Phase III randomized trial of definitive chemoradiotherapy (CRT) with FOLFOX or cisplatin and fluorouracil in esophageal cancer (EC): Final results of the PRODIGE 5/ACCORD 17 trial.

2012 ◽  
Vol 30 (18_suppl) ◽  
pp. LBA4003-LBA4003 ◽  
Author(s):  
Thierry Conroy ◽  
Marie-Pierre Galais ◽  
Jean Luc Raoul ◽  
Olivier Bouche ◽  
Sophie Gourgou-Bourgade ◽  
...  
Keyword(s):  
Squamous Cell ◽  
Treatment Options ◽  
Complete Response ◽  
Phase Iii ◽  
Eligibility Criteria ◽  
Randomized Phase Ii ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
Ecog Ps

LBA4003 Background: CRT is one of the best treatment options for localized EC. As new combinations are required to improve safety and survival, we launched a randomized phase II study to assess the complete response (CR) rate of CRT with FOLFOX versus 5FU/cisplatin in 97 pts with localized EC (Conroy 2010). The trial having met its objectives, it has been pursued as a phase III trial. Stratified randomization was performed centrally in a 1:1 ratio according to histological type, pretreatment weight loss in the prior 6 months (<10% vs ≥10%), ECOG PS (0 vs 1 vs 2), and center. Methods: Pts with technically unresectable cancer or those with surgical contraindications or who refused to undergo surgery were eligible. Eligibility criteria also included age >18 years (y), PS ≤ 2, previously untreated adenocarcinoma or squamous cell EC (any T, N0 or N1, M0 or M1a). The radiation dose was 50 Gy (2Gy/fr) 5 d/wk for 5 wks in both arms. In Arm A, pts received 6 bimonthly cycles (cy): oxaliplatin 85 mg/m2 d1 and leucovorin 200 mg/m2 followed by 5-FU 400 mg/m2 bolus d1 then 1,600 mg/m2 46h continuous infusion (ci) ; the first 3 cy were delivered during RT, the 3 other after. In Arm B, pts received 4 cy: cisplatin 75 mg/m2 d1 followed by 5FU 1,000 mg/m2/d ci d1-4, the first 2 cy during RT and 2 other after. The primary endpoint was PFS. Main secondary endpoints were OS, grade 3-4 toxicities, and quality of life. A total of 266 pts would provide 90% power to detect a 20% 3y-PFS difference (α=0.05). Results: 267 pts were enrolled between 10/2004 and 08/2011. Treatment cohorts were well balanced: male 81%; median age 61 y; PS 0 53%, squamous cell 85.8%, stage III 52%, IVA 6.0% and IVB 3.0%. Full treatment was delivered to 67.9% and 72.2% of pts in arms A/B, respectively. 7 toxic deaths occurred in each arm. Grade 3/4 toxicities per pt (%) in arms A/B were neutropenia 30.6/31.3, febrile neutropenia 5.3/7.0, anemia 5.4/11.0, asthenia 17.6/10.2, respectively. The median FU time was 25.3 mos. 3y-PFS was 18.2/17.4 % (HR=1.07; 95%CI =0.80-1.43) and median OS was 20.2 /17.5 m (HR=1.06; 95%CI =0.77-1.46). Conclusions: CRT with FOLFOX does not improve PFS compared to cisplatin and 5-FU and has similar toxicities.

Palbociclib (P) in patients (pts) with soft tissue sarcoma (STS) with CDK4 amplification: Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 11565-11565
Author(s):  
Scott Schuetze ◽  
Michael Rothe ◽  
Pam K. Mangat ◽  
Liz Garrett-Mayer ◽  
Funda Meric-Bernstam ◽  
...  
Keyword(s):  
Treatment Options ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
Stage Design ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
Ecog Ps ◽  
Stage 1 ◽  
Anti Tumor Activity

11565 Background: TAPUR is a phase II basket study evaluating anti-tumor activity of commercially available targeted agents in pts with advanced cancers with genomic alterations. Results in a cohort of STS pts with CDK4 amplification treated with P are reported. Methods: Eligible pts had advanced STS, no standard treatment options, measurable disease, ECOG PS 0-2, and adequate organ function. Genomic testing was performed in CLIA-certified, CAP-accredited site selected labs. Pts received P at 125 mg orally once daily for 21 days, followed by 7 days off until disease progression. Pts matched to P had CDK4 amplification and no RB mutations. Simon 2-stage design tested the null disease control (DC) - defined as partial (PR), complete response (CR) or stable disease at 16+ weeks (SD 16+) - rate of 15% vs. 35% (power = 0.85; α = 0.10). If ≥2 of 10 pts in stage 1 have DC, 18 more pts are enrolled. If ≥7 of 28 pts have DC, the null DC rate is rejected. Secondary endpoints are progression-free survival (PFS), overall survival (OS) and safety. Results: 29 pts (66% male) with STS with CDK4 amplification were enrolled from July 2016 to Nov 2019. 1 pt was not evaluable and excluded from efficacy analyses. Demographics and outcomes are summarized in Table. One pt with partial response (PR) and 12 pts with SD16+ were observed for DC and objective response (OR) rates of 48% (95% CI: 31%, 62%) and 3.7% (95% CI: 0.1%, 19%), respectively, and the null DC rate of 15% was rejected (p<0.001). 9/13 pts with DC continued on treatment for >32 weeks. 14 pts had at least one grade 3-4 AE at least possibly related to P with the most common being low WBC/platelets. Other grade 3 AEs included increased alanine aminotransferase, anemia, and fatigue. Conclusions: Monotherapy P demonstrated anti-tumor activity in heavily pre-treated pts with STS with CDK4 amplification. Additional study is warranted to confirm the efficacy of P in pts with STS with CDK4 amplification. Clinical trial information: NCT02693535. [Table: see text]

A phase III study comparing amrubicin and cisplatin (AP) with irinotecan and cisplatin (IP) for the treatment of extended-stage small cell lung cancer (ED-SCLC): JCOG0509.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7003-7003 ◽  
Author(s):  
Yoshikazu Kotani ◽  
Miyako Satouchi ◽  
Masahiko Ando ◽  
Kazuhiko Nakagawa ◽  
Nobuyuki Yamamoto ◽  
...  
Keyword(s):  
Standard Treatment ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Eligibility Criteria ◽  
Severe Diarrhea ◽  
Secondary Endpoints ◽  
Phase Iii Study ◽  
Ecog Ps ◽  
To Receive

7003 Background: IP is the standard treatment for ED-SCLC, however often cause severe diarrhea. AP have shown promising activity in SCLC with fewer diarrhea. We conducted a phase III trial comparing AP with IP. Methods: Eligibility criteria included patients (pts) with chemotherapy-naïve, ED-SCLC, aged 20 to 70, and ECOG PS 0-1. Pts were randomized to receive either IP or AP, balancing for site, sex, and PS. IP comprised administration of I (60 mg/m2) iv on days 1, 8, and 15, and P (60 mg/m2) iv on day1,every 4 weeks. AP comprised administration of A (40 mg/m2) iv on day 1-3, and P (60 mg/m2) iv on day1, every 3 weeks. The planned sample size was 141 pts in each arm with a one-sided alpha of 5% and power of 70% and a non-inferiority margin of hazard ratio (HR) as 1.31. The primary endpoint was overall survival (OS). The secondary endpoints were response rate (RR), progression-free survival (PFS), adverse events (AEs), and quality of life (QOL). We evaluated pts’ QOL twice: at the baseline and after completion of the second course. Results: 284 pts were randomized to IP (n=142) and AP (n=142). Median age was 63, 84% were male, and 56% had PS 0. When 191pts enrolled, more febrile neutropenia (FN) was observed in AP than anticipated, and the initial dose of A was decreased from 40 mg/m2 to 35 mg/m2. At the second interim analysis conducted after the completion of patient accrual, the median OS of AP (15.0 m) was much worse than that of IP (18.3 m) and the HR (1.41; 96.3% CI, 1.03-1.93) exceeds even the non-inferiority margin, so the Data and Safety Monitoring Committee recommended early publication of the results. Median PFS was 5.7 (IP) vs. 5.2 months (AP) (HR 1.43, 95% CI, 1.13-1.82). RR was 69.5% (IP) vs. 77.9% (AP) (p=0.14). AEs in IP and AP arm were Grade 4 neutropenia (22.5% vs. 78.6%), G3-4 FN (10.7% vs. 32.1%), and G3-4 diarrhea (7.1% vs.1.4%). Proportion of improvement in physical status of QOL was 37.1%(IP) vs. 31.7%(AP), (odds ratio 0.72; 95%CI, 0.43-1.22; P=0.227). Conclusions: AP showed more bone marrow suppression than expected although it caused less diarrhea. The non-inferiority of AP to IP was not demonstrated and IP remains the standard treatment for ED-SCLC.

Docetaxel (D) and estramustine (E) as first-line chemotherapy for patients (pts) with hormone-refractory advanced prostate cancer (HRPC): Final results of a multicentric phase II randomized trial

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15552-15552 ◽  
Author(s):  
O. Caffo ◽  
T. Sava ◽  
E. Comploj ◽  
M. Giampaolo ◽  
F. Zustovich ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Phase Iii ◽  
Eligibility Criteria ◽  
Psa Response ◽  
Psa Progression ◽  
Hormone Refractory ◽  
Grade 3 ◽  
Ecog Ps

15552 Background: Preclinical data showed a synergism between E and D and several studies supported an advantage in associating E and D. Nevertheless, D is considered a standard treatment for HRPC pts and the role of D+E combination remains controversial. Purpose of this study was to evaluate the activity, in terms of PSA decline (PSA↓), the safety and quality of life (QoL) of D±E in HRPC pts. Methods: Eligibility criteria included: HRPC diagnosis, hormone-refractory advanced disease (PSA progression after at least two hormonal therapy), ECOG PS < 2, adequate renal, hepatic and hematological functions, no prior chemotherapy. Pts were randomized to D 70 mg/m2 IV d1 q3w (arm A) or D 70 mg/m2 IV d1 q3w + E 280 mg/TID PO starting 1 day prior to D, for 5 consecutive days (arm B). The treatments were planned until best PSA response achievement or PSA progression. Toxicity was recorded according to NCIC criteria. Qol was assessed by self-filled questionnaires during the treatment. Results: Between 04/2003 and 09/2005, 95 pts (median age 69 years, range 48–86, median PSA 80 ng/ml, range 5–2,166 and measurable disease in 45) were randomized to arm A (49) or arm B (46). In arm A, pts received 321 cycles (median 6, range 0–28) with only 13 (4 %) delays = 7 days. In arm B, pts received 338 cycles (median 7, range 0–20) with only 16 (4.7%) delays. Grade 3–4 hematological toxicities consisted of neutropenia, 4% in arm A and 6% in B. One pt in arm B had febrile neutropenia and grade 3 diarrhea. Grade 3–4 non-hematologic toxicities were vomiting (1 pt in both arms), stomatitis (1 pt in arm A and 2 pts in B) and diarrhoea (1 pt in arm B). Two cases of stroke were reported in arm A. No treatment related death was recorded. Responses, in terms of PSA↓ >50% were: 40% in arm A and 75%in arm B with PSA normalization in 5% and 32% respectively. After a median follow-up of 17 months, 65 patients are died (31 in Arm A and 34 in Arm B). Progression free survival (biochemical) was 20 weeks in arm A and 30 in B. Conclusions: D-based regimens are active in HRPC with a manageable toxicity profile. From this preliminary data, DE combination appears promising, in terms of activity and tolerability so, front-to-front formal comparison in a phase III trial can be recommended. No significant financial relationships to disclose.

A prospective multicenter phase II trial of capecitabine plus oxaliplatin (CapOx) in advanced biliary system adenocarcinomas: The final results

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4136-4136 ◽  
Author(s):  
O. Nehls ◽  
H. Oettle ◽  
J. Hartmann ◽  
R. Hofheinz ◽  
H. Hass ◽  
...  
Keyword(s):  
Disease Control ◽  
Survival Data ◽  
Sensory Neuropathy ◽  
Complete Response ◽  
Biliary System ◽  
Disease Control Rate ◽  
Eligibility Criteria ◽  
Grade 3 ◽  
Ecog Ps ◽  
Peripheral Sensory

4136 Background: To investigate the safety and efficacy of capecitabine and oxaliplatin combination therapy (CapOx) in unresectable or metastatic adenocarcinomas of the biliary system. Methods: 65 patients (pts) (27 male, and 38 female) were enrolled (median age, 61 yrs). Major eligibility criteria: histologically proven, measurable disease, age ≤ 75 yrs, ECOG PS 0–2. A total number of 364 cycles (median, 5; range, 1–16) of oxaliplatin (130 mg/m2, d1) plus capecitabine (2 g/m2, d 1–14) were administered 3 weekly for gallbladder carcinoma (GBC) (27 pts), extrahepatic (20 pts), and intrahepatic (18 pts) cholangiocarcinoma (CCC). Response rates were assessed according to WHO criteria. Clinical outcome was determined separately for pts with either GBC/extrahepatic CCC or intrahepatic CCC (mass-forming type). Results: Grade 4 toxicities (WHO): diarrhea in 1 pt (1% of cycles), thrombocytopenia in 1 pt (1%), leukocytopenia in 1 pt (1%), and fever in 2 pts (1%); grade 3 toxicities: nausea/vomiting in 1 pt (1%), diarrhea in 2 pts (1%), thrombocytopenia in 3 pts (2%), and fever in 1 pt (1%). Grade 3/4 peripheral sensory neuropathy (Lévis scale) was found in 13 pts (14% of cycles). Two pts were excluded from study because of oxaliplatin-related allergic reactions. One patient died due to sepsis and another due to cerebral insult during the first treatment cycle. The overall disease control rate in 47 pts with GBC or extrahepatic CCC was 72% (complete response (CR), n = 2 (4%); partial response (PR), n = 11 (23%); stable disease (NC), n = 21 (45%)), whereas progressive disease (PD) was found in 13 pts (28%). In 18 pts with intrahepatic mass-forming CCC, no CR or PR was observed, 5 pts (28%) had SD, and 13 pts (72%) experienced PD. Conclusions: The CapOx protocol is well tolerated and remarkably active for advanced GBC as well as extrahepatic CCC with a disease-control rate of 72%. However, activity appears to be limited in the subset of pts with intrahepatic mass-forming type tumors. Survival data will be presented at the meeting. No significant financial relationships to disclose.

JASPAC 01: Randomized phase III trial of adjuvant chemotherapy with gemcitabine versus S-1 for patients with resected pancreatic cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4008-4008 ◽  
Author(s):  
Akira Fukutomi ◽  
Katsuhiko Uesaka ◽  
Narikazu Boku ◽  
Hideyuki Kanemoto ◽  
Masaru Konishi ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Adjuvant Chemotherapy ◽  
Interim Analysis ◽  
Standard Treatment ◽  
Dose Intensity ◽  
Phase Iii ◽  
Secondary Endpoints ◽  
Full Analysis ◽  
Grade 3 ◽  
Ecog Ps

4008 Background: Adjuvant chemotherapy with gemcitabine (G) has been standard treatment for resected pancreatic cancer (PC). In the GEST study, S-1 (S) had shown non-inferiority to G in overall survival (OS) for unresectable PC. The aim of this phase III study is to investigate non-inferiority of S to G on OS as adjuvant chemotherapy for resected PC. Methods: Patients (pts) after macroscopically curative resection of PC with an ECOG PS of 0-1 and adequate organ functions were randomly assigned to G (1000 mg/m2, iv, d1, 8 and 15, q4w, for 6 courses) or S (80/100/120 mg/day based on BSA, po, d1-28, q6w, for 4 courses) with balancing by surgical margins (R), nodal status (N) and institution. Primary endpoint was OS. With 180 pts per arm, the study had 80% power to prove non-inferiority with a margin of hazard ratio (HR) 1.25 on the basis of expected HR 0.87, with 0.05 two-sided alpha. Secondary endpoints were relapse-free survival (RFS), safety, and quality of life (EQ-5D). One interim analysis was planned after 180 deaths. Results: From 4/2007 to 6/2010, 385 pts were enrolled from 33 hospitals in Japan. 378 pts (G/S: 191/187) were included in the full analysis set. Pts characteristics (G/S) were well balanced (PS0: 67%/70%, R0: 86%/88%, N0: 38%/36%). Based on the interim analysis with 205 OS events, IDMC recommended to publish the results. OS at 2-years were 53% for G and 70% for S. HR for S to G was 0.56 (95% CI, 0.42-0.74, p<0.0001 for non-inferiority, p<0.0001 for superiority). On subgroup analysis, HRs for R0/R1, N0/N1 pts were 0.57 (95% CI, 0.42-0.78)/0.53 (0.27-1.05), 0.48 (0.28-0.83)/0.58 (0.41-0.80), respectively. RFS at 2-years were 29% for G and 49% for S. HR of relapse for S to G was 0.56 (95% CI, 0.43-0.71, log-rank p<0.0001). Incidences of grade 3/4 toxicities in G/S were leukopenia 39%/9%, hemoglobin decrease 17%/13%, thrombocytopenia 9%/4%, elevated AST 5%/1%, fatigue 5%/5%, and anorexia 6%/8%. Relative dose intensity of G/S was 84%/97%. EQ-5D QOL score in S was significantly better than that in G (p<0.0001). Conclusions: S-1 adjuvant chemotherapy is shown non-inferior, and furthermore, even superior to GEM. S-1 is considered as the new standard treatment for resected PC pts. Clinical trial information: UMIN000000655.

SPIRITT (study 20060141): A randomized phase II study of FOLFIRI with either panitumumab (pmab) or bevacizumab (bev) as second-line treatment (tx) in patients (pts) with wild-type (WT) KRAS metastatic colorectal cancer (mCRC).

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 454-454 ◽  
Author(s):  
J. Randolph Hecht ◽  
Allen Lee Cohn ◽  
Shaker R. Dakhil ◽  
Mansoor N. Saleh ◽  
Bilal Piperdi ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Eligibility Criteria ◽  
Grade 5 ◽  
Randomized Phase Ii ◽  
Secondary Endpoints ◽  
Previously Treated

454 Background: Pmab has demonstrated significant improvement in progression-free survival (PFS) in pts with WT KRAS mCRC as 2nd-line tx in a phase III trial comparing pmab + FOLFIRI vs FOLFIRI alone. Here, we describe the results of SPIRITT, a multicenter, randomized phase II study evaluating pmab + FOLFIRI and bev + FOLFIRI in pts with WT KRAS mCRC previously treated with a 1st-line bev + oxaliplatin (Ox)-based chemotherapy regimen. Methods: Pts were randomized 1:1 to pmab 6.0 mg/kg + FOLFIRI Q2W or to bev 5.0 or 10.0 mg/kg + FOLFIRI Q2W. Eligibility criteria included: WT KRAS mCRC, ECOG ≤ 1, no prior irinotecan or anti-EGFR tx, and tx failure of prior 1st-line bev + Ox-based therapy (≥ 4 cycles). The primary endpoint was PFS; secondary endpoints included overall survival (OS), objective response rate (ORR), and safety. No formal hypothesis was tested. Results: 182 pts with WT KRAS mCRC were randomized. All pts received tx. Efficacy results are shown (table). Worst grade of 3/4 adverse events (AE) occurred in 78% of pts in the pmab + FOLFIRI arm and 65% in the bev + FOLFIRI arm. Grade 5 AEs occurred in 7% of pts in the pmab + FOLFIRI arm and 7% in the bev + FOLFIRI arm. Tx discontinuation due to any AE was 29% in the pmab + FOLFIRI arm and 25% in the bev + FOLFIRI arm. Conclusions: In this estimation study of pts with WT KRAS mCRC that previously received bev + Ox-based tx, the PFS hazard ratio (HR) was 1.01 (95% CI: 0.68 - 1.50). The OS HR was 1.06 (95% CI: 0.75 - 1.49). The observed ORR was higher in the pmab + FOLFIRI arm. 54% of bev + FOLFIRI pts received subsequent anti-EGFR tx. The safety profile for both arms was similar to previously reported studies. Tx discontinuation rates due to AEs were similar between the arms. Clinical trial information: NCT00418938. [Table: see text]

A randomized phase II trial comparing switch to nivolumab with TKI continuation after 12 weeks of TKI induction therapy in metastatic renal cell carcinoma patients (NIVOSWITCH).

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 678-678 ◽  
Author(s):  
Viktor Grünwald ◽  
Carsten Grüllich ◽  
Philipp Ivanyi ◽  
Manfred Wirth ◽  
Peter Staib ◽  
...  
Keyword(s):  
Induction Therapy ◽  
Kinase Inhibitors ◽  
Treatment Options ◽  
Premature Closure ◽  
Randomized Phase Ii ◽  
Safety Population ◽  
Adequate Organ Function ◽  
Grade 3 ◽  
Ecog Ps

678 Background: Tyrosine kinase inhibitors (TKI) and Nivolumab (NIVO) are standard treatment options for mRCC. We tested whether TKI followed by early switch to NIVO improved outcome in mRCC patients (pts). Methods: Main inclusion criteria: measurable advanced or metastatic clear cell RCC, ECOG PS 0-2, adequate organ function, PR or SD to induction therapy with sunitinib (50 mg, 4-2 regime) or pazopanib (800 mg OD). 1:1 randomization at 12 wks.: TKI continuation vs. switch to NIVO (240 or 480 mg IV q2-4wks). Strata were MSKCC risk, TKI used and response to TKI. Imaging was performed q12w. 49 of 244 planned pts were randomized between Dec 2016 and Aug 2018, which led to premature closure of the trial. We report the second interim analysis with data base lock on 31.07.19. ORR was assessed according to RECIST 1.1. Efficacy and safety analyses were performed in ITT and safety population, respectively. Log-Rank analyses were used for survival analyses. Results: 25 and 24 pts received NIVO or TKI, respectively. Median age was 65 y (range: 35-79), 82% were male and 4% had ECOG PS 2. Metastases occurred predominantly in lung (47%), lymph nodes (27%) and liver (24%). MSKCC risks were: favorable (31%), intermediate (65%), and poor (4%), which were balanced between arms. 55% received sunitinib. ORR for NIVO vs. TKI differed when assessed from start of induction therapy (64 vs. 70%, P=0.76) or from time of randomization (16 vs. 48%; P=0.032). Accordingly, PFS from randomization was 3.0 vs. 11.9 mo. (HR = 1.72 [95% CI: 1.19 – 2.48]; P=0.0026) in favor of TKI continuation. At a median follow-up of 12.9 mo. median OS was not reached, but HR = 1.86 (95% CI: 0.85 – 4.07) P=0.10 showed a trend for TKI continuation. All grades AE for NIVO vs. TKI occurred in 96% vs. 100%, grade 3-5 48% vs. 71% and serious AE 40% vs. 46%. Conclusions: In TKI-sensitive pts, continuation of TKI is more efficacious than early switch to NIVO. The major limitation of our trial is the premature closure and its limited sample size. Clinical trial information: NCT02959554.

A multicentric phase II randomized trial of docetaxel (D) plus estramustine (E) versus docetaxel (D) as first line chemotherapy for patients (pts) with hormone-refractory advanced prostate cancer (HRPC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4625-4625 ◽  
Author(s):  
O. Caffo ◽  
T. Sava ◽  
E. Comploj ◽  
A. Fariello ◽  
F. Zustovich ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Phase Iii ◽  
Synergistic Activity ◽  
Eligibility Criteria ◽  
Psa Progression ◽  
Hormone Refractory ◽  
Grade 3 ◽  
Anticoagulant Prophylaxis ◽  
Ecog Ps

4625 Background: D is presently considered a standard treatment for HRPC pts. E has shown a synergistic activity with D in vitro, however the role of D+E combination remains to be defined in the clinical practice. We attempted to evaluate the activity, in terms of PSA decline (PSA↓), the safety and quality of life (QoL) of D ± E in HRPC pts. Methods: eligibility criteria were: HRPC diagnosis, hormone-refractory advanced disease (PSA progression after at least two hormonal therapy), ECOG PS ≤ 2, adequate renal, hepatic and hematological functions. Pts were randomized to D 70 mg/m2 IV d1 q3w (arm A) or D 70 mg/m2 IV d1 q3w + E 280 mg/TID PO starting 1 day prior to D, for 5 consecutive days (arm B). The treatments were planned until best PSA response achievement or PSA progression. No anticoagulant prophylaxis was planned in ARM B pts. Qol was assessed by self-filled questionnaires during the treatment. Results: Between 04/2003 and 09/2005, 95 pts (median age 69 years, range 48–86, median PSA 80 ng/ml, range 5–2166 and measurable disease in 45) were randomized to arm A (49) or arm B (46). To date, 9 pts and 6 pts are still on treatment in arm A and B respectively. In arm A, pts received 257 cycles (median 5, range 1–14) with only 10 (3.9%) delays ≥ 7 days. In arm B, pts received 317 cycles (median 7, range 0–20) with only 15 (4.7%) delays. Median follow-up was 19.5 months. Grade 3–4 hematological toxicities consisted of neutropenia, 4% in arm A and 8% in B, anemia, 0% and 2% respectively and 1 pt with febrile neutropenia and grade 3 diarrhea (Arm B). Grade 3−4 non-hematologic toxicities were vomiting (1 pt) in arm A, stomatitis (2 pts) and vomiting (1 pt) in arm B. Two cases of stroke were reported in arm A. Responses, in terms of PSA↓ >50% were: 43% in arm A and 70% in arm B with PSA normalization in 8% and 38% respectively. Progression free survival (biochemical) was 20 weeks in arm A and 31 in B. Analysis concerning QoL outcomes is planned at the treatment completion of all pts. Conclusions: D-based regimens are active in HRPC with a low toxicity profile. From this preliminary data, DE combination appears promising, in terms of activity and tolerability so, front-to-front formal comparison in a phase III trial can be recommended. No significant financial relationships to disclose.

Comparable safety and response rate with bevacizumab in combination with capecitabine/oxaliplatin (CapOx/Bev) versus capecitabine/irinotecan (CapIri/Bev) in advanced CRC (mCRC): A randomized phase II study of the AIO GI tumor study group

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4034-4034 ◽  
Author(s):  
W. H. Schmiegel ◽  
A. Reinacher-Schick ◽  
W. Freier ◽  
G. Dietrich ◽  
D. Arnold ◽  
...  
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Treatment Plan ◽  
Phase Iii ◽  
Tumor Control ◽  
Eligibility Criteria ◽  
Randomized Phase Ii ◽  
Hand Foot Syndrome ◽  
Ecog Ps ◽  
Unacceptable Toxicity

4034 Background: Bevacizumab (Bev) combined with 5-FU/FA and both, irinotecan or oxaliplatin are standard regimens for mCRC. Recently, a phase III trial has demonstrated that infusional 5-FU can be substituted by capecitabine (cape) when combined with oxaliplatin and Bev whereas conflicting data are available for feasibility and efficacy of cape/irinotecan combinations. This randomized phase II trial was to compare safety and efficacy of Bev with either CapOx or CapIri in untreated mCRC. Methods: Eligibility criteria: untreated mCRC pts, ECOG PS <= 2, measurable lesion(s), adequate hematologic and organ function. Primary endpoint was % of pts progression-free after 6 months. Treatment plan: Bev 7.5 mg/kg day (d)1 with either oxaliplatin (130 mg/m2 d1)/cape (1,000 mg/m2 bid d1–14; CapOx/Bev, arm A) or irinotecan (200 mg/m2 d1)/cape (800 mg/m2 bid d 1–14; CapIri/Bev, arm B), all q d22. Arm B doses were 20% lower for both, cape and irinotecan, compared to previous trials reporting an unacceptable toxicity profile (Köhne, ASCO 2005). Treatment was continued until progression or unacceptable toxicity. Results: So far, toxicity data are available on 228 (118/110 pts arm A/B) of total 240 pts. Baseline characteristics (arm A/B): median age 64/65 yrs, male 67%/68%. A total of 684/719 cycles (median 6/6 cycles) have been administered. Most common CTC grade 3/4 toxicities (% of pts): Diarrhea 17.0/15.5, hand-foot-syndrome 5.9/2.7, peripheral neuropathy 15.3/0.0. Specific AE′s such as thrombosis, 3° hypertension and GI perforation occurred in 3.4/4.5%, 3.4/0.9% and 0.9/0.9% of pts, respectively. Among 185 evaluable pts (96/89), tumor control rates (CR+PR+SD) in arm A/B were 81.4%/82.8%, overall response rates (CR+PR) were 49.0%/52.7%. Conclusions: Both regimens, CapOx/Bev and CapIri/Bev, are well tolerated without differences in toxicity (except neuropathy). Interestingly, despite the protocol defined dose reduction of CapIri there is seemingly no difference in efficacy as measured by tumor control and response rate. Meanwhile, the trial has finished accrual and data including PFS rate will be presented at the meeting. [Table: see text]

Palbociclib (P) in patients (pts) with head and neck cancer (HNC) with CDKN2A loss or mutation: Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 6043-6043
Author(s):  
Evan P. Pisick ◽  
Michael Rothe ◽  
Pam K. Mangat ◽  
Liz Garrett-Mayer ◽  
Francis P. Worden ◽  
...  
Keyword(s):  
Lung Metastases ◽  
Treatment Options ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
Clinically Significant ◽  
Grade 3 ◽  
Ecog Ps ◽  
Stage 1 ◽  
Anti Tumor Activity

6043 Background: TAPUR is a phase II basket study evaluating anti-tumor activity of commercially available targeted agents in pts with advanced cancers with genomic alterations. Results in a cohort of HNC pts with CDKN2A loss or mutation treated with P are reported. Methods: Eligible pts had advanced HNC, no standard treatment options, measurable disease, ECOG PS 0-2, and adequate organ function. Genomic testing was performed in CLIA-certified, CAP-accredited site selected labs. Pts received P at 125 mg orally once daily for 21 days, followed by 7 days off until disease progression. Pts matched to P had CDKN2A loss or mutation and no RB mutations. Simon 2-stage design tested the null disease control (DC) - defined as partial (PR), complete response (CR) or stable disease at 16+ weeks (SD 16+) - rate of 15% vs. 35% (power = 0.85; α = 0.10). If ≥2 of 10 pts in stage 1 have DC, 18 more pts are enrolled. If ≥7 of 28 pts have DC, the null DC rate is rejected. Secondary endpoints are progression-free survival (PFS), overall survival (OS) and safety. Results: 28 pts (64% male) with HNC with CDKN2A loss (20 pts) or mutation (8 pts) were enrolled from June 2016 to Sept 2019. All were eligible for efficacy and toxicity. Demographics and outcomes are summarized in Table. No objective response (OR) and 10 pts with SD16+ (9 with CDKN2A loss, 1 with mutation) were observed for a DC rate of 37% (95% CI: 21%, 50%); the null DC rate of 15% was rejected (p=0.005). 14 pts had at least one grade 3-5 adverse or serious adverse event (AE/SAE) at least possibly related to P with the most common being low WBC/platelets. Other grade 3-4 AEs included anemia, fatigue, hypocalcemia, and syncope. There was one pt with grade 5 respiratory failure likely due to extensive lung metastases and aspiration but P-related pneumonitis could not be ruled out. Conclusions: Monotherapy P demonstrated modest anti-tumor activity and clinically significant AEs in heavily pre-treated pts with HNC with CDKN2A loss or mutation. Additional study is warranted to confirm the efficacy of P in pts with HNC with CDKN2A loss or mutation. Clinical trial information: NCT02693535. [Table: see text]

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