Phase II clinical study of concurrent durvalumab and radiation therapy (DUART) followed by adjuvant durvalumab in patients with localized urothelial cancer of bladder: Results for primary analyses and survival. BTCRC-GU15-023.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 398-398 ◽  
Author(s):  
Monika Joshi ◽  
Matthew Kaag ◽  
Leonard Tuanquin ◽  
Jason Liao ◽  
Deepak Kilari ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Bladder Cancer ◽  
Radiation Therapy ◽  
Phase Ii ◽  
Statistical Power ◽  
Treatment Options ◽  
Locally Advanced ◽  
Drop Out ◽  
Unresectable Tumor ◽  
One Year

398 Background: Bladder cancer (BC) patients (pts) who are cisplatin ineligible/unfit for surgery, or locally advanced and unresectable have limited treatment options. DUART investigates if the combination of radiation therapy (RT) and checkpoint inhibitor, durvalumab (durva) is safe and effective in these pts. We recently reported that the combination was safe, tolerable and disease control rate (DCR) was 92% post durvaRT. Here we present interim efficacy data of our phase II study. Methods: Pts with pure or mixed urothelial bladder cancer (T2-4 N0-2 M0) were enrolled if their tumor was unresectable (35%), were unfit for surgery (50%) and/or cisplatin ineligible (89%). Primary endpoints: a) PFS at 1-yr b) DCR post adjuvant durva; Secondary endpoints: a) CR post durvaRT b) median PFS c) median OS. Pts were treated with durva (1500mg) Q4 wks x2 doses along with definitive RT (64.8Gy, 36 fractions over 7 wks) to the bladder and involved nodes followed by adjuvant durva Q4 wks x 1 yr. Response was evaluated with CT scan and cystoscopy+biopsy. Sample size was based on assumption that this regimen would increase 1 yr PFS by 25% compared to RT alone (50% to 75%); we assumed DCR of 75%. A total of 26 pts were needed to reach a statistical power of at least 80% at one-sided alpha of 5% and to allow for 10% drop out rate. Results: Twenty-six pts (19 males, 7 females) were enrolled, median age 74 yr (51-94). Sixty two percent of pts had >T2 disease, 31% had positive lymph nodes; 62% with unresectable tumor or were unfit for surgery due to comorbidities. At data cut off (9/30/2020) 20/26 pts were evaluable for DCR post adjuvant durva (3 pts with CR post durvaRT, did not get adjuvant therapy; 1 pt withdrew after 3 cycles for adjuvant durva and was on f/u with unconfirmed CR; 2 pts are still on adjuvant durva) and 25/26 for PFS and all 26 pts for OS. Post completion of adjuvant durva, DCR was seen in 70 % (14/20 with 10 CR; 3 PR; 1 SD; 6 PD). One-year probability of PFS was 73% (95% CI 56.4%, 94.4%), median PFS was 18.5 months. One-year OS probability was 83.8% (95% CI 70.4%, 99.7%) with two-year OS probability of 76.8 (95% CI 60.2%, 98%). Median OS has not been reached. We did not observe any correlation between clinical outcome and baseline tumor PD-L1 expression. Conclusions: DurvaRT followed by adjuvant durva demonstrated promising efficacy with 1-year PFS probability of 73%, 1- year OS probability of 83.8% and DCR of 70% in MIBC and locally advanced BC pts with comorbidities. Results will be updated prior to the final presentation. Efficacy was also seen in node (+) pts which led to the design of prospective randomized NCTN study. Induction chemo followed by chemo+durvaRT+ adjuvant durva vs. chemoRT combination is being evaluated in the ongoing EA8185 clinical trial (ECOG-ACRIN/NRG study) for node (+) BC pts. Clinical trial information: NCT02891161.

Concurrent durvalumab and radiation therapy followed by adjuvant durvalumab in patients with locally advanced urothelial cancer of bladder (DUART): Btcrc-GU15-023.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 513-513 ◽  
Author(s):  
Monika Joshi ◽  
Leonard Tuanquin ◽  
Matthew Kaag ◽  
Deepak Kilari ◽  
Sheldon L. Holder ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Statistical Power ◽  
Treatment Options ◽  
Locally Advanced ◽  
Drop Out ◽  
Total N ◽  
Primary Endpoints ◽  
Secondary Endpoints ◽  
Grade 3

513 Background: Bladder cancer (BC) patients (pts) who are cisplatin ineligible/unfit for surgery, unresectable have limited treatment options. In this study, we investigate if the combination of radiation therapy (RT) and checkpoint inhibitor, durvalumab (durva) is safe and effective in these pts. Our results from phase (ph) Ib suggested that the combination was safe. Here we present the response rate post durvaRT and updated treatment related adverse events (TRAEs) amongst our evaluable pts in ph II. Methods: This is a single arm ph Ib-II study for T2-4 N0-2 M0 pts. The ph II primary endpoints a) PFS rate at 1 yr b) disease control rate (DCR); secondary endpoints were a) CR post durvaRT b) PFS c) OS. Pts were treated with durva (1500mg) Q4 wks x2 doses along with definitive RT (64.8Gy, 36 fractions over 7 wks) to the bladder and involved nodes followed by adjuvant durva Q4 wks x 1 yr. Response was evaluated with CT scan and cystoscopy+biopsy post durvaRT. We anticipated that durvaRT followed by durva would increase PFS at 1 yr from 50% to 75% when compared to RT; we assumed DCR of about 75%. A total of 26 pts were needed to reach a statistical power of at least 80% at one-sided alpha of 5% and to allow for 10% drop out rate. Results: Total N = 26 patients (male 19; female 7, median age 74yr). At the time of data cut off, 21/26 pts were evaluable for response post durvaRT. Post completion of durvaRT time point, clinical CR was seen in 15/21 pts (71.4%); PR 1/21 pts (4.7%); SD 4/21 (19%); PD 1/21 (4.7%). DCR was seen in 20/21 pts (95%) post durvaRT. Median follow up from D1 to last follow up was 6.1 mos. Grade ≥ 3 TRAE amongst 26 pts: anemia (1/26), lipase/amylase (1/26), immune nephritis (1/26), dyspnea (gr 4, copd/immune), fatigue (1/26), lymphopenia (6/26). Other TRAEs: Fatigue was the most common TRAE (16/26); UTI (5/26); cystitis (3/26). No fatal TRAEs were observed. Conclusions: DurvaRT demonstrated promising efficacy with clinical CR of 71.4% and DCR of 95% in unresectable, cisplatin ineligible locally advanced BC. It was generally well tolerated. Ph II study has completed accrual and longer-term results will further our understanding of this regimen’s efficacy in locally advanced BC. Clinical trial information: NCT02891161.

A randomized, phase II clinical trial of preoperative stereotactic body radiation therapy versus conventionally fractionated chemoradiation for resectable, borderline-resectable, or locally advanced type a pancreatic adenocarcinoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS4167-TPS4167
Author(s):  
William Adrian Hall ◽  
Susan Tsai ◽  
Anjishnu Banerjee ◽  
Ben George ◽  
Paul S. Ritch ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Radiation Therapy ◽  
Neoadjuvant Chemotherapy ◽  
Pancreatic Adenocarcinoma ◽  
Phase Ii ◽  
Stereotactic Body Radiation Therapy ◽  
Locally Advanced ◽  
Phase Ii Clinical Trial ◽  
Borderline Resectable ◽  
Conventionally Fractionated

TPS4167 Background: There is growing consensus for the use of neoadjuvant therapy in patients with potentially operable pancreatic adenocarcinoma (PC). However, there is not consensus on the type and duration of chemotherapy or radiation therapy (RT) dose. Stereotactic body radiation therapy (SBRT) has gained popularity despite the absence of prospective data for its use in the preoperative setting. Furthermore, SBRT preoperatively has not been standardized. At present, there exists no randomized data comparing preoperative SBRT with conventionally fractionated concurrent chemo-RT. We designed this trial to examine differences between pre-op RT dose and fractionation schedules. Methods: This study is a prospective, randomized, two-arm, phase II clinical trial. Eligible patients must have cytologically confirmed PC and be deemed suitable for surgical resection with resectable, borderline resectable, or locally advanced type A disease, based on cross-sectional imaging. Before randomization patients are stratified by clinical node positivity, neoadjuvant chemotherapy, and stage of disease. Patients are then randomized to either 50.4 Gy over 28 fractions with concurrent weekly Gemcitabine vs SBRT to a total dose of 25-35 Gy over 5 fractions. The primary endpoint of the study is pathologic node positivity. We hypothesize that patients treated with neoadjuvant chemotherapy followed by conventionally fractionated chemo-RT will have a lower rate of pathologic node positivity as compared to those patients treated with neoadjuvant chemotherapy followed by SBRT. Secondary endpoints include patient reported quality of life, local recurrence, primary tumor pathologic response, margin status, surgical complications, MR based treatment response, and overall survival. We anticipate a node positivity rate of 37% when using preoperative chemotherapy followed by SBRT. We hypothesize that treatment with chemotherapy followed by conventionally fractionated chemo-RT will reduce the rate of node positivity to 17%. Using a one-sided Type I error rate of 0.1, approximately 88 total patients (44 per arm) provide an 80% power to detect the hypothesized difference in pathologic node positivity between the two arms. To address patient dropout, an additional 14 patients (about 15%) will be enrolled for a total target accrual of 102 patients. The trial opened in November 2018 and 8 of the planned 102 patients have been enrolled. Clinical trial information: NCT03704662.

A phase II trial of risk enabled therapy after initiating neoadjuvant chemotherapy for bladder cancer (RETAIN BLADDER): Interim analysis.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 397-397
Author(s):  
Daniel M. Geynisman ◽  
Philip Abbosh ◽  
Eric A. Ross ◽  
Matthew R. Zibelman ◽  
Pooja Ghatalia ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Bladder Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Phase Ii ◽  
Metastatic Disease ◽  
Phase Ii Trial ◽  
Locally Advanced ◽  
Intravesical Therapy ◽  
Ecog Ps

397 Background: Cisplatin-based neoadjuvant chemotherapy (NAC) followed by cystectomy (Cx) or chemoradiation (CRT) is the standard of care for urothelial carcinoma (UC) pts with muscle invasive bladder cancer (MIBC). Both Cx and CRT have potential short and long-term toxicity and QOL implications. Mutations in DNA damage repair/response genes are associated with pathologic downstaging after NAC. Methods: We conducted a phase II, multi-institutional clinical trial (NCT02710734) to evaluate a risk-adapted approach to treatment of MIBC. Pts with cT2-T3N0M0 UC of the bladder, ECOG PS 0-1 and CrCl≥50 mL/min, underwent NAC with accelerated methotrexate, vinblastine, doxorubicin, and cisplatin (AMVAC). Pre-NAC TURBT specimens were sequenced (Caris Life Sciences) for mutations (pathogenic or VUS) in ATM, ERCC2, FANCC or RB1. Pts with at least one mutation and no clinical evidence of disease by restaging TUR and imaging post-NAC began pre-defined active surveillance (AS). Remaining pts underwent bladder-directed therapy: intravesical therapy ( < cT2 post-NAC), CRT or Cx. The primary endpoint was metastasis-free survival (MFS) at 2 years which is not mature. We herein report key interim results of clinically-meaningful intermediate endpoints. Results: Seventy-one (ITT) pts were enrolled over 33 months at four academic centers. Median age was 70 years (47-83), 74% were male, 92% Caucasian, 81% ECOG PS 0 and 79% cT2. 90% completed 3 cycles of NAC and with 17% grade 3-4 TRAEs and one death during AMVAC. At the time of data cut-off (September 11, 2020), for the ITT pts, 32 pts have had a Cx, 5 underwent CRT and 7 underwent intravesical therapy, at some point during the trial. Thirty-three pts (46%) had a mutation of interest and 28 pts (39%) started AS (2 of the 28 pts on AS did not have a mutation but elected to start AS after achieving cT0 post AMVAC). 76% of those with a mutation were cT0 at post-NAC TURBT. With a median follow-up of 14.9 mo (range: 3.1-35.3 mo), 14 AS pts recurred (50%). Of the 14 recurrences, 2 recurred with locally advanced or metastatic disease and have died, 5 had MIBC with one eventual metastatic recurrence, and 7 had NMIBC. Six (14%) non-AS pts have died. Out of the 40 pts who did not go to upfront Cx [AS (N = 28), CRT (N = 5), intravesical tx (N = 7)], 3 (7.5%) (all in the AS group) went on to Cx later. The bladder preservation rate is 55% for ITT pts and 89% for the AS group. In the AS cohort, mutations were seen in RB1 (50%), ATM (42%), ERCC2 (31%), FANCC (4%) with lowest rate for recurrence in ERCC2 (25% recurrence) vs RB1 (62% recurrence). Conclusions: Interim results of a phase II trial of risk enabled therapy utilizing a selection of clinical and genomic factors in pts with cT2-T3 MIBC demonstrates a 50% rate of any UC recurrence and a 11% rate of locally advanced/metastatic disease in the AS group. 89% of AS pts have retained their bladder. Follow-up continues for the primary endpoint of 2-year MFS. Clinical trial information: NCT02710734.

A phase II study of docetaxel and carboplatin with concurrent radiation therapy for locally advanced head and neck cancer

2011 ◽  
Vol 38 (1) ◽  
pp. 108-113 ◽  
Author(s):  
Imjai Chitapanarux ◽  
Vicharn Lorvidhaya ◽  
Ekasit Tharavichitkul ◽  
Somvilai Mayurasakorn ◽  
Pichit Sittitrai ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Head And Neck Cancer ◽  
Head And Neck ◽  
Phase Ii ◽  
Neck Cancer ◽  
Phase Ii Study ◽  
Locally Advanced ◽  
Advanced Head
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