A phase II study of everolimus in patients with aggressive RAI refractory (RAIR) thyroid cancer (TC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 6023-6023 ◽  
Author(s):  
Jochen H. Lorch ◽  
Naifa Busaidy ◽  
Daniel T Ruan ◽  
Pasi A. Janne ◽  
Sewanti Atul Limaye ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Protein A ◽  
Progression Free Survival ◽  
Complete Response ◽  
Negative Regulator ◽  
High Rate ◽  
Loss Of Function ◽  
Open Label ◽  
Mechanistic Basis

6023 Background: We present results of an open label phase II study of the mTOR inhibitor Everolimus in patients (pts) with RAIR TC. Methods: Pts with metastatic, incurable RAIR TC who had shown radiographic progression within 6 months prior to enrollment received Everolimus 10mg orally once daily. Responses were monitored by CT's every two months. The primary endpoint was progression free survival. Sequential biopsies were obtained in selected pts. Results: Enrollment to the differentiated TC (DTC) cohort finished in Jan 2013 and included 33 pts, among them 11 with Hurthle cell TC. Exploratory cohorts enrolled 10 pts with medullary [MTC] and 5 with anaplastic [ATC] with 2 added openings remaining for ATC. For the DTC cohort, median time on study to date is 10 months (mo) (<1-23+). 31 pts are evaluable at this time. PFS in the DTC cohort by Kaplan-Meier (K-M) analysis is 16.0 mo (95%CI 10-NR). Currently, disease stability for 6 and 12 mo or more was achieved in 18 and 10/31 pts, respectively, 11 pts remain on study. Median OS was not reached but 1 year survival by K-M analysis was 76%. One pt achieved a PR. 3 pts with DTC underwent sequential biopsies which revealed activation of autophagy while markers for apoptosis were not detected. Among 10 MTC pts, one achieved a PR and 9 pts had stable disease for 6 mo or more (6-33+). Among 5 ATC pts, 3 progressed, one has ongoing disease stability for 5 mo. One patient achieved a complete response that lasted for 18 mo and whole exome sequencing revealed somatic loss of function mutation affecting the Tuberous Sclerosis 2 (TSC2) protein, a negative regulator of mTOR activity [TSC2 (Q1178*) and FLCN (R17fs)]. Most common treatment-related adverse events were as anticipated and included fatigue, stomatitis and infections. Grade (gr) 3 events included infection 5, weight loss 3, leukopenia 3, thrombocytopenia 3, fatigue 3, hypophosphatemia 2, stomatitis 2, pneumonitis 1 and thrombosis 1pts. One pt had gr 4 hypercholesterinemia and one pt had gr 4 leukopenia. Conclusions: Everolimus has significant anti-tumor activity in pts with advanced TC. Activation of autophagy could account for high rate of disease stability. Sequencing may identify mechanistic basis and predictive markers for treatment response. Clinical trial information: NCT00936858.

RAMSETE: A single-arm, multicenter, single-stage phase II trial of RAD001 (everolimus) in advanced and metastatic silent neuro-endocrine tumours in Europe.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4122-4122 ◽  
Author(s):  
Marianne E. Pavel ◽  
Bertram Wiedenmann ◽  
Jaume Capdevila ◽  
Nicholas Reed ◽  
Juan W. Valle ◽  
...  
Keyword(s):  
Phase Ii ◽  
Objective Response ◽  
Mammalian Target Of Rapamycin ◽  
Progression Free Survival ◽  
Complete Response ◽  
High Rate ◽  
Mucosal Inflammation ◽  
Duration Of Treatment ◽  
Open Label ◽  
Best Response

4122 Background: The mammalian target of rapamycin (mTOR) signaling pathway is involved in the pathogenesis of neuroendocrine tumors (NET). Everolimus (RAD001), an oral mTOR inhibitor, has antitumor activity in patients (pts) with advanced NET. In this open-label, multicenter, phase II study (RAMSETE), the safety and efficacy of everolimus monotherapy was evaluated in pts with advanced nonsyndromic, nonpancreatic NET. Methods: Pts with advanced (unresectable or metastatic), progressive, nonsyndromic, nonpancreatic NET received everolimus (10 mg/day) as monotherapy. The primary endpoint was objective response rate (proportion of pts with best overall complete response [CR] or partial response [PR] per RECIST v1.0) by central radiologic review. A secondary endpoint included progression-free survival (PFS). Results: By database soft lock (December 1, 2011), 73 pts from 16 European clinics received everolimus (median duration of treatment: 193 days). Fifty-five (75%) pts discontinued; reasons included disease progression (n=23), adverse events (AEs [n=23]), withdrawal of consent (n=4), death (n=3), and protocol deviation (n=2). In the per protocol population (N=60), 32 (53%) pts received prior antineoplastic therapy. The best response by central review was stable disease in 55%. By local review, 3 (5%) pts had a PR, with SD in 39 (65%) pts. Median PFS by central review was 185 days (95% CI: 158-255). Median PFS by local investigator review was 285 days (95% CI: 231-not estimable). 69 (95%) pts reported treatment-related AEs of any grade, including rash (n=28; 38%), diarrhea (n=20; 27%), mucosal inflammation (n=18; 25%), and decreased appetite (n=17; 23%). Treatment-related grades 3 and 4 AEs and serious AEs were reported by 27 (37%) and 18 (25%) pts, respectively. Conclusions: In this open-label trial of everolimus in pts with advanced, nonsyndromic, extrapancreatic NET, a high rate of disease stabilization was achieved after prior tumor progression with favorable median PFS. This study further supports efficacy of everolimus in types of NET other than those studied in RADIANT-3 (pancreatic NET) and RADIANT-2 (NET associated with carcinoid syndrome).

A phase II study of oxaliplatin reintroduction in patients pretreated with oxaliplatin and irinotecan for advanced colorectal cancer (RE-OPEN study).

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 758-758
Author(s):  
Mitsukuni Suenaga ◽  
Nobuyuki Mizunuma ◽  
Satoshi Matsusaka ◽  
Eiji Shinozaki ◽  
Masato Ozaka ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Phase Ii ◽  
Primary Endpoint ◽  
Stable Disease ◽  
Tumor Response ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Complete Response ◽  
Open Label ◽  
Treatment Start

758 Background: Re-introduction of oxaliplatin (L-OHP) for patients with metastatic colorectal cancer (mCRC) refractory to standard chemotherapy regimens including L-OHP, irinotecan (CPT-11), and fluorouracil was thought to be effective approach. We performed a single arm, open-label phase II study (UMIN ID: 000004884), and the reported results of interim analysis were promising. Methods: Patients with prior chemotherapy including L-OHP and CPT-11 achieved tumor response or stable disease during prior L-OHP based therapy, and 6 months or over from confirmed progression disease during previous L-OHP based therapy was eligible for this study. Patients received FOLFOX regimens every two weeks. Primary endpoint was disease control rate (DCR) after 12 weeks of treatment start. Tumor response was evaluated by RECIST v1.1, and DCR was defined as complete response (CR), partial response (PR) or stable disease. This trial followed a Simon’s two-stage minimax design. Assuming the expected and threshold DCR after 12 weeks of treatment start would be 40% and 20%, 33 patients (18 in Step I and 15 in Step II) were required with a one sided α-level of 5% and a power of 80%. Results: Between February 2011 and August 2013, 33 patients were enrolled in this study. Characteristics of patients were as follows (n=33): median age of 62 years (35-77); male/female: 19/14; ECOG PS0: 84.8%; and colon/rectum: 14/19. All patients received mFOLFOX6 regimen. The DCR after 12 weeks of treatment start was 39.4% (95% CI: 21.8-57.0%), and the primary endpoint was met. The response Rate (CR or PR) was 6.1%. The median number of courses of chemotherapy was five, and the median total dose of L-OHP was 366.9 mg/m2. The median progression free survival was 98 days and the median overall survival was 300 days. The incidence of allergic reaction was 24.4% and peripheral neuropathy was 90.9%, graded as mild to moderate events. There were no other severe adverse events and treatment related deaths. Conclusions: Reintroduction of L-OHP was effective and could be a new salvage option for patients with mCRC refractory to previous L-OHP based therapy. Clinical trial information: 000004884.

A phase II study of ziv-aflibercept (Z) + FOLFIRI in Japanese patients (pts) with metastatic colorectal cancer (mCRC).

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 707-707 ◽  
Author(s):  
Taroh Satoh ◽  
Tadamichi Denda ◽  
Tetsuya Hamaguchi ◽  
Naotoshi Sugimoto ◽  
Takashi Ura ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
Complete Response ◽  
Japanese Patients ◽  
Phase Iii ◽  
Open Label ◽  
Secondary Endpoints ◽  
Phase Iii Study

707 Background: VEGF promotes tumor angiogenesis and metastasis. Z blocks the activity of VEGF-A/-B, and placental growth factor and was shown in the VELOUR phase III study (NCT00561470) outside of Japan to significantly improve overall survival (OS), progression-free survival (PFS), and overall response rate (ORR) in mCRC pts as a second-line treatment given with FOLFIRI. Goals of the current open-label, multicenter phase II study were to assess the efficacy and safety of Z + FOLFIRI in a post-oxaliplatin setting in mCRC pts in Japan. Methods: Pts received Z (4 mg/kg) + FOLFIRI (400 mg/m2 bolus 5-fluorouracil [FU]; 2400 mg/m2 continuous infusion 5-FU; 200 mg/m2 levofolinate; 180 mg/m2 irinotecan) every 2 weeks until progression, unacceptable toxicity, or study withdrawal. Primary endpoint: ORR (required 60 pts in order to obtain a 95% CI width of 16–20%, assuming an ORR of 10–20%). Secondary endpoints: PFS, OS, and safety. Tumors were assessed by independent reviewers every 6 ± 1 weeks until progression. Results: Study enrolled 62 pts; 50 pts (83.3%) had received prior bevacizumab. Of 60 pts evaluable for response, 5 had a partial response and none had a complete response, resulting in an ORR of 8.3% (95% CI: 1.3–15.3%). The median PFS was 5.42 months (95% CI: 4.140–6.702), and the median OS was 15.59 months (range 11.20–19.81). Forty-one pts (66.1%) died due to progression; none died due to study treatment. Pts underwent a median of 8 treatment cycles (range 1–31) lasting a median of 21.8 weeks (range 2–73). The median relative dose intensity was 0.99 (range 0.2–1.0) for Z, 0.87 (range 0.4–1.0) for irinotecan, and 0.96 (range 0.7–1.0) for 5-FU. All pts had ≥1 treatment emergent adverse event (TEAE; see table). Conclusions: The ORR was 8.3% (95% CI: 1.3–15.3%), and the median OS was 15.59 months. The safety profile was consistent with that reported previously. Registered as NCT01882868. Clinical trial information: NCT01882868. [Table: see text]

A phase II study of epacadostat and pembrolizumab in patients with advanced sarcoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 11049-11049 ◽  
Author(s):  
Ciara Marie Kelly ◽  
Ping Chi ◽  
Mark Andrew Dickson ◽  
Mrinal M. Gounder ◽  
Mary Louise Keohan ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Objective Response ◽  
Progression Free Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Complete Response ◽  
Open Label ◽  
Intracellular Enzyme ◽  
Recist 1.1 ◽  
Advanced Sarcoma

11049 Background: Tumors express IDO1, an intracellular enzyme involved in the degradation of tryptophan to kynurenine, in order to evade immunosurveillance. Epacadostat inhibits IDO1 and shifts the tumor microenvironment from an immunosuppressive state to an immune-stimulated state. Pembrolizumab previously demonstrated activity in select sarcoma subtypes. We performed an open-label, single-center, phase II study of epacadostat and pembrolizumab in patients with advanced sarcoma. Methods: Patients received the recommended phase II dose of oral epacadostat (100mg) twice per day and intravenous pembrolizumab (200mg/dose) every 3 weeks. The primary endpoint was best objective response rate (ORR) (complete response and partial response [PR]) at 24 weeks by RECIST 1.1. Secondary endpoints included adverse events (AEs), ORR by irRECIST, progression free survival (PFS) and overall survival (OS). Correlative studies performed on pre/on-treatment biopsy specimens included PD-L1, IDO1, and kynurenine expression and characterization of tumor infiltrating lymphocytes by IHC, whole exome and RNA sequencing. Results: Twenty-nine patients were enrolled [median age 53 years (range, 24-78), 57% male, ECOG PS 0 83%]. Histological subtypes included leiomyosarcoma (17%), UPS (17%), myxofibrosarcoma (7%), liposarcoma (10.5%), EHE (10.5%), angiosarcoma (3%), “other” sarcoma subtype (35%). Patients were refractory to 0 (21%), 1 (38%), 2 (24%) and ≥ 3 (17%) prior lines of therapy. The most common ( > 20% of pts) grade (G)1 or 2 treatment related AEs (TRAEs) observed included fatigue (31%), rash (31%) and ALT elevation (24%). G3 TRAEs included AST elevation (10%), ALT elevation, anemia, hypophosphatemia and increased lipase each occurred in 3% of pts. Three patients discontinued therapy due to G3 immune mediated hepatitis. Among the 29 evaluable patients 1 (3%) confirmed PR (leiomyosarcoma), 13 stable diseases (45%) and 15 progressions (52%) were observed by RECIST 1.1. The median PFS was 8.0 weeks (two-sided 95% CI: 6.9 ~ 26.7) and the PFS rate at 24 weeks was 27.9% (two-sided 95% CI: 15.0% ~ 52.2%). The median OS was not estimable (two-sided 95% CI: 40.9 weeks ~ NE). The OS at 24 weeks was 85.2% (95% CI: 72.8%, 99.7%). Conclusions: Epacadostat in combination with pembrolizumab was generally well tolerated. Limited anti-tumor activity was observed among advanced sarcoma patients. Correlative analyses including determination of adequacy of IDO1 inhibition will be reported. Clinical trial information: NCT03414229.

Long-term analyses from L-MIND, a phase II study of tafasitamab (MOR208) combined with lenalidomide (LEN) in patients with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 7513-7513
Author(s):  
Johannes Düll ◽  
Kami J. Maddocks ◽  
Eva Gonzalez-Barca ◽  
Wojciech Jurczak ◽  
Anna Marina Liberati ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Objective Response ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
Open Label ◽  
Efficacy Analysis

7513 Background: L-MIND (NCT02399085) is an ongoing, open-label, Phase II study of tafasitamab (MOR208), an Fc-modified, humanized, anti-CD19 monoclonal antibody, plus LEN in ASCT-ineligible patients (pts) with R/R DLBCL. Primary analyses and 2-year efficacy results were previously presented; we report an updated efficacy analysis with ≥35 months follow up (cut-off: October 30, 2020). Methods: Pts were aged ≥18 years with ASCT-ineligible R/R DLBCL, had 1–3 prior systemic therapies (Tx), including ≥1 CD20-targeting regimen, with an ECOG status of 0–2. Pts received 28-day cycles (C) of tafasitamab (12 mg/kg IV), once weekly during C1–3, with a loading dose on Day 4 of C1, then every 2 weeks (Q2W) during C4–12. LEN (25 mg PO) was administered on Days 1–21 of C1–12. After C12, progression-free pts received tafasitamab Q2W until disease progression. The primary endpoint was objective response rate (ORR), assessed by IRC. Secondary endpoints included duration of response (DoR), progression-free survival (PFS) and overall survival (OS). Results: Eighty of 81 enrolled pts received tafasitamab + LEN and were included in the full analysis set (1 prior Tx, n=40; 2+ prior Tx, n=40). At data cut-off, the overall ORR was 57.5% (n=46/80), including complete response (CR) in 40% of pts (n=32/80) and partial response (PR) in 17.5% of pts (n=14/80) (Table). Kaplan-Meier estimates: median DoR=43.9 months (95% CI: 26.1–not reached [NR]), and NR in pts who achieved a CR (95% CI: 43.9–NR); median PFS=11.6 months (95% CI: 6.3–45.7), with median follow-up 33.9 months; median OS=33.5 months (95% CI: 18.3–NR), with median follow-up 42.7 months. There were no unexpected toxicities or new safety signals. Conclusions: Combination Tx with tafasitamab + LEN followed by tafasitamab monotherapy provided durable responses in pts with R/R DLBCL not eligible for ASCT, with a manageable safety profile. These long-term data indicate the potential of tafasitamab + LEN followed by extended tafasitamab monotherapy in achieving prolonged remission and survival benefit in this patient population, especially at first relapse. Clinical trial information: NCT02399085. [Table: see text]

scholarly journals Phase II study of metronomic treatment with daily oral vinorelbine as first-line chemotherapy in patients with advanced/metastatic HR+/HER2− breast cancer resistant to endocrine therapy: VinoMetro—AGO-B-046

2021 ◽  
Author(s):  
Slavomir Krajnak ◽  
Thomas Decker ◽  
Lukas Schollenberger ◽  
Christian Rosé ◽  
Christian Ruckes ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
First Line ◽  
Open Label ◽  
Oral Vinorelbine ◽  
Her2 Breast Cancer ◽  
Line Chemotherapy

Abstract Purpose Metronomic chemotherapy (MCT) is an increasingly used treatment option in hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) advanced/metastatic breast cancer (MBC) after failure of endocrine-based therapies. Methods VinoMetro was a multicentre, open-label, single-arm, phase II study of metronomic oral vinorelbine (VRL; 30 mg/day) as a first-line chemotherapy (CT) in patients with HR+/HER2− MBC after endocrine failure. The primary endpoint was the clinical benefit rate (CBR) at 24 weeks. Results Between January 2017 and April 2019, nine patients were enrolled. The CBR was 22.2% (90% confidence interval [CI] 4.1–55.0), p = 0.211. The median progression-free survival (PFS) was 12.0 weeks (95% CI 11.3–12.7). Grade 3–4 adverse events (AEs) occurred in 22.2% of patients. One patient died of febrile neutropenia. Conclusion VinoMetro (AGO-B-046) was closed early after nine patients and occurrence of one grade 5 toxicity in agreement with the lead institutional review board (IRB). Metronomic dosing of oral VRL in HR+/HER2− MBC as first-line CT after failure of endocrine therapies showed only limited benefit in this population. Trial registration number and date of registration ClinicalTrials.gov Identifier: NCT03007992; December 15, 2016.

scholarly journals Oral vinorelbine and cisplatin as first-line therapy for advanced squamous NSCLC patients: a prospective randomized international phase II study (NAVoTrial 03)

2021 ◽  
Vol 13 ◽  
pp. 175883592110229
Author(s):  
Francesco Grossi ◽  
Piotr Jaśkiewicz ◽  
Marion Ferreira ◽  
Grzegorz Czyżewicz ◽  
Dariusz Kowalski ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Current Knowledge ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Comparable Efficacy ◽  
Open Label ◽  
Oral Vinorelbine ◽  
First Line Therapy ◽  
Nsclc Patients

Objective: The study investigated the efficacy and safety of oral vinorelbine-cisplatin (OV-CDDP) and gemcitabine-cisplatin (GEM-CDDP) in patients with squamous non-small cell lung cancer (sq-NSCLC). Patients and methods: This was an open-label, prospective, multicenter, international phase II study that enrolled untreated patients with advanced sq-NSCLC. Patients were randomized to receive 3-week cycles of either 60–80 mg/m2 OV days 1 and 8 in combination with 80 mg/m2 CDDP day 1 (arm A) or 1250 mg/m2 GEM days 1 and 8 in combination with 75 mg/m2 CDDP day 1 (arm B). After four cycles, patients without disease progression continued maintenance dose of OV or GEM until progression or unacceptable toxicity. The primary objective was disease control rate (DCR). Secondary objectives included progression-free survival (PFS), time to treatment failure (TTF), overall survival (OS), safety, and quality of life (QoL). Results: A total of 114 patients with sq-NSCLC were randomized, and 113 were treated (57 in arm A and 56 in arm B). DCR was high in both arms: 73.7% (95%CI: 62.4–100.0) in arm A and 75.0% (95%CI: 63.7–100.0) in arm B. Median PFS and TTF were similar in arm A and B 4.2 and 2.8 months, and 4.3 and 3.1 months, respectively. Even though the difference was not significant, the OS was 10.2 for arm A and 8.4 months for arm B. The safety profiles were consistent with the current knowledge of adverse events. QoL results revealed an improvement in patients under OV treatment. Conclusion: The OV-CDDP combination showed comparable efficacy to GEM-CDDP with acceptable safety profile and enhanced patients’ QoL. Trial registration: The study was registered under EudraCT number 2012-003531-40.

Cisplatin and Gemcitabine Treatment for Malignant Mesothelioma: A Phase II Study

1999 ◽  
Vol 17 (1) ◽  
pp. 25-25 ◽  
Author(s):  
M. J. Byrne ◽  
J. A. Davidson ◽  
A. W. Musk ◽  
J. Dewar ◽  
G. van Hazel ◽  
...  
Keyword(s):  
Partial Response ◽  
Phase Ii ◽  
Malignant Mesothelioma ◽  
Phase Ii Study ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
Complete Response ◽  
Symptom Improvement ◽  
Median Response ◽  
Grade 3

PURPOSE: We performed a phase II study of combined cisplatin 100 mg/m2, given intravenously on day 1, and gemcitabine 1,000 mg/m2, given intravenously on days 1, 8, and 15 of a 28-day cycle for six cycles among patients with advanced measurable pleural mesothelioma. PATIENTS AND METHODS: Pleural tumor was measured at three levels on computed tomographic scans at study entry and before the second, fourth, and sixth cycles and every 2 months thereafter to disease progression. Of the 21 patients treated, 19 were male; the median age was 62 years (range, 46 to 74 years); 62% had epithelial tumors; and 18 were classified as tumor-node-metastasis system stage III or IV. Ninety-four cycles were given (median, six; mean, 4.5 per patient), with a mean relative dose intensity of cisplatin 96.7% and gemcitabine 82.5%. RESULTS: Best objective responses achieved were as follows: complete response, no patients; partial response, 10 patients (complete response + partial response, 47.6% [95% confidence interval, 26.2% to 69.0%]); no change, nine patients; and progressive disease, two patients. Median response duration was 25 weeks, progression-free survival was 25 weeks, and overall survival was 41 weeks. Nine of the 10 responders (90%) and three of nine patients with no change had significant symptom improvement. Serial measurements of vital capacity were performed on three of the responders; all showed a significant increase during the time of remission. Toxicity was mainly gastroenterologic and hematologic. Grade 3 nausea and vomiting occurred in 33% of patients, grade 3 leukopenia in 38%, grade 3 thrombocytopenia in 14%, and grade 4 thrombocytopenia in 19%. CONCLUSION: Combined cisplatin and gemcitabine is an active combination in malignant mesothelioma and produces symptomatic benefit in responding patients.

A Phase II Study of Intravenous Azacitidine Alone in Patients with Myelodysplastic Syndromes NCT00384956.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1451-1451
Author(s):  
Richard Walgren ◽  
Crystal Dao ◽  
Frederieke Kreisel ◽  
Peter Westervelt ◽  
Camille Abboud ◽  
...  
Keyword(s):  
Median Time ◽  
Phase Ii ◽  
De Novo ◽  
Phase Ii Study ◽  
Study Drug ◽  
Complete Response ◽  
Subsequent Treatment ◽  
Open Label ◽  
Erythroid Response

Abstract Rationale: 5-Azacytidine (Aza), a DNA hypomethylating agent, has now been shown in 2 clinical trials involving high-risk MDS patients to provide a survival benefit over supportive/conventional care regimens. While one phase II study used a continuous 7-day IV infusion, Aza was administered subcutaneously (SQ) in most pre-approval studies. However, injection site reactions are not uncommon with SQ dosing, especially in thrombocytopenic patients. Aza given as a short intravenous (IV) infusion is anticipated to be efficacious from pharmacokinetic profiling and is FDA approved, but prospective efficacy data for short IV infusion are lacking. Study aim and design: To determine the efficacy of IV Aza when given as a short infusion, we have undertaken an open-label, single-arm, single-center phase II study of Aza in patients with MDS, either de novo or secondary, defined by FAB classification. Previously treated subjects were ineligible if they had already received Aza or decitabine. Treatment consisted of Aza 75 mg/m2 given as a 20 minute IV infusion once daily on Days 1–5 of a 28-day cycle. Response was evaluated by IWG 2000 criteria. After two cycles at the 75 mg/m2 dose, patients failing to achieve a CR were eligible for an increased dose of 100 mg/m2. After 6 cycles of therapy, patients must have demonstrated at least a hematologic improvement to continue on study. Study endpoints include determination of the complete response (CR) and partial response (PR) rates, and secondary endpoints examined the rates of hematological improvement, time to progression, and cytogenetic response. Results: Accrual began 8/17/06 with a target of 21 subjects. As of 7/31/07, 15 subjects have accrued with a median follow-up of 77 days (range 4 to 246). Subjects consisted of 9 males and 6 females with a median age of 69.6 yr (range 53 to 82). The median time from diagnosis is 213 days (range 0 days to 4 yr). By FAB criteria, subjects consist of 4 RA, 9 RAEB, 1 RAEB-t, and 1 CMML, and subjects are categorized by IPSS risk as 1 Low, 4 Int-1, and 10 Int-2. Two patients had therapy related MDS. The data remain preliminary with subjects having completed a mean of 3 cycles (range 1 to 6). None of the 5 subjects who have completed at least 4 cycles of therapy have achieved a CR. However, 2 (40%) of these subjects achieved a PR. Additionally, 1 (20%) patient had a major erythroid response, while another had a minor erythroid response. Median time to response was 2 months. Ten subjects remain on study, 1 patient withdrew due to progressive disease (in first week of therapy), and 4 deaths have occurred on study (2 due to sepsis, 1 each due to pneumonia and acute MI). No deaths were attributed to study drug. Common adverse events include nausea, emesis, and hematologic toxicities. Grade 2–3 nausea and grade 2–3 emesis each occurred in 5 subjects. Observed grade 3 or 4 hematologic toxicities included: anemia (n=7), thrombocytopenia (n=4), leukopenia (n=3), neutropenia (n=7), and febrile neutropenia (n=1). Hematologic toxicities have resulted in transient treatment delays (&lt; 4 weeks) and dose reduction, but hematologic toxicities have not prevented subsequent treatment on study. Conclusions: Although follow-up is short for assessment of efficacy, this is the first prospective study to report on efficacy and toxicity of short infusional Aza in the treatment of MDS.

Phase II study of ifosfamide, carboplatin and etoposide (ICE) in recurrent glioblastoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 2066-2066
Author(s):  
T. Aoki ◽  
K. Nojima ◽  
T. Mizutani ◽  
M. Ishikawa ◽  
A. Takasu ◽  
...  
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Recurrent Glioblastoma ◽  
First Line ◽  
Open Label ◽  
Free Survival ◽  
Secondary Endpoints

2066 Background: To evaluate the efficacy and tolerability of ifosfamide, carboplatin and etoposide ( ICE ) in patients with recurrent glioblastoma. Methods: This was an open-label, single-center phase II trial. Forty-two patients with first recurrent glioblastoma after surgery, standard radiotherapy and a first-line temozolomide-based or ACNU-based chemotherapy, were enrolled.The primary endpoint was progression-free survival at 6 months ( PFS-6 ), and secondary endpoints were response rate, toxicity, and survival. Chemotherapy consisted of Ifosfamide ( 700 mg / m2 on day 1, 2 and 3 ), carbopaltin ( 100 mg / m2 on day 1 ), etoposide ( 70 mg / m2 on day 1, 2, and 3 ), every 6 weeks. Results: PFS-6 was 37 %. The median PFS was 17 weeks. Response rate was 27 %. Adverse events were generally mild ( grade 1 or 2 ) and consisted mainly of alopecia. Conclusions: This regimen is well tolerated and has activity in patients with recurrent glioblastoma. No significant financial relationships to disclose.

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