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.

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.

scholarly journals Phase II Trial of Ixabepilone As Second-Line Treatment in Advanced Endometrial Cancer: Gynecologic Oncology Group Trial 129-P

2009 ◽  
Vol 27 (19) ◽  
pp. 3104-3108 ◽  
Author(s):  
Don S. Dizon ◽  
John A. Blessing ◽  
D. Scott McMeekin ◽  
Sudarshan K. Sharma ◽  
Paul DiSilvestro ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Phase Ii ◽  
Response Rate ◽  
Gynecologic Oncology ◽  
Progression Free Survival ◽  
Gynecologic Oncology Group ◽  
Second Line ◽  
Chemotherapeutic Regimen ◽  
Recurrent Endometrial Cancer ◽  
Grade 3

Purpose A phase II study was conducted to determine the response rate of ixabepilone (BMS-247550, National Cancer Institute (NCI)–supplied agent investigational new drug No. 59,699) in patients with persistent or recurrent endometrial cancer who have progressed despite standard therapy. Patients and Methods Eligible patients had recurrent or persistent endometrial cancer and measurable disease. One prior chemotherapeutic regimen, which could have included either paclitaxel or docetaxel, was allowed. Patients received ixabepilone 40 mg/m2 as a 3-hour infusion on day 1 of a 21-day cycle. Treatment was continued until disease progression or until unacceptable toxicity occurred. Results Fifty-two patients were entered on the study, and 50 of these were eligible. The median age was 64 years (range, 40 to 83 years). Prior treatment included radiation in 21 patients (42%) and hormonal therapy in eight patients (16%). All patients had prior chemotherapy, and 47 (94%) received prior paclitaxel therapy. The overall response rate was 12%; one patient achieved a complete remission (2%), and five achieved partial remission (10%). Stable disease for at least 8 weeks was noted in 30 patients (60%). The median progression-free survival (PFS) was 2.9 months, and the 6-month PFS was 20%. Major grade 3 toxicities were neutropenia (52%), leukopenia (48%), gastrointestinal (24%), neurologic (18%), constitutional (20%), infection (16%), and anemia (14%). Conclusion In a cohort of women with advanced or recurrent endometrial cancer who were previously treated with paclitaxel, ixabepilone showed modest activity of limited duration as a second-line agent.

A Phase II Study of Leuprolide in Advanced/Recurrent Endometrial Cancer

1997 ◽  
Vol 64 (1) ◽  
pp. 126-129 ◽  
Author(s):  
A. Covens ◽  
G. Thomas ◽  
P. Shaw ◽  
I. Ackerman ◽  
R. Osborne ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Recurrent Endometrial Cancer

A multicenter phase II study of gemcitabine and S-1 combination therapy (GS therapy) in patients with metastatic pancreatic cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4550-4550 ◽  
Author(s):  
H. Ueno ◽  
T. Okusaka ◽  
J. Furuse ◽  
K. Yamao ◽  
A. Funakoshi ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Combination Therapy ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Study ◽  
Phase Iii ◽  
Metastatic Pancreatic Cancer ◽  
Good Survival ◽  
Multicenter Phase ◽  
Grade 3

4550 Background: As shown in our previous phase I study (Oncology 2005, 69:421–427), gemcitabine and S-1 combination therapy (GS therapy) appears to be feasible and effective against advanced pancreatic cancer. The present multicenter phase II study was conducted to confirm the efficacy and toxicity of GS therapy for metastatic pancreatic cancer. Methods: Patients with histologically or cytologically proven pancreatic adenocarcinoma with at least one measurable metastatic lesion were eligible for the study. Other eligibility criteria included: no previous treatment for pancreatic cancer except surgery, age =20 and =74 years, ECOG performance status of 0 or 1, and adequate organ function. Gemcitabine was given intravenously at a dose of 1,000 mg/m2 over 30 min on days 1 and 8, and S-1 was given orally at a dose of 40 mg/m2 twice daily from day 1 to day 14, repeated every 3 weeks. The objective response rate was assessed according to RECIST. Results: A total of 55 patients from 10 institutions were enrolled between October 2004 and July 2005. The efficacy and toxicity were analyzed in 54 patients who received at least one course of GS therapy. The median number of treatment courses was 7 (range, 1–24+). Although no complete response was seen, a partial response was achieved in 24 patients, resulting in an overall response rate of 44% (95% CI, 30.9–58.6%). Twenty-six patients (48%) had stable disease. The median progression-free survival was 5.9 months (95% CI, 4.1–6.9 months) and the median overall survival was 10.1 months (95% CI, 8.5–10.8 months) with a 1-year survival rate of 33%. The major grade 3–4 toxicities were neutropenia (80%), leucopenia (59%), thrombocytopenia (22%), anorexia (17%), rash (7%), nausea (6%) and fatigue (6%). Hematological toxicity was mostly transient and there was only one episode of infection with grade 3–4 neutropenia. No treatment-related deaths occurred during the study. Conclusions: GS therapy produced a high response rate and good survival associated with an acceptable toxicity profile in patients with metastatic pancreatic cancer. A randomized phase III trial to confirm the efficacy of GS therapy is planned. No significant financial relationships to disclose.

Phase II–III Study of Gemtuzumab Ozogamicin Monotherapy versus Best Supportive Care in Older Patients with Newly Diagnosed AML Unfit for Intensive Chemotherapy: First Results of the EORTC-GIMEMA AML-19 Trial

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 762-762 ◽  
Author(s):  
Sergio Amadori ◽  
Stefan Suciu ◽  
Dominik Selleslag ◽  
Giuliana Alimena ◽  
Liliana Baila ◽  
...  
Keyword(s):  
Supportive Care ◽  
Phase Ii ◽  
Older Patients ◽  
Phase Ii Study ◽  
Best Supportive Care ◽  
Gemtuzumab Ozogamicin ◽  
Phase Iii ◽  
Intensive Chemotherapy ◽  
Grade 3 ◽  
To Receive

Abstract Treatment of AML in the elderly remains challenging. In particular, few therapeutic options exist for patients (pts) who are not considered medically fit for intensive chemotherapy. Gemtuzumab ozogamicin (GO), a humanized anti-CD33 monoclonal antibody conjugated to calicheamicin, has demonstrated single agent efficacy in older patients with relapsed AML. In a previous trial we reported a complete response rate of 17% when the licensed dose/schedule of GO was used as frontline monotherapy for older unfit pts with AML, but excess hematologic and liver toxicity suggested changes in both dosing and scheduling to improve feasibility. The AML-19 study was designed as a sequential phase II–III trial in pts of age 61 or over with untreated AML, who could not be considered candidates for, or must have declined, conventional intensive chemotherapy. The primary objective of the phase II study was to investigate whether any of two different schedules of lower dose GO monotherapy (total delivered dose 9 mg/m2 in 2 or 3 fractions over one week) is sufficiently effective and tolerable frontline therapy to continue phase III comparison with best supportive care (BSC). Pts had to have adequate renal and hepatic function, and the WBC count had to be less than 30,000/cmm at the time of registration. Two-thirds of the pts were randomly assigned to receive a single induction course of either GO 3 mg/m2 iv on days 1, 3 and 5 (arm A), or GO 6 mg/m2 iv on day 1 and 3 mg/m2 on day 8 (arm B); the remaining third was assigned to the BSC arm. Randomization was stratified by age, performance status (PS), initial WBC, CD33 expression on marrow blasts, and Institution. Pts with no evidence of objective disease progression were eligible to receive continuation treatment with monthly outpatient infusions of GO at 2 mg/m2 for a maximum of 8 months. Primary end-point of the phase II study was clinical benefit rate (CBR) defined as the number of pts either achieving a remission (CR, CRp, PR) or maintaining a stable disease (SD) in each experimental arm. The arm associated with the highest CBR would be selected for phase III assessment, providing that it is at least 48% (Simon design). Between 06/2004 and 12/2006, 56 pts were randomized in the two experimental arms (arm A 29; arm B 27). The two arms were comparable in terms of age (arm A: median 77 yrs; arm B: median 78 yrs), PS >2 (arm A: 7%; arm B: 4%), secondary AML (arm A: 45%; arm B: 37%), and CD33 expression on ≥20% marrow blasts (arm A: 86%; arm B: 85%). In arm A, 6 pts achieved CR, 2 PR, and 3 maintained SD for an overall CBR of 38% (90% CI, 23%–55%); in arm B, 5 pts achieved CR, 1 CRp, and 11 maintained SD for an overall CBR of 63% (90% CI, 45%–78%). Most toxicities were <grade 3 in both arms and included nausea/vomiting, diarrhea, fatigue, stomatitis and transient elevations of serum transaminases and bilirubin. The rate of grade ≥3 infection was slightly higher in arm B (48% vs 31%), as was the incidence of severe bleeding (11% vs 0%). All-cause early mortality (<6 wks) occurred in 17% of pts in arm A (2 infection, 3 AML) and in 11% of pts in arm B (1 infection, 1 AML, 1 infection+AML). In summary, lower dose GO is a tolerable and active primary therapy for older AML pts who are considered unsuitable for intensive chemotherapy. The day 1+8 schedule (arm B) is associated with a more favourable efficacy profile, meeting the statistical criteria to be selected as the preferred regimen for phase III comparison with BSC. Accrual to the phase III trial is ongoing.

scholarly journals A phase II study of frontline paclitaxel/carboplatin/bevacizumab, paclitaxel/carboplatin/temsirolimus, or ixabepilone/carboplatin/bevacizumab in advanced/recurrent endometrial cancer

2018 ◽  
Vol 150 (2) ◽  
pp. 274-281 ◽  
Author(s):  
Carol Aghajanian ◽  
Virginia Filiaci ◽  
Don S. Dizon ◽  
Jay W. Carlson ◽  
Matthew A. Powell ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Recurrent Endometrial Cancer

Phase I/II Trial of Capecitabine, Oxaliplatin, and Radiation for Rectal Cancer

2003 ◽  
Vol 21 (16) ◽  
pp. 3098-3104 ◽  
Author(s):  
Claus Rödel ◽  
Gerhard. G. Grabenbauer ◽  
Thomas Papadopoulos ◽  
Werner Hohenberger ◽  
Hans-Joachim Schmoll ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Tumor Regression ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Sphincter Preservation ◽  
Phase Iii ◽  
Grade 3

Purpose: The purpose of this study was to establish the feasibility and efficacy of preoperative radiotherapy (RT) with concurrent capecitabine and oxaliplatin (XELOX-RT) in patients with rectal cancer. Patients and Methods: Thirty-two patients with locally advanced (T3/T4) or low-lying rectal cancer received preoperative RT (total dose, 50.4 Gy). Capecitabine was administered concurrently at 825 mg/m2 bid on days 1 to 14 and 22 to 35, with oxaliplatin starting at 50 mg/m2 on days 1, 8, 22, and 29 with planned escalation steps of 10 mg/m2. End points of the phase II study included downstaging, histopathologic tumor regression, resectability of T4 disease, and sphincter preservation in patients with low-lying tumors. Results: Dose-limiting grade 3 gastrointestinal toxicity was observed in two of six patients treated with 60 mg/m2 of oxaliplatin. Thus, 50 mg/m2 was the recommended dose for the phase II study. Toxicities observed at this dose level were generally mild, with only two cases of short-lived grade 3 diarrhea. Myelosuppression, mainly leukopenia, was restricted to grade 2 in 19% of patients. T-category downstaging was achieved in 17 (55%) of 31 operated patients, and 68% of patients had negative lymph nodes. Pathologic complete response was found in 19% of the resected specimens. Radical surgery with free margins could be performed in 79% of patients with T4 disease, and 36% of patients with tumors ≤ 2 cm from the dentate line had sphincter-saving surgery. Conclusion: Preoperative XELOX-RT is a feasible and well tolerated treatment. This regimen is proposed for phase III evaluation comparing standard fluorouracil-based therapy with XELOX chemoradiotherapy.

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