Cetuximab/radiotherapy (CET+RT) versus concomitant chemoradiotherapy (cCHT+RT) with or without induction docetaxel/cisplatin/5-fluorouracil (TPF) in locally advanced head and neck squamous cell carcinoma (LASCCHN): Preliminary results on toxicity of a randomized, 2x2 factorial, phase II-III study (NCT01086826).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5513-5513 ◽  
Author(s):  
Maria Grazia Ghi ◽  
Adriano Paccagnella ◽  
Daris Ferrari ◽  
Paolo Foa ◽  
Franco Nole ◽  
...  
Keyword(s):  
Phase Ii ◽  
Standard Treatment ◽  
Treatment Options ◽  
Locally Advanced ◽  
Disease Stage ◽  
Advanced Head ◽  
Concomitant Chemoradiotherapy ◽  
Primary Endpoints ◽  
Ecog Ps

5513 Background: The standard treatment options for LASCCHN are cCHT+RT or CET+RT. Strategies to improve the efficacy with the integration of induction chemotherapy are being investigated. Primary endpoints of this study were to compare: 1) the overall survival (OS) of induction vs. no induction arms; 2) the Grade(G)3-4 in-field toxicity of cCHT+RT vs. CET+RT. Methods: Patients (pts) with unresectable LASCCHN, stage III-IV, ECOG PS 0–1 were randomized to a 2x2 factorial design: Arm A1: cCHT+RT (2 cycles of ciplatin/5fluorouracil); Arm A2: CET+RTX; Arm B1: 3 cycles of TPF followed by the same cCHT+RT; Arm B2: 3 cycles of TPF followed by CET+RT. A total of 204 deaths over 420 pts ( including the 101 randomized in the phase II part of the study comparing cCHT+RT with or w/o induction TPF) were required to detect a HR of death of 0.675 (A1+A2 vs. B1+B2; 2-sided a=0.05; b=0.20) and a 10% difference in G3-4 in-field mucosal toxicity (A1+B1 vs. A2+B2). Results: By February 2012, 387 pts over 413 pts were evaluable for toxicity. 82% of pts were male; median age was 60y; PS: 0=77.8% and 1=22.2%. Disease stage was III (31%) or IV (69%). Sites of disease were oral cavity (21.7%), oropharynx (54.8%), hypopharynx (23.5%). At a median follow-up of 21 months, 126 deaths occurred. Data on G3-4 in-field toxicity (primary endpoint) and compliance to cCHT+RT vs CET+RT are shown in the table. Conclusions: No advantage for CET+RT over cCHT+RT was observed regarding G3-4 in-field toxicities and feasibility. Pts are still being followed-up to assess OS. [Table: see text]

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 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.

Phase II study of irinotecan (cpt-11) and cisplatin (cddp) regimen (IP) with concurrent thoracic radiotherapy (TRT) in limited-stage small cell lung cancer (LS-SCLC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7084-7084 ◽  
Author(s):  
D. Castellano ◽  
A. Bartolomé ◽  
A. Font ◽  
A. Lopez-Martín ◽  
P. Diz ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Median Number ◽  
Prior Therapy ◽  
Concurrent Therapy ◽  
Primary Endpoints ◽  
Grade 3 ◽  
Number Of Cycles ◽  
Ecog Ps

7084 Background: the combination of CPT-11 and CDDP (IP) is an active regimen for SCLC. (Noda et al NEJM ’02, Hanna et al ASCO 2005). We performed a multicenter phase II study to assess the efficacy and toxicity of IP regimen with concurrent TRT in previously untreated LS-SCLC pts. Methods: Eligible pts were required to have histologically confirmed SCLC, measurable disease, no prior therapy, ECOG PS of 0–2, adequate organ functions, and to give informed consent. Treatment consisted of: CDDP 60 mg/m2 D1, I 60mg/m2 IV D1, 8 Q 21D for 4 cycles, and concurrent TRT 2.0 Gy daily to a total of 60.0 Gy, beginning with the 2nd cycle. I was adjusted to 50 mg/m2 at 2nd and 3rd cycles (during TRT). Pts were restaged after 4 cycles. Pts without progression or undue toxicity received 2 additional cycles. PCI (2.0 Gy X 10) was offered to CR pts. The primary endpoints were response rate and OS. Results: Twenty-six pts were included and 25 pts were evaluable for response (median age 62; M/F, 22/4; PS 0/1/2, 9/17; T2–4N0,T2–4N+ 6/20pts). Among 126 cycles administered, the relative dose-intensities of I and CDDP were 80% and 92% respectively. Median number of cycles/pt was 5 (1–6), and 22 pts completed the IP + TRT program. Fifteen pts achieved a CR and 6 pts a PR, for an overall RR of 84%. Median TTP was 12 months. At a median follow-up of 14 months, 19 pts are alive, and estimated median survival is 17 months. Grade 3–4 (NCI-CTC 3.0) toxicity (per cycle) during concurrent therapy included: neutropenia (25%), anemia (3%), thrombocytopenia (3%), diarrhea (10%), vomiting (5%), esophagitis (10%). There were no treatment-related deaths. Two pts required hospitalization during the concurrent therapy due to g3 diarrhea (1 pt) and febrile neutropenia (1 pt). Conclusions: The concurrent regimen of IP + TRT is highly effective in pts with LS-SCLC. The associated toxicity profile is predictable and adequate. Further study is warranted. No significant financial relationships to disclose.

Final analysis of a phase II study of Yale-modified FOLFIRINOX (mFOLFIRINOX) in metastatic pancreatic cancer (MPC).

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 395-395 ◽  
Author(s):  
Edward Samuel James ◽  
Xiangyu Cong ◽  
Xiaopan Yao ◽  
Carol Hahn ◽  
Kristin Kaley ◽  
...  
Keyword(s):  
Phase Ii ◽  
Historical Data ◽  
Locally Advanced ◽  
Final Analysis ◽  
Open Label ◽  
Peritoneal Disease ◽  
Full Dose ◽  
Entire Cohort ◽  
Ecog Ps

395 Background: Although FOLFIRINOX is superior to gemcitabine in MPC, the regimen is associated with significant toxicities (Conroy et al. N Engl J Med 2011;364:1817). In our prior retrospective analysis, efficacy was not compromised by dose attenuations of FOLFIRINOX (Gunturu et al. Med Oncol 2013;30:361). Based on this analysis, a prospective phase II open label study to evaluate the efficacy and tolerability of mFOLFIRINOX in pts with locally advanced (LAPC) and MPC was conducted. Herein, we report the final analysis of the toxicity in LAPC and MPC, and the efficacy in MPC. Methods: Previously untreated pts with MPC or LAPC received mFOLFIRINOX every two wks with 25% dose reductions of irinotecan & bolus 5FU until progression, unacceptable toxicity, or surgical resection. All pts received prophylactic pegfilgrastim. CAT scans were obtained every 4 cycles for response assessment by RECIST. Toxicities in the entire cohort, and response rate (RR) & pt characteristics in the MPC cohort were compared to historical data reported by Conroy. PFS was determined for MPC cohort. Results: 31 pts with LAPC and 43 pts with MPC with ECOG PS 0/1 were enrolled between 11/11 and 01/14. Characteristics of evaluable (37/43) MPC pts were: med age, 61 yrs (range 50-76); male, 21; ECOG PS 0, 17; med # metastatic sites, 2; peritoneal disease, 14; biliary stent, 9; med # of cycles 10 (range 4-31). Grade 3/4 toxicities in entire cohort were: vomiting & peripheral neuropathy, 2.7%; ALT elevated, thromboembolism and febrile neutropenia, 4.1%; anemia, 5.4%; diarrhea,16.2% (no grade 4 diarrhea reported); neutropenia & fatigue, 12.2%; thrombocytopenia, 9.5%. Neutropenia (p<0.0001), vomiting (p=0.0014), and fatigue (0.0194) were significantly decreased compared to historical data. RR in 37 pts with MPC was 35.1% (0 CR, 13 PR, 19 SD, 5 PD) and similar to historical data (36.9%; p 0.86). PFS in MPC pts was 6.11 mo with 95% CI (5.29, 8.31). Conclusions: mFOLFIRINOX with prophylactic pegfilgrastim in pts with MPC is associated with improved tolerability compared to full dose FOLFIRINOX, while RR and PFS in pts with MPC is similar to that reported by Conroy et all using full dose FOLFIRINOX. MPC pts are in follow-up for OS. Follow up for LAPC patients is ongoing. Clinical trial information: NCT01523457.

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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