A randomized phase II trial of adjuvant pembrolizumab versus observation following curative resection for stage I non-small cell lung cancer (NSCLC) with primary tumors between 1-4 cm: Big Ten Cancer Research Consortium BTCRC-LUN18-153.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS8583-TPS8583
Author(s):  
Greg Andrew Durm ◽  
Muhammad Furqan ◽  
Lawrence Eric Feldman ◽  
Malini Patel ◽  
Richard Delmar Hall ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Research ◽  
Phase Ii ◽  
Metastatic Disease ◽  
The United States ◽  
Stage I ◽  
Big Ten ◽  
Randomized Phase Ii ◽  
Research Consortium ◽  
Lead Site

TPS8583 Background: There are approximately 35,000 cases of stage I lung cancer in the United States each year. While these patients have better 5-year overall survival (OS) rates than their counterparts with locally advanced and metastatic disease, there is still considerable room for improvement. Based on a recent publication validating the 8th edition of the TNM classification, the 5-year OS for node-negative pathologically-staged NSCLC between 1-4cm ranges from 73-86%, and recurrence rates for resected stage I NSCLC can range from 18-38%. Previous studies looking at adjuvant chemotherapy in this setting have shown no benefit for stage IA tumors, and the current standard of care is observation alone. Checkpoint blockade with PD-1/PD-L1 inhibitors has shown considerable activity in NSCLC including in metastatic disease, as consolidation in stage III disease after chemoradiation, and in studies evaluating neoadjuvant immunotherapy. Given this activity and their favorable safety profile, we designed a study of adjuvant PD-1 inhibition following resection in stage I NSCLC. Methods: This study is a randomized phase II multicenter trial of adjuvant Pembrolizumab versus observation alone following complete resection of stage I NSCLC with tumors between 1-4cm. The trial will enroll 368 patients randomized 1:1 to either Pembrolizumab 400mg IV every 6 weeks for up to 9 cycles or observation alone with scheduled CT scans and routine clinical follow-up. Stratification factors include PD-L1 ≥50% vs. < 50% and tumor size of 1-2cm vs. > 2-4cm. The lead site is Indiana University, and the trial will be conducted through the Big Ten Cancer Research Consortium. The primary endpoint is disease free survival (DFS), and secondary endpoints include OS, DFS at 1-, 2-, and 3-year time points, and toxicity. The trial opened to accrual at the lead site in May 2020, and there are currently 6 patients enrolled. Clinical trial information: NCT04317534.

A Big Ten Cancer Research Consortium phase II trial of pembrolizumab with carboplatin and paclitaxel for advanced or recurrent endometrial cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 6022-6022
Author(s):  
Mario Javier Pineda ◽  
Jeanne Schilder ◽  
Emily K. Hill ◽  
Deanna Gek Koon Teoh ◽  
Emma Longley Barber ◽  
...  
Keyword(s):  
Cancer Research ◽  
Endometrial Cancer ◽  
Phase Ii ◽  
Hormonal Therapy ◽  
Phase Ii Study ◽  
Phase Iii ◽  
Big Ten ◽  
Recurrent Endometrial Cancer ◽  
Grade 3 ◽  
Research Consortium

6022 Background: There are limited chemotherapeutic options for patients (pts) with advanced or recurrent endometrial cancer (EC). Reported objective response rates (ORR) for first-line doxorubicin/cisplatin/ paclitaxel combination therapy was 57%; with a median progression-free survival (PFS) of 8.3 months. The goal of this phase II study was to assess the efficacy and safety of pembrolizumab in combination with standard carboplatin/paclitaxel in pts with measurable advanced or recurrent EC. Methods: This was a single-arm, open-label, multi-center phase II study for pts with RECIST measurable advanced or recurrent EC coordinated by the Big Ten Cancer Research Consortium. Patients may have had received 1 prior platinum-based regimen, with a platinum free interval > 6 months, < one non-platinum chemotherapy, or prior hormonal therapy. Pts received carboplatin AUC 6, paclitaxel 175mg/m2 (CT) and pembrolizumab 200mg IV every 3 weeks for up to 6 cycles; with dose reduced for prior radiation. The primary endpoint was ORR per immune-related RECIST. Planned sample size of 46 subjects provided 77% power to detect 15% ORR improvement compared to historical controls, with one-tailed test and 10% type I error rate. Results: 46 pts were enrolled. Median age was 67 (range: 43-86). 32 pts had recurrent and 14 had primary metastatic EC. Histological types were: 26 endometrioid, 11 serous, 3 clear cell, 6 other. 19 patients had received prior carboplatin/paclitaxel, 23 pelvic EBRT, 14 brachytherapy, 1 adriamycin and 1 hormonal therapy. Grade 3-4 adverse events (AEs) included: laboratory abnormalities (20), hematological (8), metabolism (6), nervous system (4), gastrointestinal (2), and others (6). There were 15 grade 3-4 SAEs occurring in 7 pts: vomiting (1), anaphylaxis (3), fever (2), dehydration (1), syncope (2), vascular (2), fatigue (1), neurological (2), thrombocytopenia (1), and no grade 5 SAEs. 36 patients were evaluable for response at the time of abstract submission. ORR was 77.8% (28/36) and median PFS was 10.55 months. Conclusions: The addition of pembrolizumab to standard of care CT chemotherapy for advanced or recurrent EC induced a clinically significant improvement in ORR compared to historical outcomes and toxicity did not exceed anticipated toxicity with standard treatment, supporting further testing in a phase III trial. Clinical trial information: NCT02549209.

A phase II study of durvalumab following multimodality therapy for locally advanced esophageal adenocarcinoma: Big Ten Cancer Research Consortium BTCRC-ESO14-012 study.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. TPS194-TPS194
Author(s):  
Hirva Mansurali Mamdani ◽  
Laith I. Abushahin ◽  
Bryan J. Schneider ◽  
Rozina A. Chowdhery ◽  
Borys Hrinczenko ◽  
...  
Keyword(s):  
Cancer Research ◽  
Esophageal Adenocarcinoma ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Locally Advanced ◽  
Big Ten ◽  
Surgical Specimen ◽  
Free Survival ◽  
Persistent Disease ◽  
Research Consortium

TPS194 Background: The standard of care for locally advanced esophageal adenocarcinoma is concurrent chemoradiation (CRT) followed by esophagectomy with lymphadenectomy. Approximately 30% of patients achieve a complete pathologic response (pCR) with this multimodality approach, which has been correlated with improved disease-free survival. The risk of relapse in the remaining 70% of patients who have pathologic evidence of persistent disease in the surgical specimen is extremely high and estimated at 60-70%. Preclinical studies have demonstrated that radiation with or without concurrent chemotherapy upregulates the programmed cell death receptor- 1 (PD-1) pathway by inducing a local inflammatory response, an effect that persists for a number of months after cessation of therapy. Durvalumab is a selective, high affinity, engineered human IgG1 monoclonal antibody that blocks PD-L1 binding to PD-1 and CD80, and has shown activity in metastatic esophageal cancer. The aim of this study is to evaluate efficacy of post-operative durvalumab with respect to decreasing the relapse rate in patients who do not achieve pCR following CRT. Methods: Patients with esophageal adenocarcinoma who have pathologic evidence of persistent disease in the surgical specimen following neoadjuvant concurrent CRT (carboplatin plus paclitaxel or cisplatin plus 5-FU) and R0 resection are eligible for enrollment on this single arm phase II study. Durvalumab 1500mg IV every 4 weeks is started within 1-3 months of surgery and continued for up to 1 year. The primary endpoint is 1-year relapse free survival (RFS). Secondary endpoint is to assess the incidence and severity of overall and treatment related adverse events. Exploratory endpoints include PDL1 expression in tumor and tumor infiltrating lymphocytes, assessment of Immunoscore within the center and invasive margin of the tumor, and the correlation between changes in circulating tumor cell numbers in response to PD-L1 inhibition. The study is currently open to accrual at 5 sites in the Big Ten Cancer Research Consortium and 17 of the planned 23 patients have been enrolled within the past 14 months. Clinical trial information: NCT02639065.

Randomized Phase II Study of Bevacizumab in Combination With Chemotherapy in Previously Untreated Extensive-Stage Small-Cell Lung Cancer: Results From the SALUTE Trial

2011 ◽  
Vol 29 (16) ◽  
pp. 2215-2222 ◽  
Author(s):  
David R. Spigel ◽  
Peter M. Townley ◽  
David M. Waterhouse ◽  
Liang Fang ◽  
Ibrahim Adiguzel ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Placebo Group ◽  
Small Cell Lung Cancer ◽  
Phase Ii ◽  
Cell Lung Cancer ◽  
Single Agent ◽  
Small Cell ◽  
Small Cell Lung ◽  
Randomized Phase Ii ◽  
Extensive Stage

PurposeBecause of promising efficacy signals in single-arm studies, a placebo-controlled, double-blind, randomized phase II trial was designed to assess the efficacy and safety of adding bevacizumab to first-line standard chemotherapy for treatment of extensive-stage small-cell lung cancer (SCLC).Patients and MethodsPatients with SCLC were randomly assigned to receive bevacizumab or placebo, with cisplatin or carboplatin plus etoposide, for four cycles followed by single-agent bevacizumab or placebo until progression or unacceptable toxicity. The primary end point was progression-free survival (PFS).ResultsFifty-two patients were randomly assigned to the bevacizumab group and 50 to the placebo group; 69% versus 66%, respectively, completed four cycles of therapy. Median PFS was higher in the bevacizumab group (5.5 months) than in the placebo group (4.4 months; hazard ratio [HR], 0.53; 95% CI, 0.32 to 0.86). Median overall survival (OS) was similar for both groups (9.4 v 10.9 months for bevacizumab and placebo groups, respectively), with an HR of 1.16 (95% CI, 0.66 to 2.04). Overall response rates were 58% (95% CI, 43% to 71%) for the bevacizumab group and 48% (95% CI, 34% to 62%) for the placebo group. Median duration of response was 4.7 months for the bevacizumab group and 3.2 months for the placebo group. In the bevacizumab and placebo groups, 75% versus 60% of patients, respectively, experienced one or more grade 3 or higher adverse events. No new or unexpected safety signals for bevacizumab were observed.ConclusionThe addition of bevacizumab to cisplatin or carboplatin plus etoposide for treatment of extensive-stage SCLC improved PFS, with an acceptable toxicity profile. However, no improvement in OS was observed.

scholarly journals Randomized Phase II Trial of Sequential Chemotherapy in Advanced Non-Small Cell Lung Cancer (SWOG 9806)

2004 ◽  
Vol 10 (15) ◽  
pp. 5022-5026 ◽  
Author(s):  
Martin J. Edelman ◽  
Joseph I. Clark ◽  
Kari Chansky ◽  
Kathy Albain ◽  
Nirmala Bhoopalam ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Phase Ii ◽  
Cell Lung Cancer ◽  
Phase Ii Trial ◽  
Small Cell ◽  
Small Cell Lung ◽  
Sequential Chemotherapy ◽  
Randomized Phase Ii

Randomized Phase II Study of Ixabepilone or Paclitaxel Plus Carboplatin in Patients With Non–Small-Cell Lung Cancer Prospectively Stratified by Beta-3 Tubulin Status

2013 ◽  
Vol 31 (16) ◽  
pp. 1990-1996 ◽  
Author(s):  
Martin J. Edelman ◽  
Claus-Peter Schneider ◽  
Chun-Ming Tsai ◽  
Heung-Tae Kim ◽  
Elisabeth Quoix ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Prognostic Factor ◽  
Small Cell Lung Cancer ◽  
Phase Ii ◽  
Cell Lung Cancer ◽  
Phase Ii Study ◽  
Small Cell ◽  
Clinical Activity ◽  
Small Cell Lung ◽  
Randomized Phase Ii

Purpose Retrospective studies have reported that tumor expression of the beta-3 tubulin (β3T) isoform is an unfavorable prognostic factor in non–small-cell lung cancer (NSCLC) treated with tubulin-inhibiting chemotherapy. Ixabepilone is a tubulin-inhibiting agent with low susceptibility to multiple resistance mechanisms including β3T isoform expression in several tumor models. This randomized phase II study evaluated ixabepilone-based chemotherapy in stage IIIb/IV NSCLC, compared with paclitaxel-based chemotherapy. Tumor specimens were prospectively evaluated for β3T expression. Patients and Methods Patients were stratified by β3T status (positive v negative) and randomly assigned at a ratio of 1:1 to receive ixabepilone (32 mg/m2) and carboplatin (area under concentration-time curve [AUC], 6) or paclitaxel (200 mg/m2) and carboplatin (AUC, 6) for up to six cycles. The primary end point was progression-free survival (PFS) in the β3T-positive subgroup. Results Ninety-five patients (β3T positive, 52; β3T negative, 43) received ixabepilone plus carboplatin; 96 patients (β3T positive, 49; β3T negative, 47) received paclitaxel plus carboplatin. No significant differences in median PFS were observed between arms for either subgroup (β3T positive, 4.3 months in both arms; β3T negative, 5.8 v 5.3 months). Ixabepilone did not significantly improve overall survival (OS) for the β3T-positive subset or the overall population. Adverse events were similar between the two arms and comparable with those in previous studies. Conclusion There was no predictive value of β3T in differentiating clinical activity of ixabepilone- or paclitaxel-containing regimens. Ixabepilone did not improve PFS or OS in patients with β3T-positive tumors. β3T-positive patients had worse PFS relative to β3T-negative patients, regardless of treatment; hence, β3T expression seems to be a negative prognostic factor, but not a predictive factor, in advanced NSCLC treated with either ixabepilone or paclitaxel platinum-based doublets.

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