Phase II study of nimustine, carboplatin, vincristine, and interferon-β with radiotherapy for glioblastoma multiforme: experience of the Kyoto Neuro-Oncology Group

2006 ◽  
Vol 105 (3) ◽  
pp. 385-391 ◽  
Author(s):  
Tomokazu Aoki ◽  
Jun A. Takahashi ◽  
Tetsuya Ueba ◽  
Natsuo Oya ◽  
Masahiro Hiraoka ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Phase Ii ◽  
Median Duration ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Karnofsky Performance Scale ◽  
Interferon Β ◽  
Free Survival ◽  
Scale Scores ◽  
Grade 3

Object This Phase II study was performed to determine the safety, tolerability, and efficacy of combining nimustine (ACNU)–carboplatin-vincristine-Interferon-β (IFNβ) chemotherapy. Methods Ninety-seven patients with Karnofsky Performance Scale scores of 50 or greater were enrolled in the study. Nimustine (60 mg/m2), carboplatin (110 mg/m2), vincristine (0.6 mg/m2), and IFNβ (10 μg) were administered on Day 1 concomitant with radiotherapy (63 Gy); vincristine (0.6 mg/m2) and IFNβ (10 μg) on Days 8 and 15; and IFNβ alone (10 μg) three times per week throughout the course of radiotherapy. Fifty-six days after radiotherapy ended, the time schedule for chemotherapy was reset and ACNU, carboplatin, vincristine, and IFNβ were again administered on the new Day 1 and vincristine and IFNβ on the new Days 8 and 15. This course was repeated every 56 days. Instances of nonhematological toxicity were rare and mild. During the course of radiotherapy, the percentages of patients who experienced Grade 3 toxicity were 14% with neurocytopenia and 7% with thrombocytopenia. Seven percent of all adjuvant chemotherapy cycles following radiotherapy were associated with Grade 3 toxicity, as manifested in neurocytopenia or thrombocytopenia. No instance of Grade 4 toxicity was observed. The median duration of progression-free survival was 10 months (95% confidence interval [CI] 8–12 months) and the median duration of overall survival was 16 months (95% CI 13–20 months). Conclusions The combination of ACNU-carboplatin-vincristine-IFNβ chemotherapy and radiotherapy is safe and well tolerated, and may prolong survival in patients with glioblastoma multiforme.

Phase II Study of ET-743 in Advanced Soft Tissue Sarcomas: A European Organisation for the Research and Treatment of Cancer (EORTC) Soft Tissue and Bone Sarcoma Group Trial

2005 ◽  
Vol 23 (3) ◽  
pp. 576-584 ◽  
Author(s):  
A. Le Cesne ◽  
J.Y. Blay ◽  
I. Judson ◽  
A. Van Oosterom ◽  
J. Verweij ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Phase Ii ◽  
Median Duration ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Advanced Soft Tissue Sarcoma ◽  
Free Survival ◽  
Grade 3 ◽  
Line Chemotherapy

Purpose This nonrandomized multicenter phase II study was performed to evaluate the activity and safety of Ecteinascidin (ET-743) administered at a dose of 1.5 mg/m2 as a 24-hour continuous infusion every 3 weeks in patients with pretreated advanced soft tissue sarcoma. Patients and Methods Patients with documented progressive advanced soft tissue sarcoma received ET-743 as second- or third-line chemotherapy. Antitumor activity was evaluated every 6 weeks until progression, excessive toxicity, or patient refusal. Results One hundred four patients from eight European institutions were included in the study (March 1999 to November 2000). A total of 410 cycles were administered in 99 assessable patients. Toxicity mainly involved reversible grade 3 to 4 asymptomatic elevation of transaminases in 40% of patients, and grade 3 to 4 neutropenia was observed in 52% of patients. There were eight partial responses (PR; objective regression rate, 8%), 45 no change (NC; > 6 months in 26% of patients), and 39 progressive disease. A progression arrest rate (PR + NC) of 56% was observed in leiomyosarcoma and 61% in synovialosarcoma. The median duration of the time to progression was 105 days, and the 6-month progression-free survival was 29%. The median duration of survival was 9.2 months. Conclusion ET-743 seems to be a promising active agent in advanced soft tissue sarcoma, with no cumulative toxicities. The 6-months progression-free survival observed in advanced soft tissue sarcoma compares favorably with those obtained with other active drugs tested in second-line chemotherapy in previous European Organisation for the Research and Treatment of Cancer trials. The median overall survival was unusually long in these heavily pretreated patients mainly due to the high number of patients who benefit from the drug in terms of tumor control.

A phase II study of irinotecan combined with S-1 in patients with advanced or recurrent cervical cancer previously treated with platinum based chemotherapy

2019 ◽  
Vol 29 (3) ◽  
pp. 474-479
Author(s):  
Seiji Mabuchi ◽  
Eriko Yokoi ◽  
Kotaro Shimura ◽  
Naoko Komura ◽  
Yuri Matsumoto ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Recurrent Cervical Cancer ◽  
Free Survival ◽  
Platinum Based Chemotherapy ◽  
Previously Treated ◽  
Grade 3

ObjectivesWe conducted a phase II study to investigate the efficacy and toxicities of irinotecan plus oral S-1 in patients with advanced or recurrent uterine cervical cancer.MethodsPatients with advanced or recurrent cervical cancer previously treated with platinum based chemotherapy were enrolled. Irinotecan (150 mg/m2) was administered intravenously over the course of 90 min on day 1, and S-1 (80 mg/m2) was given orally in two divided doses from days 1 to 14 of a 21 day cycle. The primary endpoint of this phase II study was response rate. Secondary endpoints included safety, progression free survival, and overall survival.ResultsA total of 19 patients were enrolled and treated. The response rate was 29.4%. Grade 3–4 hematologic toxicities were observed in three patients (15.7%). The only grade 3–4 non-hematologic toxicity observed was grade 3 diarrhea. The median progression free survival and overall survival were 3 months and 9 months, respectively.ConclusionS-1 plus irinotecan in a 3 weekly setting is safe and active in women with advanced or recurrent cervical cancer previously treated with platinum based chemotherapy. Future corroborative clinical studies are warranted.

NGR-hTNF and doxorubicin in relapsed small-cell lung cancer (SCLC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7085-7085 ◽  
Author(s):  
Raffaele Cavina ◽  
Vanesa Gregorc ◽  
Silvia Novello ◽  
Francesco Grossi ◽  
Armando Santoro ◽  
...  
Keyword(s):  
Phase Ii ◽  
Median Duration ◽  
Human Tumor ◽  
Progression Free Survival ◽  
Free Survival ◽  
Platinum Sensitive ◽  
Platinum Resistant ◽  
Grade 3 ◽  
Further Development ◽  
Necrosis Factor

7085 Background: By selectively damaging tumor vasculature, NGR-hTNF (asparagine-glycine-arginine human tumor necrosis factor) is able to improve intratumoral uptake of doxorubicin (D). A phase I trial selected NGR-hTNF 0.8 µg/m2/day(d)1 and D 75 mg/m2/d1 every 3 weeks (q3w) for phase II. Methods: SCLC pts failing one or more platinum-based regimen received NGR-hTNF until progressive disease (PD) and D up to 550 mg/m2. This phase II trial (n=27 pts) had progression-free survival (PFS) as primary end point, with tumor response assessed q6w by RECIST, while secondary end points included adverse events (AEs), disease control rate (DCR), and overall survival (OS). Results: Among 28 pts enrolled (median age 63 years; M/F 19/9; PS 0/1-2 13/15; prior lines 1/2-3 20/8), 16 pts had platinum-resistant (R) disease (PD≤3 months) and 12 pts platinum-sensitive (S) disease (PD>3 months). At baseline, median neutrophil to lymphocyte ratio (NLR) was 4 (range 1-20). A total of 114 cycles were given (range 1-10), with 13 pts (46%) having ≥ 4 cycles and 9 pts (32%) ≥ 6 cycles. No grade 3/4 AEs related to NGR-hTNF were noted, while grade 1/2 AEs were transient chills (61%). NGR-hTNF did not apparently increase D-related AEs. Median PFS was 3.2 months (95% CI 2.6-3.8) and 1-year OS rate was 34%. Overall, DCR was 55% (95% CI 35-74), comprising 6 partial responses (22%; median duration: 6.3 months) and 9 stable diseases (33%; median duration: 4.1 months). Mean changes from baseline in target tumor size after 2, 4, and 6 cycles were -9%, -29%, and -32%, respectively for R disease and -11%, -20%, and -43%, respectively for S disease. In pts pretreated with ≥ 2 lines, DCR was 75%, median PFS was 5.1 months, and 1-year OS rate was 44%. In pts with R or S disease, DCR were 50% and 58% (p=.72), median PFS were 2.7 and 4.1 months (p=.07), and 1-year OS rates were 27% and 42% (p=.65), respectively. At multivariate analyses, PFS was not related to baseline characteristics, while an improved OS was associated only with a low NLR. The 1-year OS rate was 48% in pts with NLR ≤ 4 and 10% in pts with NLR > 4 (p=.007), while in pts with NLR ≤ 4, 1-year OS rate was 46% in R disease and 50% in S disease. Conclusions: This combination is well tolerated and active in platinum resistant and sensitive SCLC and further development is of interest.

Phase II study of biweekly administration of CPT-11 and gemcitabine in chemotherapy-naive patients with metastatic pancreatic cancer in Japan.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15150-e15150
Author(s):  
Ryoji Takada ◽  
Tatsuya Ioka ◽  
Nobuko Ishida ◽  
Takuo Yamai ◽  
Nobuyasu Fukutake ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Phase Ii ◽  
Combination Chemotherapy ◽  
Phase Ii Study ◽  
Single Agent ◽  
Progression Free Survival ◽  
Current Standard ◽  
Free Survival ◽  
Metastatic Pancreatic Adenocarcinoma ◽  
Grade 3

e15150 Background: The current standard therapies for metastatic pancreatic adenocarcinoma in Japan are the single-agent Gemcitabine (Gem) or S-1 and Gem plus erlotinib. Irinotecan (CPT-11) is one of the promising drugs for Gem-refractory PC pts. Both Irinotecan and Gem have shown activity against these diseases with different mechanisms and are non-cross-resistant with each other. Japanese pts have the different metabolism with Irinotecan rather than pts in western countries. Methods: The aim of this phase II study was to evaluate the efficacy and safety of CPT-11 and Gem in Japanese pancreatic cancer pts. Patients with MPC and PS 0-2 were enrolled in this phase II trial. CPT-11, 100mg/m (2), was administered in 90 min. and Gem, 1000mg/m (2), was administered in 30 min. soon after CPT-11 on day1. Chemotherapy was repeated biweekly. Results: From May 2002 to May 2006 40 pts, with median age of 62 (40-74) years, were enrolled in this study. The overall response rate (RR) was 15% with disease control rate of 50%. The median progression-free survival (PFS) was 4.0 months (range: 1.0-15.0 months), and median overall survival (OS) was 7.5 months (range: 3.0-24.0 months). Grade 3/4 anemia, leucopenia occurred in 26.3, 5.2% of pts. The most common non-hematologic toxities were fatigue, diarrhea, nausea/vomiting and anorexia. Grade 3 diarrhea and nausea occurred in 10.5% of pts. Conclusions: The combination chemotherapy with Gem and CPT-11 showed favorable RR as expected and the treatment was manageable in Japanese pts with MPC. We plan to evaluate this combination chemotherapy for MPC pts after progression of FOLFIRINOX in near the future. Clinical trial information: UMIN000009963.

Prospective phase II study of sunitinib rechallenge in metastatic renal cell carcinoma (mRCC): A G.I.O.N. trial.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e16081-e16081 ◽  
Author(s):  
Camillo Porta ◽  
Vittorio D. Ferrari ◽  
Paolo Andrea Zucali ◽  
Giuseppe Fornarini ◽  
Antonio Bernardo ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Treatment Options ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Cross Resistance ◽  
Stage Design ◽  
Free Survival ◽  
Prospective Phase ◽  
Grade 3

e16081 Background: Sunitinib is a 1st-line standard of care in mRCC. Lack of cross-resistance to sequential VEGF-targeting drugs and the possibility of a successful rechallenge with Sunitinib have been postulated. Whether mRCC patients (pts) could benefit from rechallenge with Sunitinib after progressing on 1st-line Sunitinib and 2nd-line Everolimus was the aim of this phase II study Methods: 39 mRCCpts were prospectively treated with Sunitinib (50 mg/daily, 4:2); main inclusion criteria were: histologically proven RCC with clear cell component, previous 1st-line Sunitinib with a Disease Control Rate lasting at least 10 months, 2nd-line Everolimus, and written informed consent. The primary end-point of this study was 6-months progression-free survival (PFS). A Simon’s 2-stage design was used; after testing Sunitinib on 12 pts in the first stage, the trial would have been terminated if 5 or fewer had a PFS of less than 6 months. Otherwise, the trial would have proceeded to the second stage, enrolling a total of 38 pts. If the total number of pts free of progression at 6 months would have been less than or equal to 18, Sunitinib would have been rejected Results: As a whole, 39 pts (30 males, 9 females) were enrolled. The study quickly moved from the first stage to its completion and ultimately succeeded; indeed, 6-months PFS was 60%, median PFS being 8.6 months (average: 9.59, range: 0.7-24.6 months). In terms of safety no unexpected toxicities were observed. Tx-related grade 3-4 AEs observed in ≥5% of the pts were: hand-foot skin reaction, fatigue, nausea, hypertriglyceridemia, hypophosphatemia, hypocalcemia, hyperglycemia, and neutropenia. One case each of myocardial infarction, atrial flutter and spontaneous pneumothorax were also reported, but resolved Conclusions: Despite an ineluctable time-lead-bias, median PFS on Sunitinib rechallenge was high (8.6 months), clearly showing that many pts may become sensitive again to VEGFRs-inhibition. Although many agents are presently available from 2nd-line on, in countries where treatment options are still limited, Sunitinib rechallenge could still represent a reasonable treatment option. EudraCT number: 2012-000473-23. Clinical trial information: 2012-000473-23.

RECIST and iRECIST criteria for the evaluation of nivolumab + ipilimumab combination in patients (pts) with microsatellite instability-high/mismatch repair-deficient (MSI/dMMR) metastatic colorectal cancer (mCRC): Results of the GERCOR NIPICOL phase II study.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 101-101 ◽  
Author(s):  
Romain Cohen ◽  
Jaafar Bennouna ◽  
Julie Henriques ◽  
Christophe Tournigand ◽  
Christelle De La Fouchardiere ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Checkpoint Inhibitors ◽  
Low Frequency ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Free Survival ◽  
Previously Treated ◽  
Grade 3 ◽  
Clinical Trial Information

101 Background: Immune checkpoint inhibitors (ICKi) are highly effective for MSI/dMMR mCRC pts. RECIST1.1 criteria are reported to underestimate response to ICKi. The GERCOR NIPICOL phase II study aimed to evaluate disease control rate (DCR) using RECIST1.1 and iRECIST for MSI/dMMR mCRC pts treated with nivolumab (NIVO) and ipilimumab (IPI). Methods: MSI/dMMR mCRC pts previously treated with fluoropyrimidines (FP), oxaliplatin (OX) and irinotecan (IRI) ± targeted therapies received NIVO 3 mg/kg + IPI 1 mg/kg Q3W for 4 cycles then NIVO 3 mg/kg Q2W until progression or a maximum of 20 cycles. CT-scan tumor assessments were done every 6 weeks during 24 weeks and then every 12 weeks. Primary objective was DCR at 12 weeks (12wDCR) according to RECIST1.1 and iRECIST by central review. Response rates and progression-free survival (PFS) by central review were secondary objectives. A one-stage Fleming design was used with a targeted improvement of 12wDCR from 70% to 85%. Results: Of 57 pts included between Dec 2017 and Nov 2018, 43.9% had received ≥ 3 prior lines including FP (100%), OX (100%), IRI (95.5%), antiangiogenics (57.9%) and anti-EGFRs (45.6%). 17.5% of pts had BRAF mutation and 27.5% Lynch syndrome. Grade 3-4 treatment-related adverse events were reported in 49.1% of pts, mainly hepatitis (12.3%). 12wDCR was 86.0% and 87.7% using RECIST1.1 and iRECIST respectively, with only 1 pseudo-progression (1.8%) observed during the first 12 weeks, and one later. Kappa coefficient between RECIST and iRECIST 12wDCR was 0.92 (95%CI 0.77-1.0). Best observed responses with RECIST1.1/iRECIST were: 2/2 complete responses (3.5/3.5%), 19/19 partial responses (33.3/33.3%), 30/31 stable diseases (52.6/54.4%) and 3/2 disease progressions (5.3/3.5%), with 3 pts not evaluable (cancer-related deaths before first evaluation). Conclusions: Combination of NIVO and IPI in MSI/dMMR mCRC is associated with a low frequency of pseudo-progression and high DCR rate. PFS will be evaluated in Dec 2019, with all pts having completed the predefined 1-year of ICKi therapy. Clinical trial information: NCT033501260.

scholarly journals Multicenter Phase II Study of a New Effective S-1 and Irinotecan Combination Schedule in Patients with Unresectable Metastatic or Recurrent Colorectal Cancer

2013 ◽  
Vol 7 ◽  
pp. CMO.S10769 ◽  
Author(s):  
◽  
Yutaka Ogata ◽  
Takaho Tanaka ◽  
Yoshito Akagi ◽  
Nobuya Ishibashi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Phase Ii ◽  
Median Overall Survival ◽  
Overall Response Rate ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Recurrent Colorectal Cancer ◽  
Free Survival ◽  
Multicenter Phase ◽  
Grade 3

Introduction This multicenter phase II study determined the efficacy and safety of new daily oral S-1 and weekly irinotecan (CPT-11) combination schedule in patients with previously untreated advanced or recurrent colorectal cancer. Patients and Methods Patients received first-line chemotherapy comprising S-1 80 mg/m2/day given on days 3 to 7, 10 to 14, and 17 to 21 and 60 mg/m2 CPT-11 administered intravenously on days 1, 8, and 15 of a 28-day cycle. Results A total of 45 eligible patients were enrolled in this study. The overall response rate was 48.9%. Median progression-free survival and median overall survival was 8.1 months and 20.9 months, respectively. The rates of grade 3 or 4 toxicity were as follows: neutropenia, 8.9%; anemia, 4.4%; anorexia, 6.7%; and diarrhea, 6.7%. Conclusions This new S-1 and irinotecan combination schedule appeared to be an effective, well-tolerated, and convenient regimen in patients with advanced colorectal cancer as compared with conventional regimens such as FOLFIRI and IRIS.

scholarly journals Nivolumab and Ipilimumab in Metastatic Uveal Melanoma: Results From a Single-Arm Phase II Study

2020 ◽  
pp. JCO.20.00605 ◽  
Author(s):  
Meredith S. Pelster ◽  
Stephen K. Gruschkus ◽  
Roland Bassett ◽  
Dan S. Gombos ◽  
Michael Shephard ◽  
...  
Keyword(s):  
Uveal Melanoma ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Single Agent ◽  
Progression Free Survival ◽  
Complete Response ◽  
Combination Regimen ◽  
Poor Overall Survival ◽  
Free Survival ◽  
Grade 3

PURPOSE Metastatic uveal melanoma has poor overall survival (OS) and no approved systemic therapy options. Studies of single-agent immunotherapy regimens have shown minimal benefit. There is the potential for improved responses with the use of combination immunotherapy. PATIENTS AND METHODS We conducted a phase II study of nivolumab with ipilimumab in patients with metastatic uveal melanoma. Any number of prior treatments was permitted. Patients received nivolumab 1 mg/kg and ipilimumab 3 mg/kg for four cycles, followed by nivolumab maintenance therapy for up to 2 years. The primary outcome of the study was overall response rate (ORR) as determined by RECIST 1.1 criteria. Progression-free survival (PFS), OS, and adverse events were also assessed. RESULTS Thirty-five patients were enrolled, and 33 patients were evaluable for efficacy. The ORR was 18%, including one confirmed complete response and five confirmed partial responses. The median PFS was 5.5 months (95% CI, 3.4 to 9.5 months), and the median OS was 19.1 months (95% CI, 9.6 months to NR). Forty percent of patients experienced a grade 3-4 treatment-related adverse event. CONCLUSION The combination regimen of nivolumab plus ipilimumab demonstrates activity in metastatic uveal melanoma, with deep and sustained confirmed responses.

Phase II study of ifosfamide, carboplatin, and etoposide in patients with a first recurrence of glioblastoma multiforme

2010 ◽  
Vol 112 (1) ◽  
pp. 50-56 ◽  
Author(s):  
Tomokazu Aoki ◽  
Tomohiko Mizutani ◽  
Kuniharu Nojima ◽  
Takehisa Takagi ◽  
Ryosuke Okumura ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Recurrent Glioblastoma Multiforme ◽  
Open Label ◽  
Free Survival ◽  
Quality Life ◽  
First Recurrence

Object The prognosis of recurrent glioblastoma multiforme (GBM) remains unsatisfactory. The authors conducted a Phase II study of ifosfamide, carboplatin, and etoposide (ICE) for a first recurrence of GBM to determine whether it prolonged a patient's good-quality life. Methods This trial was an open-label, single-center Phase II study. Forty-two patients with a first GBM relapse after surgery followed by standard radiotherapy (60 Gy) and first-line temozolomide- or nimustine-based chemotherapy were eligible to participate. The primary end point was progression-free survival at 6 months after the ICE treatment (PFS-6), and secondary end points were response rate, toxicity, and overall survival. Chemotherapy consisted of ifosfamide (1000 mg/m2 on Days 1, 2, and 3), carboplatin (110 mg/m2 on Day 1), etoposide (100 mg/m2 on Days 1, 2, and 3), every 6 weeks. Results Progression-free survival at 6 months after ICE treatment was 35% (95% CI 22–50%). The median duration of PFS was 17 weeks (95% CI 10–24 weeks). The response rate was 25% (95% CI 9–34%). Adverse events were generally mild and consisted mainly of alopecia. Conclusions This regimen was well tolerated and has some activity and could be one of the options for patients with recurrent GBM.

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