A Phase II Trial of FM (Oral Fludarabine and Mitoxantrone) Chemotherapy Followed by Yttrium 90 (90Y) Ibritumomab Tiuxetan (Zevalin®) for Previously Untreated Follicular Lymphoma (FL) Patients.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2479-2479 ◽  
Author(s):  
Pier Luigi Zinzani ◽  
Alessandro Pulsoni ◽  
Manuela Balocco ◽  
Monica Tani ◽  
Stefano Fanti ◽  
...  
Keyword(s):  
Phase Ii ◽  
Performance Status ◽  
Safety Data ◽  
Stage Iv ◽  
Bone Marrow Examination ◽  
Stage Ii ◽  
Efficacy And Safety ◽  
Ibritumomab Tiuxetan ◽  
Open Label ◽  
Grade 3

Abstract We conducted a prospective, multicenter, single-arm, open-label, non-randomized, phase II study to evaluate the efficacy and safety of 90Y Ibritumomab Tiuxetan of a new approach combining induction chemotherapy with oral Fludarabine and Mitoxantrone (FM) followed by consolidation with 90Y Ibritumomab Tiuxetan for patients with previously untreated FL. Patient eligibility was represented by: age ≥ 18 years with biopsy-proven, untreated; stage II – IV FL grade I–II; WHO performance status of 0 to 2. All patients signed a written informed consent. Patients were treated with standard FM chemotherapy (Fludarabine was administered orally at the dose 40 mg/m2/day for 3 consecutive days) every 28 days for 6 cycles. Patients were restaged 4 to 8 weeks after completion of the sixth cycle of FM. Patients achieving at least a PR after 6 cycles of FM chemotherapy were eligible for consolidation with 90Y Ibritumomab Tiuxetan provided the granulocyte count was > 1500/μL, the platelet count >100.000/μL, lymphocytes expressing the CD20 antigen and the bone marrow examination at the completion of FM demonstrated < 25% involvement with lymphoma. All patients were to receive a single dose of 90Y Ibritumomab Tiuxetan 14.8 MBq/kg (0.4 mCi/kg) up to a maximum dose of 1184 MBq (32 mCi). At data reporting for this abstract, 62 patients were enrolled and 41 were evaluable for response. Of these 41 patients, all are evaluable for induction FM regimen and 19 of them also are evaluable after 90Y Ibritumomab Tiuxetan treatment. 15 were male and 26 female; the median age was 52.5 years (range 36–70); 5 were stage II, 12 stage III, and 24 stage IV. After the FM treatment the OR rate was 100%, including 73% complete remissions (CR + CRu) and 27% PR. Time to event analyses, including TTP and duration of response are pending further follow-up. Treatment was well tolerated; grade ≥ 3 AEs were seen in 20 patients; the most common grade ≥ 3 AEs was neutropenia. Among the actual 19 evaluable patients subsequentially treated with 90Y Ibritumomab Tiuxetan, 3/5 (60%) patients improved their remission status from PR to CR. The 90Y Ibritumomab Tiuxetan toxicity included grade ≥ 3 hematologic AEs in 12 patients. These preliminary data indicate: 1) FM regimen including oral fludarabine presents the same activity of i.v. formulation one without significant gastrointestinal toxicity and with a better patient compliance; 2) feasibility, tolerability, and efficacy of the FM plus 90Y Ibritumomab Tiuxetan regimen for untreated FL. Final efficacy and safety data will be presented.

A Phase II Trial of FM (Fludarabine and Mitoxantrone) Chemotherapy Followed by Yttrium 90 (90Y) Ibritumomab Tiuxetan (Zevalin®) for Previously Untreated Indolent Non-Follicular Lymphoma Patients.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2478-2478
Author(s):  
Pier Luigi Zinzani ◽  
Monica Tani ◽  
Stefano Fanti ◽  
Gerardo Musuraca ◽  
Alessio Perrotti ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Induction Chemotherapy ◽  
Phase Ii ◽  
Safety Data ◽  
Stage Iv ◽  
Stage Iii ◽  
Efficacy And Safety ◽  
Ibritumomab Tiuxetan ◽  
Common Grade ◽  
Grade 3

Abstract We conducted a prospective, single-arm, open-label, non-randomized, multicenter, phase II to evaluate the efficacy and safety of 90Y Ibritumomab Tiuxetan of a novel new approach combining induction chemotherapy with Fludarabine and Mitoxantrone (FM) followed by consolidation with 90Y Ibritumomab Tiuxetan for patients with previously untreated indolent non-follicular lymphoma (indolent non-FL). Patient eligibility was represented by: patients age 18 years or older with biopsy-proven, untreated, bidimensionally measurable stage II, stage III, or stage IV indolent non-FL expressing the CD20 antigen; WHO performance status of 0 to 2. All patients were notified of the investigational nature of this study and signed a written informed consent approved in accordance with institutional guidelines, including the Declaration of Helsinki. The study was approved by the institutional review boards. Patients were treated with standard FM chemotherapy every 28 days for 6 cycles. Patients were restaged 4 to 8 weeks after completion of the sixth cycle of FM chemotherapy. Patients achieving at least a partial response after 6 cycles of FM chemotherapy were eligible for consolidation with 90Y Ibritumomab Tiuxetan provided the granulocyte count was greater than 1500/μL, the platelet count exceeded 100.000/μL, and the bone marrow examination at the completion of FM chemotherapy demonstrated no more than 25% involvement with lymphoma. All patients were to receive a single dose of 90Y Ibritumomab Tiuxetan 14.8 MBq/kg (0.4 mCi/kg) up to a maximum dose of 1184 MBq (32 mCi). At data reporting for this abstract, 29 patients were enrolled and 26 were evaluable for response. Of these 26 patients, all are evaluable for induction chemotherapy FM regimen and 17 of them also are evaluable after 90Y Ibritumomab Tiuxetan treatment. Histologically, 11 had marginal zone lymphoma, 10 had lymphoplasmacytic lymphoma, and 5 had small lymphocytic lymphoma; 10 were male and 16 female; the median age was 61 years (range 45–82); 4 were stage III, and 21 stage IV. After the FM treatment the overall response rate was 81%, including 50% CR and 31% PR. Time to event analyses, including TTP and duration of response are pending further follow-up. Treatment was well tolerated; grade ≥ 3 AEs were seen in 13 patients; the most common grade ≥ 3 AEs was neutropenia. Among the actual 17 evaluable patients subsequentially treated with 90Y Ibritumomab Tiuxetan, 2/4 (50%) patients improved their remission status from PR to CR. The 90Y Ibritumomab Tiuxetan toxicity included grade ≥ 3 hematologic AEs in 15 patients; the most common grade ≥ 3 AEs were neutropenia (10 patients) and thrombocytopenia (15 patients). Transfusions of red cells and/or platelets were given to 6 patients. These preliminary data indicate the feasibility, tolerability, and efficacy of the FM plus 90Y Ibritumomab Tiuxetan regimen for patients with untreated indolent non-FL. Final efficacy and safety data will be presented.

Efficacy and safety of nivolumab (NIVO) in patients with advanced melanoma (MEL) and poor prognostic factors who progressed on or after ipilimumab (IPI): Results from a phase II study (CheckMate 172).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9524-9524 ◽  
Author(s):  
Dirk Schadendorf ◽  
Paolo Antonio Ascierto ◽  
John B. A. G. Haanen ◽  
Enrique Espinosa ◽  
Lev V. Demidov ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Brain Metastases ◽  
Phase Ii ◽  
Response Rate ◽  
Performance Status ◽  
Objective Response ◽  
Safety Data ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Open Label

9524 Background: In the phase III CheckMate 037 study, NIVO improved the objective response rate and progression-free survival with less toxicity vs chemotherapy in patients (pts) with MEL who progressed after prior IPI treatment. We report the first efficacy and updated safety data from pts with MEL in CheckMate 172, including those with rare melanoma subtypes (uveal, mucosal), brain metastases, or an ECOG performance status (PS) of 2. Methods: In this ongoing phase II, single-arm, open-label, multicenter study, pts with MEL who progressed on or after IPI were treated with NIVO 3 mg/kg Q2W for up to 2 years until progression or unacceptable toxicity (NCT02156804). We report efficacy and updated safety data from 734 treated pts with ≥1 year of follow-up (database lock: November 2016). Results: Of 734 pts, 50% had LDH>ULN, 7% ECOG PS 2, 66% M1c disease, 15% a history of brain metastases, and 23% received ≥3 prior therapies. Overall, 593 pts (81%) received more than 4 doses of NIVO. Overall, response rate at 12 weeks was 32%, with a complete response in 1% (Table). The 1-year overall survival (OS) rate was 63%. Any grade and grade 3/4 treatment-related adverse events (AEs) occurred in 66% and 17% of pts, respectively. Discontinuations due to treatment-related AEs occurred in 4% of pts. The most common treatment-related select (potentially immune-related) AEs were diarrhea (12%), hypothyroidism (9%), and pruritus (7%). Conclusions: CheckMate 172 is the largest study of NIVO efficacy and safety in pts with MEL who progressed on or after IPI. NIVO demonstrated a safety profile consistent with that of prior clinical trials. Efficacy outcomes were encouraging in some difficult-to-treat subgroups of pts with poor prognostic factors, such as mucosal melanoma and brain metastases. Clinical trial information: NCT02156804. [Table: see text]

Phase II Study of Uracil-Tegafur With Leucovorin in Elderly (≥ 75 years old) Patients With Colorectal Cancer: ECOG 1299

2007 ◽  
Vol 25 (34) ◽  
pp. 5397-5402 ◽  
Author(s):  
Howard S. Hochster ◽  
Weixiu Luo ◽  
Elizabeta C. Popa ◽  
Bruce T. Lyman ◽  
Mary Mulcahy ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Elderly Patients ◽  
Survival Time ◽  
Phase Ii ◽  
Performance Status ◽  
Progression Free Survival ◽  
Open Label ◽  
Old Patients ◽  
Gi Toxicity ◽  
Grade 3

Purpose To evaluate the tolerability and effectiveness of uracil-tegafur (UFT) with leucovorin (LV) in the treatment of elderly patients with advanced colorectal cancer. Patients and Methods Patients ≥ 75 years of age with previously untreated colorectal cancer were eligible for this phase II, single-arm, open-label, multicenter cooperative group clinical trial. UFT 100 mg/m2 plus LV 30 mg orally every 8 hours for 28 days every 35 days was administered until progression. Results Fifty-eight patients were enrolled between June 2000 and July 2001, and 55 were treated. The median age of treated patients was 81 years (range, 75 to 90 years), 26 patients were (47%) women, and 80% had good performance status (0 to 1). The observed overall response rate was 22% (95% CI, 11.8% to 35.0%). The estimated median overall survival time was 13.0 months (95% CI, 9.6 to 17.4 months), and median progression-free survival time was 4.6 months (95% CI, 2.6 to 6.7 months). Among the 56 treated patients (including one ineligible patient), 31 (55%) experienced grade 3 to 4 toxicities, most commonly diarrhea (25%) and GI toxicity (36%), with patients older than 85 years of age at highest risk. Conclusion The results of this trial support the efficacy of oral UFT/LV in elderly patients with colorectal cancer. The regimen is tolerated moderately well overall, particularly as compared with other fluoropyrimidine regimens, although there is increased GI toxicity in the most elderly. These results suggest that studies using newer oral fluoropyrimidine analogs should be investigated in this patient population.

E7389, a novel anti-tubulin, in patients with refractory breast cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 653-653 ◽  
Author(s):  
J. BlumL. Forero ◽  
M. K. Heiskala ◽  
N. Meneses ◽  
K. Chandrawansa ◽  
F. Fang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Performance Status ◽  
Safety Data ◽  
Synthetic Analog ◽  
Open Label ◽  
Ecog Performance Status ◽  
Group 2 ◽  
Grade 3 ◽  
Cycle Group ◽  
Group 1

653 Background: E7389 is a synthetic analog of halichondrin B, with a broad anti- proliferative activity against tumor cells. Methods: E7389 was evaluated in an open-label, single-arm Phase II trial as monotherapy for patients with refractory breast cancer (≥2 prior chemotherapy regimens, which must have included an anthracycline and a taxane). E7389 was administered as an IV bolus of 1.4 mg/m2 on Days 1, 8, and 15 of a 28-day cycle (group 1), or on Days 1 and 8 of a 21-day cycle (group 2). The primary efficacy endpoint was ORR. Results: As of 9 December 2005, 88 patients had received treatment, 68 in group 1 and 20 in group 2. Median age was 55 yrs (range 36–84) and ECOG performance status 0–1. Sixty-six percent of the tumors were ductal carcinomas, 6% lobular, and 27% were unclassified. Sixty percent of the tumors were ER+, 47% PR+, and 17% Her2/neu 3+. The patients had received at least two previous regimens, with a median number of 5 (range 2–14). Forty-eight percent of the patients had also used hormonal therapy. Forty-nine patients in group 1 and 12 patients in group 2 had completed their 2nd cycle of treatment, and twenty-one in group1 and 1 in group 2 their 4th cycle. Safety: The major toxicity related to study drug was neutropenia. Among 73 patients with preliminary safety data available, two patients had Grade 3 febrile neutropenia, and 31 had Grade 3 or 4 neutropenia or leukopenia. The other Grade 3 toxicities encountered in more than two patients were dehydration (4 patients) and dyspnea (4 patients). Grade 3 peripheral neuropathy was reported in 2 patients. Efficacy: At the end of cycle four there were 10 (15.2%) confirmed partial responses (PRs) out of 66 evaluable patients in group 1, and 1 confirmed PR (5.6%) out of 18 evaluable patients in group 2. The median duration of confirmed responses was 113 days. Conclusions: Based on the safety and efficacy in this refractory breast cancer population, E7389 appears to be a therapy worthy of continued investigation in patients with heavily pretreated breast cancer. In order to comply with the current demand for individualized cancer care, bio-markers which would predict the sensitivity to E7389 are being searched in the tumor samples of the patients in the current and forthcoming studies. [Table: see text]

Preliminary results of a phase II trial of FOLFOX4 regimen in Chinese patients with unresectable primary liver cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14065-14065 ◽  
Author(s):  
S. K. Qin ◽  
Y. J. Wang ◽  
Q. Wu ◽  
B. C. Xing
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Phase Ii ◽  
Primary Liver Cancer ◽  
Safety Data ◽  
Median Number ◽  
Chinese Patients ◽  
Efficacy And Safety ◽  
Open Label ◽  
Number Of Cycles

14065 Background: Primary liver cancer (PLC) is the 3rd most common cancer in whole China. Development of systemic chemotherapy for the patients not eligible for operation as well as TACE commonly have been required. Oxalipaltin (Eloxatin)+ 5-FU/LV, namely FOLFOX 4 regimen was tried to investigate its efficacy and safety in inoperable PLC. Methods: It was an open-label, single arm and multi-center phase II study to explore RR, DCR,TTP and MST. All the pts had pathologically confirmed inoperable PLC with/without distant metastasis. The pts were treated with the standard FOLFOX 4 regimen, that is OXA 85mg/m2 d1; LV 200mg/m2 IV 2hrs d1,2; 5-FU 400mg/m2 bolus, d1,2 and 5-FU 600mg/m2 CIV 22hrs d1,2; q2w upto 6 cycles or until progression. Tumor evaluation was done every 6 weeks using RECIST criteria. Neurotoxicity was evaluated by Eloxatin specific neurotoxicity criteria (Sanofi-Aventis Co.Ltd) and other toxicities by the NCI CTC AE version 2.0. Results: From July 2004 to Sep. 2005, 27 pts (21 male, 6 female) were recruited from the 4 cancer centers with average age of 56 ±13 years old. 25 patients (92.6%) had hepatocellular carcinoma, and 2 (7.4%) cholangiocellular carcinoma. 15 pts (55.6%) had metastatic disease. 1 pt received liver transplantation before inclusion. The median number of cycles was 4 per pt. 26 pts were evaluable for efficacy and safety. The RR was 19.2% (5/26; 1 CR and 4 PR), and DCR 57.7% (15/26; including 10 SD). 4 of the 5 responsive pts had hepatocellular carcinoma, and 1 had cholangiocarcinoma. Serum AFP level was significantly decreased (mean 131,890.4ug/dl at the baseline and 1,298.6ug/dl after 6 cycles) for the first 16 pts. The first 16 pts’ safety data were available in detail: 11 NCI grade 3/4 events were observed from a total of 76 cycles administered: including 5 neutropenia, 3 leucopenia, 1 thrombocytopenia, 1 infection and 1 liver dysfunction. Grade II & III neurotoxicity was found in 3 & 2 patients respectively. The TTP,MST and further safety data were under follow-up. Conclusions: The preliminary data of the FOLFOX 4 regimen for the advanced Chinese pts with inoperable PLC have shown encouraging results with the better efficacy and favorable safety profile. Further exploration in this area is warranted, especially in hepatocellular carcinoma. No significant financial relationships to disclose.

Phase II trial of carboplatin, weekly paclitaxel, and biweekly bevacizumab in patients with unresectable stage IV melanoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8560-8560 ◽  
Author(s):  
D. G. Perez ◽  
V. Suman ◽  
T. Amatruda ◽  
M. Gornet ◽  
R. Morton ◽  
...  
Keyword(s):  
Phase Ii ◽  
Performance Status ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Uncontrolled Hypertension ◽  
Unresectable Stage ◽  
Full Study ◽  
Grade 3 ◽  
Endothelial Growth Factor ◽  
Stage Iv Melanoma

8560 Background: In patients with metastatic melanoma, the combination of chemotherapy with an agent that specifically targets vascular endothelial growth factor (VEGF) might be able to control tumor growth and progression much more effectively than chemotherapy alone. Methods: A two-stage phase II clinical trial was conducted in patients with unresectable stage IV melanoma to assess the anti-tumor activity and toxicity profile of the combination of paclitaxel (80 mg/m2 IV on days 1, 8 and 15 of a 28-day cycle), carboplatin (AUC = 6 IV on day 1) and bevacizumab (10 mg/kg IV on days 1 and 15). The primary end point of the study was the 8-week progression-free survival rate (PFS). Enrollment to the second stage of the study was opened if 8 or more of the first 20 patients enrolled remained progression-free at 8 weeks. Eligible patients had measurable disease by RECIST criteria, a performance status (PS) of 0–2 and acceptable pre-registration organ function. Exclusion criteria included: brain metastases, significant recent bleeding, uncontrolled hypertension and ongoing anticoagulation. The study opened in February 2006 and completed full study accrual in August 2006. Data from the 20 patients enrolled in the first stage are presented here. Results: Patients (60% male) had a median age of 63 and had a good performance status (85% had PS of 0). M1c disease was present in 45% of patients and 35% had undergone previous chemotherapy for stage IV melanoma (50% prior immunotherapy). Only 6 patients did not complete more than 2 cycles of chemotherapy due to refusal (3), desire for alternative treatment (1) or progression (2). Median follow-up among the 15 patients still alive was 5.5 months (range: 6 weeks - 9 months). The 8-week PFS rate was 70% (14/20). The median time to progression was 163 days. One partial response was observed. There were 3 disease-related deaths at 65, 120 and 190 days post-registration. The most common toxicities were neutropenia (95%; 45% = grade 3), anemia (95%; 15% = grade 3), fatigue (90%; 5% = grade 3), leukopenia (85%; 25% = grade 3), and thrombocytopenia (75%; 5% = grade 3). Conclusions: The combination of paclitaxel, carboplatin and bevacizumab appears to be well tolerated and clinically active in patients with stage IV melanoma. No significant financial relationships to disclose.

Phase I/II trial of CCI 779 and bevacizumab in advanced renal cell carcinoma (RCC): Safety and activity in RTKI refractory RCC patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5039-5039 ◽  
Author(s):  
J. R. Merchan ◽  
H. C. Pitot ◽  
R. Qin ◽  
G. Liu ◽  
T. R. Fitch ◽  
...  
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Performance Status ◽  
Stage Iv ◽  
Response Assessment ◽  
Response Rates ◽  
Median Number ◽  
Primary Objective ◽  
Phase 2 ◽  
Open Label

5039 Background: Combined mTOR and VEGF blockade is a potentially promising and rational strategy for the treatment of advanced RCC. We previously reported the phase I safety and efficacy results of CCI 779 (C) +bevacizumab (B) n RTKI naïve stage IV RCC patients (pts) (J Clin Oncol. 2007;25[18S Suppl]:5034). We now report the interim results of the phase 2 study of C+B in RTKI refractory RCC patients. Methods: Design: Open label, phase I/II study of C+B in advanced RCC pts. Patients with measurable stage IV RCC with a component of clear/conventional cell type, performance status 0–2 and good organ function were eligible. Up to two prior treatment regimens were allowed (at least one prior RTKI). Phase II dose was C = 25 mg IV weekly and B = 10 mg/kg every 2 weeks repeated in 4 week cycles. The primary objective of the phase II portion was to assess the proportion of patients who were progression-free 6 months after study entry. Secondary objectives were assessment of response rates and toxicity. Accrual goal = 40 pts. Results: Thirty-five pts have been enrolled into the phase 2 portion to date with 4 pts ineligible. Twenty-five pts are evaluable for response assessment and 29 pts are evaluable for toxicity. Baseline characteristics (N: 35): M/F: 28/7; Number of met. sites: 1/2/3+: 15/9/11; prior nephrectomy: 31; Number of prior therapies: 1 = 29; 2 = 2. Most common (>5%) Gr 3–4 AEs (N = 29) included fatigue (6), hypercholesterolemia (2), hypertriglyceridemia (2), anorexia (2), rash (2), and anemia (2). Responses were: PR/SD/PD = 4 (16%)/18 (72%)/3 (12%). Median number of cycles administered was 4. Six month progression free rates will mature by may 2009. Conclusions: C+B combination at the recommended phase 2 doses is feasible and well tolerated. Clinical benefit rates (PR/SD) in RTKI refractory RCC patients (88%) are encouraging. Data on 6 month progression-free rates are expected to mature in 4/09. Updated data on safety, response rates, and 6-month progression free rates will be presented on all evaluable patients. Correlative studies on available plasma, serum and tumor samples for angiogenic and molecular biomarkers are underway. Supported by N01-CM62205, R21 CA 119545–02, and Commonwealth Foundation. [Table: see text]

FORT-1: Phase II/III study of rogaratinib versus chemotherapy (CT) in patients (pts) with locally advanced or metastatic urothelial carcinoma (UC) selected based on FGFR1/3 mRNA expression.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 489-489 ◽  
Author(s):  
David I. Quinn ◽  
Daniel Peter Petrylak ◽  
Joaquim Bellmunt ◽  
Andrea Necchi ◽  
Howard Gurney ◽  
...  
Keyword(s):  
Phase Ii ◽  
Locally Advanced ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Open Label ◽  
Activating Mutations ◽  
Stage Iv Disease ◽  
Dna Alterations ◽  
Grade 3 ◽  
Muscle Invasive

489 Background: Aberrant activation of fibroblast growth receptor (FGFR) signaling plays a role in UC. Rogaratinib, a pan-FGFR1-4 inhibitor, has promising efficacy and safety in pts with advanced muscle-invasive UC, selected based on FGFR1-3 mRNA overexpression and/or FGFR3-activating mutations/translocations. This Phase II/III, randomized, open-label study evaluated the efficacy of rogaratinib vs CT in pts with FGFR-positive advanced or metastatic UC who received prior platinum CT. We present an ORR analysis for rogaratinib vs CT. Methods: FGFR1/3 mRNA was tested by in situ hybridization of archival tissue. Pts were randomized 1:1 to 800 mg rogaratinib p.o. BID continuously or CT Q3W (i.v., docetaxel 75 mg/m2, paclitaxel 175 mg/m2, or vinflunine 320 mg/m2), and stratified by PIK3CA/ RAS-activating mutations, prior immunotherapy, and modified 4-factor Bellmunt risk score. Results: 87 pts were assigned to rogaratinib and 88 to CT. Overall, 82.9% were male, median age was 69.0 yrs (range: 36-89), 96.6% had stage IV disease, and 2.3% were stage IIIB. PIK3CA/ RAS-activating mutations were present in 11.4% of pts. ORRs of 19.5% and 19.3% (1-sided p=0.56) and disease control rates of 49.4% and 55.7% (p=0.84) were observed for rogaratinib and CT, respectively; median progression-free survival was 2.7 months (95% CI 1.6, 4.2) and 2.9 months (95% CI 2.6, 4.2). Grade 3-4 treatment-emergent adverse events occurred in 40/86 pts (47%) treated with rogaratinib and 46/82 pts (56%) with CT, most commonly anemia (3% vs 15%), neutropenia (1% vs 17%), asthenia (9% vs 1%), lipase increase (8% vs 2%), fatigue (2% vs 6%), and urinary tract infection (2% vs 6%). Exploratory analysis of pts with FGFR3 DNA alterations (4 spot mutations and fusions) showed ORRs of 52.4% with rogaratinib and 26.7% with CT. Conclusions: In pts with FGFR1/3 tumor mRNA-positive UC, rogaratinib had efficacy comparable with standard CT and an acceptable safety profile. Subgroup analysis suggests rogaratinib may be more active in pts with an FGFR3 DNA alteration. Sensitivity analysis of biomarker subgroups is ongoing. Clinical trial information: NCT03410693.

scholarly journals Durvalumab in frail and elder patients with stage four NSCLC: Study protocol of the randomized phase II DURATION trial

2020 ◽  
Author(s):  
Jonas Kuon ◽  
Adriane Hommertgen ◽  
Johannes Krisam ◽  
Felix Lasitschka ◽  
Albrecht Stenzinger ◽  
...  
Keyword(s):  
Adverse Events ◽  
Elderly Patients ◽  
Phase Ii ◽  
Performance Status ◽  
Single Agent ◽  
Eastern Cooperative Oncology Group ◽  
Stage Iv ◽  
Open Label ◽  
Randomized Phase Ii ◽  
The Impact

Abstract Background: Elderly patients represent a major fraction of non-small cell lung cancer (NSCLC) patients in routine clinical practice, but they are still underrepresented in clinical trials. In particular, data regarding efficacy and safety in frail or elderly patients with respect to immunotherapy are lacking. Importantly, immunosenescence in elderly patients might interfere with activities of immune-modulating drugs such as PD-1/PD-L1 inhibitors. Thus, there is an urgent need to assess safety and efficacy of such inhibitors in this group. Methods/design: In this prospective, open label, treatment stratified, and randomized phase II study, 200 patients with stage IV NSCLC amenable at least to single-agent chemotherapy (CT). Eligible patients must be 70 years or older and/or “frail” (Charlson Comorbidity Index >1) or have a restricted performance status (Eastern Cooperative Oncology Group, ECOG >1). Patients are stratified according to modified Cancer and Age Research Group (CARG) score:”fit” patients are allocated to combination CT (carboplatin/ nab -paclitaxel), “less fit” patients receive single-agent CT (gemcitabine or vinorelbine). After allocation to strata, patients are randomized 1:1 to receive either 4 cycles of CT or 2 cycles of CT followed by 2 cycles of durvalumab and subsequent maintenance treatment with durvalumab every 4 weeks. The primary endpoint is the rate of treatment related grade III/IV adverse events (Common Terminology Criteria for Adverse Events, CTCAE V4.03). As secondary endpoints, progression-free survival (PFS) according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1, response rate (RR), overall survival (OS), descriptive subgroup analyses according to PD-L1 expression, and quality of life are addressed. Geriatric screening assessments and functional tests will be performed to complete the phenotyping of a potential “frail” and “elderly” patient cohort. The trial is accompanied by a biomaterial repository to explore potential biomarkers. Discussion: The DURATION trial will prospectively investigate the safety and tolerability of anti-PD-L1 treatment with durvalumab after chemotherapy in elderly and frail patients and thereby provide new insights into the effect of PD-L1 blockade and the impact of immunosenescence in this cohort of patients.

Natural history of diarrhea associated with the anti-CTLA4 monoclonal antibody CP-675,206

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 3038-3038 ◽  
Author(s):  
S. Antonia ◽  
J. Sosman ◽  
J. M. Kirkwood ◽  
B. Redman ◽  
T. F. Gajewski ◽  
...  
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Dose Range ◽  
Objective Response ◽  
Stage Iv ◽  
Open Label ◽  
Similar Frequency ◽  
Severe Diarrhea ◽  
Grade 3 ◽  
Stage Iv Melanoma

3038 Background: Diarrhea resulting from immune activation has been associated with CTLA4 blockade. For example, in patients (pts) with stage IV melanoma receiving ipilimumab (MDX-010), a number of pts developed grade 3/4 autoimmune enterocolitis and severe diarrhea (Attia et al, 2005). In a single-dose phase I trial of CP-675,206 at doses up to 15 mg/kg in pts with solid tumors (n = 39), 9 instances of diarrhea were reported including 3 grade 3 events (Ribas et al, 2005). The incidence and severity of diarrhea was assessed in pts receiving CP- 675,206 in a large phase I/II study. Methods: An open-label phase I/II trial of CP-675,206 was conducted in pts with stage III (unresectable) or stage IV melanoma and an ECOG PS = 1. Diarrhea was assessed in pts treated at the phase II doses: 10 mg/kg monthly (Q1M) in phase I (n = 22), or 10 mg/kg Q1M (n = 44) or 15 mg/kg every 3 months (Q3M, n = 45) in phase II. Results: Medians of 3.5 doses (range, 1 to 18) at 10 mg/kg Q1M in phase I, 3 doses (range, 1 to 26) at 10 mg/kg Q1M in phase II, and 1 dose (range, 1 to 9) at 15 mg/kg Q3M were administered with 100% dose compliance. Treatment-related diarrhea was reported by 43 (39%) of 111 pts, and grade 3 diarrhea occurred in 14 (13%) pts. One patient had grade 4 colitis resulting in a colectomy. Diarrhea (all grades) occurred with similar frequency in each dose group; however, grade 3 treatment-related diarrhea occurred in 8% of pts treated with 15 mg/kg Q3M compared with 18% of pts treated with 10 mg/kg Q1M in phase I and 14% of pts treated with 10 mg/kg Q1M in phase II. Among 9 pts with an objective response, 8 experienced diarrhea (3 of which were grade 3). The majority of cases (65%) were mild to moderate in severity with a median time to onset of 51 days (range, 1 to 583 days) and resolution of 8 days (range, 1 to 182 days). More than half of pts who reported serious events of diarrhea were treated with steroids. Conclusions: Diarrhea associated with CP-675,206 was primarily mild to moderate in severity, transient, and manageable. In addition, 15 mg/kg Q3M may be better tolerated than 10 mg/kg Q1M. Ongoing clinical trials in pts with advanced melanoma will provide further information about the incidence, severity, and optimal management of diarrhea associated with CP-675,206. No significant financial relationships to disclose.

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