An Increasing Role for Trabectedin in Gynecological Cancers: Efficacy in Uterine Sarcomas

2011 ◽  
Vol 21 (Supp 1) ◽  
pp. S3-S5 ◽  
Author(s):  
Isabelle Ray-Coquard
Keyword(s):  
Phase Ii ◽  
Progression Free Survival ◽  
Uterine Leiomyosarcoma ◽  
Uterine Sarcomas ◽  
Free Survival ◽  
Phase Ii Studies ◽  
Prospective Phase ◽  
Pretreated Patients ◽  
To Receive ◽  
A Current

Trabectedin is indicated for patients with advanced soft tissue sarcoma after failure of treatment with anthracyclines and ifosfamide or for patients who are unsuited to receive these agents. The agent has shown activity in patients with advanced uterine leiomyosarcoma, with an acceptable safety profile. Thus, the results of phase II studies have shown that treatment with trabectedin results in 30% progression-free survival at 6 months. More than 50% of these pretreated patients were alive at 1 year. The response rate, progression-free survival, and overall survival compared favorably with other single agents (eg, doxorubicin, ifosfamide, and gemcitabine), with clinical benefit in 50% of patients in second-line treatment. These results are being confirmed in a current prospective phase II study in first-line uterine leiomyosarcoma combining trabectedin with doxorubicin.

Phase II Trial of Weekly Intravenous Gemcitabine With Continuous Infusion Fluorouracil in Patients With Metastatic Renal Cell Cancer

2000 ◽  
Vol 18 (12) ◽  
pp. 2419-2426 ◽  
Author(s):  
Brian I. Rini ◽  
Nicholas J. Vogelzang ◽  
Mary C. Dumas ◽  
James L. Wade ◽  
David A. Taber ◽  
...  
Keyword(s):  
Continuous Infusion ◽  
Phase Ii ◽  
Renal Cell ◽  
Response Rate ◽  
Cell Cancer ◽  
Objective Response ◽  
Progression Free Survival ◽  
Free Survival ◽  
Phase Ii Studies ◽  
Metastatic Rcc

PURPOSE: To determine the clinical response rate of the combination of weekly intravenous (IV) gemcitabine with continuous infusion fluorouracil (5-FU) in patients with metastatic renal cell carcinoma (RCC). PATIENTS AND METHODS: Between June 1998 and February 1999, 41 patients with metastatic RCC were enrolled onto this multi-institutional phase II study of gemcitabine 600 mg/m2 over 30 minutes on days 1, 8, and 15 and 5-FU 150 mg/m2/d via continuous IV infusion through a permanent catheter on days 1 to 21 of a 28-day cycle. Patients had a Cancer and Leukemia Group B performance status of 0 or 1, with a median time since diagnosis of metastatic disease of 10 months (range, 0 to 129 months). Thirty-three patients (80%) had multiple metastatic sites, and 34 patients (83%) had prior chemotherapy or immunotherapy. RESULTS: Of the 39 assessable patients, there were no complete responses but seven partial responses (objective response rate = 17%; 95% confidence interval, 8% to 34%). Five minor responses (25% to 50% decreased tumor size) were also observed. The duration of response for the seven partial responders was 2, 3, 7, 8, 10, 11, and 14 months. Median progression-free survival for the gemcitabine/5-FU group was 28.7 weeks versus 8 weeks for a similar cohort of patients treated on previous phase II studies at the University of Chicago (P = .008). The regimen was well tolerated, with fatigue, mucositis, nausea/vomiting, and grade 2 hematologic toxicities being most common. CONCLUSION: Weekly gemcitabine with continuous infusion 5-FU is an active combination in patients with metastatic RCC. Therapy was well tolerated and produced an improvement in progression-free survival over historical controls.

Four Years of Follow-Up of 1027 Patients with Late Chronic Phase (L-CP), Accelerated Phase (AP), or Blast Crisis (BC) Chronic Myeloid Leukemia (CML) Treated with Imatinib in Three Large Phase II Trials.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 23-23 ◽  
Author(s):  
Richard T. Silver ◽  
Moshe Talpaz ◽  
Charles L. Sawyers ◽  
Brian J. Druker ◽  
Andreas Hochhaus ◽  
...  
Keyword(s):  
Phase Ii ◽  
Chronic Phase ◽  
Progression Free Survival ◽  
Cytogenetic Response ◽  
Imatinib Treatment ◽  
Phase Ii Trials ◽  
Free Survival ◽  
Phase Ii Studies ◽  
Large Phase

Abstract Background This report updates the results of 3 large phase II studies of the orally available BCR-ABL tyrosine kinase inhibitor imatinib for patients (pts) in AP, BC and late chronic phase (L-CP) CML failing prior interferon therapy (Kantarjan et al, ASH 2003; Talpaz et al, ASH 2003). Methods Between August 1999 and June 2000, 1027 pts were enrolled in phase II trials for CML in L-CP (n=532), AP (n=235) or BC (n=260). Pts in L-CP were treated with 400 mg/day and pts in AP or BC with either 400 or 600 mg/day. Dose escalation up to 800 mg/d was allowed in the late-chronic phase study. Pts with a confirmed diagnosis of AP (n=181), BC (n=229) and late-chronic phase (n=454) were evaluated for efficacy. All pts were evaluated for safety. The median time from initial diagnosis to study entry was 32 months for L-CP pts. Results As of 31-Jul-03, 5% patients with BC, 25% of CML-AP and 64% of L-CP patients still remain on treatment. At the recommended dose of 600 mg, an estimated 40% (AP) and 7% (BC) of patients remained progression-free at 36 months, and an estimated 55% (AP) and 14% (BC) patients were alive at 36 months after initiation of imatinib. The 3-year survival rates for pts with AP with a major cytogenetic response at 3 months were 85% vs. 52% for pts with no response (p<0.001). In L-CP patients with a median follow-up of 40 months, 65% of patients achieved a major cytogenetic response, which was complete in 52%. The cytogenetic responses were durable with an estimated 82% of the pts in continuos major cytogenetic response at 3 years. The estimated rates of progression-free survival and overall survival at 3 years were 80% and 88%. Pts with at least a minor cytogenetic response at 6 months ≤65% Ph+ cells) had an estimated 3-year survival rate of 96% vs. 86% for pts with a ( minimal response and 81% for pts with no cytogenetic response (p<0.001). Conclusion In large phase II studies, continuous imatinib treatment is safe and has improved progression-free survival of patients at all stages of CML. Responses to imatinib are durable and are predictive of long-term outcomes. These results will be further updated at the meeting using a data base lock planned for 20-Sept-04 (using data collected up to 31-July-04, i.e. more than 4 years after the last pts enrollment).

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.

SAPPHIRE: A randomized phase II study of mFOLFOX6 + panitumumab versus 5-FU/LV + panitumumab after 6 cycles of frontline mFOLFOX6 + panitumumab in patients with colorectal cancer.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 729-729 ◽  
Author(s):  
Masato Nakamura ◽  
Yoshinori Munemoto ◽  
Masazumi Takahashi ◽  
Masahito Kotaka ◽  
Hiroaki Kuroda ◽  
...  
Keyword(s):  
Phase Ii ◽  
Progression Free Survival ◽  
Wild Type ◽  
Primary Analysis ◽  
Free Survival ◽  
Randomized Phase Ii ◽  
Term Administration ◽  
To Receive ◽  
Clinical Trial Information

729 Background: FOLFOX therapy, an infusion of 5-fluorouracil (5-FU) with leucovorin in combination with oxaliplatin (OXA), is a common first-line chemotherapy regimen for unresectable, advanced or recurrent colorectal carcinoma (CRC). However, long-term administration of OXA is associated with peripheral neuropathy (PN); decreasing treatment length of OXA may be beneficial without reducing its efficacy. Methods: Chemotherapy-naïve pts aged ≥20 yrs with RAS wild-type advanced/recurrent CRC were enrolled to receive 6 cycles of panitumumab (Pmab) + mFOLFOX6 once every 2 wks. Pts who completed 6 cycles of Pmab + mFOLFOX6 and confirmed no progressive disease were subsequently randomized 1:1 to continue to receive Pmab + mFOLFOX6 (arm 1) or Pmab + 5-FU/LV (arm 2). The primary endpoint was progression-free survival (PFS) rate at 9 mos after randomization. The threshold PFS rate was defined as 30%, and the expected rate was set at 50%, with a 90% power and a 1-sided alpha value of 0.10. In the primary analysis, a binomial test was conducted separately for each arm. This study was designed as a phase II randomized screening comparison study which does not use direct comparison for the primary analysis. Results: Of 164 enrolled pts who received initial Pmab + mFOLFOX6 treatment, 56 were randomized to arm 1 and 57 to arm 2. PFS rates at 9 mos after randomization were significantly higher than the defined threshold at 44.6% (80% CI, 36.4–53.2) in arm 1 and 47.4% (39.1–55.8) in arm 2. Median PFS after randomization was 9.1 (8.6–11.2) and 9.3 (6.0–13.0) mos, respectively. Grade ≥2 PNs occurred in 6 (10.7%) and 1 (1.8%) pts in arms 1 and 2, respectively. Serious AEs occurred in 14 (25.0%) pts in arm 1 and in 9 (16.7%) pts in arm 2. Conclusions: The results of this trial suggest that Pmab + 5-FU/LV after 6 fixed-cycles of Pmab + mFOLFOX6 may be a treatment option in pts with RAS wild type chemotherapy-naïve advanced/recurrent CRC. Pts treated with Pmab + 5-FU/LV had a lower occurrence of grade ≥2 PNs compared with Pmab + mFOLFOX6. Clinical trial information: NCT02337946.

Randomized Multicenter Phase II Trial of Two Different Schedules of Capecitabine Plus Oxaliplatin as First-Line Treatment in Advanced Colorectal Cancer

2003 ◽  
Vol 21 (7) ◽  
pp. 1307-1312 ◽  
Author(s):  
Werner Scheithauer ◽  
Gabriela V. Kornek ◽  
Markus Raderer ◽  
Birgit Schüll ◽  
Katharina Schmid ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Survival Time ◽  
Phase Ii ◽  
Advanced Colorectal Cancer ◽  
Response Rate ◽  
Progression Free Survival ◽  
Synergistic Activity ◽  
Free Survival ◽  
Multicenter Phase ◽  
To Receive

Purpose: Capecitabine and oxaliplatin, two new agents with potential synergistic activity, have demonstrated promising antitumor efficacy in advanced colorectal cancer (ACC). Preclinical and clinical evidence indicating that dose intensification of the oral fluorouracil prodrug might result in improved therapeutic results led us to the present randomized multicenter phase II study. Patients and Methods: Eighty-nine patients with bidimensionally measurable ACC previously untreated for metastatic disease were randomly allocated to receive oxaliplatin 130 mg/m2 day 1 plus capecitabine 2,000 mg/m2/d days 1 to 14 every 3 weeks (arm A) or to receive oxaliplatin 85 mg/m2 days 1 and 14 combined with capecitabine 3,500 mg/m2 days 1 to 7 and 14 to 21 every 4 weeks (arm B). In both treatment arms, chemotherapy was continued for a total of 6 months unless there was prior evidence of progression of disease. Results: Patients allocated to the high-dose capecitabine combination arm B had a higher radiologically confirmed response rate (54.5% v 42.2%) and a significantly longer median progression-free survival time than those allocated to control arm A (10.5 v 6.0 months; P = .0013). Median overall survival times cannot be calculated for either treatment arm at this point. Despite a 34% higher dose intensity of capecitabine in arm B, there was no difference in hematologic toxicity between treatment arms (neutropenia/thrombocytopenia: 60%/43% in arm B v 56%/33% in arm A). Similarly, the incidence rate and degree of nonhematologic adverse events were comparable: The most commonly encountered symptoms (all grades, arm A and arm B) included nausea/emesis (A: 58%; B: 62%), diarrhea (A: 44%; B: 31%), peripheral sensory neuropathy (A: 80%; B: 83%), and fatigue (A: 40%; B: 50%). Conclusion: Results of this study indicate that both combination regimens are feasible, tolerable, and clinically active. The dose-intensified bimonthly capecitabine arm, however, seems to be more effective in increasing both response rate and progression-free survival time.

scholarly journals Preoperative chemotherapy and carbon ions therapy for treatment of resectable and borderline resectable pancreatic adenocarcinoma: a prospective, phase II, multicentre, single-arm study

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Viviana Vitolo ◽  
Lorenzo Cobianchi ◽  
Silvia Brugnatelli ◽  
Amelia Barcellini ◽  
Andrea Peloso ◽  
...  
Keyword(s):  
Pancreatic Adenocarcinoma ◽  
Phase Ii ◽  
Progression Free Survival ◽  
Long Term Results ◽  
Carbon Ions ◽  
Borderline Resectable ◽  
Free Survival ◽  
Carbon Ion ◽  
Local Progression ◽  
Prospective Phase

Abstract Background Pancreatic adenocarcinoma is a high-mortality neoplasm with a documented 5-years-overall survival around 5%. In the last decades, a real breakthrough in the treatment of the disease has not been achieved. Here we propose a prospective, phase II, multicentre, single-arm study aiming to assess the efficacy and the feasibility of a therapeutic protocol combining chemotherapy, carbon ion therapy and surgery for resectable and borderline resectable pancreatic adenocarcinoma. Method The purpose of this trial (PIOPPO Protocol) is to assess the efficacy and the feasibility of 3 cycles of FOLFIRINOX neoadjuvant chemotherapy followed by a short-course of carbon ion radiotherapy (CIRT) for resectable or borderline resectable pancreatic adenocarcinoma patients. Primary outcome of this study is the assessment of local progression free survival (L-PFS). The calculation of sample size is based on the analysis of the primary endpoint “progression free survival” according to Fleming’s Procedure. Discussion Very preliminary results provide initial evidence of the feasibility of the combined chemotherapy and CIRT in the neoadjuvant setting for resectable or borderline resectable pancreatic cancer. Completion of the accrual and long term results are awaited to see if this combination of treatment is advisable and will provide the expected benefits. Trial registration ClinicalTrials.gov Identifier: NCT03822936 registered on January 2019.

scholarly journals Prolonged progression-free survival after consolidating second or later remissions of neuroblastoma with Anti-GD2immunotherapy and isotretinoin: a prospective Phase II study

2015 ◽  
Vol 4 (7) ◽  
pp. e1016704 ◽  
Author(s):  
Brian H Kushner ◽  
Irina Ostrovnaya ◽  
Irene Y Cheung ◽  
Deborah Kuk ◽  
Kim Kramer ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Free Survival ◽  
Prospective Phase

A randomized phase II trial of gemcitabine plus treosulfan versus treosulfan alone in patients with metastatic uveal melanoma

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 8018-8018
Author(s):  
A. H. Schmittel ◽  
M. Schmidt-Hieber ◽  
N. E. Bechrakis ◽  
R. Schuster ◽  
J. M. Siehl ◽  
...  
Keyword(s):  
Uveal Melanoma ◽  
Phase Ii ◽  
Randomized Trials ◽  
Phase Ii Trial ◽  
Progression Free Survival ◽  
Free Survival ◽  
Randomized Phase Ii ◽  
Melanoma Patients ◽  
To Receive

8018 Background: In-vitro studies have suggested synergy of gemcitabine and treosulfan against uveal melanoma cells, and the combination of both drugs in the GeT regimen has shown activity in metastatic uveal melanoma patients. This first randomized phase II trial in this rare disease compared the efficacy of the gemcitabine/treosulfan (GeT) combination versus treosulfan alone. Methods: Chemotherapy-naïve patients with proven metastatic uveal melanoma were randomly assigned to receive 1000mg/m2 gemcitabine plus 3500mg/m2 of treosulfan (GeT) or 3500mg/m2 of treosulfan (T) alone. Chemotherapy was administered on days 1 and 8 in both arms, cycles were repeated on day 29. In the absence of disease progression a maximum of 6 cycles were administered. Results: Forty-eight patients were randomized. Seven confirmed stable diseases and one partial remission were observed in 24 patients (PR+SD=33%) treated with the GeT regimen, whereas no PR and only 3 SD (13%) were observed in the treosulfan alone arm (p=0.08). Median progression free survival was 3 months (95% CI 1.1–4.9) in the GeT arm and 2 months (95% CI interval 1.7–2.3) in the treosulfan arm (p=0.008, log-rank). Six and 12 months progression free survival was 34.8% and 17.9% and 16.7% and 0% always favouring the GeT arm. Conclusions: This first prospectively randomized trial in metastatic uveal melanoma showed a superior PFS and a trend for a higher response/stabilization rate of the GeT combination over treosulfan alone. Therefore GeT will further be investigated in randomized trials. No significant financial relationships to disclose.

scholarly journals A randomized double-blind phase II study evaluating the role of maintenance therapy with cabozantinib in high-grade uterine sarcoma after stabilization or response to doxorubicin ± ifosfamide following surgery or in metastatic first line treatment (EORTC62113)

2020 ◽  
Vol 30 (10) ◽  
pp. 1633-1637
Author(s):  
Isabelle Ray-Coquard ◽  
Helen Hatcher ◽  
Emmanuelle Bompas ◽  
Antonio Casado ◽  
Annekke Westermann ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Phase Ii ◽  
Maintenance Treatment ◽  
Progression Free Survival ◽  
Low Grade ◽  
High Grade ◽  
Standard Chemotherapy ◽  
Exclusion Criteria ◽  
Uterine Sarcomas ◽  
Free Survival

BackgroundUterine sarcomas are a group of rare tumors that include different subtypes. Patients with histopathological high-grade diseases are at high-risk of recurrence or progression, and have a poor prognosis. We aim to explore the most appropriate management in patients with uterine high-grade sarcomas.Primary objectiveTo assess the efficacy of maintenance treatment with cabozantinib in patients with high-grade uterine sarcomas who achieved clinical benefit after standard chemotherapy.Study hypothesisMaintenance treatment with cabozantinib after standard chemotherapy given as an adjuvant treatment after curative surgery, or in locally advanced or metastatic disease, increases progression-free survival compared with placeboTrial designThis is a randomized double blinded phase II trial.Major inclusion/exclusion criteriaThe study is enrolling adult patients with high-grade undifferentiated uterine sarcomas, high-grade endometrial stromal sarcomas, high-grade leiomyosarcoma, and high-grade adenosarcoma, FIGO (Federation International gynecologue Obstétricien) stage II/III to IV in stable disease or who achieved complete or partial response with doxorubicin ± ifosfamide, who are assigned 1:1 to 60 mg daily cabozantinib (experimental arm) or placebo (control arm), as maintenance therapy. Exclusion criteria include low-grade sarcoma.Primary endpointProgression-free survival at 4 months.Sample sizeThe study plans to enroll 90 patients to allow the randomization of 54 patients to detect an improvement in 4-month progression-free survival from 50% to 80% with 15% significance level and 85% power. Estimated dates for accrual completion: recruitment for the trial started in February 2015, and has currently enrolled 83 patients, of whom 35 patients have been randomized. The end of recruitment is anticipated for December 2020.Trial registration numberClinicalTrials.gov, number NCT01979393.

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