A phase II study of capecitabine and oxaliplatin (CAPOX) in metastatic adenocarcinoma of the small bowel (SBA) or ampulla of Vater

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14025-14025
Author(s):  
M. J. Overman ◽  
S. Chedid ◽  
J. Morris ◽  
S. Waldrum ◽  
R. A. Wolff
Keyword(s):  
Small Bowel ◽  
Performance Status ◽  
Complete Response ◽  
Ampulla Of Vater ◽  
Ecog Performance Status ◽  
Ampullary Adenocarcinoma ◽  
Highly Active ◽  
Common Grade ◽  
Grade 3 ◽  
Tumor Types

14025 Background: Metastatic SBA and ampullary adenocarcinoma (AAC) are incurable, aggressive malignancies. Limited data exists regarding the role of systemic chemotherapy in these diseases. Given the marked activity of CAPOX in other cancers of the gastrointestinal tract, we have investigated the activity of this combination in these two tumor types. Methods: Patients (pts) with either metastatic or unresectable SBA and AAC who had adequate organ function, ECOG performance status (PS) ≤2 and measurable disease per modified RECIST criteria were enrolled. Prior use of 5-FU or capecitabine as adjuvant therapy, neoadjuvant therapy, or with radiation was allowed. CAPOX was administered as a 21 day cycle with oxaliplatin 130mg/m2 IV on day 1 and capecitabine 750mg/m2 PO BID days 1–14. Up to 30 pts will be enrolled. The primary endpoint is overall response rate (ORR). Results: Eleven pts have been enrolled from 11/04 to 12/05 (6 with AAC and 5 with SBA). Ten pts have received ≥2 cycles and are evaluable for response. All pts had metastatic disease and none had received prior chemotherapy. Patient (pt) characteristics: median age 59 (49–76); M/F (4/7); 91% PS 0–1. Grade 3/4 toxicities included fatigue (5), neuropathy (1), anorexia (1), thrombocytopenia (1), hypokalemia (1), hyponatremia (1), and musculoskeletal (1). Common grade 1/2 toxicities included neuropathy (8), nausea (8), diarrhea (6), and fatigue (5). Four pts required dose reduction and 1 pt discontinued due to toxicity (grade 3 fatigue). Six pts, 3 AAC and 3 SBA, responded with an ORR of 60% (95% CI 31 to 83%). Five responses have been confirmed and 1 AAC pt obtained a complete response after 5 cycles of treatment. Median time to progression was 6.8m (95% CI 4.4 to 9.3+m). Conclusions: The combination of CAPOX is both well-tolerated and highly active. The ORR of 60% is one of the highest yet reported in the literature for the treatment of adenocarcinoma of the small bowel and ampulla of Vater. Enrollment continues on this trial. (Supported by a research grant from Sanofi-Aventis). [Table: see text]

A phase I clinical study of biweekly carboplatin and gemcitabine in patients with advanced solid tumors

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 12024-12024
Author(s):  
P. Kumar ◽  
M. Keshtgarpour ◽  
H. Kumar ◽  
A. Dudek
Keyword(s):  
Performance Status ◽  
Median Number ◽  
Maximum Tolerated Dose ◽  
Hematological Toxicity ◽  
Ecog Performance Status ◽  
Primary Tumors ◽  
Grade 3 ◽  
Number Of Cycles ◽  
Tumor Types ◽  
Dose Levels

12024 Background: Carboplatin (CBDCA) and gemcitabine (GEM) in combination is used commonly in lung cancer and is administered on a 21 day cycle. The purpose of this study was to determine the maximum tolerated dose (MTD) of CBDCA and GEM administered on a biweekly schedule and to assess safety and efficacy of this schedule. Methods: GEM was given intravenously (IV) over 30 minutes followed by CBDCA also given IV over 30 minutes. This combination was given on day 1 every 2 weeks. The dose levels examined are shown in the Table . A total of 26 patients were studied (18 male, 8 female) with median age of 56 (range 41–83 years); ECOG performance status of 24 patients were 0 (5), 1 (16), 2 (2), 3 (1); prior chemotherapy ranged from 0 to 4 regimens; median number of cycles administered per patient was 3 (range 1–9) with a total of 81 cycles. The primary tumors were lung (11), melanoma (4), head and neck (3), squamous cell penile/toe (2), bladder (2), kidney (1), gastric (1), esophageal (1) and ovary (1). Results: No DLTs were seen in any of these patients and the MTD was not reached. Delay in treatment was seen in total of 6 cycles due to myelosuppression and 1 cycle due to nausea and anorexia. Grade 3/4 hematological toxicity rates: anemia - 3/81 cycles (3.7%), neutropenia - 20/81 cycles (25%), and thrombocytopenia - 4/81 cycles (5%). Non-hematological toxicity was mild. The median time to progression was 40 days (range 4–133) and of 18 evaluable patients partial response or stable disease was seen in 7 (38.8%). Conclusions: Even at maximum tested dose of GEM at 2000 mg/m2 and CBDCA at AUC of 3.0, this schedule is well tolerated. Hematological toxicity such as neutropenia and thrombocytopenia was minimal. We plan to study this schedule of GEM and CBDCA in appropriate tumor types in combination with biologic agents. [Table: see text] [Table: see text]

Induction chemotherapy with S-1 plus cisplatin in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 15501-15501
Author(s):  
J. Chung ◽  
Y. Choi ◽  
H. Shin ◽  
G. Choi ◽  
W. Lee ◽  
...  
Keyword(s):  
Performance Status ◽  
Locally Advanced ◽  
Local Treatment ◽  
Complete Response ◽  
Hematological Toxicity ◽  
Common Grade ◽  
Adequate Organ Function ◽  
Grade 3 ◽  
And Performance ◽  
Mild Toxicity

15501 Background: This study was to assess the efficacy and safety profiles of the combination treatment with S-1 and Cisplatin in patients with locally advanced SCCHN. Methods: Eligible patients were defined as histologically confirmed SCCHN, stage III or IV with no evidence of distant metastasis, evaluable lesions, adequate organ function, age of 20–80 years, and performance status 0,1 or 2. Cisplatin was infused over 1 hour on day 1 (75 mg/m2) and S-1 was administered orally for 14 consecutive days (day 2–15). The dosages of S-1 were assigned according to the patients’ body surface area (BSA): 50 mg twice a day (BSA < 1.5m2), 60 mg twice a day (BSA > 1.5m2). Each course was repeated every 3 weeks. After 2 course, tumor response were evaluated by CT scan and laryngoscopy. If the patients achieved a response (complete response: CR, or partial response: PR), they received one more course of chemotherapy before undergoing the radiotherapy or operation as a definitive local treatment. Results: All 22 patients were assessable for response and toxicity. The overall response was 80.9% (CR: 3, PR: 14). The adverse reactions occurred 120 times in 54 courses of 22 cases. The most common grade 3/4 adverse events were neutropenia, which occurred in 8 patients. Non-hematological toxicity of grade 3 and 4 included nausea and vomiting in 4 patients, fever in one patient and, fatigue in one patient. Since the observation period is short, the analysis about survival rate is not obtained so far. Conclusions: S-1 plus Cisplatin combination chemotherapy is effective against locally advanced SCCHN with mild toxicity. No significant financial relationships to disclose.

Trastuzumab deruxtecan (T-DXd; DS-8201) in patients with HER2-mutated metastatic non-small cell lung cancer (NSCLC): Interim results of DESTINY-Lung01.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9504-9504 ◽  
Author(s):  
Egbert F. Smit ◽  
Kazuhiko Nakagawa ◽  
Misako Nagasaka ◽  
Enriqueta Felip ◽  
Yasushi Goto ◽  
...  
Keyword(s):  
Topoisomerase I ◽  
Performance Status ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
Clinical Activity ◽  
Antibody Drug Conjugate ◽  
Ecog Performance Status ◽  
Platinum Based Chemotherapy ◽  
Grade 3

9504 Background: T-DXd is an antibody-drug conjugate composed of an anti-HER2 antibody, cleavable tetrapeptide-based linker, and topoisomerase I inhibitor payload. In a phase I trial, patients (pts) with HER2-mutated NSCLC who received T-DXd had a confirmed objective response rate (ORR) of 72.7% (8/11) (Tsurutani et al, WCLC 2018). DESTINY-Lung01 (NCT03505710) is an ongoing, multicenter, phase II study of T-DXd in pts with non-squamous NSCLC overexpressing HER2 or containing a HER2-activating mutation. We report data for the cohort with HER2 mutations after a median follow-up of 8.0 mo (range, 1.4-14.2 mo). Methods: Pts were treated with T-DXd 6.4 mg/kg every 3 weeks. The primary endpoint was confirmed ORR (complete response [CR] + partial response [PR]) by ICR. Additional endpoints were disease control rate (DCR; CR + PR + stable disease), duration of response (DOR), progression-free survival (PFS), and safety. Results: At data cutoff (25 Nov 2019), 42 pts (64.3% female) had received T-DXd. Median age was 63.0 years (range, 34-83 years; < 65 y, 59.5%); 45.2% had central nervous system metastases; ECOG performance status was 0 in 23.8% of pts and 1 in 76.2%. HER2 mutations were predominantly in the kinase domain (90.5%). Most pts (90.5%) had prior platinum-based chemotherapy and 54.8% had anti–PD-1 or –PD-L1 treatment; median number of prior treatment lines was 2 (range, 1-6). Median treatment duration was 7.75 mo (range, 0.7-14.3 mo); 45.2% of pts remained on treatment. Confirmed ORR by ICR among the 42 pts was 61.9% (95% CI, 45.6%-76.4%); median DOR was not reached at data cutoff; 16 of 26 responders remained on treatment at data cutoff; DCR was 90.5% (95% CI, 77.4%-97.3%); estimated median PFS was 14.0 mo (95% CI, 6.4-14.0 mo). All pts (42/42) had treatment-emergent adverse events (TEAEs); 64.3% were grade ≥ 3 (52.4% drug-related), including decreased neutrophil count (26.2%) and anemia (16.7%). There were 5 cases (11.9%) of drug-related interstitial lung disease (ILD) as adjudicated by an independent committee (all grade 2, no grade ≥ 3) and 1 case of grade 1 ILD is pending adjudication. TEAEs led to dose interruption in 25 pts (59.5%), dose reduction in 16 pts (38.1%), and treatment discontinuation in 10 pts (23.8%). Conclusions: T-DXd demonstrated promising clinical activity with high ORR and durable responses in pts with HER2-mutated NSCLC. The safety profile was generally consistent with previously reported studies. Clinical trial information: NCT03505710 .

Capecitabine and oxaliplatin as induction and concomitant with radiotherapy in rectal cancer: A phase II study.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 604-604
Author(s):  
J. A. Gutierrez ◽  
G. Martinez-Martinez ◽  
A. J. Silva ◽  
J. Gomez Rangel ◽  
M. Palmerin ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Performance Status ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Induction Treatment ◽  
Ecog Performance Status ◽  
Dermatologic Toxicity ◽  
Grade 3 ◽  
Experienced Grade

604 Background: Preoperative combined modality chemoradiation with fluoropyrimidine-based schedules is widely accepted as the current standard of care for localized rectal cancer. Current strategies have focused on intensifying the neoadjuvant systemic treatment to improve pCR. Methods: From January 2009 to January 2010, 18 patients with locally advanced rectal cancer (T3, any N, M0) were included according to Simon's design. Treatment was 2 cycles of capecitabine 1000 mg/m2 bid (D1-14) and oxaliplatin 85 mg/m2 (D1) every 3 weeks as induction followed by chemoradiation (45 Gy). During radiotherapy patients received 2 cycles of capecitabine 750 mg/m2 bid (D1-14) and oxaliplatin 85 mg/m2 (D1 and 8) every 3 weeks. Surgery was planned 5-10 weeks after completion of radiotherapy. The primary endpoint was pCR. Results: 18 patients were assessable for response. Median age was 55 y (41-65), 11 patients with ECOG performance status of 1 (61%), all 18 patients were staged as T3, 10 were staged N+ (56%). Of the 18 patients, 17 patients were given CRT and 13 patients (76%) underwent radical resection. Of the patients who did not underwent resection, 1 patient was considered unresectable at the time of surgery, 2 patients refused surgery because of clinical complete response and 1 patient experienced progressive disease to the spine after chemoradiation. During induction treatment 1 patient (6%) experienced grade 3-4 toxicity (diarrhea). During chemoradiation 1 patient (6%) experienced grade 3 diarrhea and nausea and 1 patient (6%) experienced grade 3 radio-induced dermatologic toxicity; overall grade 3-4 toxicity of 12%. No grade 4 toxicity or treatment related deaths were observed. Of the 13 patients who underwent resection, 12 patients (92%) had a complete resection (R0). Pathologic complete response rate was observed in 1 patient (6%) according to intent to treat. The study was closed after the first stage because it did not reach the minimum required number of pCR. Conclusions: Induction chemotherapy with capecitabine and oxaliplatin before chemoradiation is feasible. Given that we did not reach the prespecified pCR rate required to continue the trial, the study was closed after the first stage. No significant financial relationships to disclose.

Efficacy of concurrent cetuximab (CTX) and nivolumab (NIVO) in previously untreated recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 6017-6017
Author(s):  
Christine H. Chung ◽  
Nabil F. Saba ◽  
Conor Ernst Steuer ◽  
Jiannong Li ◽  
Priyanka Bhateja ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Performance Status ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Infusion Reaction ◽  
Unknown Primary ◽  
Current Standard ◽  
Ecog Performance Status ◽  
Common Grade ◽  
Grade 3

6017 Background: Current standard of care for patients (pts) with previously untreated R/M HNSCC that are incurable is either pembrolizumab (pembro) with/without chemotherapy depending on the Programmed Death-Ligand 1 (PD-L1) combined positive score (CPS). We evaluated the combination of CTX and NIVO for its efficacy. Methods: Pts were treated with CTX 500 mg/m2 IV on Day (D) -14 as a lead-in followed by CTX 500 mg/m2 IV and NIVO 240 mg/m2 IV on D1 and D15 every 28-D cycle (C). Pts with CTX infusion reaction or who did not receive C1D1 for any reason were non-evaluable and replaced. NIVO dose reduction was not allowed. Results: Fifty-four evaluable pts were analyzed. Median age was 62 (42-85). ECOG performance status at baseline was 0 (20, 37%), 1 (30, 56%), and 2 (4, 7%). Primary sites were oral cavity 19 (35%), oropharynx 22 (41%), hypopharynx 3 (6%), larynx 9 (17%), and unknown primary 1 (2%). p16 status is positive 22 (41%), negative 29 (54%), and unknown 3 (6%). PD-L1 CPS is < 1 in 6 (11%), >1 in 26 (48%), and unknown 22 (41%). Median follow up time for overall survival (OS) was 12.2 months. The most common grade 3 treatment-related adverse events (TRAEs) occurring in ≥2 pts were hypomagnesemia 2 (4%), hypophosphatemia 2 (4%), fatigue 4 (7%), and rash-acneiform 4 (7%). The only grade 4 TRAEs were hypomagnesemia in 1 (2%) and CTX infusion reaction in 1 (2%). The most common grade 3 immune-related adverse event (IRAE) occurring in ≥2 was fatigue 2 (4%). No grade 4 IRAEs is observed. Median progression-free survival (PFS) and OS were 7.8 and 14.5 months, while 1-year PFS and 1-year OS were 39% and 61%, respectively. There were no statistically significant differences in either PFS and OS based on tumor p16 or PD-L1 status. Conclusions: The clinical trial met its primary endpoint of 1-year OS. Our data indicate the combination of CTX and NIVO is safe and effective in pts with previously untreated incurable R/M HNSCC. Clinical trial information: NCT03370276.

Initial results of a phase II study of biweekly pemetrexed and gemcitabine in patients with advanced NSCLC

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7128-7128
Author(s):  
A. Dudek ◽  
T. Larson ◽  
M. McCleod ◽  
D. J. Schneider ◽  
J. E. Dowell ◽  
...  
Keyword(s):  
Advanced Nsclc ◽  
Performance Status ◽  
Dose Intensity ◽  
Complete Response ◽  
Median Number ◽  
Median Dose ◽  
Ecog Performance Status ◽  
Response Data ◽  
Grade 3 ◽  
Ecog Ps

7128 Background: Pemetrexed (P), a multi-targeted antifolate, is synergisitic with gemcitabine (G) in preclinical models. A phase I study examining a biweekly schedule established a recommended phase 2 dose of G 1500 mg/m2 followed by P 500mg/m2. Methods: Patients with Stage IIIB (with pleural effusion) or IV NSCLC, ECOG PS of 0 or 1, no prior systemic chemotherapy, immunotherapy, or biological therapy were enrolled. G was infused over 30 minutes, followed immediately by P given intravenously over 10 minutes once on day 1 every 14 days. Cycles were repeated until 12 treatments or progressive disease. All patients received folic acid, vitamin B12 and steroid prophylaxis. Results: Data on 53 patients (29 male, 24 female) are currently available. Median age: 64 (range: 35, 80), ECOG performance status 0:1 = 38%:60%, Stage IIIB:IV = 19%:81%. Three hundred twelve cycles of treatment were administered with 14 dose reductions (26.4%); median number of doses was 5 for both G and P, and median dose intensity was 98.05% for both G and P. Response data included 1 complete response (1.9%), 14 partial responses (26.4%), 24 stable diseases (45.3%), and 10 progressive diseases (18.9%), with a response rate of 28.3% (95% CI: 16.8–42.3%). Patient-based Grade 3/4 hematologic events included febrile neutropenia (9.4%), neutropenia (28.3%), and thrombocytopenia (1.9%). Grade 3/4 non-hematologic events included fatigue (22.6%), dyspnea (7.5%), dehydration (7.5%), diarrhea (5.7%), constipation (3.8%), and pneumonia (1.9%). Preliminary median survival was 7.8 months (95% CI: 6.0–10.8) with 43.4% patients censored and median TTPD was 4.6 months (95% CI: 2.8–6.1). Conclusion: Biweekly G and P appear to be well tolerated in advanced NSCLC. A clinical benefit rate (ORR + SD) of 73.6% indicates activity in patients with advanced NSCLC. The dose intensity for biweekly G and P is higher than a previously reported 6-cycle, 21-day regimen with median dose intensity of 83.2% for P and 82.2% for G (West, et al. Proc ASCO 2005; 7117). [Table: see text]

Phase II trial of pemetrexed (P) and bevacizumab (B) in patients (pts) with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC): An interim analysis

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 6049-6049 ◽  
Author(s):  
M. V. Karamouzis ◽  
D. Friedland ◽  
R. Johnson ◽  
K. Rajasenan ◽  
B. Branstetter ◽  
...  
Keyword(s):  
Performance Status ◽  
Single Agent ◽  
Median Number ◽  
Tube Placement ◽  
Bleeding Complications ◽  
Ecog Performance Status ◽  
Curative Therapy ◽  
Highly Active ◽  
Hemorrhagic Events ◽  
Grade 3

6049 Background: P is a multi-targeted antifolate with single-agent activity in recurrent or metastatic HNSCC (RR 26%, Pivot et al. Br J Cancer 2001;85:649–55) and a preferable toxicity profile compared with cisplatin or the taxanes. B is a monoclonal antibody against the vascular endothelial growth factor that has been successfully incorporated in the treatment of other advanced solid tumors. Methods: Eligible pts had pathologically documented HNSCC, ECOG performance status 0–1, measurable disease, no history of bleeding diathesis or hemoptysis, and were not on anticoagulation. Pts had no prior systemic therapy for recurrent or metastatic HNSCC; chemotherapy as part of initial potentially curative therapy, but without P or B, was allowed if completed >6 months earlier. Treatment consisted of P 500 mg/m2 and B 15 mg/Kg, both given intravenously every 21 days, until disease progression or intolerable toxicity. All patients received folic acid, vitamin B12, and corticosteroid prophylaxis. The primary endpoint was the time to progression (TTP) with a sample size of 40 pts (one stage design) with planned interim safety analysis after the first 6 and 12 pts. Results: 14 pts have been enrolled. Median age 64 years (35–84); male/female 13/1; PS 0/1: 7/7; prior chemotherapy: 8; primary site: oropharynx (7), larynx (4), oral cavity (3). Median number of cycles 5 (1–10). With a median follow up of 5.5 months, median TTP was 6 months (95% CI, 4–8). 11 pts were evaluable for response using RECIST. Best response was CR: 2, PR: 3, SD: 6, PD: 0, with ORR 45%. There were no grade 4 toxicities in 14 evaluable pts; 2 pts had grade 3 hemorrhagic events in the first cycle (1 tumor-related and 1 due to gastric ulcer post gastrostomy tube placement), and both discontinued treatment. 3 other pts had grade 1–2 hemorrhagic events. The relationship of these events to treatment was difficult to ascertain. Other grade 3 toxicities were stomatitis, dysphagia, and fatigue (all occurred in 1 pt). Conclusions: Preliminary results show that P plus B is a novel, highly active regimen that may represent a new treatment paradigm in HNSCC. However, bleeding complications were frequent in pts with susceptibility to such events. Study accrual continues. No significant financial relationships to disclose.

Phase I results of the randomized, placebo controlled, phase I/II study of the novel oral c-Met inhibitor, ARQ 197, irinotecan (CPT-11), and cetuximab (C) in patients (pts) with wild-type (WT) KRAS metastatic colorectal cancer (mCRC) who have received front-line systemic therapy.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 527-527 ◽  
Author(s):  
C. Eng ◽  
J. C. Bendell ◽  
A. Bessudo ◽  
N. Y. Gabrail ◽  
J. Diamond ◽  
...  
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Performance Status ◽  
Locally Advanced ◽  
Standard Of Care ◽  
Complete Response ◽  
Ecog Performance Status ◽  
Tumor Cell Migration ◽  
Arq 197 ◽  
Grade 3

527 Background: ARQ 197 selectively inhibits the c-Met receptor tyrosine kinase (RTK), which has been implicated in tumor cell migration, invasion, proliferation, and angiogenesis. CPT-11 plus C is a standard of care for CPT-11-refractory mCRC pts with WT KRAS tumors. Resistance to C has been associated with activation of alternative RTK pathways including c-Met. We hypothesize that adding ARQ 197 to CPT-11 plus C may decrease resistance to C therapy and improve pt outcomes. Methods: The primary objectives of phase I were to evaluate safety and tolerability of ARQ 197 administered in combination with CPT-11 plus C, and to define a recommended phase II dose (RPTD). Pts with surgically unresectable locally advanced or mCRC who received at least 1 prior line of chemotherapy, KRAS WT and ECOG performance status < 2 were eligible. Cohorts of 3 pts each were treated with CPT-11 (180 mg/m2) and C (500 mg/m2) every 2 weeks along with escalating doses of ARQ 197 (120, 240, 360 mg) PO BID. Blood and tissue were collected for PK, biomarker, and other analyses. If no DLTs were observed during the first 28-day cycle in 3 pts treated in cohort 3, 360 mg BID would be defined as the RPTD. Responses were assessed every 8 weeks per RECIST v1.1. Results: Nine pts were treated in 3 cohorts. Median age: 53 yrs (range 30-77); ECOG PS 0/1: 4/5; median prior therapies: 2 (range 1-4). No DLTs were observed. The RPTD for ARQ 197 was 360 mg BID. To date, two pts have discontinued (1 disease progression and 1 withdrew consent after achieving complete response) and 7 pts remain on study. The reported grade 3/4 adverse events were: neutropenia (3/4: 1/1), and one case each of grade 3 fatigue, leucopenia, acneiform rash, vomiting, anemia and syncope. Preliminary efficacy data in 9 evaluable pts include 1 CR (after 4 cycles), 2 PR (after 2 cycles), 5 SD, and 1 PD as best response. Conclusions: The combination of ARQ 197 and CPT-11 plus C was well tolerated with encouraging preliminary antitumor activity. The RPTD for ARQ 197 was 360 mg BID. The randomized phase II portion of the study continues accrual. [Table: see text]

Phase II trial of pazopanib and weekly paclitaxel in metastatic urothelial cancer (UC).

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 299-299 ◽  
Author(s):  
Sandy Srinivas ◽  
Sujata Narayanan ◽  
Lauren Christine Harshman ◽  
Anthony P. Lam ◽  
Ulka N. Vaishampayan ◽  
...  
Keyword(s):  
Phase Ii ◽  
Urothelial Cancer ◽  
Phase Ii Study ◽  
Performance Status ◽  
Progression Free Survival ◽  
Complete Response ◽  
Weekly Paclitaxel ◽  
Ecog Performance Status ◽  
Metastatic Urothelial Cancer ◽  
Grade 3

299 Background: Currently, there are no standard treatments for relapsed or refractory urothelial carcinoma (UC). Discouraging results have been achieved in trials evaluating drugs as single agents or in combination regimens. Paclitaxel has activity when used alone and in combination in urothelial cancer, and pazopanib is active in solid tumors secondary to its potent anti-angiogenic effect. We report the results of an ongoing multicenter phase II study evaluating the combination of paclitaxel with pazopanib in refractory UC. Methods: Patients (pts) eligible for the study have histologically confirmed UC, with relapse after receiving up to 2 chemotherapeutic regimens. Pazopanib (800 mg) is administered daily, with weekly paclitaxel (80mg/m2) for 3 weeks in a 28 day cycle. Treatment is continued until disease progression or unacceptable toxicity. Primary endpoint of the study is the response-rate (RR) based on RECIST criteria. Secondary endpoints include safety, and progression free-survival (PFS). For designing the study, Simon’s two-stage method was applied, and 9 pts were recruited in the first stage. After having ≥1 response in the first group, a full enrollment of 32 pts has been initiated. Results: 25 pts were enrolled from April 2010 to September 2013. Their median age was 67 years (47-89), with a median ECOG performance status of 1 (0-2). 10 pts (40%) had UC of the upper urinary tract and 15 had primary bladder/ureter tumors. All pts had multiple metastatic sites, including 11 (44%) with liver metastases. Median number of prior cytotoxic regimens was 2, and 50% were considered cisplatin responsive. Based on RECIST (v1.1) criteria,13 pts (52%) had partial response (PR), 5 (20%) had stable disease (SD), and 2 (8%) had complete response (CR) (80% clinical benefit). The side effects included grade 3 hypertension (n=2), grade 3 fatigue (n=4), grade 3 thrombosis (n=2) and grade 4 neutropenia (n=2). 14 pts required growth factor support. Conclusions: Our phase II study combining paclitaxel and pazopanib demonstratedsignificant anti-tumor activity of combining paclitaxel in relapsed/refractory UC. This combination is safe, and is worthy of evaluation in larger studies. Clinical trial information: 1108055.

Safety of weight-based dosing of nivolumab with or without ipilimumab by body mass index (BMI) stratified by sex across 14 CheckMate clinical trials.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15114-e15114
Author(s):  
Jennifer Leigh McQuade ◽  
Hans J. Hammers ◽  
Helena Furberg ◽  
Andreas Engert ◽  
Thierry Andre ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Smoking Status ◽  
Performance Status ◽  
Ecog Performance Status ◽  
Female Patients ◽  
Grade 3 ◽  
Risk Prognosis ◽  
Tumor Types ◽  
Obesity And Cancer ◽  
The Impact

e15114 Background: Associations between obesity and cancer risk, prognosis, and therapeutic outcomes have been extensively researched. However, the impact of BMI on safety in patients receiving immunotherapy has not been well described. Methods: A descriptive, retrospective analysis examined associations between BMI (kg/m2) (underweight/normal, BMI < 25; overweight, 25 ≤ BMI < 30; obese, BMI ≥ 30) and incidence of any-grade and grade 3/4 immune-mediated adverse events (imAEs) in patients receiving ≥ 1 dose of nivolumab 3 mg/kg as monotherapy (NIVO3; n = 2746). Data were pooled from CheckMate clinical trials across 8 tumor types. Data from nivolumab in combination with ipilimumab cohorts (n = 1026) and safety analyses by specific imAEs and tumor types will be presented. Results: Select NIVO3 monotherapy cohort patient demographics were: 68.5% male, median age of 61 years, median 10 doses received, and median BMI of 25.3 kg/m2. Results showed a trend towards higher incidence of any-grade, but not grade 3/4, imAEs in obese vs overweight and obese vs underweight/normal BMI patients (Table). BMI associations with imAE incidence were consistent with the overall trend across pre-defined subsets, including smoking status, age, and ECOG performance status. Both male and female patients had an increased incidence of any-grade imAEs with obesity; however, obese female patients had a higher incidence of grade 3/4 imAEs vs underweight/normal BMI (Table). Conclusions: This was a novel analysis of BMI and safety in 2746 patients across 8 tumor types in CheckMate clinical trials who were treated with nivolumab monotherapy. While obese patients showed a trend towards higher incidence of any-grade imAEs than those with overweight and underweight/normal BMI, incidence of grade 3/4 imAEs was consistent across BMI categories. Clinical trial information: CheckMate 017,026,057,025,039,205,040,066,067,141,275,142,016,214 (NCT numbers do not fit in field) . [Table: see text]

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