Randomized Phase II Study of Temozolomide Given Every 8 Hours or Daily With Either Interferon Alfa-2b or Thalidomide in Metastatic Malignant Melanoma

2003 ◽  
Vol 21 (13) ◽  
pp. 2551-2557 ◽  
Author(s):  
S. Danson ◽  
P. Lorigan ◽  
A. Arance ◽  
A. Clamp ◽  
M. Ranson ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Metastatic Malignant Melanoma ◽  
Interferon Alfa ◽  
Randomized Phase Ii ◽  
Disease Stabilization ◽  
Grade 3 ◽  
Weekly Cycles ◽  
To Receive

Purpose: Temozolomide is an imidazotetrazine with a mechanism of action similar to dacarbazine and equivalent activity in melanoma. It is well tolerated and is a candidate for combination chemotherapy and schedule manipulation. In this study, we combined temozolomide with interferon alfa-2b and, separately, with thalidomide, and we administered temozolomide alone in a compressed schedule. The objectives of this randomized phase II, two-center study were to determine response rates, overall survival, and tolerability of the regimens in patients with advanced metastatic melanoma. Patients and Methods: One hundred eighty-one patients with metastatic melanoma were randomly assigned to receive up to six 4-weekly cycles consisting of temozolomide 200 mg/m2 every 8 hours for five doses, or temozolomide 200 mg/m2 daily for days 1 to 5 plus interferon alfa-2b 5 MU (million International Units) subcutaneously three times a week, or temozolomide 150 mg/m2 (increased after one cycle to 200 mg/m2) daily on days 1 to 5 plus thalidomide 100 mg daily days 1 to 28. Results: The treatment arms were well balanced for known prognostic factors. Median survival was 5.3 months for 8-hourly temozolomide, 7.7 months for temozolomide/interferon, and 7.3 months for temozolomide/thalidomide; and 1-year survivals were 18%, 26%, and 24%, respectively. Response or disease stabilization occurred in 20% of patients (95% confidence interval [CI], 10% to 33%) given 8-hourly temozolomide, 21% (95% CI, 12% to 33%) given temozolomide/interferon, and 25% (95% CI, 15% to 38%) given temozolomide/thalidomide. Grade 3 or 4 nonhematologic toxicities were similar in each arm except for infection, which was more frequent with 8-hourly temozolomide. There were fewer instances of grade 3 or 4 myelotoxicity with temozolomide/thalidomide. Conclusion: Of the three regimens tested, the combination of temozolomide and thalidomide seems the most promising for future study.

A randomized phase II study comparing oral S-1 plus 24-hour infusion of irinotecan (Iri) and bevacizumab (Bev) with FOLFIRI plus bevacizumab in patients with metastatic colorectal cancer (MCRC).

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 613-613
Author(s):  
Sotaro Sadahiro ◽  
Toshiyuki Suzuki ◽  
Akira Tanaka ◽  
Kazutake Okada ◽  
Gota Saito ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Line Treatment ◽  
First Line ◽  
Randomized Phase Ii ◽  
Grade 3 ◽  
To Receive ◽  
First Line Treatment

613 Background: FOLFOX or FOLFIRI plus Bev is a first-line treatment for MCRC. Recent studies have confirmed that oral S-1 combined with Iri and Bev is equivalent to FOLFIRI plus Bev. Iri is usually administered as a short-term 90-min. infusion. However, the cytocidal activity is S-phase specific, and carboxylesterases, that convert Iri into SN-38, are less likely to become saturated when Iri is given as a long-term infusion. Therefore, a low dose of Iri given as a long-term infusion is expected to enhance antitumor activity. We conducted a randomized phase II study to compare this regimen with FOLFIRI plus Bev. Methods: The subjects comprised 120 chemotherapy-naïve patients with MCRC. The study group received 24-hr infusion of Iri at a dose of 125 mg/m2 on days 1 and 15, combined with oral S-1 80 mg/m2 on days 1 to 14. The FOLFIRI group received Iri at a dose of 150 mg/m2, 5-FU given at a dose of 400 mg/m2 as a bolus injection and at a dose of 2400 mg/m2 as a 46 hr-infusion, 200 mg/m2 of leucovorin on days 1 and 15. Bev was given at a dose of 5.0 mg/kg on days 1 and 15 in both groups. Treatment was repeated every 4 weeks. The primary endpoint was the 1 y progression-free survival (PFS). Secondary endpoints were PFS, response rates (RR), overall survival (OS), and adverse events (AEs). Results: From October 2013 through December 2017, a total of 61 patients assigned to receive IRIS plus Bev (the A group) and 59 patients assigned to receive FOLFIRI plus Bev (the B group) were included in the analysis. The 1y RFS was 37.3% in the A group and 17.0% in the B group (p = 0.0281). The PFS was 10.2 mon in the A group and 10.0 mon in the B group, and the median OS was 27.0 mon and 28.6 mon, respectively (p = 0.26, p = 0.68). RR was significantly higher in the A group (87.0%) than in the B group (61.7%) (p = 0.005). The main grade 3 or 4 AEs were neutropenia (27.8%) and diarrhea (11.1%) in the A group and neutropenia (23.4%) and leukopenia (6.4%) in the B group. Conclusions: Our results showed that Iri, given biweekly as a 24-hour infusion in combination with oral S-1 and Bev, is a highly effective and well-tolerated regimen for the first-line treatment of MCRC. Clinical trial information: UMIN000014664.

Randomized Multicenter Phase II Study Comparing a Combination of Fluorouracil and Folinic Acid and Alternating Irinotecan and Oxaliplatin With Oxaliplatin and Irinotecan in Fluorouracil-Pretreated Metastatic Colorectal Cancer Patients

2001 ◽  
Vol 19 (22) ◽  
pp. 4195-4201 ◽  
Author(s):  
Yves Bécouarn ◽  
Erick Gamelin ◽  
Bruno Coudert ◽  
Sylvie Négrier ◽  
Jean-Yves Pierga ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Folinic Acid ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Survival Times ◽  
Activity Data ◽  
Randomized Phase Ii ◽  
Grade 3 ◽  
Intent To Treat ◽  
Colorectal Cancer Patients

PURPOSE: To assess antitumor activity and safety of two regimens in advanced colorectal cancer (CRC) patients with proven fluorouracil (5-FU) resistance in a randomized phase II study: 5-FU/folinic acid (FA) combined with alternating irinotecan (also called CPT-11) and oxaliplatin (FC/FO tritherapy), and an oxaliplatin/irinotecan (OC) combination. PATIENTS AND METHODS: Sixty-two patients were treated: arm FC/FO (32 patients) received, every 4 weeks, FA 200 mg/m2 followed by a 400-mg/m2 5-FU bolus injection, then a 600-mg/m2 continuous infusion of 5-FU on days 1 and 2 every 2 weeks administered alternately with irinotecan (180 mg/m2 on day 1) and oxaliplatin (85 mg/m2 on day 15). Arm OC (30 patients) received oxaliplatin 85 mg/m2 and irinotecan 200 mg/m2 every 3 weeks. RESULTS: In an intent-to-treat analysis, two partial responses lasting 10.7 and 16 months were observed with the tritherapy regimen, and seven (median duration, 11 months; range, 10.6 to 11.4 months) were observed with the bitherapy regimen. Median progression-free and overall survival times were 8.2 and 9.8 months, respectively, in the FC/FO arm and 8.5 and 12.3 months, respectively, in the OC arm. Main grade 3/4 toxicities were, respectively, neutropenia, 53% and 47%; febrile neutropenia, 13% and 3%; diarrhea, 19% and 10%; vomiting, 6% and 13%; and neurosensory toxicity, 3% and 3%. No treatment-related deaths occurred. CONCLUSION: The every-3-weeks OC combination is safe and active in advanced 5-FU–resistant CRC patients. The lower activity data seen with the tritherapy regimen may be related to the lower dose intensities of irinotecan and oxaliplatin in this schedule.

Phase II study of continuous infusion fluorouracil and interferon alfa-2b in the palliation of malignant neuroendocrine tumors.

1995 ◽  
Vol 13 (6) ◽  
pp. 1486-1492 ◽  
Author(s):  
H J Andreyev ◽  
P Scott-Mackie ◽  
D Cunningham ◽  
V Nicolson ◽  
A R Norman ◽  
...  
Keyword(s):  
Continuous Infusion ◽  
Neuroendocrine Tumors ◽  
Phase Ii ◽  
Advanced Disease ◽  
Phase Ii Study ◽  
Symptom Control ◽  
Objective Response ◽  
Interferon Alfa ◽  
Carcinoid Tumors ◽  
Disease Stabilization

PURPOSE AND METHODS Twenty-four patients with rapidly progressive neuroendocrine tumors were treated with a new regimen of continuous infusion fluorouracil for 20 weeks (200 mg/m2/d) together with interferon alfa-2b (5 MU three times per week). Maintenance interferon alfa at the same dose was continued after the initial 20-week period. RESULTS Of 15 patients with carcinoid tumors, seven (47%) had an objective response, with a median duration of 20.5 months (range, 8.5 to 41), and five (33%) had stabilization of disease for between 3.5 and 42 months. Improvement in symptoms was reported by 10 patients (67%). Three early deaths occurred, all in patients with advanced disease. Of nine patients with neuroendocrine tumors other than carcinoid, three (33%) had an objective response that lasted 2.5 to 24.5 months, and five had disease stabilization for between 2.5 and 16 months. CONCLUSION These data, particularly in respect to carcinoid tumors, are encouraging, especially since serious complications from treatment were limited. This regimen is not generally toxic, is well tolerated, and offers useful palliation and symptom control in patients with disease that does not respond to simple pharmacologic manipulations.

Long-Term Follow Up Of a Randomized Phase II Study Of The JAK2-Selective Inhibitor Fedratinib (SAR302503) In Patients With Myelofibrosis (MF)

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4047-4047 ◽  
Author(s):  
Animesh Pardanani ◽  
Ayalew Tefferi ◽  
Catriona HM Jamieson ◽  
Nashat Y Gabrail ◽  
Claudia Lebedinsky ◽  
...  
Keyword(s):  
High Risk ◽  
Disease Progression ◽  
Phase Ii ◽  
Research Funding ◽  
Phase Ii Study ◽  
Hematologic Toxicity ◽  
Costal Margin ◽  
Spleen Volume ◽  
Randomized Phase Ii ◽  
Grade 3

Abstract Background We previously reported that patients with MF enrolled in a randomized Phase II study of fedratinib (SAR302503) (ARD11936; NCT01420770) had clinically meaningful reductions in splenomegaly and improvements in MF-associated constitutional symptoms after 24 weeks of treatment (Haematologica 2013;98:S1113). Here, we report updated efficacy and safety results from this study after 48 weeks of treatment (end of Cycle 12). Methods Patients with intermediate risk-2 or high-risk MF were randomized to receive once-daily fedratinib at doses of 300 mg, 400 mg, or 500 mg, for consecutive 4-weekly cycles, until disease progression or unacceptable toxicity. Eligible patients were aged ≥18 years, with palpable splenomegaly (5 cm below costal margin), and a platelet count ≥50 × 109/L. The primary measure for this study was percent change in spleen volume from baseline at the end of Cycle 3 (Blood 2012:120;Abstract 2837. Haematologica 2013;98:S1113). Endpoints for the current analysis included spleen response (≥35% reduction in spleen volume from baseline, assessed by a blinded independent central review by MRI), safety, and changes in bone marrow fibrosis (BMF). Results A total of 31 patients were randomized and treated: median age 63 years, 52% male, 58% primary MF, 58% high-risk MF, 90% JAK2V617F positive. The median numbers of treatment cycles were 12, 14, and 13 in the 300 mg, 400 mg and 500 mg dose groups, respectively, with median durations of exposure of 48.2, 56.2, and 52.4 weeks. At the cut-off date for this analysis, 21 patients (68%) remained on treatment; the most common reasons for treatment discontinuation were adverse events (AEs) (n=5) and withdrawal of consent (n=2). Overall, 58% (18/31) of patients achieved a spleen response at any time during treatment. The median spleen response duration was >35 weeks at all doses (Table). At Week 48, a spleen response was achieved by 30% (3/10), 80% (8/10), and 45% (5/11) of patients in the 300 mg, 400 mg, and 500 mg groups, respectively. Responses were generally maintained across all treatment groups. From Week 24 to Week 48 two additional patients achieved a spleen response (both in the 400 mg group), while one patient in the 500 mg group did not maintain a response (this patient had a fedratinib dose reduction to 200 mg). Changes in BMF up to Week 48 are being evaluated. The most common non-hematologic AE was diarrhea, with a Grade 3 rate of 13% (4/31 patients) but no Grade 4 cases were recorded. The rates of diarrhea decreased after the first cycle of treatment; from Cycle 2, the incidence of diarrhea (any grade) did not exceed 16% (5/31) at any cycle, and only one case of diarrhea was reported at Week 48 (end of Cycle 12). Anemia was the most-common hematologic toxicity, with a Grade 3 rate of 58% (18/31); no Grade 4 cases were reported. All Grades thrombocytopenia occurred in 55% (17/31) of patients, Grade 3 in three patients, and Grade 4 in two patients. Discontinuation of treatment due to AEs occurred in five patients over the 48 weeks (300 mg [n=2]; 400 mg [n=2]; 500 mg [n=1]), with two cases reported after Week 24 (dyspnea and leukocytosis [400 mg]; anemia and thrombocytopenia [500 mg]). There were 2 deaths (one in the 300 mg group due to unknown reasons [85 days after fedratinib discontinuation] and one in the 500 mg group due to disease progression [36 days after fedratinib discontinuation]). No cases of leukemic transformation were reported. Conclusions This updated analysis of the ARD11936 Phase II trial shows that treatment with fedratinib results in durable reductions in splenomegaly in patients with MF. No additional safety signals were observed with prolonged exposure to fedratinib. This study was sponsored by Sanofi. Disclosures: Pardanani: Sanofi, Bristol Myers Squibb, PharmaMar and JW Pharma: Clinical trial support Other. Jamieson:J&J, Roche: Research Funding; Sanofi: Membership on an entity’s Board of Directors or advisory committees. Lebedinsky:Sanofi: Employment. Gao:Sanofi: Employment. Talpaz:Novartis, Bristol-Myers Squibb, Ariad, Deciphera: Research Funding; Novartis, Bristol-Myers Squibb, Ariad, Deciphera: Speakers Bureau.

Risk of severe radiation pneumonitis in gemcitabine (GEM) based consolidation chemotherapy after concurrent chemo-radiation (C-RT) in stage III non-small-cell lung cancer (NSCLC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 17079-17079 ◽  
Author(s):  
T. Mok ◽  
L. Zhang ◽  
M. Liao ◽  
M. Boyer ◽  
J. Yang ◽  
...  
Keyword(s):  
Phase Ii ◽  
Radiation Pneumonitis ◽  
Phase Ii Study ◽  
Small Cell Lung ◽  
Consolidation Chemotherapy ◽  
Randomized Phase Ii ◽  
Recent Phase ◽  
Ecog Ps ◽  
Fraction Dose ◽  
To Receive

17079 Background: Recent phase II study (S9504) showed that 3 cycles of consolidation docetaxel after C-RT is associated with prolonged survival but 6 pts (7%) had severe (≥gr 3) radiation pneumonitis and 2 (2.4%) died.(None at S9019) LCRG, a multinational Asian study group, designed a randomized phase II study aiming to assess the treatment outcomes of consolidation GEM or GEM/Carboplatin (CAR) after C-RT. GEM is a potent radiation sensitizer with known recall phenomena, thus we evaluated the risk of severe radiation pneumonitis with GEM-based consolidation chemotherapy after C-RT in this interim report. Methods: Enrollment criteria: Histologic proven NSCLC; attained CR/PR/SD after C-RT (Cisplatin-based chemotherapy between 25 mg/m2 and 40 mg/m2 per week or 60 mg/m2 to 100mg/m2 every 3 to 4 weeks; fraction dose not more than 2.0 Gy; total dose not less than 54 Gy and not higher than 64 Gy); ECOG PS 0–1; adequate hematologic/renal/liver function. Patients were screened for eligibility within 6 weeks after C-RT. Eligible patients are randomized to receive GEM 1250mg/m2 day 1,8 q21days with or without CAR 5XAUC day 1. Results: Between 3/04 and 9/05 we screened 51 patients and excluded 19. Six (31.5%) were excluded due to radiation pneumonitis.(gr 1=5 and gr 3 = 1). C-RT induced toxicity was the main reason for difficulty with accrual to this trial. We enrolled 32 patients (m:f 29:3; mean age 58 (40–78); adeno:scc:other 14:16:2; IIIa:IIIb 4:28) Median RT fraction and dose was 30 (27–32) and 60 Gy (54–64), respectively. 19 pts received GEM and 13 received GEM/CAR. Severe (≥gr 3) radiation pneumonitis was reported in 3 pts (9.3%) and 1 (3.1%) died from the complication. Another 10 and 6 pts had grade 1 and 2 radiation pneumonitis, respectively, but without significant clinical compromise. Conclusions: Radiation pneumonitis is common after C-RT with or without consolidation chemotherapy. However, severe radiation pneumonitis is relatively uncommon in pts who received GEM based consolidation chemotherapy after C-RT. A possible explanation is that we have screened out the high risk pts prior to enrollment. [Table: see text]

A randomized phase II trial comparing two doses of lenalidomide for the treatment of stage IV ocular melanoma

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e20012-e20012 ◽  
Author(s):  
J. B. Zeldis ◽  
C. Heller ◽  
G. Seidel ◽  
N. Yuldasheva ◽  
D. Stirling ◽  
...  
Keyword(s):  
Phase Ii ◽  
Stable Disease ◽  
Phase Ii Trial ◽  
Stage Iv ◽  
Ocular Melanoma ◽  
Eligibility Criteria ◽  
Randomized Phase Ii ◽  
Animal Data ◽  
Disease Stabilization ◽  
Grade 3

e20012 Background: Ocular melanoma is the most common primary intraocular malignancy in adults with an incidence of 4.3 new cases per million. Approximately 50% of patients will develop metastases and the mean survival of those with liver metastases is 8–10 months. There are no effective systemic therapies. Pre-clinical studies of the antiangiogenic and immunomodulatory agent, lenalidomide, have shown promise in animal models of human ocular melanoma. We therefore conducted a phase II trial comparing two doses of oral lenalidomide. Methods: Patients with stage IV ocular melanoma, who met eligibility criteria and demonstrated disease progression, were enrolled on an IRB approved prospective random assignment trial comparing 5 mg and 25 mg of lenalidomide administered once a day orally for 21 days with a 7 day recovery (one cycle). Lesions were measured at baseline and every 3 months and scored for response by RECIST criteria. Patients who completed 3 cycles were eligible for response evaluation. Patients with responding lesions or with stable disease could continue receiving the agent. Toxicity was assessed using the NCI Common Toxicity Criteria. Results: Seventeen patients (13 female, 4 male; mean age 53) met eligibility criteria and were randomized to 5 mg (9 patients) or 25 mg (8 patients) of lenalidomide. The agent was well tolerated at both doses with only three grade 3 toxicities (two decreased ANC and one rash/puritis) requiring dose adjustments. Sixteen patients were eligible for response assessments. Nine patients had progressive disease by RECIST criteria following 3 cycles of therapy. Seven patients (44%) had stable disease for a mean of 7 months (range 6–12 months). There were no RECIST defined responders. There were no differences between the two dose groups with respect to toxicity or disease stabilization. Conclusions: Lenalidomide is well tolerated at doses of 5 mg and 25 mg orally for a 21 day cycle by patients with stage IV ocular melanoma. While no responses were seen, disease stabilization for a mean of 7 months was seen in 44% of patients. This effect was consistent with the pre-clinical animal data. Based on these results, further development of lenalidomide in combination with other agents should be considered for the treatment of metastatic ocular melanoma. [Table: see text]

Sorafenib and continued erlotinib or sorafenib alone in patients with advanced non-small cell lung cancer progressing on erlotinib: A randomized phase II study of the Sarah Cannon Research Institute (SCRI).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7587-7587 ◽  
Author(s):  
Victor Gian ◽  
Mark S. Rubin ◽  
Dianna Shipley ◽  
Howard A. Burris ◽  
Joseph Kaplan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Growth Factor ◽  
Small Cell Lung Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Single Agent ◽  
Small Cell ◽  
Small Cell Lung ◽  
Randomized Phase Ii ◽  
Grade 3

7587 Background: Erlotinib is an oral epidermal growth factor receptor kinase inhibitor used in the treatment of advanced non-small-cell lung cancer (NSCLC). Resistance develops in patients (pts) who initially respond to erlotinib leading to progressive disease (PD). Sorafenib is an oral inhibitor of vascular endothelial and platelet-derived growth factor receptors and Raf kinases which play important roles in PD. This randomized phase II study evaluated the role of sorafenib and continued erlotinib or sorafenib alone in pts with progressive NSCLC following initial benefit with erlotinib. Methods: Eligible pts had IIIB/IV NSCLC, an ECOG PS 0-2, and had received ≤2 lines of therapy with the last being single-agent erlotinib. Pts must have PD following clinical benefit (complete/partial response/stable disease) from erlotinib for >8 weeks. Pts were randomized 1:1 to continue erlotinib at the dose administered at the time of PD with the addition of sorafenib 400 mg orally twice daily (Arm A) or to sorafenib alone (Arm B). Cycles were 28 days with restaging every 2 cycles. The primary endpoint was progression-free survival (PFS). Results: 52 pts were enrolled from 2/2008 to 3/2011 (A 24; B 28). Baseline characteristics were balanced between arms and included: median age 65 years (41-87); 65% female; 69% adenocarcinoma/large cell; and 96% PS <2. 41% of pts were either never smokers or smoked <100 cigarettes/lifetime. Pts received a median of 8 weeks of treatment per arm (0.6–67 weeks). The median PFS was 3.1 (95% CI 1.7-3.7) and 2.3 (1.7-3.6) months for A and B, respectively (p=.84). There were no grade 3/4 hematologic toxicities in either arm except grade 3 anemia in 1 pt (A). Severe nonhematologic toxicities in >5% included: fatigue 17%(A)/7%(B); diarrhea 17%/0; dehydration 13%/7%; hand-foot skin reaction 8%/8%, and anorexia 4%/7%. Conclusions: Sorafenib has modest activity when used in combination with erlotinib or as a single agent in pts with PD following benefit with erlotinib alone. Additional study to identify potential subsets of refractory pts who might derive the greatest benefit from sorafenib are warranted.

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