Randomized phase III Trial of MEDI4736 (durvalumab) as concurrent and consolidative therapy or consolidative therapy alone for unresectable stage 3 NSCLC: A trial of the ECOG-ACRIN Cancer Research Group (EA5181).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS8584-TPS8584
Author(s):  
John M. Varlotto ◽  
Zhuoxin Sun ◽  
Suresh S. Ramalingam ◽  
Heather A. Wakelee ◽  
Christine M. Lovly ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Locally Advanced ◽  
Concurrent Chemotherapy ◽  
Phase Iii ◽  
Fixed Dose ◽  
Hematologic Toxicity ◽  
Eligibility Criteria ◽  
Unresectable Stage ◽  
One Year

TPS8584 Background: Platinum-based concurrent chemoradiation(CRT) followed by one year of the human immunoglobulin G1 kappa (IgG1κ) monoclonal antibody, durvalumab, which blocks the interaction of PD-L1 with its receptors PD-1 and CD80, is the standard of care for locally advanced, unresectable non-small cell lung cancer (NSCLC). Early studies have noted the feasibility of concomitant administration of radiotherapy and immune checkpoint inhibition in NSCLC. EA5181 will evaluate the use of concomitant durvalumab with chemo-radiotherapy for locally advanced NSCLC. Methods: EA5181 is a randomized, multi-center, phase III study for patients with unresectable Stage III NSCLC comparing the efficacy of CRT with concomitant durvalumab to CRT, followed by one year of durvalumab. Eligibility criteria include: an ECOG PS of 0-1, adequate pulmonary function (FEV1 and DLCO both > 40%), no history of auto-immune disease and no past chemotherapy or RT for this lung cancer. Stratification factors include age, sex, stage, and planned concurrent chemotherapy type. Eligible patients with be randomized 1:1 to receive 60Gy RT (2Gy fractions) CRT and durvalumab (Arm A) or 60Gy CRT (Arm B). Investigators will be allowed to choose from three different chemotherapy options: cisplatin/etoposide q 28 days, Pemetrexed/cisplatin q 21 days, and weekly paclitaxel/Carboplatin. Arm A will use 750mg fixed of durvalumab (considered equivalent to 10mg/kg) on days 1, 11, and 21 of RT. Assuming no disease progression, patients in both arms will be followed by monthly (q28 days) fixed dose of 1500mg durvalumab for one year which will be given optimally within 14 days of radiation or when (non)hematologic toxicity is < Grade 2. The primary endpoint is overall survival. Secondary endpoints include progression-free survival, incidence of local/distant progression and toxicity. The target sample size is 660 patients, anticipated to recruit over 55 months, with follow up for an additional 42 months. This provides approximately 82% power if the true hazard ratio for overall survival was 0.75 or less, with 2-sided alpha of 0.05, and assuming a median survival of 42.5 months in the control arm. The study was activated on 04/09/20 and has currently accrued 90 patients on 02/03/21. Clinical trial information: NCT04092283.

scholarly journals Tecemotide in unresectable stage III non-small-cell lung cancer in the phase III START study: updated overall survival and biomarker analyses

2015 ◽  
Vol 26 (6) ◽  
pp. 1134-1142 ◽  
Author(s):  
P. Mitchell ◽  
N. Thatcher ◽  
M.A. Socinski ◽  
E. Wasilewska-Tesluk ◽  
K. Horwood ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Phase Iii ◽  
Stage Iii ◽  
Small Cell Lung ◽  
Unresectable Stage

Randomized Phase III Trial of Gemcitabine Plus Cisplatin Compared With Gemcitabine Alone in Advanced Pancreatic Cancer

2006 ◽  
Vol 24 (24) ◽  
pp. 3946-3952 ◽  
Author(s):  
Volker Heinemann ◽  
Detlef Quietzsch ◽  
Frank Gieseler ◽  
Michael Gonnermann ◽  
Herbert Schönekäs ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Median Overall Survival ◽  
Statistical Significance ◽  
Single Agent ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Hematologic Toxicity ◽  
Free Survival

Purpose To compare the effectiveness and tolerability of gemcitabine plus cisplatin with single-agent gemcitabine as first-line chemotherapy for locally advanced or metastatic pancreatic cancer. Patients and Methods Patients with advanced adenocarcinoma of the pancreas were randomly assigned to receive either gemcitabine 1,000 mg/m2 and cisplatin 50 mg/m2 given on days 1 and 15 of a 4-week cycle (GemCis arm) or gemcitabine alone at a dose of 1,000 mg/m2 on days 1, 8, and 15 of a 4-week regimen (Gem arm). The primary end point was overall survival; secondary end points were progression-free survival, response rate, safety, and quality of life. Results One hundred ninety-five patients were enrolled and showed baseline characteristics well balanced between treatment arms. Combination treatment in the GemCis arm was associated with a prolonged median progression-free survival (5.3 months v 3.1 months; hazard ratio [HR] = 0.75; P = .053). Also, median overall survival was superior for patients treated in the GemCis arm as compared with the Gem arm (7.5 v 6.0 months), an advantage which did not, however, reach statistical significance (HR = 0.80; P = .15). Tumor response rates were comparable between treatment arms (10.2% v 8.2%). The rate of stable disease was, however, greater in the combination arm (60.2% v 40.2%; P < .001). Grade 3 to 4 hematologic toxicity did not exceed 15% in both treatment arms. Conclusion These results support the efficacy and safety of an every-2-weeks treatment with gemcitabine plus cisplatin. Median overall survival and progression-free survival were more favorable in the combination arm as compared with gemcitabine alone, although the difference did not attain statistical significance.

Phase III Trial of Gemcitabine Plus Carboplatin Versus Single-Agent Gemcitabine in the Treatment of Locally Advanced or Metastatic Non–Small-Cell Lung Cancer: The Swedish Lung Cancer Study Group

2005 ◽  
Vol 23 (33) ◽  
pp. 8380-8388 ◽  
Author(s):  
Christer Sederholm ◽  
Gunnar Hillerdal ◽  
Kristina Lamberg ◽  
Karl Kölbeck ◽  
Monika Dufmats ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Lung Cancer ◽  
Overall Survival ◽  
Single Agent ◽  
Locally Advanced ◽  
Small Cell ◽  
Phase Iii ◽  
Time To Progression ◽  
Small Cell Lung

PurposeThis phase III study compared overall survival in patients with locally advanced or metastatic non–small-cell lung cancer (NSCLC) when treated with single-agent gemcitabine versus gemcitabine/carboplatin. Secondary objectives were to compare response, time to progression, toxicity, and quality of life.Patients and MethodsChemotherapy-naive patients received either gemcitabine alone (1,250 mg/m2on days 1 and 8; gemcitabine arm) or with carboplatin (area under the curve 5 on day 1; GC arm) every 21 days.ResultsDemographics and disease characteristics of 334 randomly assigned patients were comparable on both arms. An intent-to-treat analysis showed significantly better overall survival (log-rank P = .0205) and 2-year survival (15% v 5%; P = .009) favoring the GC arm. Per Cox multivariate analysis, only two covariates, treatment arm (GC v G) and baseline performance status (0 or 1 v 2), independently influenced survival. Per-protocol analyses showed significantly longer median time to progression (5.7 v 3.9 months; P = .0001) and significantly higher objective response rate (29.6 v 11.3%; P < .0001) in the GC arm. Grade 3 to 4 leucopenia and thrombocytopenia were significantly more pronounced in the GC arm (P for both variables < .001) but importantly without associated increases in fever, infection, bleeding, or hospitalizations. There was no discernible difference in global quality-of-life patterns between treatment arms.ConclusionIn advanced NSCLC, gemcitabine/carboplatin therapy resulted in significant survival benefit compared with single-agent gemcitabine without undue increase in toxicity.

Randomized phase III study of carboplatin and paclitaxel versus vincristine, doxorubicin and cyclophosphamide chemotherapy in intermediate and poor prognosis small cell lung cancer: Preliminary results

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7059-7059 ◽  
Author(s):  
S. Baka ◽  
S. Mullamitha ◽  
L. Ashcroft ◽  
S. Nagel ◽  
R. Board ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Poor Prognosis ◽  
Response Rate ◽  
Prognostic Score ◽  
Phase Iii ◽  
Severe Neutropenia ◽  
Significant Difference ◽  
Grade 3 ◽  
One Year

7059 Background: The combination of paclitaxel and carboplatin has been found to be effective in lung cancer and well tolerated. Method: This is a phase III randomized trial of paclitaxel and carboplatin (PC) versus vincristine, doxorubicin and cyclophosphamide (CAV) chemotherapy in limited or extensive stage disease patients but with a prognostic score in the intermediate or poor prognosis range.The aim of the study is to determine the one year survival rate, the objective response rate and toxicity. Patients were randomized to: four cycles of PC (paclitaxel 200mg/m2 by IV 3 hour infusion), followed by carboplatin (AUC of 6) by IV injection, 3-weekly or four cycles of CAV (cyclophosphamide 750mg/ m2, doxorubicin 40mg/ m2, vincristine 1.3mg/ m2 by IV injection) every 3-weeks. Thoracic radiotherapy was considered for appropriate patients. Results: 219 patients (110 for CAV and 109 for PC) patients were randomized. Pre-treatment characteristics were well balanced for stage, performance status, and age. There was significantly more grade 3/4 neutropenia in the CAV arm than the PC arm, 67% vs 38% (p < 0.005), whereas the PC arm, had more grade 3/4 thrombocytopenia (19% versus 8% p = 0.012). The PC arm had more grade 2 and 3 neuropathy. 56% grade 3 and 4 infections were observed on CAV arm and 35% on the PC arm (p < 0.005). Hospitalization required for severe neutropenia and infections was less with PC, compared to CAV (146 days for IV antibiotics compared to 308 days for CAV, p < 0.005). Response rates for CAV and PC were 59% and 61% respectively. One-year survival rates for the CAV arm was 6% and 13% for the PC arm. The intention to treat analysis concluded that there is statistical difference on the overall survival time in favor of PC (P = 0.014). Median survival was 94 days (CAV) and 154 (PC). Conclusions: CAV chemotherapy in SCLC patients is associated with higher risk of neutropenic sepsis than taxane based PC chemotherapy with no significant difference on the response rate. The overall survival was better for the PC arm. Final results will follow. No significant financial relationships to disclose.

Randomized Phase III Study of Exatecan and Gemcitabine Compared With Gemcitabine Alone in Untreated Advanced Pancreatic Cancer

2006 ◽  
Vol 24 (27) ◽  
pp. 4441-4447 ◽  
Author(s):  
Ghassan K. Abou-Alfa ◽  
Richard Letourneau ◽  
Graydon Harker ◽  
Manuel Modiano ◽  
Herbert Hurwitz ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Single Agent ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Water Soluble ◽  
Phase Iii ◽  
Eligibility Criteria

Purpose Exatecan mesylate is a hexacyclic, water-soluble, topoisomerase-1 inhibitor. Exatecan has single-agent and combination activity with gemcitabine in advanced pancreatic cancer. A multicenter, randomized, phase III trial comparing exatecan plus gemcitabine versus gemcitabine alone in advanced pancreatic cancer was conducted. Patients and Methods Eligibility criteria included Karnofsky performance status ≥ 60%, locally advanced or metastatic pancreatic adenocarcinoma, and no prior chemotherapy. Radiation alone for locally advanced disease was permitted. Patients were randomly assigned on a 1:1 basis. For the exatecan plus gemcitabine arm, exatecan 2.0 mg/m2 and gemcitabine 1,000 mg/m2 were administered on days 1 and 8, every 3 weeks. Gemcitabine alone was dosed at 1,000 mg/m2 up to 7 weeks in the first cycle, then once a week for the first 3 weeks of a 4-week cycle. Tumor assessment was performed every 6 weeks. The primary end point was overall survival. An intent-to-treat analysis was used. Results From August 2001 to January 2003, 349 patients were randomly assigned, 175 to exatecan plus gemcitabine and 174 to gemcitabine alone. Twenty-four patients (6.9%) were not treated. The median survival time was 6.7 months for exatecan plus gemcitabine and 6.2 months for gemcitabine alone (P = .52). One complete response (CR; < 1%) and 11 partial responses (PRs; 6.3%) were observed in the exatecan plus gemcitabine treatment group, and one CR (< 1%) and eight PRs (4.6%) were observed in the gemcitabine-alone group. Grade 3 and 4 toxicities were higher for the exatecan plus gemcitabine arm versus the gemcitabine alone arm; neutropenia (30% v 15%) and thrombocytopenia (15% v 4%). Conclusion Exatecan plus gemcitabine was not superior to gemcitabine alone with respect to overall survival in the first-line treatment of advanced pancreatic cancer.

A phase II trial of ZD6474 plus docetaxel in patients with previously treated NSCLC: Follow-up results

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7016-7016 ◽  
Author(s):  
J. V. Heymach ◽  
B. E. Johnson ◽  
D. Prager ◽  
E. Csada ◽  
J. Roubec ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Survival Data ◽  
Locally Advanced ◽  
Primary Objective ◽  
Phase Iii ◽  
Double Blind Study ◽  
Once Daily ◽  
Platinum Based Chemotherapy

7016 Background: ZD6474, a once-daily oral agent, targets key signaling pathways in cancer by inhibiting VEGF, EGF and RET receptor tyrosine kinases. ZD6474 in combination with docetaxel (Doc) was assessed in patients (pts) with refractory non-small-cell lung cancer (NSCLC). Methods: Pts eligible for this randomized, double-blind study had locally advanced or metastatic (stage IIIB/IV) NSCLC after failure of 1st-line platinum-based chemotherapy. The primary objective was to determine whether once-daily oral ZD6474 (100 or 300 mg) + Doc (75 mg/m2 i.v. infusion every 21 days) prolonged progression-free survival (PFS) vs Doc alone (80% power to detect 50% prolongation at P<0.2). Overall survival was a secondary objective. Results: A total of 127 pts (73 male/54 female; median age 59 yrs, range 29–82) received ZD6474 100 mg + Doc (n=42), ZD6474 300 mg + Doc (n=44) or Doc (n=41). The study met its primary objective of PFS prolongation with the addition of ZD6474: median PFS was 19 wks for ZD6474 100 mg + Doc (HR=0.64; P=0.074); 17 wks for ZD6474 300 mg + Doc (HR=0.83; P=0.461); and 12 wks for Doc. A total of 64 pts (50%) presented with histology other than adenocarcinoma, including 37 with squamous, and 13 pts (10%) entered with CNS metastases. Exploratory subgroup analyses suggest advantages in PFS for ZD6474 + Doc vs Doc both for adenocarcinoma and for other lung cancer histologies. Common adverse events (AEs) included diarrhea, rash and asymptomatic QTc prolongation, all responded to standard management or dose interruption/reduction. Four pts with squamous experienced hemoptysis (ZD6474 100 mg + Doc, n=2 CTC grade 1/2; Doc, n=2 CTC grade 3/4). No fatal episodes of hemoptysis or any CNS hemorrhage AEs were reported in pts receiving ZD6474. Overall survival data were immature at the time of PFS analysis, and a mature survival analysis will be conducted at ∼75% of deaths (anticipated April 2006, and will be presented at the meeting). As of December 2005, 40/127 (31%) pts were alive, 5 of whom continue to receive ZD6474. The minimum follow-up of pts still alive was 17 months. Conclusions: ZD6474 + Doc prolonged PFS vs Doc alone, and these promising data have led to the initiation of Phase III evaluation of ZD6474 + Doc in 2nd-line NSCLC. [Table: see text]

Vandetanib plus docetaxel versus docetaxel as second-line treatment for patients with advanced non-small cell lung cancer (NSCLC): A randomized, double-blind phase III trial (ZODIAC)

2009 ◽  
Vol 27 (18_suppl) ◽  
pp. CRA8003-CRA8003 ◽  
Author(s):  
R. S. Herbst ◽  
Y. Sun ◽  
S. Korfee ◽  
P. Germonpré ◽  
N. Saijo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Objective Response ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Phase Iii ◽  
Positive Trend ◽  
Primary Analysis ◽  
Eligibility Criteria ◽  
Double Blind

CRA8003 Background: Vandetanib is a once-daily oral inhibitor of VEGFR, EGFR and RET signaling. Addition of vandetanib to docetaxel (doc) prolonged progression-free survival (PFS) in a randomized phase II study in patients (pts) with previously treated NSCLC (Heymach et al, JCO, 2007). Methods: The primary objective was to determine whether vandetanib 100 mg/day + doc 75 mg/m2 every 21 days (max 6 cycles) prolonged PFS vs placebo + doc. Secondary endpoints included overall survival, objective response rate (ORR), time to deterioration of symptoms (TDS) and safety. Efficacy and safety in females were assessed as a co-primary analysis population. Eligibility criteria included stage IIIB/IV NSCLC, PS 0–1, and previous first-line chemotherapy. Results: Between May 2006 and April 2008, 1,391 pts (mean age, 58 years; 30% female; 25% squamous; 10% brain mets) were randomized to vandetanib + doc (n=694) or placebo + doc (n=697). Baseline characteristics were similar in both arms. Median duration of follow-up was 12.8 months, with 87% patients progressed and 59% dead. Addition of vandetanib to doc showed a statistically significant improvement in PFS vs doc (hazard ratio [HR] 0.79, 97.58% CI 0.70–0.90; P<0.001), and a similar advantage in females (HR 0.79; P=0.024). Significant advantages for vandetanib + doc were also seen for ORR (17% vs 10%, P<0.001) and TDS (HR 0.78, P=0.002; FACT-L Lung Cancer Subscale). Overall survival showed a positive trend for vandetanib + doc that was not statistically significant (HR 0.91, 97.52% CI 0.78–1.07; P=0.196). The adverse event (AE) profile was consistent with that previously observed for vandetanib in NSCLC. Common AEs occurring more frequently in the vandetanib arm included diarrhea (42% vs 33%), rash (42% vs 24%) and neutropenia (32% vs 27%). Nausea (23% vs 32%), vomiting (16% vs 21%) and anemia (10% vs 15%) were less frequent in the vandetanib arm. The incidence of protocol-defined QTc prolongation was <2% in pts receiving vandetanib. Conclusions: The study met its primary objective of PFS prolongation with vandetanib + doc vs doc. Vandetanib is the first oral targeted therapy in phase III trials to show significant evidence of clinical benefit when added to standard chemotherapy in NSCLC. [Table: see text]

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