ABOUND.70+: Safety and efficacy of nab-paclitaxel/carboplatin (nab-P/C) in elderly patients (pts) with advanced non-small cell lung cancer (NSCLC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9059-9059 ◽  
Author(s):  
Corey J. Langer ◽  
Eric C. Anderson ◽  
Robert M. Jotte ◽  
Jonathan Wade Goldman ◽  
Daniel Ernest Haggstrom ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Type I Error ◽  
Locally Advanced ◽  
Dose Intensity ◽  
Median Number ◽  
Phase Iii ◽  
Type I ◽  
Weekly Dose ◽  
Safety And Efficacy ◽  
Grade 3

9059 Background: Treatment (tx) of elderly pts with NSCLC is challenging. nab-P/C demonstrated efficacy in a subset of pts with NSCLC ≥ 70 y in a phase III trial. ABOUND.70+ was designed to determine whether a 1-week break can further improve tolerability of nab-P/C in pts ≥ 70 y with NSCLC. Safety and efficacy were evaluated and are reported. Methods: Pts ≥ 70 y with tx-naive locally advanced/metastatic NSCLC were randomized (1:1) nab-P 100 mg/m2 d 1, 8, 15 + C AUC 6 d 1 q3w (Arm A) or the same nab-P/C dose q3w followed by a 1-week break (Arm B). Primary endpoint: percentage of pts with either grade ≥ 2 peripheral neuropathy (PN) or grade ≥ 3 myelosuppression AEs. Key secondary endpoints: PFS, ORR, OS, for which statistical analyses do not control for type I error ( Pvalues unadjusted). Results: At interim evaluation, the primary endpoint was similar across arms, resulting in early closure of enrollment. In Arms A and B, 71 and 72 pts were randomized; median age was 76 and 75 y, majority of pts were male (57.7% vs 55.6%) and had ECOG PS 1 (70.4% vs 72.2%). There were no differences in histology across tx arms. See table for primary endpoint data. Median number of tx cycles for Arms A and B was 4.0 and 5.5, median cumulative nab-P dose was 875.0 and 1287.5 mg/m2, and median weekly dose intensity was 62.0 and 54.1 mg/m2. nab-P dose modifications (Arms A and B): ≥ 1 dose reduction in 64.7% and 58.6%, ≥ 1 dose delay in 58.8% and 48.6%, and ≥ 1 missed dose in 80.9% and 72.9%, respectively. Median PFS (Arms A and B) 3.9 vs 7.0 mo (HR 0.49; 95% CI, 0.30 - 0.79; P = 0.003), confirmed ORR 23.9% vs 40.3% ( P = 0.037), and median OS 15.2 vs 16.2 mo (HR 0.76; 95% CI, 0.46 - 1.26; P= 0.292). Conclusions: Incidence of grade ≥ 2 PN or grade ≥ 3 myelosuppression AEs was similar between the 2 nab-P/C schedules in pts ≥ 70 y with advanced NSCLC. There appears to be a signal of improvement in PFS and ORR observed in Arm B, potentially due to increased tx exposure. NCT02151149 Clinical trial information: NCT02151149. [Table: see text]

Randomized double blind (DB) placebo (Plcb) controlled phase III study assessing the efficacy of xaliproden (X) in reducing the cumulative peripheral sensory neuropathy (PSN) induced by the oxaliplatin (Ox) and 5-FU/LV combination (FOLFOX4) in first-line treatment of patients (pts) with metastatic colorectal cancer (MCRC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3507-3507 ◽  
Author(s):  
J. Cassidy ◽  
G. A. Bjarnason ◽  
T. Hickish ◽  
C. Topham ◽  
M. Provencio ◽  
...  
Keyword(s):  
Cumulative Dose ◽  
Significant Risk ◽  
Dose Intensity ◽  
Sensory Neuropathy ◽  
Median Number ◽  
Phase Iii ◽  
First Line ◽  
Double Blind ◽  
Grade 3

3507 Background: X, an orally administered non-peptide neurotrophic agent developed by sanofi-aventis, was shown in vitro to minimize neuritic damage induced by Ox (co-culture of Schwann cells and dorsal roots ganglia explant). The probability of occurrence of Grade (Gr) 3–4 PSN at a cumulative dose of Ox of 1000 mg/m2, was consistently reported to be of 18–20%. Methods: First line MCRC pts were randomized to receive, in a DB fashion, FOLFOX4 and either Plcb or X 1mg daily. X was administered from the 1st day of chemotherapy till 15 days post last Ox cycle. Co-primary objectives were reduction in the risk of occurrence of Gr 3–4 PSN relative to cumulative dose of Ox (Kaplan-Meier method) and non-inferiority in response rate (RR). Secondary endpoints included evaluation of sensory action potential (SAP) and safety. Results: From July 2002 to May 2004, 649 pts were randomized (324 Plcb, 325 X). Pts characteristics were well balanced across arms, median number of Ox cycles was 12 in both arms, median relative dose intensity (%) was 83.8 (Plcb) and 85.2 (X). A significant risk reduction of 39% in the probability of Grade 3–4 PSN in favor of X was reported (hazard ratio [95% CI] = 0.61 [0.40; 0.93], p= 0.0203). Overall RR [95 % CI] was: Plcb 42.6% [37.1; 48.2] and X 44.9% [39.4; 50.6]. As prospectively defined in the protocol, the lower bound of the CI of the RR ratio above 0.8 confirms noninferiority in RR (1.055 [0.88; 1.26]). In both arms the mean % of change in SAP worsens as a function of PSN severity. 17.3 (Plcb) and 13.5% (X) of the pts discontinued Ox because of PSN. Severe toxicities (% Gr 3–4), reported with a ≥2% difference between arms, were (plcb vs X): diarrhea 10.9 vs 13.0, pulmonary embolism 0.9 vs 3.1, fatigue 3.7 vs 1.5, neutropenia 43.0 vs 37.8. Conclusion: X was shown to be efficient in reducing the risk of Grade 3–4 oxaliplatin-induced PSN without impacting FOLFOX4 antitumor activity. No significant financial relationships to disclose.

GDC-0449 in patients with advanced chondrosarcomas: A French Sarcoma Group (FSG)/French and U.S. National Cancer Institutes phase II collaborative study.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10005-10005 ◽  
Author(s):  
Antoine Italiano ◽  
Axel Le Cesne ◽  
Philippe A Cassier ◽  
Isabelle Ray-Coquard ◽  
Julien Domont ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Type I Error ◽  
Tumour Size ◽  
Collaborative Study ◽  
Molecular Data ◽  
Oral Route ◽  
Type I ◽  
Phase 2 Clinical Trial ◽  
Grade 3 ◽  
Unacceptable Toxicity

10005 Background: Chondrosarcomas (CS) exhibit a strong activation of hedgehog (Hh) signaling which plays a crucial role in cartilage tumorigenesis. Preclinical data show that hedgehog blockade reduces strongly chondrosarcoma cell proliferation and tumour size. GDC-0449 is a small-molecule antagonist of the Hh pathway. Methods: This is a multicentric single-arm phase 2 clinical trial based on two-stage Simon’s design which assesses safety and efficacy of GDC-0449 in patients (pts) with advanced CS. All pts had to have documented progressive disease (PD) as per RECIST 1.1 before study entry. Pts receive GDC-0449 150mg (oral route), daily until PD or unacceptable toxicity. The primary endpoint is the 6-month non-PD rate according to RECIST. Based on the following hypotheses: 20% 6-month non-PD rate (H0), 40% acceptable 6-month non-PD rate (H1), 10% type I error rate, 90% power, a total of 37 assessable pts are necessary (17 for the first stage + 20 for the second stage). Following the inclusion of the first 17 pts, if ≥ four pts are progression-free at 6 months, the accrual will continue. In order to account for not assessable pts (+/- 10%), 41 pts will be recruited. Accrual started in February 2011 in six centers of the FSG. Results: As of January 24 2012, 40 pts (28 males, 12 females) have been included in the study. Median age is 59 years (30-86). The most frequent histological subtype is conventional CS (n=32). Twenty eight pts (70%) had grade 1 or 2 adverse events (AE) possibly related to the drug whereas 3 pts (7.5%) had grade 3 or 4 AE. The planned interim statistical analysis performed after central histological and radiological review showed that four patients out of the first 17 evaluable patients had stable disease indicating that GDC-0449 had reached the primary endpoint to justify continuing accrual after the 1st step of the study. 15 pts are still on treatment. Molecular analyses are available for 21 pts. No mutation of SMO was detected. qRT-PCR experiments and PTCH sequencing are ongoing. Conclusions: GDC-0449 is well tolerated and shows some activity in a subset of pts with advanced CS. Final clinical and molecular data will be presented at the meeting.

Capecitabine plus irinotecan versus 5-FU/FA/irinotecan ± celecoxib in first line treatment of metastatic colorectal cancer (CRC). Long-term results of the prospective multicenter EORTC phase III study 40015

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3577-3577 ◽  
Author(s):  
J. De Grève ◽  
C. Koehne ◽  
J. Hartmann ◽  
I. Lang ◽  
P. Vergauwe ◽  
...  
Keyword(s):  
Small Sample Size ◽  
Dose Intensity ◽  
Median Number ◽  
Small Sample ◽  
Phase Iii ◽  
Long Term Results ◽  
Safety Issues ◽  
Grade 3 ◽  
Ecog Ps ◽  
Stratified Analysis

3577 Background: Oral fluoropyrimidines in combination with irinotecan may be an alternative to infusional 5-FU/FA+irinotecan. Cox-2 inhibitors may enhance the antineoplastic activity of chemotherapy (CT). Methods: Patients with ECOG PS<2, age>18 and measurable disease were randomised in a 2×2 factorial design to FOLFIRI (Douillard’s regimen) or capecitabine 2×1g/m2 d1–14 plus irinotecan 250mg/m2 d1, qd22 (CAPIRI), and to daily celecoxib 2x400mg (C) or placebo (P). 692 patients were planned to compare PFS as primary endpoint. The trial was suspended after 85 pts (44 CAPIRI and 41 FOLFIRI) due to the occurrence of 8 fatal events unrelated to disease progression (Köhne, ASCO 2005, A3525). Results: Baseline characteristics were well balanced. Three pts did not start treatment. Of the pts who started CT, 53% (23/43) in the CAPIRI and 33% (13/39) in the FOLFIRI arms required a dose reduction. Grade ≥3 diarrhoea occurred in 37% (16/43) and 13 % (4/39) on CAPIRI and FOLFIRI, respectively. Median number of CT cycles: 3 (CAPIRI) and 5 (FOLFIRI). Median dose intensity for irinotecan: 83% (CAPIRI) and 85% (FOLFIRI). Response rate (RR): 5/23 (22%) in CAPIRI+C, 10/21 (48%) in CAPIRI+P, 6/19 (32%) in FOLFIRI+C and 10/22 (45%) in FOLFIRI+C. RR for CAPIRI vs FOLFIRI: 15/44 (34%) versus 16/41 (39%), RR for Celecoxib vs Placebo: 11/42 (26%) vs. 20/43 (46 %). Median PFS: 5.9 months (95% CI: 4.4–8.9) with CAPIRI vs 9.6 months (95% CI: 6.9–11.8) with FOLFIRI (HR=1.31, 95%CI: 0.8–2.1), and 6.9 months (95% CI: 5.5–10.4) with C vs 7.8 months (95% CI: 6.0–12.0) with P (HR=1.1, 95%CI: 0.7–1.8). Median OS: 14.8 months (95% CI: 10.7–18.3) with CAPIRI vs 19.9 months (95% CI: 18.9-n.a.) with FOLFIRI (HR=3.2, 95%CI: 1.4–7.3), and 18.3 months (95% CI: 10.2-n.a.) with C versus 19.9 months (95% CI: 16.7-n.a.) with P (HR=1.25, 95%CI: 0.6–2.6). Conclusions: The data suggest that celecoxib might reduce response to CT and this warrants further preclinical investigation. The stratified analysis failed to demonstrate the non-inferiority of CAPIRI as compared to FOLFIRI. Small sample size and confounding safety issues prevent us from drawing definitive conclusions. Results of larger studies would be needed. No significant financial relationships to disclose.

EORTC 18991: Long-term adjuvant pegylated interferon-alpha2b (PEG-IFN) compared to observation in resected stage III melanoma, final results of a randomized phase III trial

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8504-8504 ◽  
Author(s):  
A. M. Eggermont ◽  
S. Suciu ◽  
M. Santinami ◽  
W. Kruit ◽  
A. Testori ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Dose Intensity ◽  
Phase Iii ◽  
Stage Iii ◽  
Nodal Involvement ◽  
Free Survival ◽  
Ifn Therapy ◽  
Stage Iii Melanoma ◽  
Grade 3

8504 Background: EORTC 18991 is the largest adjuvant trial ever conducted in stage III melanoma. It assessed the efficacy and toxicity of long term PEG-IFN vs Observation (Obs.). Methods: PEG-IFN (Induction at 6μg/Kg/wk, sc, 8 weeks; followed by Maintenance at 3μg/Kg/wk, sc) for a total treatment duration of 5 years was compared to Obs. in 1256 patients (pts) with stage III melanoma (anyTN1–2M0 without in-transit metastases). Randomization was stratified for nodal involvement N1 (microscopic) vs N2 (palpable nodes), # of nodes, Breslow and ulceration of primary, sex and center. Distant Metastasis-Free Survival (DMFS) was the primary endpoint. Relapse-Free Survival (RFS) was the pre-specified regulatory primary endpoint. Overall survival (OS) was the secondary endpoint. Intent-to-treat analysis was performed. Results: Median follow-up was 3.8 yrs: HR = Hazard Ratio; NR = Not Reached In N1-pts (n=543) the benefit of PEG-IFN seemed more pronounced than in N2-pts (n=713): RFS (HR 0.73 p=0.02 and HR 0.86 p=0.12 for N1 and N2, respectively), DMFS (HR 0.75 p=0.03 and HR 0.94 p=0.53) and OS (HR 0.88 p=0.43 and HR 1.01 p=0.91). PEG-IFN therapy relative dose intensity (actual/planned dose while treated) reached median 88% (induction) and 83% (maintenance). 251 pts (40 %) stopped PEG-IFN because of toxicity. Grade 3–4 - mostly grade 3 - toxicities were reported in 45% (PEG-IFN), vs 12% (Obs.), including most frequently fatigue (15%), hepatotoxicity (10%) and depression (6%) with ECOG 0–1 Performance Status maintained in 83% of pts during maintenance. Conclusions: Long term PEG-IFN therapy in stage III melanoma had a significant and sustained impact on RFS, but not on DMFS and OS. Pts with only microscopic nodal involvement (Sentinel Node positive) seemed to have greater benefit in terms of both RFS and DMFS. Similar better effects of adjuvant IFN therapy in pts with lower disease burden are observed in 2 consecutive EORTC trials (18952 and 18991) involving 2644 pts. [Table: see text] [Table: see text]

Efficacy and safety of panobinostat (LBH-589), a histone-deacetylase inhibitor (HDACi), in patients (pts) with advanced, previously treated soft tissue sarcoma (STS) and sex cord tumors (SCT): A study from the French Sarcoma Group.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10027-10027 ◽  
Author(s):  
Philippe Alexandre Cassier ◽  
Anne Lefranc ◽  
Nicolas Penel ◽  
Christine Chevreau ◽  
Binh Bui Nguyen ◽  
...  
Keyword(s):  
Phase Ii ◽  
Type I Error ◽  
Treatment Options ◽  
Median Number ◽  
Type I ◽  
Phase Ii Trials ◽  
Open Label ◽  
End Point ◽  
Best Response ◽  
Grade 3

10027 Background: Treatment options are limited for pts with advanced pretreated STS. HDACi have shown activity in preclinical models of STS and SCT Methods: Pts with advanced pretreated STS and SCT were enrolled in this open label, single arm, multicenter phase II study. Panobinostat was given orally, 40 mg thrice per week. The primary end-point was 3-month progression-free rate according to RECIST 1.1 using central review. Fleming-A’Hern single-stage design for phase II trials was used, and assuming a type I error alpha of 5% with 90% power, 15/47 pts were needed to be progression free at 3 months to reject a rate of 20%. Results: Fifty three pts were enrolled between January 2010 and January 2011. Median age was 59 (range 21-79) years, and 22 (42%) pts were males, 13 had translocation-related sarcoma (TRS) and 4 had SCT. All but 5 pts had metastatic disease. The most common sites were the lung and the liver. All but one pt had documented disease progression prior to study entry. The median number of prior lines of therapy was 2 (range 1-7). Panobinostat dose was lowered to 20 mg thrice a week after 11 pts were enrolled based on the recommendation of an independent safety committee. Fifty-two pts were evaluable for toxicity (1 pt never received treatment), 48 pts (92%) reported at least one adverse event (AE) and 22 (42%) reported at least one treatment-related grade 3 or 4 AE. The most common grade 3/4 AEs were thrombocytopenia, fatigue and anemia. Fifty pts were evaluable for the primary end-point, of these, 12 pts (24%, 95%CI[13-38%]) were progression-free at 3 months, including 4/13 pts (31%, 95%CI[9-61%]) with TRS and 2/4 pts (50%, 95%CI[7-93%]) with SCT. No CR was seen, two patients (4%) with SCT had a PR and 19 pts (37%) had SD as their best response. Seven pts were progression-free at 6 months: 2 pts with SCT, 2 with TRS, 1 with liposarcoma, 1 with malignant solitary fibrous tumor and 1 with leiomyosarcoma. Conclusions: Panobinostat was poorly tolerated at 40 mg thrice a week. Efficacy in unselected advanced STS was limited although some patients had prolonged SD. Activity in pts with SCT warrants further investigation.

Radiation and Concurrent Carboplatin Administration in Locally Advanced Head and Neck Cancer

1995 ◽  
Vol 81 (5) ◽  
pp. 354-358 ◽  
Author(s):  
◽  
George Fountzilas ◽  
Dimosthenis Skarlos ◽  
Angelos Nikolaou ◽  
Anna Kalogera-Fountzila ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Head And Neck ◽  
Neck Cancer ◽  
Performance Status ◽  
Combined Treatment ◽  
Locally Advanced ◽  
Dose Intensity ◽  
Phase Iii ◽  
Concurrent Administration ◽  
Grade 3

Aims and Background To improve local control in patients with locally advanced inoperable head and neck cancer we administered carboplatin concurrently with radiation. Methods Thirty-nine patients entered the study. There were 35 men and 4 women with a median age of 58 years (range, 24-74) and a median performance status of 90 (range, 60-100) of the Karnofsky scale. The primary site included nasopharynx (5 patients), oropharynx (n=10), hypopharynx (n=5), larynx (n=12), oral cavity (n=2), paranasal sinuses (n=3), salivary glands (n=1) and unknown (n=1). Histology was squamous cell carcinoma in all cases. All patients were irradiated with a 60Co unit. According to the protocol, they should receive 66-70 Gy to the tumor area and 45 Gy to the tumor-free area of the neck. Carboplatin was administered at a dose of 400 mg/m2 on days 2, 22 and 42. Results Totally, 112 cycles of carboplatin were administered, of which 106 (95%) were at full dose. Median dose intensity of carboplatin actually delivered was 170 mg/m2/week (range, 57-200). All patients were irradiated, although only 30 (77%) received >66 Gy. After the completion of combined treatment, 23 (59%, 95% C.I. 42-74%) achieved a CR and 10 (26%, 95% C.I. 13-42%) a PR. Grade 3-4 myelotoxicity was noticed in 60% of the patients. Other grade 3-4 toxicities included stomatitis (13%), dysphagia (5%) and weight loss (3%). Median time to progression was 18 months (range, 2-25). Conclusions Radiation and concurrent administration of carboplatin determined a high CR rate in patients with HNC, although the superiority of this combined modality approach over radiation alone has to be proven in phase III trials.

NEOSCOPE: A randomised Phase II study of induction chemotherapy followed by either oxaliplatin/capecitabine (OXCAP) or carboplatin/paclitaxel (CarPac) based chemoradiation (CRT) as pre-operative regimen for resectable oesophageal adenocarcinoma.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 3-3 ◽  
Author(s):  
Somnath Mukherjee ◽  
Chris Hurt ◽  
Sarah Gwynne ◽  
Andrew Bateman ◽  
Simon Gollins ◽  
...  
Keyword(s):  
Type I Error ◽  
Patient Characteristics ◽  
Complete Response ◽  
Phase Iii ◽  
Oesophageal Adenocarcinoma ◽  
Type I ◽  
Surgical Morbidity ◽  
Loss To Follow Up ◽  
Grade 3 ◽  
Tumour Characteristics

3 Background: NEOSCOPE compared toxicity and efficacy of 2 pre-op CRT regimens. Methods: Eligibility: Resectable ACA of the oesophagus/GOJ ≥ T3 and/or ≥ N1. Randomisation: 1:1 to OXCAP-CRT (oxaliplatin 85 mg/m2 Day 1,15,29; capecitabine 625 mg/m2 bd on days of RT) or CarPac-CRT (Carboplatin AUC2; paclitaxel 50 mg/m2 Day 1,8,15,22,29); concurrent RT: 45Gy/25 fractions/5 weeks. Both arms received induction chemo: 2 cycles of OXCAP (oxaliplatin 130 mg/m2 D1, Cape 625 mg/m2D1-21, q 3wk). Surgery: 6-8 weeks after naCRT. Detailed RT and pathology quality assurance was built into the protocol. Primary end-point: pathological complete response (pCR). Secondary: toxicity, surgical morbidity/mortality, R1 rate, OS. Statistics: A pCR of 15% would not warrant further investigation but a pCR of 35% would. 76 patients (38/arm) gave 90% power and one-sided type I error of 10% meaning that either arm having ≥10 pCR out of first 38 patients would be considered for Phase III. 85 patients to be recruited (allows 10% loss to follow up). Results: 85 patients were randomised between Oct 2013 and Feb 2015 from 17 UK centres. Patient characteristics: median age 65 yrs, Male (81%), WHO PS 0 (85%). Tumour characteristics: T3 (86%), N1 (48%), lower third/GOJ (90%), median tumour length 5.8cm. CTCAE grade 3/4 toxicity rate during CRT was OXCAP-CRT 42.1%, CarPac-CRT 52.4% (p=0.358). Protocol dose RT OXCAP-CRT 90.5%, CarPac-CRT 93%. Conclusion:Both regimens were well tolerated. CarPac-CRT passed the criteria for taking forward to a phase III study but OXCAP-RT did not. Funding: Cancer Research UK (C44694/A14614), ClinicalTrials.gov: NCT01843829, coordinated by Wales Cancer Trials Unit. Clinical trial information: NCT01843829. [Table: see text]

Phase II study of copanlisib in combination with gemcitabine and cisplatin in advanced cholangiocarcinoma.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 556-556
Author(s):  
Elaine Tan ◽  
Dae Won Kim ◽  
Rutika Mehta ◽  
Biwei Cao ◽  
Jongphil Kim ◽  
...  
Keyword(s):  
Phase Ii ◽  
Primary Endpoint ◽  
Type I Error ◽  
Phase Ii Study ◽  
Study Drug ◽  
Drug Discontinuation ◽  
Type I ◽  
First Line ◽  
Grade 3 ◽  
Gemcitabine And Cisplatin

556 Background: First line therapy for advanced cholangiocarcinoma (CCA) is currently gemcitabine and cisplatin. However, survival rarely exceeds one year with this regimen. PI3K/AKT activation has been shown to increase resistance to chemotherapy in CCA; therefore, inhibiting this pathway may improve chemotherapy’s efficacy. This phase II study evaluated the safety and efficacy of copanlisib, a potent and reversible pan-class I PI3K inhibitor, with gemcitabine and cisplatin in advanced CCA. Methods: Between July 2016 and April 2019, pts with histologically confirmed advanced/unresectable CCA received cisplatin (25 mg/m2), gemcitabine (1000mg/m2), and copanlisib 60mg on day 1 and 8, every 21 days as first line treatment. The primary endpoint was PFS at 6 months. Secondary endpoints were RR, median OS and PFS, and safety profile. A single-arm Simon’s two-stage minimax design with one-sided 10% type I error and 80% power was used. Based on ABC-01 and ABC-02 studies, PFS6 for gemcitabine and cisplatin were 57.1% and 59.3%, respectively. Therefore, PFS6 of 57% was considered not to warrant further study and ≥72% to warrant further investigation. Results: Twenty-four pts received at least one dose of the study drug (62.5% female, median age 64 years), with 70.8% intrahepatic, 16.7% extrahepatic, and 12.5% gallbladder cancer. For all pts, median OS was 13.9 months (95% CI: 6.8-17.9) and median PFS was 6.2 months (95% CI: 1.3-11.1). PFS at 6 and 12 months was 57.0% and 42.2%, and 6 and 12-month OS was 73.9% and 53.2%, respectively. Only 19 pts were considered evaluable for RR. Five pts were either lost to follow up, withdrew consent, or died before a second scan was done. Six pts achieved PR (31.5%) and 11 (57.9%) had SD. Grade 3 or higher adverse events (AE) occurred in 75% of pts. The most common grade 3/4 AEs were decreased neutrophil count (40%) and increased lipase (20%). Treated related AEs led to drug discontinuation for 3 pts (12.5%) and dose modification for 7 pts (29.2%). Conclusions: Gemcitabine, cisplatin, and copanlisib in combination did not meet the primary endpoint of 6-month PFS. However, additional correlative work is ongoing to identify a possible biomarker for copanlisib. Clinical trial information: NCT02631590.

A phase III study of pemetrexed (Pem) plus carboplatin (Cb) plus bevacizumab (Bev) followed by maintenance pem plus bev versus paclitaxel (Pac) plus cb plus bev followed by maintenance bev in stage IIIb or IV nonsquamous non-small cell lung cancer (NS-NSCLC): Overall and age group results.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8004-8004 ◽  
Author(s):  
Mark A. Socinski ◽  
Jyoti D. Patel ◽  
Edward B. Garon ◽  
Ramaswamy Govindan ◽  
Craig H. Reynolds ◽  
...  
Keyword(s):  
Type I Error ◽  
Safety Data ◽  
Sensory Neuropathy ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Type I ◽  
Cox Models ◽  
Phase Iii Study ◽  
Grade 3 ◽  
Ecog Ps

8004 Background: This study compared Pem+Cb+Bev followed by Pem+Bev maintenance (Pem arm) to Pac+Cb+Bev followed by Bev maintenance (Pac arm). The primary endpoint of improved overall survival (OS) for the Pem arm was not met. Methods: Advanced NS-NSCLC pts, ECOG PS 0/1, were randomized to 4 cycles of induction Pem+Cb+Bev with folic acid+vitamin B12 or Pac+Cb+Bev (Pem 500 mg/m2or Pac 200 mg/m2; Cb AUC 6; Bev 15 mg/kg) every 3 weeks. Eligible pts received maintenance Pem+Bev or Bev. OS, progression-free survival (PFS), overall response (ORR), and toxicity were evaluated. A hazard ratio (HR) of 0.80 required 676 OS events/900 pts with 2-sided type-I error .05 and at least 80% power for superiority of Pem over Pac arm. Exploratory Cox models estimated treatment HRs with 95% confidence intervals (CIs) for each age subgroup analyzed: ≤ or >65, 70 (prespecified) and ≤ or >75 yrs (not prespecified). Results: 939 pts (median age, 64.7) were randomized. Median (m) OS for ITT pem and pac arms was 12.6 vs 13.4 mos (HR 1.00, p=0.949); mPFS was 6.0 vs 5.6 mos (HR 0.83, p=0.012) Subgroup efficacy is shown in the Table; ≤ or >65 data were similar to ITT. Pem pts had significantly more drug-related grade 3/4 thrombocytopenia, anemia (except >75 yrs) and fatigue (except >70 and >75 yrs). Pac pts had significantly more grade 3/4 neutropenia (except >70 and >75 yrs), sensory neuropathy (except >75 yrs) and grade 1/2 alopecia. Results parallel overall safety data. Conclusions: OS was not significantly different in any of the age subgroups. PFS was significantly longer in Pem arm overall and for pts ≤70, but was similar for pts >70, >75 yrs. Toxicity profiles differed; subgroup safety data paralleled overall data. Clinical trial information: NCT00762034. [Table: see text]

Randomized phase III trial of concurrent chemoradiation followed by nivolumab or placebo for locally advanced non-small cell lung cancer (NSCLC) (RTOG 3505).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS8579-TPS8579 ◽  
Author(s):  
David E. Gerber ◽  
James John Urbanic ◽  
Corey J. Langer ◽  
Chen Hu ◽  
I-Fen Chang ◽  
...  
Keyword(s):  
Type I Error ◽  
Checkpoint Inhibitors ◽  
Performance Status ◽  
Locally Advanced ◽  
Drop Out ◽  
Phase Iii ◽  
Concurrent Chemoradiation ◽  
Type I ◽  
Eligibility Criteria ◽  
Patient Reported

TPS8579 Background: Despite aggressive therapy with concurrent chemoradiation, fewer than 25% of patients with stage 3 NSCLC achieve 5-year survival and are presumably cured. To date, treatment modifications—including consolidation chemotherapy, maintenance therapy with molecularly targeted agents, concomitant administration of monoclonal antibodies, and escalation of radiation therapy (RT) dose—have not improved these outcomes. Immune checkpoint inhibitors represent an effective treatment for advanced NSCLC and may enhance RT-associated anti-tumor immunity. RTOG 3505 will test whether the addition of the anti-programmed death 1 (PD1) antibody nivolumab after chemoradiation improves overall survival (OS) and progression-free survival (PFS) in this population. Methods: Key eligibility criteria include surgically unresectable stage 3 NSCLC, ECOG 0-1, adequate organ function, available archival tissue, and absence of active autoimmune disease. Patients will receive thoracic RT to 60 Gy with concurrent cisplatin 50 mg/m2 IV on Days 1, 8, 29, and 36, and etoposide 50 mg/m2 IV on Days 1-5 and 29-33. This regimen was selected to (1) minimize risk of pulmonary toxicity and steroid requirements, and (2) optimize timing of immunotherapy. Between 4 and 12 weeks after completion of chemoradiation, eligible patients will be randomized to nivolumab 240 mg IV or placebo every 2 weeks for 1 year. Stratification factors include performance status, histology, and tumor PD-L1 status. Co-primary endpoints are OS and PFS, as determined by central radiology review. Secondary objectives include toxicity assessment, patient-reported outcomes and quality of life, and OS and PFS according to PD-L1 expression. Exploratory objectives include biomarkers to predict treatment efficacy and toxicity. A total of 660 patients will be enrolled to provide ≥90% power to detect (1) a hazard ratio (HR) of 0.7 for OS with two-sided type I error of 0.04, and (2) HR of 0.667 for PFS two-sided type I error of 0.01, allowing a 16.7% drop-out rate before randomization. Clinical trial information: NCT02768558.

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