A phase II trial of 5-weekly S-1 plus cisplatin (CDDP) combination with trastuzumab (Tmab) for HER2-positive advanced gastric or esophagogastric junction (EGJ) cancer: WJOG7212G (T-SPACE) study.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 126-126 ◽  
Author(s):  
Yuji Miura ◽  
Toshimi Takano ◽  
Yasutaka Sukawa ◽  
Katsuhiko Nosho ◽  
Shuichi Hironaka ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Progression Free Survival ◽  
Weekly Schedule ◽  
Her2 Positive ◽  
Primary Tumor Site ◽  
Common Grade ◽  
Accrual Rate ◽  
First Results ◽  
Grade 3

126 Background: Five-weekly schedule of S-1 plus CDDP (5-weekly SP) is the standard first-line chemotherapy for the patients (pts) with advanced gastric cancer (AGC) in Japan. Tmab with fluoropyrimidine plus CDDP chemotherapy has shown a survival benefit for pts with HER2-positive AGC and EGJ cancer. However, little information on the efficacy and safety of 5-weekly SP combined with Tmab is available. Methods: We conducted a prospective, single arm, multicenter, phase II trial of 5-weekly SP (S-1 40-60 mg bid for 21 days plus CDDP 60 mg/m2on day 8, every 5 weeks) combined with Tmab (8 mg/kg as a loading dose then 6 mg/kg, every 3 weeks) for pts with HER2-positive (IHC 3+ or IHC 2+ and FISH positive) AGC or EGJ cancer. Primary endpoint was response rate (RR) evaluated by independent review committee, using RECIST v1.1. Secondary endpoints included progression-free survival (PFS), overall survival (OS) and safety. With power of 80% and one-sided alpha of 10%, thirty-five pts were required to reject 40% of RR under expected 60% RR. During the study, protocol was amended based on the favorable accrual rate. Pts were enrolled over 35 to improve precision, until pts enrollment up to 55 (power 85% and alpha 5%) or the end of predetermined accrual period, whichever came first. Results: Between August 2012 to January 2014, 44 pts were enrolled. Pts’ characteristics were: males 34 (77%), median age 62.6 years, PS 0-1 42 (95%), primary tumor site of stomach 37 (84%), histology of diffuse type 18 (41%). IHC 3+ was recorded in 32 (73%) pts. The RR was 64% (95% CI 48-78, one-sided p<0.001). The median PFS was 6.0 months (95% CI 5.1-10.9). The median OS was not reached. The toxicities in the first four courses were assessed. The most common grade 3 to 4 adverse events were anorexia (23%), diarrhea (11%), neutropenia (23%), anemia (16%), and thrombocytopenia (11%). One (2%) treatment-related death was reported. Conclusions: 5-weekly SP combined with Tmab showed a good efficacy with acceptable toxicities for pts with advanced AGC or EGJ cancer. Clinical trial information: UMIN000008389.

A phase II trial of temsirolimus (TEM) and bevacizumab (BEV) in patients with advanced hepatocellular carcinoma (HCC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4099-4099 ◽  
Author(s):  
Jennifer J. Knox ◽  
Rui Qin ◽  
Jonathan R. Strosberg ◽  
Andreas Kaubisch ◽  
Anthony B. El-Khoueiry ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Single Agent ◽  
Progression Free Survival ◽  
Advanced Hepatocellular Carcinoma ◽  
Vegf Inhibitor ◽  
Common Grade ◽  
Prior Systemic Therapy ◽  
Grade 3 ◽  
Stage 1

4099 Background: There is strong rationale to combine an m-TOR inhibitor (TEM) with a VEGF inhibitor (BEV) as a potentially active and well tolerated treatment for HCC. Both agents have shown modest single agent activity in HCC and so evaluated here in a phase II trial. Methods: A modified 2-stage Simon design planned 25 or 50 patients (pts) to test the null hypothesis that true tumor response rate is at most 10% andtrue 6-mo progression-free survival rate (PFS) (by RECIST) is at most 65%, or no better than single agent BEV (6 mo PR >2 pts or PFS 6 mo >18 out of 25.) Toxicity, TTP, PFS and survival were 2nd endpoints. Eligible pts had confirmed HCC with disease unresectable or amenable to other localised therapies, Child Pugh A liver status and no prior systemic therapy involving the VEGF or m-TOR class of agents. TEM was administered at starting dose 25 mg IV d1,8,15,22 with BEV at 10mg/kg IV d 1, 15, all q 28 days (1 cycle). Imaging was q 8 wks. Results: From 09/09 to 09/11, 27 eligible pts were enrolled with 25 evaluable for toxicity and efficacy. Med age 59 yrs, 85% male, PS 0/1: 35/65, 58% metastatic, >85% BCLC stage C. With med 6 cycles (range 1-14) delivered, most pts (88%) experienced a grade 3+ adverse event (a/e.) Common grade 3 a/es related to treatment included thrombocytopenia (40%), neutropenia (20%), leucopenia (12%), fatigue (8%), anemia, mucositis, dyspnea, diarrhea, bleeds, fistula, infections (4% each). There was one possible treatment related death. Per protocol dose reductions/discontinuation for TEM-related a/es were most common. There were 2 confirmed PRs and 16 pts progression-free by 6 mos. A third pt developed a late PR at cycle 13. Median TTP on study was 6 mos, median PFS was 7.4 mos and median survival was 8.3 mos, with 13 pts still alive. Accrual closed at end of stage 1 as neither the number of responses nor the PFS at 6 mos passed the futility stopping rule set for this combination. Conclusions: This multicenter study is the first HCC trial evaluating the BEV/TEM doublet. Despite manageable toxicity, the ORR and 6 mo PFS did not surpass assumptions based on single agent BEV in HCC. Further study of BEV/TEM combination in this advanced HCC population is not recommended.

TRYHARD, a randomized phase II trial (RTOG Foundation 3501) of concurrent accelerated radiation plus cisplatin (cis) with or without lapatinib (Lap) for stage III- IV Non-HPV head and neck carcinoma (HNC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 6014-6014
Author(s):  
Stuart J. Wong ◽  
Pedro A. Torres-Saavedra ◽  
Nabil F. Saba ◽  
George Shenouda ◽  
Jeffrey Bumpous ◽  
...  
Keyword(s):  
Overall Survival ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Stage Iii ◽  
Adverse Event Rate ◽  
Rank Test ◽  
Days Of Therapy ◽  
Grade 3

6014 Background: Chemoradiation (CRT) with cis or anti-EGFR Ab has been shown to improve survival of patients with stage III-IV HNC. Since Lap, a dual EGFR and HER2 inhibitor, has shown effectiveness with CRT in a pilot non-HPV HNC cohort, the RTOG Foundation launched a phase II trial to test the hypothesis that adding Lap to the RT-cis for frontline therapy of stage III-IV Non-HPV HNC improves progression-free survival (PFS). Methods: Patients with stage III-IV carcinoma of the oropharynx (p16-negative), larynx, and hypopharynx, having Zubrod performance of 0-1, and meeting predefined blood chemistry criteria were enrolled after providing consent. Patients were randomized (1:1) to 70 Gy (6 weeks) + 2 cycles of CDDP (q3 weeks) plus either Lap (1500 mg daily, Arm A) or placebo (Arm B) starting 1 week prior to RT and concurrent with RT and for 3 months post RT. PFS was the primary endpoint. The protocol specified 69 PFS events (142 patients) for the final analysis based on HR = 0.65, 80% power, 1-sided alpha 0.20, and one interim efficacy and futility analysis at 50% information. PFS rates between arms for all randomized patients were compared by 1-sided log-rank test (1-sided alpha 0.1803). Overall survival (OS) was a secondary endpoint. Results: From 10/’12 to 04/’17, 142 patients were enrolled, of whom 127 were randomized, 63 to Arm A and 64 to Arm B. Arms A vs B, respectively, were similar in baseline patient characteristics, radiation delivery, completing ≥ 70 Gy (85.7% vs. 82.8%) and cisplatin delivery, completing 200 (±5%) mg/m2 (65.1% vs 70.3%), but dissimilar in Lap/placebo delivery (median dose, 87000 mg vs. 125250 mg). Median follow-up was 4.1 years for surviving patients. The final analysis suggests no improvement in PFS of adding Lap to CRT (HR [A/B]: 0.91, 95% confidence interval CI 0.56-1.46; P= 0.34; 2-year rates: 50.6%, CI 37.5-63.7% vs. 56.2% CI 43.0-69.4%), or in OS (HR: 1.06, CI 0.61-1.86; P = 0.58; 2-year rates: 71.8% CI 60.1-83.5% vs. 76% CI 64.5-87.4%), death within 30 days of therapy (3.3% vs. 3.4%), and overall treatment-related grade 3-5 adverse event rate (86.7% vs. 84.7%). Grade 3-4 mucositis rates on Arm A and Arm B were 21.7% vs. 23.7%, all grade dysphagia and rash rates were 43.3% vs. 59.3%, and 13.3% vs. 6.8%, respectively. Conclusions: The addition of Lap to the radiation-cisplatin platform did not improve progression-free or overall survival in unselected non-HPV HN. Thus, dual EGFR, HER-2 inhibition does not appear to enhance the effects of chemoradiation. Although we showed that accrual to a non-HPV HN specific trial is feasible, new strategies must be investigated to improve the outcome for this poor prognosis HN population.

Phase II trial of oxaliplatin as first-line chemotherapy in metastatic colorectal cancer patients. Digestive Group of French Federation of Cancer Centers.

1998 ◽  
Vol 16 (8) ◽  
pp. 2739-2744 ◽  
Author(s):  
Y Bécouarn ◽  
M Ychou ◽  
M Ducreux ◽  
C Borel ◽  
F Bertheault-Cvitkovic ◽  
...  
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Sensory Neuropathy ◽  
Progression Free Survival ◽  
Free Survival ◽  
Duration Of Response ◽  
Grade 3 ◽  
Colorectal Cancer Patients ◽  
Peripheral Sensory

PURPOSE To evaluate the objective tumor response rate and safety profile of oxaliplatin when administered to patients with previously untreated metastatic colorectal adenocarcinoma. PATIENTS AND METHODS A total of 39 patients were entered onto this phase II trial. One patient was excluded for having had a second cancer, so the study was based on 38 patients. Patients were treated with oxaliplatin 130 mg/m2 as a 2-hour infusion on day 1, every 21 days. Patients were assessed for response every three courses. All clinical and radiologic data were reviewed by an external panel of experts, with their assessment being considered definitive. RESULTS Nine partial responses (PRs) were observed (response rate, 24.3%; 95% confidence interval, 11.8% to 41.2%). The median duration of response was 216+ days. Fifteen patients (40.5%) had stable disease and 13 (35.2%) had progressive disease. The median progression-free survival time for all patients was 126+ days (range, 21 to 447+). The main toxicity was peripheral sensory neuropathy. Grade 3 neurotoxicity (National Cancer Institute common toxicity criteria [NCI-CTC]) was reported in 13%. Hematologic and gastrointestinal toxicities were mild. The incidence of grade 3 neutropenia was 5.2%, while that of grade 3 or 4 thrombopenia was 7.9%. Vomiting (grade 3 or 4) occurred in 7.9% of patients and grade 3 diarrhea in 2.6%. CONCLUSION This phase II study provides clear evidence of the safety and efficacy of oxaliplatin monotherapy at this dose and schedule in patients with previously untreated metastatic colorectal carcinoma.

Regorafenib in patients with refractory metastatic pancreatic cancer: a Phase II study (RESOUND)

2019 ◽  
Vol 15 (35) ◽  
pp. 4009-4017
Author(s):  
Silvia Bozzarelli ◽  
Lorenza Rimassa ◽  
Laura Giordano ◽  
Simona Sala ◽  
Maria Chiara Tronconi ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Progression Free Survival ◽  
Clinical Trial Registration ◽  
Free Survival ◽  
End Point ◽  
Best Response ◽  
Cancer Types ◽  
Grade 3 ◽  
Experienced Grade

Aim: Regorafenib may be active in different cancer types. This Phase II trial included patients with various refractory cancer types treated with regorafenib. Here, we report the results of the pancreatic adenocarcinoma cohort. Methods: The primary end point was progression-free survival (PFS) rate at 8 weeks; further investigation of regorafenib would be warranted with a PFS rate ≥50%. Results: A total of 20 patients were enrolled. The best response was stable disease in four patients (20%). The 8-week PFS rate was 25% with a median PFS of 1.7 months (95% CI: 1.5–2.0). A total of 13 patients (65%) experienced grade 3–4 treatment-related adverse events. Conclusion: The study did not meet its primary end point. Further investigation of regorafenib monotherapy in this setting is not recommended. Clinical Trial Registration: NCT02307500

A Phase II Trial of Doxil, Vincristine and Reduced Schedule Dexamethasone (DVd) for Patients with Relapsed or Refractory Multiple Myeloma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2415-2415 ◽  
Author(s):  
Paul Masci ◽  
Mary A. Karam ◽  
Luba Platt ◽  
Steven Andresen ◽  
Alan Lichtin ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Phase Ii ◽  
Liposomal Doxorubicin ◽  
Phase Ii Trial ◽  
Pegylated Liposomal Doxorubicin ◽  
Progression Free Survival ◽  
Response Rates ◽  
Free Survival ◽  
Median Progression Free Survival ◽  
Grade 3

Abstract Patients with newly diagnosed multiple myeloma (MM) typically have responses to initial cytotoxic or steroid based therapy. Disease relapse occurs in all patients. As high as 90% of patients with relapsed or refractory disease will have over-expression of the multi-drug resistance (MDR) gene. Pharmacokinetic data suggest that prolonged exposure to high concentrations of doxorubicin can overcome MDR. Pegylated liposomal doxorubicin can theoretically achieve this goal as the angiogenic activity of the MM bone marrow is significantly increased. We proceeded with a phase II trial to evaluate the response rate of patients with relapsed or refractory MM (R/R-MM) to the DVd regimen. Eligible patients had clinically active R/R-MM following at least one prior cytotoxic based treatment regimen. Patients received intravenous (IV) pegylated liposomal doxorubicin 40 mg/m2 day 1, vincristine 2 mg day 1 and oral or IV dexamethasone 40 mg daily days 1–4. Cycles were repeated every 28 days for a minimum of 6 cycles and 2 cycles after best response. Myeloma parameters were measured at the start of each cycle. SWOG criteria were used to determine response. Thirty-five patients (21 male and 14 female) with R/R-MM clinically active disease were enrolled. Median age was 59 years (range 43–87). Patients received a median of 2 (range 1–4) prior cytotoxic based treatments. All patients received at least one cycle of treatment (median=5; range 1–12) and were evaluable for response. Ten (29%) patients responded to therapy; 5 partial responses (PR &gt; 50%) and 5 responses (R &gt; 75%) were observed after a median of 2 cycles (range 1–9). Median progression free survival of responding patients (PR + R) was 4.5 mos. (range 0.67–44.8). Patients achieving R had a median progression free survival of 32.5 mos. (3.0–44.8). Thirteen (37%) patients had stable disease (SD) for a median of 1.4 mos. (range 0.8–9.9). Twelve (34%) patients had progressive disease after a median of 1 cycle (range 1–5). The most common toxicities were hematologic; there were four occurrences of febrile neutropenia. Three patients experienced grade 3 constipation and one grade 3 palmar-plantar erythrodysethesia was observed. This study suggests that in patients with R/R-MM, DVd alone yields response rates similar to bortezomib with patients achieving an R experiencing a durable plateau phase. Ongoing studies of DVd in combination with thalidomide or CC-5013 in patients with R/R-MM have resulted in higher and better quality response rates (comparable to autologous SCT) translating to a durable progression free survival. We would not recommend the DVd regimen in patients with R/R-MM without the addition of an immune modulator such as thalidomide.

Weekly bortezomib in the treatment of patients (pts) with previously treated multiple myeloma: A phase II trial of the Minnie Pearl Cancer Research Network

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7547-7547 ◽  
Author(s):  
F. A. Greco ◽  
D. R. Spigel ◽  
J. H. Barton ◽  
C. Farley ◽  
M. T. Schreeder ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Research Network ◽  
High Dose ◽  
Weekly Schedule ◽  
High Dose Therapy ◽  
Dose Therapy ◽  
Previously Treated ◽  
Grade 3

7547 Background: Bortezomib, administered on a twice-weekly schedule, is now a standard part of treatment for patients with multiple myeloma. Weekly bortezomib schedules have shown activity in other cancer types, and are more convenient than twice weekly schedules. In this multicenter, community-based phase II trial, we evaluate the feasibility, toxicity, and efficacy of weekly bortezomib in pts with previously treated multiple myeloma. Methods: Eligibility criteria included a diagnosis of multiple myeloma treated with 1 or 2 previous systemic regimens (only 1 if first-line therapy included high-dose therapy); ECOG PS 0–2; creatinine < 2.0 mg/dL; WBC ≥ 3000/μL; ANC > 1000/μL; platelets ≥ 50,000/μL; no peripheral neuropathy > grade 1; informed consent. All pts received bortezomib 1.6mg/m2 IV on days 1, 8, 15, and 22 of each 5-week cycle. Pts were reevaluated at 10-week intervals; treatment continued for 8 cycles (40 weeks) or until myeloma progression. Results: Between 5/04 and 12/05, 37 pts entered this trial. Pt characteristics: median age 70 years; male/female, 20/17; 24 pts (65%) had received 2 previous regimens (previous high dose therapy, 2 pts); elevated β-2 microglobulin, 27 pts (73%). Of 26 pts evaluated, 13 pts (50%) had major responses, 11 pts (42%) stable disease, and 2 pts (8%) had progression. After a median follow-up of 7 months, projected median PFS is 9.6 months; overall survival at 1 year is 81%. Weekly bortezomib was well tolerated by most pts. Grade 3/4 toxicities included fatigue (21%), diarrhea (11%), neutropenia (7%), thrombocytopenia (4%), all others < 5%. No grade 3/4 neuropathy occurred. Only 1 pt required bortezomib dose reduction during treatment, and 2 pts discontinued treatment because of toxicity (myelosuppression, 1; fatigue/dehydration, 1). Conclusions: Weekly bortezomib is a convenient, well tolerated treatment for pts with previously treated multiple myeloma. Overall response rates with this schedule are similar to those previously reported with the standard twice-weekly schedule. Further followup is necessary to better evaluate the duration of response and the incidence of cumulative toxicities. [Table: see text]

Randomized phase II study of S-1/CDDP plus TSU-68 versus S-1/CDDP in patients with advanced gastric cancer.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 72-72
Author(s):  
Kensei Yamaguchi ◽  
Wasaburo Koizumi ◽  
Hisashi Hosaka ◽  
Yasutaka Takinishi ◽  
Norisuke Nakayama ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Growth Factor ◽  
Phase Ii ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Open Label ◽  
Parallel Group ◽  
Common Grade ◽  
Grade 3 ◽  
Endothelial Growth Factor

72^ Background: Gastric cancer (GC) is the second leading cause of cancer death in Japan as well as globally. Effective treatment of GC remains a therapeutic challenge. Although in the AVAGAST trial, bevacizumab was found to offer no survival benefit. Angiogenesis continues to be the standard treatment for GC, and thus, clinical trials on many anti-angiogenic drugs have been conducted. TSU-68 (orantinib) is an oral, angiokinase inhibitor targeting the vascular endothelial growth factor receptor 2, platelet-derived growth factor receptor β, and fibroblast growth factor receptor 1. The present study evaluated the progression-free survival (PFS) and pharmacokinetics (PK) of TSU-68 in combination with Japanese standard S-1 and cisplatin (S-1/CDDP) in patients with advanced GC. Methods: In this open-label, multicenter, randomized, controlled, parallel-group, phase II trial, patients were randomized to Arm A (S-1/CDDP) or Arm B (TSU-68 plus S-1/CDDP). All patients received oral S-1 (40-60 mg/m2) twice daily for 21 days followed by a 14 day rest plus intravenous CDDP (60 mg/m2) on Day 8, repeated every 35 days. In Arm B pts received oral TSU-68 (400 mg/dose) alone, twice daily by addition 35 days. The primary endpoint was PFS. Results: In total, 93 patients were enrolled. For Arm A [male:female ratio], n=47 [35:11]; Arm B, n=45 [30:15]; the respective median age was 63.5 and 62.0 years. The median PFS was 7.0 and 6.8 months in Arms A and B, respectively (HR, 1.23; 95%CI, 0.74 to 2.05; P=0.425); the respective response rates were 56.5% and 62.2%. The most common grade 3/4 toxicities were neutropenia (Arms A and B, 34.8% and 31.1%) and hemoglobin (Arms A and B, 26.1% and 48.9%). There were no differences in other toxicities between the 2 arms, both treatments were tolerated, and no treatment-related deaths were observed. In the PK study, although Arm B had a significantly lower plasma exposure to FT, CDHP, and Oxo compared to Arm A, the exposure to 5-FU was not different between the 2 arms. The exposure to CDDP in Arm B was significantly but slightly lower than that in arm A. Conclusions: Thus,TSU-68 plus S-1/CDDP therapy did not prolong PFS of patients with advanced GC as compared with S-1/CDDP. Clinical trial information: JapicCTI-101327.

Phase II trial of temozolomide and veliparib combination therapy for sorafenib-refractory advanced hepatocellular carcinoma (HCC).

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 240-240 ◽  
Author(s):  
Aiwu Ruth He ◽  
Anteneh Tesfaye ◽  
Daniel Smith ◽  
John Marshall ◽  
Michael J. Pishvaian ◽  
...  
Keyword(s):  
Dna Repair ◽  
Disease Progression ◽  
Cancer Progression ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Advanced Hepatocellular Carcinoma ◽  
Advanced Hcc ◽  
Common Grade ◽  
Grade 3

240 Background: The combination of the imidazotetrazine derivative temozolomide (TMZ) and poly(ADP-ribose) polymerase inhibitor veliparib (ABT-888) has shown in vivo activity against a variety of tumor types through the alkylating effects of TMZ and DNA repair inhibition by ABT-888. To date, no studies have examined the combination of TMZ and ABT-888 in treating advanced HCC refractory to sorafenib. Methods: This is a single arm Phase II trial. Eligible HCC patients have Child Pugh A/B cirrhosis and have failed prior treatment with sorafenib either through intolerance or disease progression. All patients have received ABT-888 40 mg daily on days 1-7 and Temozolomide 150 mg/m2 daily on days 1-5 in 28 day cycles for a maximum of 6 cycles. Tumor response is analyzed every 2 cycles using RECIST criteria. The primary endpoint is time to disease progression. The trial is being conducted using a modified Simon’s two-stage design optimal design as implemented by Hanfelt, et al. Results: The trial is currently in Simon Stage 1 with 16 patients recruited: 9 patients have stopped the study due to disease progression, 3 patients are still on protocol, and 4 patients stopped the study for reasons other than disease progression. 7 patients had disease progression at two months, 1 patient had cancer progression at 4 months, and 1 patient had disease progression at 16 months. Median time to progression in these 9 patients was 56 days (range 42-486 days). The four patients that stopped the study prematurely were for the following reasons: hiccups/dehydration, Mallory-Weiss tear secondary to refractory nausea, intraperitoneal bleeding from exophytic HCC lesion, and development of hepatorenal syndrome in a paracentesis-dependent patient. The most common grade 3 toxicities in this cohort so far have been nausea/vomiting (in 2 subjects), and anemia/thrombocytopenia (in 2 subjects). Defects in DNA repair pathways are being tested from the liver biopsy in the patient who had response to TMZ and ABT-888 for 16 months. Conclusions: The combination of TMZ and ABT-888 is fairly tolerated in patients with advanced HCC. So far, the treatment did not show activities in majority of patients with advanced HCC. Clinical trial information: NCT01205828.

Randomized, open-label, phase II study comparing five-weekly S-1 plus cisplatin (SP) with tri-weekly capecitabine plus cisplatin (XP) in chemotherapy-naïve patients with HER2 negative advanced gastric cancer (AGC): OGSG 1105 HERBIS-4A trial.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 102-102
Author(s):  
Atsushi Takeno ◽  
Youichi Makari ◽  
Shunji Endo ◽  
Jin Matsuyama ◽  
Ryohei Kawabata ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Open Label ◽  
Group 13 ◽  
Common Grade ◽  
Open Label Phase ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
To Receive

102 Background: This phase II study aimed to investigate the safety and efficacy of XP compared to SP in the first-line treatment of HER2 negative AGC. Methods: Patients were randomly assigned to receive either SP (S-1 at 40–60 mg twice daily for 21 days plus cisplatin at 60 mg/ m2 on day 8, every 5 weeks) or XP (capecitabine 1,000 mg/m2 twice daily for 14 days plus cisplatin 80 mg/m2 on day 1, every 3 weeks). Primary endpoint was response rate (RR), and secondary endpoints were progression-free survival (PFS), overall survival (OS), time to treatment failure (TTF), and adverse events. Results: 84 eligible patients were randomly assigned to receive SP ( N = 41) or XP ( N = 43). No statistical difference was observed in overall RR between the SP and XP groups [51.2% (95% CI, 35.1% to 67.1%) vs. 53.5% (95% CI, 37.7% to 68.8%), P = 1.000]. Despite not significant, however, SP vs. XP showed a trend toward better PFS [median, 5.9 months vs. 4.1 months; hazard ratio (HR), 0.763; 95% CI, 0.462 to 1.259; P = .284] and OS (median, 13.5 months vs. 10.0 months; HR, 0.776; 95% CI, 0.485 to 1.244; P = .290). This trend in the SP vs. XP comparison was more pronounced in TTF (median, 4.5 months vs. 3.1 months; HR, 0.651; 95% CI, 0.421 to 1.006; P = .052). Common grade 3 to 4 hematological toxicities were neutropenia and anemia (SP group, 23% and 23%; XP group, 35% and 28%). Grade 3-4 anorexia and hyponatremia were more frequently seen in the XP group (31% and 16%) compared to the SP group (13% and 5%). Treatment-related deaths occurred in one patient (2.3%) in the XP group. Conclusions: XP failed to demonstrate the superior efficacy over SP. Higher incidence of severe toxicities by XP suggests SP as the standard 1st line chemotherapy for HER2 negative AGC in Japan. Clinical trial information: UMIN000006755.

scholarly journals A phase II trial of neoadjuvant doxorubicin plus cyclophosphamide followed by lapatinib plus docetaxel sequential with adjuvant trastuzumab for treatment of early HER2 positive breast cancers

2017 ◽  
Vol 7 (2) ◽  
pp. 28
Author(s):  
Gregory A. Vidal ◽  
Namratha Vontela ◽  
Mary Chen ◽  
Julie M. Ryder ◽  
Struti Sheth ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Breast Conservation ◽  
Breast Cancers ◽  
Her2 Positive ◽  
Adjuvant Trastuzumab ◽  
Skin Reactions ◽  
Grade 3

Background: The use of HER2 targeting therapy has revolutionized the treatment of HER2 positive breast cancers. Here, we investigate whether a sequential approach to dual HER2 blockade of lapatinib followed by trastuzumab will result in improved clinical outcomes.Methods: This was a single institution, open label, single arm, phase II trial in women with HER2 positive breast cancer. Volunteers were treated with sequential neoadjuvant doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2) (AC) for 4 cycles followed by docetaxel (100 mg/m2) concurrent with lapatinib (1,250 mg) (TL) daily for 21 days for four cycles before definitive surgery. The primary end point was pathologic complete response (pCR).Results: The study accrued only 21 of the 71 planned patients from 2/28/2007 to 5/25/2010. All patients (100%) experienced down staging. The pCR rate was 41% (7/18). 11 patients had tumor size of T3 or greater, 3 of which experienced pCR and only 1 underwent breast conservation (lumpectomy). The most common hematologic AE (all grades) was anemia 17/21 (81%). There were no incidences of grade 3 or 4 anemia. 10 of 21 (48%) patients experience a non-hematologic grade 3 AE. The most common non-hematologic AEs (all grades) were irregular menses 20/21 (95%) and hand-foot-skin reactions 20/21 (95%). No increase cardiac abnormalities were noted. The DFS at data cut off was 87.5%.Conclusion: The provocative pCR and DFS results in this high risk locally advanced patient population should be viewed with caution given results of the Adjuvant Lapatinib And/Or Trastuzumab Treatment Optimisation study (ALTTO) clinical trial.

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