A phase Ib study to evaluate the safety and efficacy of AMG 655 in combination with gemcitabine (G) in patients (pts) with metastatic pancreatic cancer (PC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4501-4501 ◽  
Author(s):  
H. L. Kindler ◽  
L. Garbo ◽  
J. Stephenson ◽  
J. Wiezorek ◽  
T. Sabin ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Single Agent ◽  
Objective Response ◽  
Death Receptor ◽  
Progression Free Survival ◽  
Median Number ◽  
Metastatic Pancreatic Cancer ◽  
Death Receptor 5 ◽  
Number Of Cycles ◽  
Ecog Ps

4501 Background: AMG 655 is an investigational, fully human agonist monoclonal antibody (IgG1) that binds human death receptor 5 (DR5), activates caspases, and induces apoptosis in sensitive tumor cells. In preclinical PC models, cooperative activity is observed when G is added to AMG 655. We performed a multi-center phase I trial to evaluate AMG 655 + G in metastatic PC pts. The primary endpoint was dose-limiting toxicity (DLT). Secondary endpoints included toxicity, pharmacokinetics, antibody formation, objective response rate, progression-free survival (PFS), 6-month and overall survival. Methods: Eligible pts had previously untreated metastatic PC and ECOG PS 0 or 1. Pts enrolled into sequential cohorts and received AMG 655 3 or 10 mg/kg IV days (D) 1 and 15 and G 1000 mg/m2 IV D 1, 8, and 15 every 28 D. CT scans were obtained Q8 weeks. Results: 13 pts (3 mg/kg cohort = 6; 10 mg/kg cohort = 7) enrolled from 7/07–11/07. Pt characteristics: females 61%; ECOG PS 1 69%; median age 65 (range 35–81); liver metastases 77%. Median number of cycles: 6 (range 2–12). There were no DLT. Nine (69%) pts had grade 3–4 toxicity, the most common were: thrombocytopenia (4 pts), neutropenia (2 pts), and abdominal pain (2 pts). No anti-AMG 655 antibodies were detected. After one 3 or 10 mg/kg dose of AMG 655 after G, the Cmax and AUC of AMG 655 were similar to those in the first- in-human single-agent study (LoRusso JCO 2007; 25: abstract 3534). Preliminary data indicate no effect of AMG 655 on PK of G. Partial response 31% (4 pts, 2 unconfirmed); stable disease 38%. Median PFS: 5.3 months (95% CI, 3.5, 6.2); 6-month survival rate: 76.2% (95% CI: 42.7%-91.7%). Conclusions: AMG 655 + G is well-tolerated and may have activity in metastatic pancreatic cancer. A randomized phase II trial of G ± AMG 655 at 10-mg/kg is currently enrolling. [Table: see text]

Safety and efficacy of AMG 655 plus modified FOLFOX6 (mFOLFOX6) and bevacizumab (B) for the first-line treatment of patients (pts) with metastatic colorectal cancer (mCRC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4079-4079 ◽  
Author(s):  
L. Saltz ◽  
J. Infante ◽  
L. Schwartzberg ◽  
J. Stephenson ◽  
C. Rocha-Lima ◽  
...  
Keyword(s):  
Disease Progression ◽  
Human Monoclonal Antibody ◽  
Single Agent ◽  
Objective Response ◽  
Death Receptor ◽  
Maximum Tolerated Dose ◽  
Primary Objective ◽  
Death Receptor 5 ◽  
Grade 3 ◽  
Ecog Ps

4079 Background: AMG 655 is an investigational fully human monoclonal antibody (IgG1) agonist of human death receptor 5 (DR5). AMG 655 activates caspases and induces apoptosis in sensitive tumor cells. The primary objective of this phase 1b study was to determine the maximum tolerated dose (up to a target dose of 10 mg/kg IV every 2 weeks) of AMG 655 that can be safely administered in combination with mFOLFOX6-B to mCRC pts. Methods: Eligible pts were ≥ 18 years old with previously untreated mCRC, ECOG PS of 0 or 1, and adequate hematologic, hepatic, and renal function. Pts were enrolled into sequential cohorts of 3- or 10-mg/kg AMG 655 + mFOLFOX6-B administered on day 1 of each 14-day cycle. Study endpoints included incidence of dose-limiting toxicities (DLT), adverse events (AE), pharmacokinetic (PK) parameters of AMG 655, and objective response rate (by modified RECIST). Results: As of 09/08, 12 pts (6 per cohort) were enrolled and received ≥ 1 cycle of treatment; 8 were female. Median (range) age was 54 (37–75), median (range) time on AMG 655 treatment was 6.9 (1.6 to 11.4+) months; 8 pts continue on study treatment. There were no DLTs in the first 28 days of treatment. Eight pts had grade 3–4 AE; the most common were diarrhea, febrile neutropenia, peripheral neuropathy, neutropenia, DVT, and pulmonary embolism (2 pts each). Post baseline laboratory parameters grade ≥ 3: no ALT and AST; 1 grade 3 bilirubin (due to disease progression), and 3 grade 3 lipase (asymptomatic). No anti-AMG 655 antibodies were detected. AMG 655 PK values (Cmax, Cmin) were similar to those observed with single-agent AMG 655 (LoRusso JCO 2007; 25: abstract 3534). AMG 655 did not appear to affect PK of oxaliplatin or bevacizumab. Best overall tumor response: 5 partial responses (2 unconfirmed, both underwent resection); 6 stable disease; 1 pt had non-measurable disease at baseline. Time to disease progression (3 patients): 8, 42, and 44 weeks. Conclusions: The addition of AMG 655 does not appear to substantially alter the safety profile of mFOLFOX6-B. The randomized phase 2 part of the trial (mFOLFOX6-B ± AMG 655) is in progress. [Table: see text]

scholarly journals Oral mTOR Inhibitor Everolimus in Patients With Gemcitabine-Refractory Metastatic Pancreatic Cancer

2009 ◽  
Vol 27 (2) ◽  
pp. 193-198 ◽  
Author(s):  
Brian M. Wolpin ◽  
Aram F. Hezel ◽  
Thomas Abrams ◽  
Lawrence S. Blaszkowsky ◽  
Jeffrey A. Meyerhardt ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Adverse Events ◽  
Single Agent ◽  
Progression Free Survival ◽  
Mtor Inhibitors ◽  
Mtor Pathway ◽  
Metastatic Pancreatic Cancer ◽  
Clinical Activity ◽  
Antitumor Effects ◽  
Gemcitabine Refractory

PurposeThe PI3K/Akt/mTOR pathway is activated in the majority of pancreatic cancers, and inhibition of this pathway has antitumor effects in preclinical studies. We performed a multi-institutional, single-arm, phase II study of RAD001(everolimus), an oral inhibitor of mTOR, in patients who experienced treatment failure on first-line therapy with gemcitabine.Patients and MethodsThirty-three patients with gemcitabine-refractory, metastatic pancreatic cancer were treated continuously with RAD001 at 10 mg daily. Prior treatment with fluorouracil in the perioperative setting was allowed. Patients were observed for toxicity, treatment response, and survival.ResultsTreatment with single-agent RAD001 was well-tolerated; the most common adverse events were mild hyperglycemia and thrombocytopenia. No patients were removed from the study because of drug-related adverse events. No complete or partial treatment responses were noted, and only seven patients (21%) had stable disease at the first restaging scans performed at 2 months. Median progression-free survival and overall survival were 1.8 months and 4.5 months, respectively. One patient (3%) had a biochemical response, defined as ≥ 50% reduction in serum CA19-9.ConclusionAlthough well-tolerated, RAD001 administered as a single-agent had minimal clinical activity in patients with gemcitabine-refractory, metastatic pancreatic cancer. Future studies in metastatic pancreatic cancer should assess the combination of mTOR inhibitors with other agents and/or examine inhibitors of other components of the PI3K/Akt/mTOR pathway.

Irinotecan monotherapy as second-line treatment in advanced pancreatic cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15111-15111 ◽  
Author(s):  
Y. Park ◽  
S. Yi ◽  
H. Kim ◽  
S. Lee ◽  
I. Hwang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Stable Disease ◽  
Single Agent ◽  
Advanced Pancreatic Cancer ◽  
Median Number ◽  
Line Treatment ◽  
Second Line ◽  
Best Response ◽  
Grade 3 ◽  
Number Of Cycles

15111 Background: The aim of this phase II study was to determine whether second line therapy with single agent irinotecan could provide any clinical benefit in patients with gemcitabine- pretreated advanced pancreatic cancer. Methods: From January 2004 to October 2006, patients with advanced pancreatic cancer previously treated with gemcitabine alone or combination were treated with single agent irinotecan(150 mg/m2, biweekly), until unacceptable toxicity or disease progression. Primary endpoint was response rate with single stage design. Results: Twenty-eight patients were enrolled(22 male, 6 female, median age : 54.5 years (39–76)). Nine patients are still alive and 3 remain on therapy with stable disease. The median number of cycles was 3.5(1–12). Twenty-four patients were assessable for toxicity and 21 for response. The most common toxicities was diarrhea (grade 3, 12.5%). Grade 3 neutropenia in 1 patient was observed. Other hematological and non-hematological toxicities were mild and manageable. Partial responses were observed in 3 patients (3/21, 14%). An additional 9 patients (9/21, 43%) had stable disease as their best response. 12 patients have progressed with a median time-to-progression of 4.0 months. Conclusions: Single-agent irinotecan was tolerated with manageable toxicity, offering encouraging activity as second-line treatment of patients with advanced pancreatic cancer, refractory to gemcitabine. No significant financial relationships to disclose.

Phase II trial of irinotecan/docetaxel for advanced pancreatic cancer with randomization between irinotecan/docetaxel and irinotecan/docetaxel plus C225, a monoclonal antibody to the epidermal growth factor receptor (EGF-r) : Eastern Cooperative Oncology

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4519-4519 ◽  
Author(s):  
B. A. Burtness ◽  
M. Powell ◽  
J. Berlin ◽  
D. Liles ◽  
A. Chapman ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Median Survival ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Advanced Pancreatic Cancer ◽  
Growth Factor Receptor ◽  
Distant Metastases ◽  
Median Number ◽  
Number Of Cycles ◽  
Ecog Ps

4519 Background: Gemcitabine (G) is standard for metastatic pancreatic cancer (PC), with median survivals of 6 months (m). Second cytotoxic or biologic agents do not substantially advance survival. EGFR is expressed on PC and a phase II trial of G plus cetuximab (C) resulted in favorable 1 year survival. A phase II trial of irinotecan/docetaxel (I/D) chemotherapy reported a median survival for metastatic patients (pts) of 9 m. We conducted this randomized phase II trial to confirm the activity of this non-G regimen, and determine whether combining it with C was feasible and active. The primary endpoint was response. Methods: Pts required histologic confirmation of adenocarcinoma of the pancreas, evidence of distant metastases, ECOG PS 0–1, normal bilirubin, written informed consent, and were randomly assigned to Arm A (N=47) or B (N=45). Imaging with CT or MR within 4 weeks (wk) was used for tumor measurement. Dexamethasone was given 12 hours (h), 1 h before and 12 h after chemotherapy. Pts on Arm A received D 35 mg/m2 over 1 h and I 35 mg/m2 over 30 minutes weekly x 4 in a 6 wk cycle. Pts on Arm B received the same therapy, but C (loading dose 400 mg/m2 wk 1, 250 mg/m2 weekly thereafter) was given before D. Pts not receiving therapeutic anticoagulation received enoxaparin 40 mg per day. Pts were restaged (RECIST) after 2 cycles. Results: Median age Arm A: 59.9, Arm B: 60.2 years. Arm A 55% male, 32% PS 0, 97% EGFR immuno+. Arm B 84% male, 42% PS 0, 97% EGFR +. Median number of cycles for each arm 2 (1 -10). >4 cycles were delivered to 10.5% of pts Arm A, 20.9% Arm B. Grade ¾ neutropenia 26% Arm A, 33% Arm B. Grade 3 nausea 28% Arm A, 18% Arm B; Grade ¾ diarrhea 33% Arm A, 44.4% Arm B. 1 treatment-related death per arm. Median overall survival (OS), with 70.2% of pts known to have died, 6.5m [(95% CI (4.8, 8.6)] in Arm A. With 86.7% of pts known to have died in Arm B, OS 7.4 m [95% CI (4.4, 10.7)]. Response/progression data will be available at time of presentation. Conclusions: Weekly I/D ± C is associated with high rates of grade ¾ neutropenia/diarrhea. Median survival is 6.5m for I/D and 7.4m for I/D/C. Non-G containing therapy is active in metastatic PC. [Table: see text]

Safety and tolerability of combined gemcitabine (G) and erlotinib (E) plus sorafenib (S) in the first-line treatment of metastatic pancreatic cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15594-e15594 ◽  
Author(s):  
D. J. Cohen ◽  
T. Ryan ◽  
T. Moskovits ◽  
N. Cazeau ◽  
E. Newman ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Kinase Inhibitor ◽  
Bowel Perforation ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Median Number ◽  
Metastatic Pancreatic Cancer ◽  
Pancreatic Tumors ◽  
Disease Stabilization ◽  
Ecog Ps

e15594 Background: The addition of E to G results in improved survival for patients(pts) with locally advanced and metastatic pancreatic cancer. Many pancreatic tumors have constitutively activated ras/raf pathways and overexpress VEGF. Sorafenib, a multitargeted tyrosine kinase inhibitor which targets VEGR 1–3, PDGFR-α and β and the RAF/MEK/ERK pathway, when combined with G and E may synergize with these agents resulting in a more complete blockade of the signal transduction cascade in pancreatic cancer growth and progression and therefore improve outcome. Methods: Pts with previously untreated, histologically confirmed, unresectable pancreatic adenocarcinoma, ECOG PS 0–1, and adequate organ function were eligible and received G 1,000 mg/m2 over 30 min weekly × 3 every 4 weeks. E 150 mg PO daily and S 400 mg PO bid were given continuously. CT scans were performed every 2 cycles (8 weeks). Endpoints included safety and tolerability of the novel combination, PFS at 4 months, response rate, and OS. Results: Between 9/07–12/08 19 pts were enrolled with a median age 59 (range 45- 75), M/F 13/6, PS (0/1) 14/5. All 19 had metastatic disease. 17 pts are evaluable for toxicity and efficacy. The median number of cycles on treatment was 2 (range 1–10). The most common grade (gr) 3 toxicities were thrombocytopenia (24%), venous thrombosis (12%), and hyperbilirubinemia (12%). The most common gr 4 toxicity was infection (12%). 1 pt each experienced gr 3 HFSR, gr 3 diarrhea, gr 3 bleeding (epistaxis) and 1 had a non-fatal bowel perforation. There was 1 PR and 6 SD for an overall RR of 6% and a DCR of 41%. Conclusions: The combination of G and E plus S in the treatment of advanced pancreatic cancer is a well tolerated regimen without significant increased toxicity as compared to gemcitabine alone, except for very manageable cutaneous reactions. Further follow up is required to determine the combination's efficacy, though some patients have achieved prolonged disease stabilization. Supported in part by grants from Bayer Healthcare Pharmaceuticals/Onyx and OSI. [Table: see text]

A phase II trial of salvage treatment with gemcitabine and S-1 combination in heavily pretreated patients with metastatic colorectal cancer.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 488-488 ◽  
Author(s):  
Sun Jin Sym ◽  
Junshik Hong ◽  
Hee Kyung Ahn ◽  
Jinny Park ◽  
Eun Kyung Cho ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Disease Control ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Treatment Options ◽  
Objective Response ◽  
Progression Free Survival ◽  
Median Number ◽  
Ecog Ps

488 Background: We conducted a phase II trial of gemcitabine with S-1 to evaluate the activity and toxicity of such a combination in heavily pre-treated patients (pts) with metastatic colorectal cancer (mCRC) who have progressed after treatment with 5-fluorouracil (5-FU), oxaliplatin and irinotecan. Methods: 34 pts were enrolled, with the following characteristics: 17 (50%) females, median age 57 years (28-72), 28 (82%) ECOG PS 0-1. S-1 was given orally (30 mg/m2) b.i.d for 14 consecutive days and gemcitabine (1000 mg/m2) was given on days 1 and 8, every 21 days, until disease progression and for a maximum of 9 cycles. The primary endpoint was objective response rate (ORR). Results: The median number of cycles was four (range 1-9). ORR was 14.7% (95% confidence interval [CI] 2.8-26.6) and disease control rate was 58.8% (95% CI 42.2-75.3) with five partial responses and fifteen stable diseases. Median duration of disease control was 5.1 months (95% CI 3.3-7.0). Median progression-free survival was 3.2 months (95% CI 2.3-4.1) and median overall survival was 11.8 months (95% CI 7.0-16.5). Grade 3-4 toxicities were neutropenia (12%), anemia (12%), thrombocytopenia (3%) and diarrhea (3%). Conclusions: Combination chemotherapy with gemcitabine and S-1 was well tolerated and efficacious for heavily pre-treated mCRC pts, and could be an alternative for pts with good PS but no further treatment options.

RX 3117: Activity of an oral antimetabolite nucleoside in subjects with pancreatic cancer–Preliminary results of stage II of the phase Ia/IIb study.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 396-396
Author(s):  
Vincent M. Chung ◽  
Jaime R. Merchan ◽  
Allyson J. Ocean ◽  
Drew W. Rasco ◽  
Hani M. Babiker ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Partial Response ◽  
Primary Endpoint ◽  
Stable Disease ◽  
Single Agent ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Metastatic Pancreatic Cancer ◽  
Cancer Data ◽  
Phase 1B

396 Background: RX-3117 is an oral small-molecule antimetabolite, cyclopentyl pyrimidyl nucleoside that is activated by uridine cytidine kinase 2. RX-3117 has shown efficacy in xenograft models of gemcitabine resistant pancreatic, bladder and colorectal cancer. Data from stage 2 of the Phase 1b/2a clinical study of RX3117 as a single agent in subjects with metastatic pancreatic cancer is described below. Methods: Stage 2 of the Phase 1b/2a study (NCT02030067) is designed to evaluate safety, tolerability and efficacy following treatment with 700 mg administered orally once-daily for 5 consecutive days with 2 days off per week for 3 weeks with 1 week off in each 4 week cycle. Eligible subjects (aged ≥ 18 years) had relapsed/refractory metastatic pancreatic cancer. The primary endpoint is a ≥ 20% rate of progression free survival (PFS) benefit (i.e., proportion of subjects with stable disease for at least 4 months) and/or a 10% of evaluable subjects with a partial response rate or better. Results: As of Sep 2017, 44 subjects have been enrolled (22 females, 22 males). The median age was 68 years, ECOG performance statuses were 0 (13 subjects) and 1 (31 subjects) and 6 subjects had received 4 or more prior therapies. One subject had an unconfirmed partial response and 21 subjects met the primary endpoint of stable disease with a duration of 30-224 days. The most frequent adverse events were mild to moderate anemia (19%), mild to moderate fatigue (15%), mild to moderate diarrhea (11%), and severe anemia (9%). Conclusions: This ongoing trial shows an early efficacy signal where RX-3117 is active against advanced pancreatic cancer. The study continues to enroll subjects with advanced pancreatic cancer into stage 2. A phase 2 study with nab-paclitaxel in first-line patients with advanced pancreatic cancer has been started. Clinical trial information: NCT02030067.

Phase II study of gemcitabine (Gem) + docetaxel (D) in combination with trastuzumab (T) in patients (pts) with HER2-overexpressing metastatic breast cancer (MBC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10730-10730
Author(s):  
D. R. Fescina ◽  
W. Gradishar ◽  
M. Orlando ◽  
J. Rubinsak ◽  
L. Haney ◽  
...  
Keyword(s):  
Single Agent ◽  
Metastatic Breast ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
Phase Iii ◽  
First Line Therapy ◽  
Metastatic Setting ◽  
Grade 3 ◽  
Number Of Cycles ◽  
Ecog Ps

10730 Background: Addition of T to chemotherapy (chemo) is assoc. with improved overall survival (OS) in pts with HER2+ tumors. Combination chemo has shown improvements in PFS and OS over single agent in recent phase III studies. Pre-clinical models suggest that the combination of G and D appears to be synergistic and that either agent is also synergistic with T. Objectives: This multi-institutional study was designed to determine overall RR (primary endpoint), TTP, OS and the toxicity profile of the combination of G + D + T as first-line therapy for MBC pts. Design: Pts with measurable HER2-overexpressing (FISH+) MBC, no prior chemo in the metastatic setting, adequate end-organ function and PS 0–2, received Gem 1,000 mg/m2 over 30 min on days 1 and 8 + D 75 mg/m2 day 1 and T on day 1 (8 mg/kg over 90 min on cycle 1, then 6 mg/kg over 30 min on subsequent cycles) of a 21-day cycle, until progressive disease or undue toxicity. Results: 8 pts have been enrolled over a period of 16 months. Median age: 53 years (range 40–74); ER status ±: 5/3 pts; ECOG PS 0 = 3 pts, 1 = 4 pts, 2 = 1 pt; Prior adjuvant therapy: Chemo ± Hormonal 3, Hormonal only 3, T 1. Sites of Disease: All pts had visceral involvement (Lung 4, Liver 5) and 5 pts ≥ 2 sites of metastatic disease. Total number of cycles administered was 52; median per pt. 7 (range 4–10). Median delivered dose intensity for G, D and T was 91%, 92% and 100% respectively. Toxicity was generally manageable. One pt discontinued therapy due to adverse events (grade 3 pneumonitis). Grade 3/4 neutropenia occurred in 27% and 10% of cycles; no grade 3/4 anemia or thrombocytopenia were recorded; Non-Heme toxicities of grade 2/3, included with dyspnea (0/2 pts), emesis (2/1), fatigue (4/1), diarrhea (1/1), dehydration (0/1), constipation (1/0). Complete alopecia was observed in 2 pts. No symptomatic cardiac toxicity was recorded. Best Overall RR assessment (N = 8): CR 3, PR 4, SD 1, PD 0, for an ORR of 7 out of 8 pts or 88% (95% CI: 47%–100%). Only 3 pts have progressed, and no pt has died. Progression-free survival at 1 year is 58%. Conclusion: According to this limited experience, the combination of G + D + T in front-line MBC is well tolerated and active. Study was discontinued due to slow accrual as of Feb 2004. Supported by Eli Lilly & Company. [Table: see text]

A phase II study of YM155, a novel survivin suppressant, administered by 168 hour continuous infusion in patients with unresectable stage III or stage IV melanoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8538-8538 ◽  
Author(s):  
R. Gonzalez ◽  
K. Lewis ◽  
W. Samlowski ◽  
L. Cranmer ◽  
J. Catlett ◽  
...  
Keyword(s):  
Continuous Infusion ◽  
Single Agent ◽  
Objective Response ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Median Number ◽  
Stage Iii ◽  
Melanoma Tumor ◽  
Minor Response ◽  
Unresectable Stage

8538 Background: In cell line studies, YM155 showed markedly potent antiproliferative activity against melanoma with 50% growth inhibition (GI50) values ranging from 0.35 nM to 910 nM. In melanoma tumor-bearing mouse xenograft models, YM155 showed significant antitumor activity including regression of tumors, at doses ranging from 1 to 10 mg/kg/day. Methods: Chemotherapy naive patients with unresectable Stage III or IV melanoma were eligible. The primary endpoint was tumor response defined by RECIST criteria. Secondary endpoints included progression-free survival and toxicity. A Simon's two stage minimax design was utilized with the first stage requiring 1 response (N=27) and a total of 2 responses required at the conclusion of stage II (N=29). Patients were considered evaluable if they completed 2 cycles. YM155 was given as a 168-hour (7-day) continuous infusion every three weeks (1 cycle) at a dose of 4.8 mg/m2/day. Results: Enrollment is complete at 34 pts in order to reach 29 evaluable with treatment ongoing. Results are available for the first 26 pts. Median age was 59 y/o, (range 29 - 88) with ECOG PS of 0–1. There is one objective response of intrabdominal lymph nodes based on Investigator assessment at Cycle 2 confirmed at Cycle 4; another patient had a minor response (24% reduction) at Cycle 6 (currently at Cycle 8). Two subjects have shown stable disease after 6 cycles and remain on study. The median number of cycles is 3 (range 1 - 9). Two of 26 pts reported a grade 3 AE considered possibly related to YM155 (chest pain - nos and catheter related thrombosis). Nineteen of 26 pts have discontinued the study (18 PD, 1 withdrew consent). Conclusions: YM155 induced responses in 2 pts and was generally well tolerated. Given this encouraging response as a single agent, studies of YM155 combined with other agents are under consideration. [Table: see text]

A phase II trial of salvage treatment with gemcitabine and S-1 combination in heavily pretreated patients with metastatic colorectal cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14137-e14137
Author(s):  
Sun Jin Sym ◽  
Junshik Hong ◽  
Minkyu Jung ◽  
Jinny Park ◽  
Eun Kyung Cho ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Disease Control ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Objective Response ◽  
Progression Free Survival ◽  
Median Number ◽  
Heavily Pretreated ◽  
Number Of Cycles

e14137 Background: We conducted a phase II trial of gemcitabine with S-1 to evaluate the activity and toxicity of such a combination in heavily pre-treated patients (pts) with metastatic colorectal cancer (mCRC) who have progressed after treatment with 5-fluorouracil, oxaliplatin and irinotecan. Methods: Between Dec 2009 and Nov 2011, 23 pts were enrolled, with the following characteristics: 12 males and 11 females, median age 57 years (28-72). S-1 was given orally (30 mg/m2) b.i.d for 14 consecutive days and gemcitabine (1000 mg/m2) was given on days 1 and 8, every 21 days, until disease progression and for a maximum of 9 cycles. The primary endpoint was objective response rate (ORR). Results: The median number of cycles was four (range 1-9). OR was 8.7% (95% confidence interval [CI] 0-20.2) and disease control rate was 56.5% (95% CI 36.4-76.9) with two partial responses and eleven stable diseases. Median duration of disease control was 8.5 months (95% CI 3.8-13.2). Median progression-free survival was 3.2 months (95% CI 1.9-4.5) and median overall survival was 11.8 months (95% CI 4.0-19.5). Grade 3-4 toxicities were neutropenia (8%) and thrombocytopenia (4%). Conclusions: Combination chemotherapy with gemcitabine and S-1 was well tolerated and efficacious for refractory mCRC pts.

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