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]

Efficacy and safety of patupilone in non-small cell lung cancer (NSCLC): A phase I/II trial

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7104-7104 ◽  
Author(s):  
J. M. Sánchez ◽  
A. Mellemgaard ◽  
M. Perry ◽  
P. Zatloukal ◽  
J. Hamm ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Brain Metastases ◽  
Phase I ◽  
Phase Ii ◽  
Performance Status ◽  
Locally Advanced ◽  
Primary Objective ◽  
Prior Treatment ◽  
Wide Range ◽  
Grade 3

7104 Background: Based on its activity in a wide range of tumors including those that are taxane resistant, the novel microtubule stabilizer patupilone (EPO906; epothilone B) has the potential to treat NSCLC. Fifty patients were enrolled in phase I to evaluate safety, efficacy, and optimal dose. The phase II part of this study is investigating the antitumor activity of patupilone in 53 patients with stage IIIB/IV NSCLC. Methods: Patients with histologically or cytologically confirmed unresectable, locally advanced, or metastatic NSCLC documented before 1st-line therapy without symptomatic or uncontrolled brain metastases received patupilone at a starting dose of 10.0 mg/m2 q3wk by 20-minute IV infusion. Additional inclusion criteria: age ≥18 years; WHO performance status 0–1; prior treatment with a platinum-containing regimen. Primary objective of the phase II, single-arm, 2-stage, multicenter trial: to determine activity of patupilone q3wk (overall response using modified RECIST) in NSCLC. An additional cohort with recurrent brain metastases from NSCLC is being accrued to evaluate safety, pharmacokinetics, and activity. Results: In phase I, all patients received prior treatment with platinum therapy; 28% had received taxanes and 78% nontaxanes. Patupilone dose was escalated from 6.5 to 13.0 mg/m2 q3wk. Dose-limiting toxicities occurred in 4 patients: 1 with grade 3 asthenia and 3 with grade 3 diarrhea at various dose levels. The most frequent adverse events (AEs) were diarrhea (66%), nausea (40%), vomiting (34%), paraesthesia (32%), abdominal pain (30%), and fatigue (30%). The most frequent grade 3 AE was diarrhea (14%); a grade 4 AE (asthenia) occurred in 1 patient. Overall phase I response: 5 PR, 16 SD, and 26 PD. Based on risk-benefit analyses, 10.0 mg/m2 q3wk was recommended as the phase II dose. Phase II is ongoing: 25 of 53 patients (15 men and 6 women with NSCLC; 2 men and 2 women with brain metastases) have been enrolled. Conclusions: In phase I, patupilone q3wk was safe and well tolerated, with antitumor activity in patients with advanced pretreated NSCLC. Data from phase II will be available at time of presentation. [Table: see text]

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.

Clofarabine (CLO) Is Active in Patients (pts) with Refractory and/or Relapsed Non-Hodgkin’s Lymphoma (NHL): A Phase I/II Study.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4462-4462
Author(s):  
Chadi Nabhan ◽  
Walter Fried ◽  
Angel G. Galvez ◽  
Parameswaran Venugopal ◽  
Phillip Gozun ◽  
...  
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Performance Status ◽  
Pneumocystis Carinii ◽  
Standard Of Care ◽  
Complete Response ◽  
Median Number ◽  
Bulky Disease ◽  
Duration Of Response ◽  
Heavily Pretreated

Abstract There is no known standard of care for pts with relapsed and/or refractory NHL who cannot undergo stem cell transplantation (SCT) or have relapsed after SCT. Such pts are candidates for new therapies. CLO is a novel nucleoside analogue with known activity in acute leukemia and myelodysplasia. Previous clinical trials with CLO have established safety and potential activity in a variety of tumors. We performed a phase I/II study of CLO in a heavily pretreated pt population with refractory and/or relapsed NHL regardless of cell type, histology, or grade. Eligible pts were adults over 18 years of age who have relapsed and/or refractory NHL with measurable disease. Pts were required to have adequate performance status, bone marrow function (unless cytopenias were related to disease involvement), renal, cardiac, and liver functions. Pts with bulky disease (>10 cm at any site), known HIV, or immune-related cytopenias were excluded. CLO was given as a 1-hour intravenous infusion for 5 consecutive days every 28 days for a maximum of 6-cycles. All enrolled pts received anti-viral and anti-pneumocystis carinii prophylaxis. Growth factors were administered at the investigator’s discretion. Pts were divided into cohorts of 3 each. CLO was given at 4 mg/m2 to the first cohort with escalated doses by 2 mg/m2 increments for each cohort. Once the dose-limiting toxicity (DLT) was reached, the phase II portion of this study was initiated at the dose below the DLT level. All pts were followed until disease progression. To date, 13 pts have been enrolled with 7 on the phase I portion and 6 on the phase II portion. For the phase I portion, the median age was 79 (range: 27–81); the median number of prior therapies was 5 (range: 2–6) with 3 pts having relapsed after prior SCT. The median number of given CLO cycles in the phase I portion was 2 (range: 1–5). The DLT at 6 mg/m2 was thrombocytpenia establishing 4 mg/m2 as the appropriate dose for phase II. For the phase II portion, the median age was 78 (range: 50–83), median number of prior therapies was 2 (range: 1–8). Taken all together (phase I and II pts), 9 out of 13 pts are evaluable for response. (All received at least 1 cycle). There was 1 complete response (CR) and 4 partial responses (PR) for an overall response rate (OR) of 55%. Four patients demonstrated stable disease (SD) with one of them progressing shortly after 2 months. Eight patients remain alive (overall survival: 61%) at a median follow up of 4 months (range: 1–13). Median times to progression and duration of response have not been reached in responding pts. CLO is active in heavily pretreated refractory and/or relapsed NHL. The drug has an acceptable toxicity profile. Myelosuppresion is the major adverse event in this heavily pretreated population. The study continues to accrue patients and will be updated at the meeting.

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.

A phase I/II multi-center study of nivolumab and carboplatin/paclitaxel with radiation therapy (RT) for patients with locally advanced esophageal squamous cell carcinoma (ESCC).

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. TPS199-TPS199
Author(s):  
Iulia Giuroiu ◽  
Geoffrey Yuyat Ku ◽  
Lawrence P. Leichman ◽  
Kevin Lee Du ◽  
Philmo Oh ◽  
...  
Keyword(s):  
Overall Survival ◽  
Phase I ◽  
Clin Oncol ◽  
Phase Ii ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Complete Response ◽  
Multi Center Study

TPS199 Background: ESCC comprises 80% of esophageal cancers worldwide. Preoperative chemoRT is a standard-of-care based on the CROSS trial ( N Engl J Med 2012;366:2074-2084), which reported encouraging pathologic complete response (pCR) and overall survival (OS). Surgery is often deferred in patients with clinical CR (cCR) based on lack of overall survival (OS) benefit ( J Clin Oncol 2005;23:2310-2317, J Clin Oncol 2007;25:1160-1168). Nivolumab has activity in advanced ESCC ( Lancet Oncol 2017;18:631-639), and adding it to chemoRT may improve outcomes. ESCC has a high somatic mutation rate and treatment with chemoRT may augment the abscopal effect. Methods: Our trial aims to establish the safety and tolerability (phase I), as well as the efficacy (phase II) of nivolumab added to a standard chemoRT backbone for patients with TanyN1-3 or T3-4N0M0 ESCC. Phase I will enroll up to 12 patients and phase II, up to 44, per an optimal two-stage design. The phase I primary endpoint is unacceptable toxicity at 28 days after the last dose of chemotherapy. Phase II primary endpoints are cCR (endoscopy + PET/CT), pCR for patients undergoing surgery, and median progression-free survival and OS, which will be estimated via Kaplan Meier curves. Extensive tumor and blood immune correlative studies are planned. Clinical trial information: NCT03278626. [Table: see text]

Dasatinib plus capecitabine (Cap) for progressive advanced breast cancer (ABC): Phase I study CA180004

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 1012-1012
Author(s):  
G. Somlo ◽  
F. Atzori ◽  
L. Strauss ◽  
A. Rybicki ◽  
X. Wu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Phase I ◽  
Phase Ii ◽  
Performance Status ◽  
Combined Treatment ◽  
Breast Cancer Cell Lines ◽  
Ecog Performance Status ◽  
Grade 3 ◽  
Study Laboratory

1012 Background: SRC family kinases (SFK) mediate numerous signal-transduction pathways relevant to breast cancer as well as osteoclast function. Dasatinib, a potent oral inhibitor of SFK and other kinases has preclinical activity in breast models and in vitro synergy with Cap in some breast cancer cell lines (KPL-4 and HCC-70). A phase I trial of dasatinib plus Cap was conducted to define dose-limiting toxicities (DLT), maximum tolerated (MTD), and recommended phase II (RP2D) doses. Methods: Sequential cohorts of pts with ABC were treated with Cap twice daily (BID) on days 1–14 and dasatinib daily in 21-day cycles using dose levels (DL) for Cap (mg/m2) and dasatinib (mg): DL1: Cap 825 + dasatinib 50 BID; DL2: Cap 825 + dasatinib 70 BID; DL3: Cap 1000 + dasatinib 70 BID; DL3a: Cap 1000 + dasatinib 100 once daily (QD). All pts had ECOG performance status 0–1, had prior anthracycline and/or taxane, and received ≤2 regimens in advanced setting. MTD was based on DLT in first cycle and RP2D also based on tolerability of additional cycles. Results: 31 pts with ABC, median age 53 years (range 36–78) were treated. Number of pts treated/evaluable for DLT/reported DLT (event) were DL1: 7/6/1 (headache, grade 3); DL2: 9/7/0; DL3: 6/6/1 (diarrhea, grade 3), and DL3a: 9/9/1 (pneumonia, grade 3). Most frequent AEs related to either drug and occurring at any time on study (n pts) were nausea (12), vomiting (7), diarrhea (6), abdominal pain (2), fatigue (8), headache (7), musculoskeletal pain (1), and pleural effusion (4); hand-foot syndrome (5) was as expected for Cap alone. 11 patients experienced a Grade 3–4 non-hematologic AE at some point during the study. Laboratory abnormalities were uncommon. To date, 20 pts have continued treatment for ≥6 weeks and 9 pts for ≥12 weeks. Number of pts who (at any time) reduced dasatinib/reduced Cap/discontinued for toxicity were DL1: 2/2/1; DL2 2/2/3; DL3: 2/1/2; DL3a: 0/1/1. Updated safety and efficacy data will be presented. Conclusions: Dasatinib + Cap was tolerated without unexpected combined-treatment toxicity; few pts required dose reduction in later cycles. The recommended phase II dose, Cap 1000 plus dasatinib 100 QD, is well tolerated and will be studied for efficacy in an expanded patient cohort. [Table: see text]

Phase I study of pemetrexed plus cisplatin in unresectable, advanced gastric carcinoma in Taiwan

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14009-14009
Author(s):  
J. Chen ◽  
Y. Chao ◽  
L. Chen ◽  
C. Li ◽  
W. Reece ◽  
...  
Keyword(s):  
Gastric Carcinoma ◽  
Phase I ◽  
Phase Ii ◽  
Performance Status ◽  
Recommended Dose ◽  
Ecog Performance Status ◽  
Advanced Gastric Carcinoma ◽  
Post Surgery ◽  
Number Of Patients ◽  
Grade 3

14009 Background: Phase I of this Phase I/II study (H3E-AA-S038) was conducted to determine the recommended dose of pemetrexed (PT) when given with cisplatin (Cis) to patients with unresectable, advanced gastric carcinoma. Methods: Patients 18 to 70 years of age, with stage IV disease or post-surgery recurrence, no prior palliative chemotherapy, and an ECOG performance status of 0 or 1 were included. Patients received PT and Cis on Day 1 every 21 days. Cis was dosed at 75 mg/m2. PT dosage was planned at 600, 700, 800, and 900 mg/m2. Vitamin B12 and folic acid supplementation, and dexamethasone (or equivalent corticosteroid) prophylaxis were required. The initial number of patients to be enrolled per dose level (DL) was 3. If 0/3 patients had dose-limiting toxicity (DLT), PT dose was escalated. If 1/3 patients had DLT, 3 more patients were enrolled at that DL. If ≥2 patients had DLT, the dose was not escalated further. The recommended dose of PT for Phase II was the highest dose at which <2/6 patients experienced DLT. The following toxicities were defined as DLT: death due to toxicity; neutropenia [<0/5 × 109/L for ≥5 days, or <1.0 × 109/L with fever (≥38.5 ºC)]; thrombocytopenia (<10.0 × 109/L, or <50.0 × 109/L with bleeding); AST or ALT >20 × ULN; and non-hematological toxicities of CTC grade 3 or 4 (except nausea and vomiting). Intra-patient dose escalation was not permitted. Results: Sixteen patients were enrolled. The mean (±SD) age of enrolled patients was 52.8 (±10.0) years, and the majority were male (62.5%). At DL1, 0/3 patients experienced DLT. At DL2, 1/6 patients had DLT. At DL3, 3/7 patients had DLT, and so PT dose was not escalated. All DLTs occurred in cycle 1; 2 involved neutropenia, 1 tumor hemorrhage, and 1 hypokalemia. Grade 3/4 toxicities were experienced by 12/16 (75%) patients, including 9 (56%) hematological and 10 (63%) non-hematological events. Five out of thirteen (38%) patients with measurable disease had a RECIST response (2 had a complete response, 1 each at DL1 and DL2; 3 had a partial response, 2 at DL2 and 1 at DL3). At this interim analysis, 2 patients were still on therapy. Conclusions: The recommended dose of PT is 700 mg/m2. Phase II will examine response and safety of PT plus Cis in advanced gastric carcinoma. [Table: see text]

A phase I/II study of S-1 plus cisplatin alternating with S-1 plus docetaxel in patients with advanced gastric cancer (AGC).

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 101-101
Author(s):  
A. Hosokawa ◽  
K. Ogawa ◽  
S. Kajiura ◽  
Y. Tsukioka ◽  
T. Kobayashi ◽  
...  
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Survival Data ◽  
Performance Status ◽  
Maximum Tolerated Dose ◽  
First Line ◽  
Ecog Performance Status ◽  
Eligibility Criteria ◽  
Starting Dose ◽  
Grade 3

101 Background: S-1 plus cisplatin has been regarded as standard first-line chemotherapy for patients with AGC in Japan, and S- 1 plus docetaxel showed promising results for AGC in clinical trials. To investigate the usefulness of S-1 plus cisplatin alternating with S-1 plus docetaxel as first-line treatment in patients with AGC, we conducted a phase I/II study to determine the maximum tolerated dose (MTD), the recommended dose (RD), preliminary efficacy and toxicity. Methods: Eligibility criteria included pathologically confirmed AGC; no prior chemotherapy; Age 20 to 74, ECOG performance status (PS) of 0 to 2; adequate organ function; and written informed consent. Cisplatin was administered on day1 and the dose was escalated by 10 mg/m2 from starting dose of 40 mg/m2 in phase I part. S-1 was given orally at 80 mg/m2 on day1-14. Docetaxel was administered at 40 mg/m2 on day 22 in combination with S-1 80 mg/m2 on days 22-35. The treatment was repeated every 6 weeks. The RD was studied in every 3-6 patients cohort and determined according to the pre-defined DLTs. Primary endpoint of phase II was the response rate (RR). Results: Between Aug 2006 and Jul 2010, 33 pts were enrolled. Nine patients entered the phase I part and 24 enrolled in phase II part. In the phase I part, the MTD of cisplatin was presumed to be 50 mg/m2, because 50% of patients (3/6) developed DLTs. Therefore, the RD of cisplatin was estimated as 40 mg/m2, and the 27 patients received the treatment at RD level. Patients characteristics were as follows: median age=65 years (range 48-74), Male: female=21:6, PS 0:1:2=11:16:0, diffuse: intestinal=19:8, initially unresectable: recurrent=24:3. The RR was 59.2% (95% CI, 40.7-77.7). Median follow-up period was 14.6 months, median PFS was 7.9 months, and median survival time was 17.2 months, although survival data remain to be confirmed. Major grade 3/4 toxicities were neutropenia (63%), leucopenia (41%), and anemia (33%). These toxicities were tolerable and manageable. No treatment-related death was observed. The updated analysis will be presented at the meeting. Conclusions: This alternating treatment seems to be effective and well tolerated in the first-line treatments in patients with AGC. No significant financial relationships to disclose.

A phase I/II multisite study of nivolumab and carboplatin/paclitaxel with radiation therapy (RT) in patients with locally advanced esophageal squamous cell carcinoma (ESCC).

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 372-372
Author(s):  
Jennifer J. Wu ◽  
Emily Catherine Atkinson ◽  
Lawrence P. Leichman ◽  
Hitendra Patel ◽  
Syma Iqbal ◽  
...  
Keyword(s):  
Phase I ◽  
Clin Oncol ◽  
Phase Ii ◽  
Locally Advanced ◽  
Standard Of Care ◽  
Grade 5 ◽  
Primary Endpoints ◽  
Common Grade ◽  
Grade 3 ◽  
Overall Survival Benefit

372 Background: Preoperative chemoRT is a standard-of-care as shown in the CROSS trial ( N Engl J Med 2012;366:2074-2084), Surgery is sometimes deferred in pts with clinical CR (cCR) based on lack of overall survival benefit ( J Clin Oncol 2005;23:2310-2317, J Clin Oncol 2007;25:1160-1168). Nivolumab has activity in advanced ESCC ( Lancet Oncol 2017;18:631-639), and adding it to chemoRT may improve outcomes. Methods: This phase I/II study was designed to assess the safety and tolerability and efficacy of nivolumab added to chemoRT (6 weekly carboplatin AUC 2, paclitaxel 50mg/m2, RT 50.4 Gy in 1.8 Gy fractions 5/7 days) for pts with TanyN1-3 or T3-4N0M0 ESCC. The phase I primary endpoint is “unacceptable toxicity” at 28 days after the last dose of chemotherapy. The phase II primary endpoints are cCR (endoscopy + PET/CT) and pCR rates for pts undergoing surgery. Nivolumab is given q2W ×2, then concurrent chemoRT with nivolumab q2W x3. If no cCR, pt proceeds to esophagectomy, then adjuvant nivolumab q2W ×3; if cCR, pt has an option of no surgery but receives nivolumab q2W ×3. Results: From 7/20/17 to 12/27/18, 6 pts were enrolled. No unacceptable or grade 5 toxicities were observed. The most common grade 1/2 AEs in >1 pt were anorexia, myelosuppression, elevated AST and nausea. Grade 3/4 AEs in >1 pt were lymphopenia and leukocytopenia. 2 pts required hospitalizations (dyspnea 1, colitis 1). All pts completed therapy; 1 pt had dose delay due to grade 2 esophagitis; 2 pts progressed, 4 achieved cCR. Of 4 pts with cCR, 2 pts chose surgery and both achieved pCR. None of the 4 pts recurred. Conclusions: ChemoRT with nivolumab is tolerable with manageable toxicities in locally advanced ESCC. Enrollment to the phase II portion ended because of slow accrual. Adverse Events. Grade 1 &2 in > 1 pt: 4/6: Anorexia & Anemia 3/6: Leukocytopenia Neutropenia Thrombocytopenia Nausea & Elevated AST 2/6: Hypomagnesemia Hypokalemia Grade 3 & 4 in > 1 pt: 5/6: Lymphopenia, 2/6: Leukocytopenia

Phase I Trial of Escalating-Dose Irinotecan Given Weekly With Cisplatin and Concurrent Radiotherapy in Locally Advanced Esophageal Cancer

2003 ◽  
Vol 21 (15) ◽  
pp. 2926-2932 ◽  
Author(s):  
David H. Ilson ◽  
Manjit Bains ◽  
David P. Kelsen ◽  
Eileen O’Reilly ◽  
Martin Karpeh ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Phase I ◽  
Induction Chemotherapy ◽  
Phase Ii ◽  
Phase I Trial ◽  
Locally Advanced ◽  
Phase Iii ◽  
Concurrent Radiotherapy ◽  
Minimal Toxicity ◽  
Grade 3

Purpose: To identify the maximum-tolerated dose and dose-limiting toxicity (DLT) of weekly irinotecan combined with cisplatin and radiation in esophageal cancer. Patients and Methods: Nineteen patients with clinical stage II to III esophageal squamous cell or adenocarcinoma were treated on this phase I trial. Induction chemotherapy with weekly cisplatin 30 mg/m2 and irinotecan 65 mg/m2 was administered for four treatments during weeks 1 to 5. Radiotherapy was delivered weeks 8 to 13 in 1.8-Gy daily fractions to a dose of 50.4 Gy. Cisplatin 30 mg/m2 and escalating-dose irinotecan (40, 50, 65, and 80 mg/m2) were administered on days 1, 8, 22, and 29 of radiotherapy. DLT was defined as a 2-week delay in radiotherapy for grade 3 to 4 toxicity. Results: Minimal toxicity was observed during chemoradiotherapy, with no grade 3 or 4 esophagitis, diarrhea, or stomatitis. DLT caused by myelosuppression was seen in two of six patients treated at the 80-mg/m2 dose level, thus irinotecan 65 mg/m2 was defined as the recommended phase II dose. Dysphagia improved or resolved after induction chemotherapy in 13 (81%) of 16 patients who reported dysphagia before therapy. Only one patient (5%) required a feeding tube. Six complete responses (32%) were observed, including four pathologic complete responses in 15 patients selected to undergo surgery (27%). Conclusion: Cisplatin, irinotecan, and concurrent radiotherapy can be administered on a convenient schedule with relatively minimal toxicity and an acceptable rate of complete response in esophageal cancer. Further phase II evaluation of this regimen is ongoing. A phase III comparison to fluorouracil or taxane-containing chemoradiotherapy should be considered.

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