Cyclandelate in the Prophylaxis of Migraine: A Placebo-Controlled Study

Cephalalgia ◽  
2001 ◽  
Vol 21 (1) ◽  
pp. 66-70 ◽  
Author(s):  
HC Diener ◽  
P Krupp ◽  
T Schmitt ◽  
G Steitz ◽  
K Milde ◽  
...  
Keyword(s):  
Baseline Period ◽  
Migraine Prophylaxis ◽  
Study Endpoint ◽  
Controlled Study ◽  
Primary Study ◽  
Parallel Group ◽  
Primary Study Endpoint ◽  
Placebo Phase ◽  
Secondary Endpoints ◽  
Autonomic Disturbances

The prophylactic action of cyclandelate was investigated in a multicentre, randomized, placebo-controlled, parallel group study. A 4-week baseline period was followed by a 4-week placebo phase and a 16-week treatment period with either 1600 mg cyclandelate or placebo. Patients ( n = 251) with two to six migraine attacks/month were randomized. Neither the primary study endpoint (reduction of migraine days from baseline to the last 28 days) nor most of the secondary endpoints (reduction in the number of migraine attacks, severity or duration of attacks, frequency of autonomic disturbances, medication for treatment of attacks) showed a difference between cyclandelate and placebo. Cyclandelate, however, was superior to placebo in a global impression of efficacy rated by the patients and the treating physicians. Both treatments were well tolerated. In conclusion, cyclandelate was not superior to placebo in the prophylaxis of migraine with regard to parameters usually used in migraine prophylaxis trials.

Bevacizumab biosimilar and reference bevacizumab in subjects with stage IIIB/IV no squamous non-small cell lung cancer (NSCLC) (STELLA study): Results for the primary endpoint in a confirmatory, double-blind, randomized, controlled study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21542-e21542
Author(s):  
Susana Millan ◽  
Dmytro Trukhin ◽  
Oleksii Kolesnik ◽  
Elena Poddubskaya ◽  
Andric Zoran ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Objective Response ◽  
Stage Iiib ◽  
Study Endpoint ◽  
Controlled Study ◽  
Primary Study ◽  
Double Blind ◽  
Study Results ◽  
Significant Difference ◽  
Secondary Endpoints

e21542 Background: MB02 is a proposed biosimilar of the reference bevacizumab. A multinational, double-blind, randomized, parallel group clinical study (STELLA) is undergoing to confirm clinical similarity between MB02 and bevacizumab in patients with stage IIIB/IV no squamous NSCLC. Methods: Subjects were randomized 1:1 to MB02 or bevacizumab (15 mg/kg) plus chemotherapy (paclitaxel [P] 200 mg/m2 and carboplatin [C] AUC6) on Day 1 of every 3-week cycle for 6 cycles (Week 18) followed by MB02/bevacizumab in blinded monotherapy until disease progression, treatment intolerance, death, patient withdrawal or end of study (Week 52). As primary study endpoint, the efficacy by means of the objective response rate (ORR) evaluated by an independent radiological committee (IRC) was compared between arms at Week 18. Secondary endpoints were Progression Free Survival (PFS) and Overall Survival (OS), safety and immunogenicity (assessed at 18 and 52 weeks). Results: 627 patients were randomized: MB02 (n = 315) and bevacizumab (n = 312). Demographic and baseline characteristics were well balanced between arms. The ORR results were comparable for subjects receiving MB02 or bevacizumab plus P/C. A Risk Ratio (RR) of 1.013 (90% CI: -0.037% to 0.059) and a Risk Difference (RD) of 0.011 (90% CI: -0.037% to 0.059), were within the similarity margin predefined by FDA (0.73, 1.36) and EMA (-12%, +12%) respectively. This ORR assessed by IRC was consistent with the investigator assessment criteria. There was no significant difference between arms for secondary efficacy endpoints (PFS/OS) at week 18. Up to primary endpoint cut-off point, the safety assessment showed no significant differences between MB02 and bevacizumab arms (including the immunogenicity assessment) in terms of nature, frequency and severity of the adverse events (AE), being anaemia and hypertension the most common IMP-related AEs, with a RD between treatment groups < 5%. New signals or observable trends were no reported for MB02-treated subjects. Additional information on the secondary endpoints will be available at week 52 (end of monotherapy period). Conclusions: The statistical analysis executed for ORRs confirm the equivalence of MB02 and bevacizumab, supporting the clinical activity of MB02 treatment. MB02 was well tolerated with manageable AEs in patients with Stage IIIB/IV NSCLC. Clinical trial information: NCT03296163.

Efficacy and Tolerability of Amitriptylinoxide in the Treatment of Chronic Tension-Type Headache: A Multi-Centre Controlled Study

Cephalalgia ◽  
1994 ◽  
Vol 14 (2) ◽  
pp. 149-155 ◽  
Author(s):  
V Pfaffenrath ◽  
H-C Diener ◽  
H Isler ◽  
C Meyer ◽  
E Scholz ◽  
...  
Keyword(s):  
Adverse Events ◽  
Tension Type Headache ◽  
Study Endpoint ◽  
Controlled Study ◽  
Primary Study ◽  
Chronic Tension Type Headache ◽  
Headache Intensity ◽  
Primary Study Endpoint ◽  
Significant Difference ◽  
Type Headache

Amitriptyline is the medication of first choice in the treatment of chronic tension-type headache. In 197 patients with chronic tension-type headache (87M and 110F with a mean age of 38 ±13 (18–68)) efficacy and tolerability of 60–90 mg amitriptylinoxide (AO) were compared with 50–75 mg amitriptyline (AM) and placebo (PL) in a double-blind, parallel-group trial consisting of a four weeks' baseline phase and 12 weeks of treatment. The primary study endpoint was a reduction of at least 50% of the product of headache duration and frequency and a reduction of at least 50% in headache intensity. Statistics used were Fisher's exact test and analysis of variance. No significant difference emerged between AO, AM and PL with respect to the primary study endpoint. Treatment response occurred in 30.3% of the AO, 22.4% of the AM and 21.9% of the PL group. A reduction in headache duration and frequency of at least 50% was found in 39.4% on AO, in 25.4% on AM and in 26.6% on PL (PAO-PL = .1384, PAM-PL = 1.000, PAO-AM = .0973). A reduction in headache intensity of at least 50% was found in 31.8% on AO, in 26.9% on AM and in 26.6% on PL (PAO-PL = .5657, PAM-PL = 1.000, PAO-AM = .5715). Trend analysis with respect to a significant reduction of headache intensity ( p < 0.05) and the product of headache duration and frequency revealed a superior effect of AO. Adverse events occurred in 75.8% on AO, 82.1% on AM and 76.6% on PL (PAO-PL = 1.000, PAM-PL =.5188, PAO-AM = .4017). Neither depressive symptoms, measured by the SCL-90-R, nor study drug-related adverse events had any influence on the results.

Randomized phase III trial comparing vincristine, actinomycin, cyclophosphamide (VAC) with VAC/V topotecan/cyclophosphamide (TC) for intermediate risk rhabdomyosarcoma (IRRMS). D9803, COG study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 9509-9509 ◽  
Author(s):  
C. A. Arndt ◽  
D. S. Hawkins ◽  
J. A. Stoner ◽  
M. D. Wharam ◽  
D. A. Rodeberg ◽  
...  
Keyword(s):  
Local Therapy ◽  
Phase Iii ◽  
Study Endpoint ◽  
Primary Study ◽  
Significant Activity ◽  
Undifferentiated Sarcoma ◽  
Primary Study Endpoint ◽  
Alpha Level ◽  
Adequate Organ Function

9509 Background: IRRMS was defined as nonmetastatic alveolar (A) RMS or undifferentiated sarcoma (UDS); stage (stg) 2 and 3, group (gr) III embryonal (E) RMS; stg 4 ERMS <10y. IRRMS had a 5 yr failure free survival (FFS) of 64% on IRS IV. Since T alone and with C has significant activity in RMS, we tested whether alternating VAC/VTC improved FFS for IRRMS compared with VAC alone. Methods: Patients (pts) < 50 y with IRRMS with adequate organ function were randomized to 39 wks of VAC (V=1.5 mg/m2, A=0.045 mg/kg, C=2.2 g/m2 q 3 wk) vs VAC alternating with VTC (T=0.75 mg/m2/d ×5, C=250 mg/m2/d ×5 q 3 wk), with additional wkly V; doses adjusted for age <3y; local therapy was after wk 12. Pts with parameningeal RMS/meningeal extension (PME) were nonrandomly treated with VAC and immediate XRT. Primary study endpoint was FFS. The study was designed with 80% power (5% 2-sided alpha level) to detect an increase in 5 yr FFS from 64% to 75%, a relative risk (RR) of 0.64, with VAC/VTC, requiring 518 randomized pts. Results reflect the 3rd of 4 planned analyses (75% information); O'Brien Fleming adjusted alpha level is 0.0166; and Cox PH model was used. Results: 620 eligible pts were entered from 9/99 to 8/05: 266 randomized to VAC, 253 to VAC/VTC, 101 PME patients were nonrandomly treated with VAC. Treatment strata were ERMS stg 2/3, gr III 37%; ERMS grp IV <10 y 6%; ARMS/UDS stg 1 or gr I 16%; ARMS/UDS other 25%; PME 16%. 3% of pts were <1 y, 69% 1–9 y, 28% ≥10 y; 13% of pts were stg 1; 26% stg 2; 54% stg 3; 7% stg 4. 77% pts had gr III tumors. Primary tumor sites were PM in 35% pts, extremity 15%, bladder/prostate 16%, retroperitoneal/perineal 15%, other 19%. Median follow up is 2.4 yrs. FFS at 2 yrs is 77% with VAC and 72% with VAC/VTC. Observed data are inconsistent with hypothesized improvement under VAC/VTC (RR=1.20, 98.34% CI: 0.78–1.85, p=0.3). Similar patients on IRS IV had 2 yr FFS of 77%. 2 yr survival (OS) with VAC: 91%; VAC/VTC: 87% (RR=0.94, CI: 0.55–1.59, p=0.8). There were 12 2nd malignancies and 10 deaths as first events. 4 of 10 deaths were from hepatopathy, which decreased in incidence following dose changes for A and C. Conclusions: In IRRMS, VAC/VTC does not significantly improve FFS nor OS versus VAC, and outcome is similar to IRS IV. No significant financial relationships to disclose.

Cetuximab with or without sorafenib in recurrent/metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 6047-6047 ◽  
Author(s):  
Jill Gilbert ◽  
Michael J. Schell ◽  
Xiuhua Zhao ◽  
Barbara A. Murphy ◽  
Tawee Tanvetyanon ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Single Agent ◽  
Infusion Reaction ◽  
Study Endpoint ◽  
Controlled Study ◽  
Primary Study ◽  
Clinical Activity ◽  
Patients Âgés ◽  
Significant Difference ◽  
The Mean

6047 Background: For patients with R/M SCCHN, cetuximab, a monoclonal antibody against EGFR, is approved as a single agent and has a survival benefit when combined with chemotherapy. We hypothesized that addition of sorafenib, a multi-kinase inhibitor of targets including VEGFR, to cetuximab may have greater clinical benefit than cetuximab alone. Methods: This trial was designed as a blinded, randomized phase II, placebo-controlled study of cetuximab at 400 mg/m2 IV on day 1 followed by 250 mg/m2 IV weekly plus placebo bid (Arm A) or cetuximab at the same dose and schedule plus sorafenib 400 mg po bid (Arm B), each in 21 day cycles. After 19 patients were enrolled, the trial was amended to remove the placebo (and blinding) due to issues with placebo tablet solubility. Target sample size was 84 patients with 83% power to detect a 2-month increase in PFS, the primary study endpoint. Interim analysis was planned at midpoint, requiring hazard ratio < 1 to proceed to the second stage of study. Serum cytokine and tumor HPV ISH and p16 analyses were performed. Results: Of 56 patients (ages 26-74, 80% male) enrolled, 53 patients received treatment and 41 were evaluable for response. Of the patients who received therapy, 26 received cetuximab only (Arm A). For Arm A, the mean number of cycles delivered was 4.3 (range 1-16) and the mean for Arm B was 3.3 (range 1-11). The most common grade 3/4 AEs were fatigue (2 A, 1 B), hypertension (3 B), infusion reaction (both arms), and diarrhea (2 B). Arm A had 2 PRs and Arm B had 4 PRs. Median OS was 7 mo and 5.9 mo respectively. Median PFS was 3.1 mo for both arms. 24 patients had pre-treatment cytokine measurements. Of the 12 measured cytokines, high TGFB1 level was significantly correlated with inferior PFS (4.6 mo vs 1.6 mo), regardless of arm (p=0.015). 38 patients had tumors available for p16 staining (31 neg and 7 pos). 3 of 7 p16 pos were also HPV ISH pos. The p16 neg patients had significantly improved PFS (3.5 mo vs 1.6 mo) regardless of arm (p=0.032) but no difference in OS (p=1.0). Conclusions: Both arms demonstrated clinical activity although no significant difference was observed. However, a subset of patients with p16 neg tumors or low serum TGFB1 may have a greater benefit with cetuximab-based therapy. Clinical trial information: NCI-2012-02847.

Randomised, Double Blind, Multicentre, Placebo Controlled Study of Sulodexide in the Treatment of Venous Leg Ulcers

2002 ◽  
Vol 87 (06) ◽  
pp. 947-952 ◽  
Author(s):  
Gaetano Scondotto ◽  
Giancarlo Agnelli ◽  
Daniele Aloisi ◽  
Ernesto Palazzini ◽  
Villiam Zamboni ◽  
...  
Keyword(s):  
Ulcer Healing ◽  
Time Course ◽  
Local Treatment ◽  
Additional Patient ◽  
Study Endpoint ◽  
Controlled Study ◽  
Primary Study ◽  
Number Needed To Treat ◽  
Leg Ulcers ◽  
Venous Leg Ulcers

SummarySulodexide, a highly purified glycosaminoglycan, was investigated for treatment of venous leg ulcers. Patients (n = 235) undergoing local treatment including wound care and compression bandaging, were randomised to receive either sulodexide or matching placebo for three months. Primary study endpoint was complete ulcer healing after 2 months; secondary endpoints were ulcer healing at 3 months and the time-course changes of ulcer areas.The proportion of patients with complete ulcer healing was higher with sulodexide at 2 months (p = 0.018) and 3 months. The “number needed to treat” to obtain one additional patient healed with sulodexide was 7 at 2 months and 5 at 3 months. The changes in ulcer surface area with time were significant for sulodexide only (p = 0.004). Fibrinogen significantly decreased in sulodexide patients (p = 0.006).In conclusion, sulodexide associated with local treatment proved to be effective and well tolerated in the management of venous leg ulcers.

scholarly journals 7.0 T MRI Detection of Cerebral Microinfarcts in Patients with a Symptomatic High-Grade Carotid artery Stenosis

2014 ◽  
Vol 34 (10) ◽  
pp. 1715-1719 ◽  
Author(s):  
Alexandra AJ de Rotte ◽  
Wouter Koning ◽  
Anne G den Hartog ◽  
Sandra M Bovens ◽  
Jaco JM Zwanenburg ◽  
...  
Keyword(s):  
Carotid Artery ◽  
Carotid Artery Stenosis ◽  
Artery Stenosis ◽  
Study Endpoint ◽  
Primary Study ◽  
High Grade ◽  
Contralateral Hemisphere ◽  
Symptomatic Carotid ◽  
Primary Study Endpoint ◽  
Fluid Attenuated Inversion Recovery

In the current study, the presence of cerebral cortical microinfarcts (CMIs) was evaluated in a series of 21 patients with a symptomatic high-grade > 50% stenosis of the carotid artery. A T2-weighted fluid-attenuated inversion recovery sequence and a T1-weighted turbo field echo sequence of the brain were obtained at 7.0 Tesla magnetic resonance imaging. Primary study endpoint was the number of CMIs and macroinfarcts. In total, 53 cerebral infarcts (35 macroinfarcts; 18 CMIs) were found ipsilateral to the symptomatic carotid artery, in 14 patients (67%). In four of these patients, both CMIs and macroinfarcts were visible. In the contralateral hemisphere, seven infarcts (five macroinfarcts and two CMIs) were found in five patients (24%). In the ipsilateral hemispheres, the number of CMIs and macroinfarcts were significantly correlated ( P = 0.02). Unpaired comparison of medians showed that the number of CMIs in the ipsilateral hemisphere was significantly higher than the number of CMIs in the contralateral hemisphere ( P = 0.04). No significant correlation was found between stenosis grade and the number of any infarct. The current study shows that in symptomatic patients with significant extracranial carotid artery stenosis, CMIs are part of the total cerebrovascular burden and these CMIs prevail with a similar pattern as observed macroinfarcts.

scholarly journals Gaboxadol in Fragile X Syndrome: A 12-Week Randomized, Double-Blind, Parallel-Group, Phase 2a Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Dejan B. Budimirovic ◽  
Kelli C. Dominick ◽  
Lidia V. Gabis ◽  
Maxwell Adams ◽  
Mathews Adera ◽  
...  
Keyword(s):  
Adverse Events ◽  
Fragile X Syndrome ◽  
Fragile X ◽  
Autism Spectrum ◽  
Tonic Inhibition ◽  
Controlled Study ◽  
Primary Study ◽  
Double Blind ◽  
Study Objective ◽  
Parallel Group

Background: Fragile X syndrome (FXS), the most common single-gene cause of intellectual disability and autism spectrum disorder (ASD), is caused by a &gt;200-trinucleotide repeat expansion in the 5’ untranslated region of the fragile X mental retardation 1 (FMR1) gene. Individuals with FXS can present with a range of neurobehavioral impairments including, but not limited to: cognitive, language, and adaptive deficits; ASD; anxiety; social withdrawal and avoidance; and aggression. Decreased expression of the γ-aminobutyric acid type A (GABAA) receptor δ subunit and deficient GABAergic tonic inhibition could be associated with symptoms of FXS. Gaboxadol (OV101) is a δ-subunit–selective, extrasynaptic GABAA receptor agonist that enhances GABAergic tonic inhibition, providing the rationale for assessment of OV101 as a potential targeted treatment of FXS. No drug is approved in the United States for the treatment of FXS.Methods: This 12-weeks, randomized (1:1:1), double-blind, parallel-group, phase 2a study was designed to assess the safety, tolerability, efficacy, and optimal daily dose of OV101 5 mg [once (QD), twice (BID), or three-times daily (TID)] when administered for 12 weeks to adolescent and adult men with FXS. Safety was the primary study objective, with key assessments including treatment-emergent adverse events (TEAEs), treatment-related adverse events leading to study discontinuation, and serious adverse events (SAEs). The secondary study objective was to evaluate the effect of OV101 on a variety of problem behaviors.Results: A total of 23 participants with FXS (13 adolescents, 10 adults) with moderate-to-severe neurobehavioral phenotypes (Full Scale Intelligence Quotient, 41.5 ± 3.29; ASD, 82.6%) were randomized to OV101 5 mg QD (n = 8), 5 mg BID (n = 8), or 5 mg TID (n = 7) for 12 weeks. OV101 was well tolerated across all 3 treatment regimens. The most common TEAEs were upper respiratory tract infection (n = 4), headache (n = 3), diarrhea (n = 2), and irritability (n = 2). No SAEs were reported. Improvements from baseline to end-of-treatment were observed on several efficacy endpoints, and 60% of participants were identified as treatment responders based on Clinical Global Impressions-Improvement.Conclusions: Overall, OV101 was safe and well tolerated. Efficacy results demonstrate an initial signal for OV101 in individuals with FXS. These results need to be confirmed in a larger, randomized, placebo-controlled study with optimal outcomes and in the most appropriate age group.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT03697161

Ligand expression of the EGFR ligands amphiregulin, epiregulin, and amplification of the EGFR gene to predict for treatment efficacy in KRAS wild-type mCRC patients treated with cetuximab plus CAPIRI and CAPOX: Analysis of the randomized AIO CRC-0104 trial.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 3519-3519 ◽  
Author(s):  
Sebastian Stintzing ◽  
Andreas Jung ◽  
Christine Kapaun ◽  
Jana Reiche ◽  
Dominik Paul Modest ◽  
...  
Keyword(s):  
Treatment Efficacy ◽  
Progression Free Survival ◽  
Study Endpoint ◽  
Primary Study ◽  
Egfr Amplification ◽  
Egfr Gene ◽  
Egfr Ligands ◽  
Mutational Status ◽  
Primary Study Endpoint ◽  
Ligand Expression

3519^ Background: We investigated the expression of the EGFR ligands amphiregulin (AREG) and epiregulin (EREG) as well as the amplification of the EGFR-gene in tumor specimens of mCRC patients (pts) treated first-line with anti-EGFR targeted cetuximab together with CAPOX or CAPIRI. Expression levels were correlated with overall response rate (ORR), progression free survival (PFS) and overall survival (OS) to determine their relationship with effectiveness in this setting. Methods: A total of 185 mCRC pts were randomized to cetuximab (400mg/m² day 1, followed by 250mg/m² weekly) plus CAPIRI (irinotecan 200mg/m², day 1; capecitabine 800mg/m² twice daily days 1-14, every 3 weeks; 20% dose reduction of both agents for pts older than 65 years) or plus CAPOX (oxaliplatin 130mg/m² day 1; capecitabine 1000mg/m² twice daily days 1-14, every three weeks). The primary study endpoint was ORR. KRAS mutational status did not correlate with treatment outcome. The cut-offs for EGFR-amplification using FISH, AREG and EREG levels determined by RT-qPCR were calculated using ROC analysis for ORR. Results: Within the subgroup of KRAS wildtype tumors, analysis of EREG- and AREG-expression was possible in 99 pts and of EGFR-amplification in 63 pts. Higher AREG levels correlated significantly with higher ORR (83% vs 46%, p=0.006, OR 0.31), longer PFS (9.6mo vs 4.9, p<0.001, HR 0.35) and longer OS (39.9mo vs 17.2mo, p<0.001, HR 0.36). Higher EREG levels showed a significant correlation with ORR (74% vs 47%, p=0.036, OR 0.54), longer PFS (7.9mo vs 4.9mo, p=0.026, HR 0.57) and OS (33.0mo vs 20.2mo, p=0.041, HR 0.57). EGFR-amplification correlated significantly with higher ORR (71% vs 33%, p=0.004, OR 0.49), longer PFS (8.4mo vs 4.6mo, p=0.004, HR 0.50) and longer OS (30.5mo vs 15.2mo, p=0.001, HR 0.44). Conclusions: In the treatment setting of cetuximab combined with CAIPIRI or CAPOX, AREG, EREG and EGFR-amplification predicted treatment efficacy. Within the subgroup of pts with KRAS wildtype tumors, EGFR-FISH and AREG expression have the strongest relationship with treatment efficacy.

A phase III, randomized, controlled study evaluating the efficacy and safety of idelalisib (GS-1101) in combination with ofatumumab for previously treated chronic lymphocytic leukemia (CLL).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. TPS7131-TPS7131 ◽  
Author(s):  
Ian Flinn ◽  
Eva Kimby ◽  
Finbarr E. Cotter ◽  
Francis J. Giles ◽  
Ann Janssens ◽  
...  
Keyword(s):  
B Cells ◽  
Lymphocytic Leukemia ◽  
Phase Iii ◽  
Study Endpoint ◽  
Controlled Study ◽  
Rank Test ◽  
Primary Study ◽  
Lymphoid Tissues ◽  
Mutational Status ◽  
Previously Treated

TPS7131 Background: PI3K-delta is critical for activation, proliferation and survival of B cells and plays a role in homing and retention in lymphoid tissues. PI3Kδ signaling is hyperactive in many B-cell malignancies. Idelalisib is a first-in-class, selective, oral inhibitor of PI3Kδ that reduces proliferation, enhances apoptosis, and inhibits homing and retention of malignant B cells in lymphoid tissues (Lannutti et al, 2011). Ofatumumab (O) is an anti-CD20 monoclonal antibody approved for the treatment of pts with CLL refractory to fludarabine and alemtuzumab. Phase 1 studies demonstrated that idelalisib, as monotherapy or combined with O, is highly active in pts with heavily pretreated CLL: pts experienced profound and rapid regression of lymphadenopathy, reductions in disease-associated chemokines, and durable clinical benefit with an acceptable safety profile (Furman et al, 2012). Methods: This study will enroll 210 pts with CLL previously treated with a purine analog and/or bendamustine, with measurable lymphadenopathy who require treatment for CLL and have disease that is not refractory to ofatumumab, and are expected to benefit from a change in therapy because of CLL progression <24 months since completion of their last prior treatment. Pts are randomized in a 2:1 ratio (Arm A:Arm B). In Arm A, pts receive idelalisib at 150 mg BID continuously in combination with 12 infusions of O at 1000 mg over ~24 weeks (weekly x 8 then monthly x 4). In Arm B, pts receive 12 infusions of O at 2,000 mg over ~24 weeks. Stratification factors address IGHV mutational status, del(17p)/p53 mutation status, and refractory vs relapsed disease. The primary study endpoint is PFS. Secondary endpoints include ORR, lymph node response rate, CR rate, and OS. This is an event-driven trial and primary endpoint evaluation will be based on independent central review. For the primary efficacy analysis, the difference in PFS between the treatment arms will be assessed in the ITT analysis set using Kaplan-Meier methods and the stratified log-rank test. The study opened for enrollment in Dec 2012. Clinical trial information: NCT01659021.

Randomized phase II study of adjuvant afatinib for three months versus two years in patients with resected stage I-III EGFR mutant NSCLC.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 8507-8507
Author(s):  
Jamie E. Chaft ◽  
Daniel Botelho Costa ◽  
Alona Muzikansky ◽  
Joseph B Shrager ◽  
Michael Lanuti ◽  
...  
Keyword(s):  
Adjuvant Therapy ◽  
Recurrence Rate ◽  
Stage I ◽  
Study Endpoint ◽  
Primary Study ◽  
Drug Discontinuation ◽  
Recurrence Rates ◽  
Primary Study Endpoint ◽  
Resected Stage

8507 Background: EGFR tyrosine kinase inhibitors are superior to chemotherapy in patients with advanced EGFR+ lung cancers. In the adjuvant setting, erlotinib for two years improves recurrence free survival (RFS) compared to historical controls. The optimal duration of adjuvant TKI is unknown. Methods: Patients with completely resected Stage I-III NSCLC with a sensitizing EGFR mutation were enrolled after standard adjuvant therapy. Pts were randomly assigned to 3 months (3m) or 2 years (2y) of adjuvant afatinib. Afatinib was started at 30 mg by mouth daily. Patients without toxicity after 28 days were allowed to escalate to 40 mg daily. Patients were imaged with CT every 6 months for 3 years and then annually or as clinically indicated. RFS was measured from the date of randomization. The primary study endpoint was recurrence rate at 2 years. 60 randomized patients would provide 82.5% power to detect a 26% difference in 2y-recurrence rate. Results: Patient characteristics are in the Table. The study was terminated for slow accrual after 46 of the planned 60 patients. Planned treatment was completed by 92% (22/24) pts in the 3m arm and 41% (9/22) of pt in the 2y arm. 22 patients required ≥1 dose modification due to toxicity including expected GI, mucosal, and skin AEs. With a median follow-up of ≥38 months there were 10 recurrences and 3 deaths in the 3m arm and there were 5 recurrences (2 on treatment) and 2 deaths in the 2y arm. Median RFS has not been reached in either arm, but recurrence was more common in the 3m arm at every landmark. 2y-recurrence rates were 29% for 3m and 15% for 2y. Conclusions: Recurrences at 2 years were 14% less common with 2y versus 3m of adjuvant afatinib. This difference did not meet the primary study endpoint. The RFS curves show a durable and clinically meaningful separation with substantial follow-up. Failure to meet significance was likely influenced by under-accrual and early drug discontinuation on the 2y arm. In the era of TKIs with improved tolerance, duration of adjuvant therapy remains an important question. Clinical trial information: NCT01746251. [Table: see text]

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