Randomized phase II study of mogamulizumab (KW-0761) plus VCAP-AMP-VECP (mLSG15) versus mLSG15 alone for newly diagnosed aggressive adult T-cell leukemia-lymphoma (ATL).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8506-8506 ◽  
Author(s):  
Tatsuro Jo ◽  
Takashi Ishida ◽  
Shigeki Takemoto ◽  
Hitoshi Suzushima ◽  
KImiharu Uozumi ◽  
...  
Keyword(s):  
Phase Ii ◽  
Primary Endpoint ◽  
Stevens Johnson Syndrome ◽  
Newly Diagnosed ◽  
Female Ratio ◽  
Adult T Cell Leukemia ◽  
Disease Subtype ◽  
Randomized Phase Ii ◽  
Johnson Syndrome ◽  
Male Female Ratio

8506 Background: Mogamulizumab (Moga), a defucosylated humanized anti-CCR4 antibody, was approved for the treatment of relapsed/refractory ATL in Japan in 2012. This multicenter, randomized, phase II trial was conducted to examine the efficacy of the combination of Moga with standard chemotherapy for untreated aggressive ATL. Methods: Previously untreated patients (pts) with CCR4-positive ATL were randomly assigned to receive mLSG15 plus Moga (arm A) or mLSG15 alone (arm B). The primary endpoint was CR rate (%CR), and secondary endpoints included ORR, PFS, OS and safety. Pts received 4 courses of mLSG15 regimen, with or without a total of 8 doses of Moga (1.0 mg/kg) once every 2 weeks. The planned sample size, 22 pts per arm, provided a probability of 80% that %CR in arm A would have larger %CR when true %CR for arm A is 15% better than that for arm B. Results: Of 54 pts randomized, 53 were treated (arm A: 29; arm B: 24). Male/female ratio was 53/47%, median age was 63 (37-81), and subtype was acute/lymphoma/unfavorable chronic, 70/25/6%. %CR and ORR in arms A and B was 52% (95%CI [CI]; 33, 71) vs. 33% (CI; 16, 55) and 86% (CI; 63, 96) vs. 75% (CI; 53, 90), respectively. The results in arm B were similar to the previously reported %CR of 40% and ORR of 72% with mLSG15 (Tsukasaki et al, JCO 2007). ORR according to the disease subtype, in arms A and B, was 55% vs. 29% for acute, 50% vs. 43% for lymphoma and 33% vs. 0% for unfavorable chronic. Median PFS was 259 days (CI; 197, -) for arm A and 192 days (CI; 147, -) for arm B. Median OS was not reached in both arms. The most common treatment-related AEs in each arm were neutropenia (100%, 96%), thrombocytopenia (100%, 96%), leukopenia (100%, 92%), lymphocytopenia (97%, 96%), anemia (97%, 92%) and febrile neutropenia (90%, 88%). In arm A, skin disorders were more frequent but manageable, and no serious skin disorder like Stevens-Johnson syndrome was observed. There was one treatment-related death, which was not related to Moga. Conclusions: The combination of Moga with mLSG15 was well tolerated and the study met its primary endpoint. These results suggest that Moga with mLSG15 is a rational treatment option for newly diagnosed aggressive ATL. Clinical trial information: NCT01173887.

Randomized phase II study of modified FOLFIRINOX versus gemcitabine plus nab-paclitaxel combination therapy for locally advanced pancreatic cancer (JCOG1407).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4017-4017
Author(s):  
Masato Ozaka ◽  
Makoto Ueno ◽  
Hiroshi Ishii ◽  
Junki Mizusawa ◽  
Hiroshi Katayama ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Phase Ii ◽  
Primary Endpoint ◽  
Response Rate ◽  
Controlled Trial ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Locally Advanced Pancreatic Cancer ◽  
Free Survival ◽  
Randomized Phase Ii

4017 Background: FOLFIRINOX, consisting of leucovorin (LV), fluorouracil (FU), irinotecan (IRI) and oxaliplatin (L-OHP), and GnP, consisting of gemcitabine (GEM) plus nab-paclitaxel (nPTX), have shown superior efficacy over GEM in patients (pts) with metastatic pancreatic cancer. Although several studies have reported the efficacy of FOLFIRINOX or GnP for pts with locally advanced pancreatic cancer (LAPC), no randomized controlled trial to compare the two regimens has been conducted in those pts. To select the most promising chemotherapy for LAPC, a randomized phase II selection design trial (JCOG1407) was conducted to compare between modified FOLFIRINOX (FOLFIRINOX with dose reduction of IRI and without bolus FU; Arm A) and GnP (Arm B) for pts with LAPC. Methods: In Arm A, 85 mg/m2 of L-OHP, 200 mg/m2 of l-LV, 150 mg/m2 of IRI, followed by 2,400 mg/m2 of continuous FU over 46 hours are infused every 2 weeks. In Arm B, 125 mg/m2 of nPTX followed by 1,000 mg/m2 of GEM are infused on days 1, 8, and 15 every 4 weeks. The primary endpoint was overall survival (the proportion of 1-year OS), and secondary endpoints included progression-free survival (PFS), distant metastasis-free survival (MFS) and response rate in pts with target lesions. The planned sample size was 124 pts to select more effective regimen in 1-year OS with a probability of at least 0.85 and to test the null hypothesis of 53% in 1-year OS with a one-sided alpha of 5% and 80% Results: From 2015 to 2019, a total of 126 pts was enrolled from 29 Japanese institutions, and were allocated to Arm A (n = 62) or Arm B (n = 64). The median (range) age was 66 (44-75) years and 58.7% were male. At the analysis, after a median (range) follow-up of 1.52 (0.55-3.99) years, 75 (59.5%) pts died. The proportion of 1-year OS was better in Arm B, 77.4% [95% CI 64.9–86.0] vs. 82.5% [95% CI 70.7–89.9], but 2-year OS was better in Arm A, 48.2% [95% CI 33.3–61.7] vs. 39.7% [95% CI 28.6–52.5]. Median OS was 2.0 years [95% CI 1.6-2.7] in Arm A and 1.8 years [95% CI 1.5-2.0] in Arm B. 1-year PFS for Arm A/B was 47.5 % [95% CI 34.5-59.4]/40.2% [95% CI 27.8-52.3], and 1-year MFS was 64.2 % [95% CI 50.9-74.8]/57.3% [95% CI 43.9-68.6]. Arm A was better OS in pts with CA19-9 <1000 U/mL and the opposite trend was observed in pts with CA19-9>1000 U/mL. Response rate was 30.9% [95% CI 19.1-44.8] in Arm A, and 41.4% [95% CI 28.6-55.1]) in Arm B. Incidences of grade 3-4 non-hematological toxicities for Arm A and Arm B were 66.1% and 67.2%, respectively. There was no treatment-related death. Conclusions: This study was the first randomized trial comparing the two regimens. The 1-year OS of the primary endpoint in GnP was better than mFOLFIRINOX, but mFOLFIRINOX achieved longer survival in 2-year OS. It is required to confirm longer OS and safety profiles which regimen should be selected as a standard regimen in LAPC. Clinical trial information: jRCTs031180085.

NABTT 0306: A randomized phase II trial of EMD 121974 in conjunction with concomitant and adjuvant temozolomide with radiation therapy in patients with newly diagnosed glioblastoma multiforme (GBM)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 2001-2001 ◽  
Author(s):  
L. B. Nabors ◽  
T. Mikkelsen ◽  
T. Batchelor ◽  
G. Lesser ◽  
M. Rosenfeld ◽  
...  
Keyword(s):  
Overall Survival ◽  
Median Survival ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Methylation Status ◽  
Newly Diagnosed ◽  
Integrin Receptor ◽  
Randomized Phase Ii ◽  
Newly Diagnosed Glioblastoma ◽  
Dose Levels

2001 Background: EMD 121974 (cilengitide) is a selective integrin receptor inhibitor that is well tolerated and has demonstrated biological activity in patients with malignant glioma. The objectives of this phase II trial were to determine safety when combined with chemoradiation and estimate the overall survival for two different doses in newly diagnosed GBM. Methods: A total of 112 patients were accrued onto the trial through the NABTT CNS consortium. Cilengitide was administered by one-hour infusion twice a week with 18 patients treated in a safety run-in phase of 6 patients at the tested dose levels of 500 mg, 1000 mg, and 2000 mg. After safety completion, 94 patients were randomly assigned to either 500 mg or 2000 mg groups. To date, 55 out of 112 (49%) patients have died. Overall survival was estimated using all patients in this trial regardless of their treating dose. Results: The median age was 55 years old (range: 22–88) and the median KPS was 90 (range: 60–100). 86 out of the 112 (76.8%) had a craniotomy as their initial surgical procedure and 25 patients (22%) had a biopsy. There were no DLTs during the safety run-in phase. The estimated median survival time is 18.9 months (95% CI: 16.3 -30.0 months) for patients treated with RT+TMZ+EMD. The trial was closed to accrual on December 31, 2007. To date, 89 out of 112 patients were alive 12 months from their initial diagnosis. The overall survival at 12 months for all patients is 79.5% (95% CI: 71–87%). MGMT methylation status and survival based on dose levels received are not currently available. Conclusions: EMD 121974 (cilengitide) is well-tolerated when combined with standard chemoradiation (TMZ+RT) and may improve survival for patients newly diagnosed with GBM given the substantial differences between the estimated median survival and that seen in the EORTC study (Stupp, N Engl J Med, 2005). [Table: see text]

Gemcitabine and oxaliplatin (GEMOX) alone or in combination with cetuximab as first-line treatment for advanced biliary cancer: Final analysis of a randomized phase II trial (BINGO).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4032-4032 ◽  
Author(s):  
David Malka ◽  
Laetitia Fartoux ◽  
Vanessa Rousseau ◽  
Tanja Trarbach ◽  
Eveline Boucher ◽  
...  
Keyword(s):  
Phase Ii ◽  
Primary Endpoint ◽  
Mutational Analysis ◽  
Metabolic Response ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Objective Response ◽  
First Line ◽  
Open Label ◽  
Randomized Phase Ii

4032 Background: Gemcitabine-platinum chemotherapy (CTx) regimens are widely accepted as first-line standard of care for patients (pts) with advanced biliary cancers (ABC). EGFR overexpression has been observed in ABC, suggesting that the combination with anti-EGFR monoclonal antibodies may be appropriate. Methods: Patients with ABC, WHO performance status (PS) 0-1, and without prior palliative CTx were eligible for this international, open-label, two-stage, non-comparative, randomized phase II trial. Patients received GEMOX (gemcitabine, 1 g/m² [10 mg/m²/min] at day [D]1 + oxaliplatin, 100 mg/m² at D2, arm A) or GEMOX + cetuximab (500 mg/m² at D1 or 2, arm B), every 2 weeks. The primary endpoint was crude 4-month progression-free survival (PFS) rate (H0, <40%; H1, ≥60%; planned sample size, 100 pts, increased to 150 pts by amendment to allow subgroup analyses). Secondary endpoints were objective response rate (ORR), disease control rate (DCR), PFS, overall survival (OS), and toxicity (NCI-CTC v3.0). Exploratory endpoints included early metabolic response as assessed by PET at 1 month, and tumor KRAS mutational analysis. Results: From Oct. 2007 to Dec. 2009, we enrolled 150 pts (median age, 62 years; male, 57%; metastatic, 79%; cholangiocarcinoma, 84%; median follow-up, 30 months) (Table). Conclusions: GEMOX-cetuximab regimen was well tolerated and met its primary endpoint (4-month PFS ≥60%). However, median PFS and OS were similar in both arms. Exploratory analyses (e.g., KRAS tumor status) are underway to identify pt subgroups deriving benefit from the addition of cetuximab to CTx. [Table: see text]

Final analysis of a phase IB/randomized phase II study of gemcitabine (G) plus placebo (P) or vismodegib (V), a hedgehog (Hh) pathway inhibitor, in patients (pts) with metastatic pancreatic cancer (PC): A University of Chicago phase II consortium study.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4012-4012 ◽  
Author(s):  
Daniel Virgil Thomas Catenacci ◽  
Nathan Bahary ◽  
Sreenivasa R. Nattam ◽  
Robert de Wilton Marsh ◽  
James Alfred Wallace ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Disease Status ◽  
Serum Levels ◽  
Newly Diagnosed ◽  
Significance Level ◽  
Phase Ib ◽  
Randomized Phase Ii

4012 Background: Sonic Hh (SHh), the ligand for the Hh pathway, is over-expressed in >80% of PC. V had activity in preclinical murine PC models leading to increased tumor perfusion, enhanced tumor delivery of G, and an improvement in survival. Methods: We conducted a placebo-controlled, phase IB/randomized phase II trial of GV or GP. Eligible pts, KPS 80-100, had untreated metastatic PC, or had completed adjuvant therapy > 6 months (mo) prior. Primary endpoint: progression-free survival (PFS). Correlatives: serial SHh serum levels; serial perfusion CT imaging. All pts received G 1000mg/m2over 30 minutes, days (D) 1, 8, 15, Q28D. A lead-in phase IB was performed. Pts, stratified by KPS (80 v 90/100), and disease status (newly diagnosed/recurrent), were randomized to V (150 mg PO daily) or P. For pts on P, cross-over was allowed at progression. Assuming a mPFS of 3.5 months for GP and 5.7 months for GV (HR=0.61), a sample size of 106 subjects (53 per group) provided 85% power to detect this difference, using a one-sided test at the 0.10 significance level. Results: No safety issues were identified in 7 pts enrolled in the phase IB study. The phase II study enrolled 106 evaluable pts (V/P 53/53) at 13 sites 2/10-6/12. Pt characteristics: median age 65/64 (range 52-82/39-83); KPS (% pts) 80: 38/30; 90: 26/38; 100: 36/32; newly diagnosed 91%/91%; recurrent: 9%/9%. Grade 3/4 toxicity (V/P, % pts, >5% in either arm): neutropenia 32/28; lymphopenia 4/15; thrombocytopenia 9/11; anemia 9/23; hyponatremia 4/15; fatigue 13/8; hyperglycemia 23/19; elevated ALT 13/9; hyperbilirubinemia 11/6; nausea 11/11. Response (%): CR 0/2, PR 8/11, SD 51/38. mPFS: 4.0/2.5 mo (95% CI: 2.5-5.3/1.9-3.8; HR 0.81 [0.54-1.21], p=0.30). 22 pts (42%) on GP crossed over to GV at progression. mOS: 6.9/6.1 mo (95% CI:5.8-8.0/5.0-8.0, HR 1.04, [0.69-1.58], p=0.84). Updated laboratory/radiological correlatives will be presented. Conclusions: Toxicity between the groups was similar. The addition of V to G in an unselected cohort does not improve response, PFS, or OS in pts with metastatic PC. Funding NCI N01-CM-62201. Clinical trial information: NCT01064622.

Randomized phase II study of pharmacodynamic separation (PDS) of pemetrexed (Pem) and erlotinib (Erl) versus pem alone in patients (pts) with advanced non-small cell lung cancer (NSCLC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8097-8097 ◽  
Author(s):  
Tianhong Li ◽  
Bilal Piperdi ◽  
William Vincent Walsh ◽  
Mimi Kim ◽  
Rasim Gucalp ◽  
...  
Keyword(s):  
Phase Ii ◽  
Primary Endpoint ◽  
Performance Status ◽  
Progression Free Survival ◽  
Dose Schedule ◽  
Phase Iii ◽  
Smoking History ◽  
Clinical Activity ◽  
P Value ◽  
Randomized Phase Ii

8097 Background: Preclinical and phase I studies showed that PDS optimizes cytotoxicity of concurrent EGFR inhibitors and chemotherapy. We conducted a randomized phase II trial to assess relative efficacy of Pem alone (Arm A) versus Pem +Erl on a PDS dose-schedule (Arm B) as 2nd-line therapy in pts with advanced NSCLC (NCT00950365). Methods: Eligible pts were randomized 2:1 (Arm B: A), stratified by sex, smoking history, and performance status (0/1 vs 2). Accrual was restricted to non-squamous histology in 2009. Treatment: Arm A – Pem 500 mg/m2IV on day 1; Arm B – Pem + Erl 150 mg po QD on days 2-17. 1 cycle = 3 weeks. Primary endpoint was progression-free survival (PFS). 50 pts in Arm B were needed to detect an increase in median PFS from ~3 to 4.5 months. Results: 83 pts were entered. Age: 63 yo. Female: 42 (53%). Smoking ≥15PY: 58 (72%). Nonsquamous: 78 (99%). The primary endpoint of the study was met: Efficacy results from 79 eligible pts showed 1.6-fold longer PFS in Arm B (4.6 m) compared to Arm A (2.8 m). Although the study was not designed to directly compare two arms, p value was 0.052. Toxicity: G3/4 Hem (A/B): 8(30%)/12(23%); Neutropenia with infection (A/B): 0/3(6%). G3/4 Non-Hem (A/B): skin rash: 0/3(6%); diarrhea: 0/2(4%); joint pain: 1(4%)/6(11.5%). Treatment related death (A/B): 0/1. Interstitial lung disease (A/B): 0/1. Conclusions: PDS of Pem and Erl is well tolerated and has promising clinical activity in 2nd-line non-squamous NSCLC. Ongoing correlative studies aim to identify a subgroup of patients who might benefit most from this treatment, which will guide the design of a confirmatory phase III study. (UL1 RR024146, P30CA093373, Lilly, Astellas) Clinical trial information: NCT00950365. [Table: see text]

A comparison of doublet versus triplet chemotherapy regimens for esophagogastric adenocarcinoma (EGC): Is more always better?

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 124-124
Author(s):  
Tiago Felismino ◽  
Ana Caroline Alves ◽  
Audrey Oliveira ◽  
Wilson Luiz da Costa ◽  
Felipe José Fernandez Coimbra ◽  
...  
Keyword(s):  
Cox Model ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Clinical Staging ◽  
Cancer Center ◽  
Newly Diagnosed ◽  
Relapse Free Survival ◽  
Female Ratio ◽  
Free Survival ◽  
Male Female Ratio

124 Background: Recent data showed that a taxane-containing triplet regimen (FLOT) was superior to an anthracycline-containing regimen (ECX/ECF). However, there is no comparison between more costly and toxic triplet (T) regimens versus doublets (D) in the perioperative setting (periCT) of EGC. Methods: A retrospective analysis of patients (pts) with newly diagnosed EGC was carried out at AC Camargo Cancer Center from 2007 to 2015. Pts received either a D with a fluopyrimidine and platin or T with addition of epirubicin or docetaxel. Variables used in the Cox model were age, site, TNM, Lauren subtype and periCT (T versus D). The selection between T and D was at physician's choice. Endpoints were Relapse Free Survival (RFS) and Overall Survival (OS). Results: A total of 128 pts were included. Median age was 59.5y (56.5y for T and 67y for D, respectively). Male/female ratio was 82/46. Sixty-six received T (DCF 26 pts, EOX 28, ECX 8, 4 others) and 62 received D (FOLFOX 47 pts, CF 13, 2 others). Primary site: gastric in 93 pts and 35 EGJ. Main clinical staging cT3 N = 81 (63.3%), cN+ 84 (65.4%). Lauren subtype: intestinal N = 48, diffuse N = 54. Regarding surgery: 114 pts were resected and median lymph nodes removed 30. Pathologic complete response was seen in N = 9 (14.5%) and N = 4 (6.1%) considering D and T regimens, respectively (p = 0.14). In multivariate analysis there was no advantage of T over D regarding RFS (HR = 1.65, 0.87 – 3.11, p = 0.12) or OS (HR = 1.29, 0.65 – 2.57, p = 0.45). The 3y RFS rate was 63.2% for D and 40.6% for T and the 3y OS was 69.4% for D and 56.1% for T. Conclusions: In our analysis outcomes of pts treated with T regimen was not superior to D. Our main T was DCF and D was FOLFOX. We consider that doublet regimens may still have a role in periCT in EGC and could be an option for frail or elderly pts. Future trials are needed to confirm our data.

Randomized Phase II Study of Temozolomide and Radiotherapy Compared With Radiotherapy Alone in Newly Diagnosed Glioblastoma Multiforme

2005 ◽  
Vol 23 (10) ◽  
pp. 2372-2377 ◽  
Author(s):  
Helen Athanassiou ◽  
Maria Synodinou ◽  
Evagelos Maragoudakis ◽  
Mihalis Paraskevaidis ◽  
Cosmas Verigos ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Malignant Gliomas ◽  
Progression Free Survival ◽  
Combined Modality Treatment ◽  
Newly Diagnosed ◽  
Randomized Phase Ii ◽  
Group A ◽  
One Year ◽  
Group B

Purpose Surgery remains the standard treatment for glioma, followed by radiotherapy (RT) with or without chemotherapy. Despite multidisciplinary approaches, the median survival time for patients with glioblastoma multiform (GBM) remains at less than 1 year from initial diagnosis. Temozolomide (TMZ), an oral alkylating agent, has shown promising activity in the treatment of malignant gliomas. We conducted a multicenter randomized phase II study comparing the efficacy and safety of TMZ administered concomitantly and sequentially to RT versus RT alone in patients with newly diagnosed GBM. Patients and Methods One hundred thirty patients with pathologically confirmed, newly diagnosed GBM were randomly assigned (110 assessable patients) to receive either TMZ 75 mg/m2/d orally, concomitantly with RT (60 Gy in 30 fractions; group A, n = 57), followed by six cycles of TMZ (150 mg/m2 on days 1 through 5 and 15 to 19 every 28 days), or RT alone (60 Gy in 30 fractions; group B, n = 53). Results Median time to progression was 10.8 months in group A and 5.2 months in group B (P = .0001). One-year progression-free survival rate was 36.6% in group A and 7.7% in group B. Median overall survival (OS) time was also significantly better in group A versus group B (13.4 v 7.7 months, respectively; P < .0001), as was the 1-year OS at 56.3% v 15.7% (P < .0001), respectively. Toxicity was mainly hematologic. One patient with grade 4 myelotoxicity died as a result of sepsis. The other side effects were mild. Conclusion TMZ combined with RT (concomitantly and sequentially) seems to be more effective than RT alone in patients with newly diagnosed GBM. The combined-modality treatment was well tolerated.

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