrandomized trials in advanced sarcomas following failure of prior chemotherapy. Methods: An international, multicenter, placebo-controlled, phase 3 trial was conducted to evaluate maintenance therapy with ridaforolimus in patients with metastatic soft-tissue or bone sarcomas who achieved disease control from prior chemotherapy. Patients were randomized (1:1) to receive oral ridaforolimus (40 mg) or placebo once daily for 5 days each week. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS) and safety and tolerability. For OS, patients were to be followed at 3-month intervals for at least 24 months and up to 60 months after randomization. Results: 702 of 711 randomized patients received treatment. At the time of the data cutoff for OS (386 deaths), patients in the study population had been followed for at least 15 months. Median OS was 93.3 weeks with ridaforolimus vs 83.4 weeks with placebo (hazard ratio [HR]=0.88; 95% confidence interval [CI]: 0.72, 1.08; P=0.23). Ridaforolimus significantly improved PFS vs placebo (HR=0.72; 95% CI: 0.61, 0.85; P=0.0001; median PFS: 17.7 weeks vs 14.6 weeks); PFS improved across all prespecified baseline characteristics. As expected from the class of mTOR inhibitors, the most common adverse events with ridaforolimus were stomatitis, thrombocytopenia, noninfectious pneumonitis, hypertriglyceridemia, hyperglycemia, infections, and rash. Conclusions: Oral ridaforolimus was generally well-tolerated and significantly improved PFS in metastatic sarcoma patients with benefit from prior chemotherapy, offering an effective treatment alternative to surveillance alone. Results of a long-term OS analysis (prespecified to occur at 67% mortality, 24 months minimum follow-up) in the intent-to-treat population will be available in early 2012.

Randomized phase III trial of regorafenib in patients (pts) with metastatic and/or unresectable gastrointestinal stromal tumor (GIST) progressing despite prior treatment with at least imatinib (IM) and sunitinib (SU): GRID trial.

2012 ◽  
Vol 30 (18_suppl) ◽  
pp. LBA10008-LBA10008 ◽  
Author(s):  
George D. Demetri ◽  
Peter Reichardt ◽  
Yoon-Koo Kang ◽  
Jean-Yves Blay ◽  
Heikki Joensuu ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Controlled Trial ◽  
Performance Status ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Double Blind Study ◽  
Open Label ◽  
Ecog Performance Status ◽  
Double Blind ◽  
Multikinase Inhibitor

LBA10008 Background: Oral multikinase inhibitor regorafenib (REG) demonstrated substantial activity in a phase II trial in pts with GIST after failure of both IM and SU (J Clin Oncol. 2011; 29:606s; abstr 10007). This phase III, randomized, double-blind, placebo-controlled trial evaluated the efficacy and safety of REG for this unmet clinical need. Methods: Eligible pts had metastatic and/or unresectable GIST, objective failure of both prior IM and SU (progressive disease [PD] on, or intolerance to, IM and PD on SU), ≥1 measurable lesion, ECOG performance status 0 or 1. Pts were randomized 2:1 to receive best supportive care plus either REG 160 mg po once daily (3 wks on/1 wk off) or placebo (PL). The primary endpoint was progression-free survival (PFS) (modified RECIST 1.1, independent central review). Secondary endpoints included overall survival (OS), disease control rate (DCR, defined as rate of partial response [PR] plus stable disease [SD] lasting for ≥12 wks), response rate and duration, safety and correlative genotype analyses. At time of PD, pts were eligible for unblinding and crossover to open-label REG. Results: Between Jan and Aug of 2011, 234 pts were screened; 199 were randomized (REG: 133, PL: 66). Pts were stratified at randomization according to number of prior systemic therapies and geographical region. Baseline characteristics were balanced between the two arms. The primary endpoint was met: median PFS was 4.8 months for REG vs. 0.9 months for PL. Hazard ratio for PFS was 0.27 (95% CI, 0.18-0.39), p<0.0001. PFS rates at 3 and 6 months were 60% and 38% for REG vs. 11% and 0% for PL. DCR was 53% (REG) vs. 9% (PL).The HR for OS was 0.77 (p=0.20) with 85% PL pts having crossed over to REG. The most common > grade 3 treatment-emergent AEs in the REG arm during double-blind study were hypertension (28%), hand-foot skin reaction (21%), and diarrhea (8%). Conclusions: This randomized trial demonstrated that REG significantly improved PFS and DCR in pts with advanced GIST after failure of at least prior IM and SU. REG was well tolerated, with AEs as expected for this class and manageable with dose modifications.

Results of a phase III, randomized, double-blind, placebo-controlled trial of pegfilgrastim (PEG) in patients (pts) receiving first-line FOLFOX or FOLFIRI and bevacizumab (B) for colorectal cancer (CRC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3575-3575
Author(s):  
Tamas Pinter ◽  
Esteban Abella ◽  
Alvydas Cesas ◽  
Adina Croitoru ◽  
Jochen Decaestecker ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Phase Iii ◽  
First Line ◽  
Double Blind ◽  
Free Survival ◽  
Clinically Significant ◽  
Grade 3

3575 Background: The literature reports that adding biologics to chemotherapy (ctx) may increase the incidence of clinically significant neutropenia. his trial was conducted to evaluate the efficacy of PEG in reducing the incidence of febrile neutropenia (FN) in pts with locally-advanced (LA) or metastatic (m)CRC receiving first-line treatment with either FOLFOX/B or FOLFIRI/B. Methods: Key eligibility: ≥ 18 years old; measurable, nonresectable CRC per RECIST 1.1. Pts were randomly assigned 1:1 to either placebo or 6 mg PEG ~24 h after ctx/B. The study treatment period included four Q2W cycles, but pts could continue their assigned regimen until progression. Pts were stratified by region (North America vs rest of world), stage (LA vs mCRC), and ctx (FOLFOX vs FOLFIRI). Estimated sample size (N = 800) was based on the expected incidence of grade 3/4 FN (primary endpoint) across the first 4 cycles of ctx/B, powered for PEG superiority over placebo. Other endpoints included overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Results: 845 pts were randomized (Nov 2009 to Jan 2012) and received study treatment; 783 pts completed 4 cycles of ctx/B. Median age was 61 years; 512 (61%) pts were male; 819 (97%) had mCRC; 414 (49%) received FOLFOX, and 431 (51%) received FOLFIRI. Grade 3/4 FN (first 4 cycles) for placebo vs PEG was 5.7% vs 2.4%; OR 0.41; p = 0.014. A similar incidence of other ≥ grade 3 adverse events was seen in both arms (28% placebo; 27% PEG). See table for additional results. Conclusions: PEG significantly reduced the incidence of grade 3/4 FN in this pt population receiving standard ctx/B for CRC. Follow-up is ongoing. Clinical trial information: NCT00911170. [Table: see text]

Randomized phase II study of pharmacodynamic separation (PDS) of pemetrexed (Pem) and erlotinib (Erl) versus pem alone in patients (pts) with advanced non-small cell lung cancer (NSCLC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8097-8097 ◽  
Author(s):  
Tianhong Li ◽  
Bilal Piperdi ◽  
William Vincent Walsh ◽  
Mimi Kim ◽  
Rasim Gucalp ◽  
...  
Keyword(s):  
Phase Ii ◽  
Primary Endpoint ◽  
Performance Status ◽  
Progression Free Survival ◽  
Dose Schedule ◽  
Phase Iii ◽  
Smoking History ◽  
Clinical Activity ◽  
P Value ◽  
Randomized Phase Ii

8097 Background: Preclinical and phase I studies showed that PDS optimizes cytotoxicity of concurrent EGFR inhibitors and chemotherapy. We conducted a randomized phase II trial to assess relative efficacy of Pem alone (Arm A) versus Pem +Erl on a PDS dose-schedule (Arm B) as 2nd-line therapy in pts with advanced NSCLC (NCT00950365). Methods: Eligible pts were randomized 2:1 (Arm B: A), stratified by sex, smoking history, and performance status (0/1 vs 2). Accrual was restricted to non-squamous histology in 2009. Treatment: Arm A – Pem 500 mg/m2IV on day 1; Arm B – Pem + Erl 150 mg po QD on days 2-17. 1 cycle = 3 weeks. Primary endpoint was progression-free survival (PFS). 50 pts in Arm B were needed to detect an increase in median PFS from ~3 to 4.5 months. Results: 83 pts were entered. Age: 63 yo. Female: 42 (53%). Smoking ≥15PY: 58 (72%). Nonsquamous: 78 (99%). The primary endpoint of the study was met: Efficacy results from 79 eligible pts showed 1.6-fold longer PFS in Arm B (4.6 m) compared to Arm A (2.8 m). Although the study was not designed to directly compare two arms, p value was 0.052. Toxicity: G3/4 Hem (A/B): 8(30%)/12(23%); Neutropenia with infection (A/B): 0/3(6%). G3/4 Non-Hem (A/B): skin rash: 0/3(6%); diarrhea: 0/2(4%); joint pain: 1(4%)/6(11.5%). Treatment related death (A/B): 0/1. Interstitial lung disease (A/B): 0/1. Conclusions: PDS of Pem and Erl is well tolerated and has promising clinical activity in 2nd-line non-squamous NSCLC. Ongoing correlative studies aim to identify a subgroup of patients who might benefit most from this treatment, which will guide the design of a confirmatory phase III study. (UL1 RR024146, P30CA093373, Lilly, Astellas) Clinical trial information: NCT00950365. [Table: see text]

Sign in / Sign up

Export Citation Format

Share Document