Phase II study of short CHOP-rituximab combination with early consolidation with ibritumomab-tiuxetan-Y90 (IT-Y90) in non-pretreated patients age 65 to 80 with CD20+ diffuse large B-cell lymphoma (DLBCL).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 6633-6633 ◽  
Author(s):  
Frederic Peyrade ◽  
Gerard Lepeu ◽  
Jocelyn Gal ◽  
Christophe Fruchart ◽  
Diane Coso ◽  
...  
Keyword(s):  
Phase Ii ◽  
Treatment Time ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
Primary Objective ◽  
Open Label ◽  
Randomised Study ◽  
Open Label Phase ◽  
Pretreated Patients

6633 Background: IT-Y90was approved in follicular lymphoma, and some data indicates that it could be used in DLBCL. It has been reported that early TEP-TDM negativity is associated with a longer survival in DLBCL, which suggest that these patients could benefit of a less intensive protocol. Methods: We conducted an international, open-label, phase II non-randomised study, in patients aged between 65 and 80 with age-adjusted (aa) IPI score of 0 and 1 and CD20+ DLBCL. The primary objective was to evaluate the efficacy of 3 cycles of RCHOP14 followed by, in case of complete response (CR), an injection of IT-Y90. Results: Thirty patients (M/F= 1) were included. Median age was 72.6 years (range 65 - 80). Patients had a stage III/IV, elevated LDH and IPI=1 in 38%, 16.6 and 57% respectively. 25 patients received the full treatment. Five obtained an uncomplete FDG-PET response and were excluded after 2 RCHOP cycles. 23 patients received the full IT-Y90 dosage (0.4mCi/Kg) and two received the attenuated dosage (0.3mCi/Kg). Mean treatment time was 54 days (median 52; min 48-max 69). The CR rate after RCHOP treatment was 85% [95% CI: 65-94]. No treatment-related deaths occurred. Grade III-IV neutropenia and thrombocytopenia was observed in 45% and 4%, respectively. Five patients experienced at least one febrile neutropenia. After IT-Y90, mean duration time for platelets <50G/l was 2.08 weeks (median 2; min 0-max 5). Two patients required platelet transfusion. With a median follow-up of 29.5 months [95% CI: 23-39], the estimated 3-year PFS was 90% [95% CI: 80-100] and the 3-year OS was 100% [95% CI: 100-100]. Among patients treated with 90Y-IT, only 3 relapsed were recorded (at 6, 16 and 24 months). Conclusions: this study suggested the feasibility, and efficacy of a short regimen including one injection of IT-Y90for selected DLBCL in complete response after 3 cycles of RCHOP14. This results need to be confirmed by further studies.

Phase II Study of Temozolomide Plus Thalidomide for the Treatment of Metastatic Melanoma

2003 ◽  
Vol 21 (17) ◽  
pp. 3351-3356 ◽  
Author(s):  
Wen-Jen Hwu ◽  
Susan E. Krown ◽  
Jennifer H. Menell ◽  
Katherine S. Panageas ◽  
Janene Merrell ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Phase Ii ◽  
Dose Escalation ◽  
Phase Ii Study ◽  
Stage Iv ◽  
Complete Response ◽  
Open Label ◽  
Open Label Phase ◽  
Metastatic Sites

Purpose: To further investigate the efficacy and safety of temozolomide plus thalidomide in patients with metastatic melanoma without brain metastases. Patients and Methods: Patients with histologically confirmed advanced-stage metastatic melanoma were enrolled in an open-label, phase II study. The primary end point was response rate. Patients received temozolomide (75 mg/m2/d × 6 weeks with a 2-week rest between cycles) plus concomitant thalidomide (200 mg/d with dose escalation to 400 mg/d for patients < 70 years old, or 100 mg/d with dose escalation to 250 mg/d for patients ≥ 70 years old). Treatment was continued until unacceptable toxicity or disease progression occurred. Results: Thirty-eight patients (median age, 62 years) with stage IV (three patients with M1a, eight with M1b, and 26 with M1c) or stage IIIc (one patient) melanoma and a median of four metastatic sites were enrolled, and received a median of two cycles of therapy. Twelve patients (32%) had an objective tumor response, including one with an ongoing complete response of 25+ months’ duration and 11 with partial responses. Five patients achieving partial response with a more than 90% reduction of disease were converted to a complete response with surgery. Treatment was generally well tolerated. Median survival was 9.5 months (95% confidence interval, 6.05 to 19.38 months), with a median follow-up among survivors of 24.3 months. Conclusion: The combination of temozolomide plus thalidomide seems to be a promising and well-tolerated oral regimen for metastatic melanoma that merits further study.

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 Daratumumab plus lenalidomide and dexamethasone in relapsed/refractory multiple myeloma: extended follow-up of POLLUX, a randomized, open-label, phase 3 study

Leukemia ◽  
2020 ◽  
Vol 34 (7) ◽  
pp. 1875-1884 ◽  
Author(s):  
Nizar J. Bahlis ◽  
Meletios A. Dimopoulos ◽  
Darrell J. White ◽  
Lotfi Benboubker ◽  
Gordon Cook ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Residual Disease ◽  
Progression Free Survival ◽  
Complete Response ◽  
Open Label ◽  
Refractory Multiple Myeloma ◽  
Open Label Phase ◽  
Intent To Treat ◽  
Line Of Therapy

Abstract In POLLUX, daratumumab (D) plus lenalidomide/dexamethasone (Rd) reduced the risk of disease progression or death by 63% and increased the overall response rate (ORR) versus Rd in relapsed/refractory multiple myeloma (RRMM). Updated efficacy and safety after >3 years of follow-up are presented. Patients (N = 569) with ≥1 prior line received Rd (lenalidomide, 25 mg, on Days 1–21 of each 28-day cycle; dexamethasone, 40 mg, weekly) ± daratumumab at the approved dosing schedule. Minimal residual disease (MRD) was assessed by next-generation sequencing. After 44.3 months median follow-up, D-Rd prolonged progression-free survival (PFS) in the intent-to-treat population (median 44.5 vs 17.5 months; HR, 0.44; 95% CI, 0.35–0.55; P < 0.0001) and in patient subgroups. D-Rd demonstrated higher ORR (92.9 vs 76.4%; P < 0.0001) and deeper responses, including complete response or better (56.6 vs 23.2%; P < 0.0001) and MRD negativity (10–5; 30.4 vs 5.3%; P < 0.0001). Median time to next therapy was prolonged with D-Rd (50.6 vs 23.1 months; HR, 0.39; 95% CI, 0.31–0.50; P < 0.0001). Median PFS on subsequent line of therapy (PFS2) was not reached with D-Rd versus 31.7 months with Rd (HR, 0.53; 95% CI, 0.42–0.68; P < 0.0001). No new safety concerns were reported. These data support using D-Rd in patients with RRMM after first relapse.

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.

A randomized, open-label, phase II study of lapatinib / capecitabine, lapatinib / vinorelbine, or lapatinib / gemcitabine in patients with ErbB2-amplified metastatic breast cancer progressing after taxane treatment: Results of an interim analysis (GLICO-0801 / EGF111792).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e11087-e11087
Author(s):  
Henry Leonidas Gomez ◽  
Silvia P. Neciosup ◽  
Celia Tosello ◽  
Patricia Xavier ◽  
Yeni Neron do Nascimento ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Phase Ii ◽  
Interim Analysis ◽  
Metastatic Breast ◽  
Primary Objective ◽  
Open Label ◽  
Open Label Phase ◽  
Hand Foot Syndrome ◽  
Number Of Cycles

e11087 Background: Lapatinib-capecitabine is approved for the treatment of ErbB2-amplified metastatic breast cancer (MBC) after failure to anthracyclines, taxanes and trastuzumab. GLICO-0801 evaluates different lapatinib-based chemotherapy combinations as 1st/2nd line treatment for ErbB2 amplified MBC progressing after taxane treatment. We present the results of a planned safety interim analysis. Methods: This is an open-label, randomized, international, phase II trial exploring lapatinib (L) 1250mg qd in combination with capecitabine 2000mg/m2 d 1-14 (Arm A) or vinorelbine 25mg/m2 d 1 and 8 (Arm B) or gemcitabine 1000mg/m2 d 1 and 8 (Arm C). Primary objective is to determine the clinical benefit rate (defined as CR+PR+SD for ≥24 weeks). This trial is registered at www.clinicaltrials.gov number: NCT01050322 Results: The first83 randomized patients (pts) (Arm A=29, B=28 and C=26) were included in this analysis. Of them, 65 (78%) have discontinued therapy with mean number of cycles of 4.7, 6.2 and 7.5 in arms A, B and C respectively. Eighteen (21%) pts are still on treatment. Median age was 52y (29-84); 80 pts (96%) had PS 0-1; 51 (61%) were postmenopausal. Fifty-six pts (67%) had visceral metastasis, 52 (63%) were treated as 2nd line therapy and 36 (43%) had received prior trastuzumab. Most reported adverse events (AE) (87%) were grade 1-2. The most common AE (any grade) in arm A: diarrhea 72%, hand-foot syndrome 45%, vomiting 39%, anemia 36%; in arm B: diarrhea 75%, neutropenia 68%, nausea 43%, vomiting 39%; in arm C: diarrhea 72%, neutropenia 60%, anemia 44%, increase in ALT 44%. The most frequent serious AE reported in arm A: diarrhea in 3 pts (10%) and thrombocytopenia in 2 pts (7%); in arm B: febrile neutropenia in 2 pts (7%) and in arm C: sepsis in 1 pt (4%). There was one toxic death related to chemotherapy in arm C. Conclusions: There were no unexpected toxicities so far in this trial with most AEs being mild to moderate and manageable. This interim analysis supports the continuation of the study.

Dulanermin with rituximab in patients with relapsed indolent B-cell lymphoma: an open-label phase 1b/2 randomised study

2015 ◽  
Vol 2 (4) ◽  
pp. e166-e174 ◽  
Author(s):  
Chan Yoon Cheah ◽  
David Belada ◽  
Michelle A Fanale ◽  
Andrea Janikova ◽  
Myron S Czucman ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Open Label ◽  
Randomised Study ◽  
Open Label Phase ◽  
Phase 1B

Phase I evaluation of vandetanib with radiation therapy (RT) ± cisplatin in previously untreated advanced head and neck squamous cell carcinoma (HNSCC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 6016-6016 ◽  
Author(s):  
V. Papadimitrakopoulou ◽  
S. J. Frank ◽  
G. R. Blumenschein ◽  
C. Chen ◽  
M. Kane ◽  
...  
Keyword(s):  
Phase I ◽  
Tyrosine Kinases ◽  
Locally Advanced ◽  
Maximum Tolerated Dose ◽  
Primary Objective ◽  
Open Label ◽  
Once Daily ◽  
Open Label Phase ◽  
To Receive

6016 Background: Vandetanib is a once-daily oral anticancer agent that selectively targets VEGF, EGF and RET receptor tyrosine kinases. We report preliminary results from an ongoing open-label phase I study of vandetanib with RT ± cisplatin in patients (pts) with previously untreated, unresected, locally advanced (stage III-IV) HNSCC. Methods: Eligible pts received once-daily vandetanib for 14 days followed by either 1) concomitant vandetanib + RT (2 Gy/d, 5 d/wk; total 70 Gy) + cisplatin (30 mg/m2, 2 h iv infusion/wk) for 7 wks, or 2) concomitant vandetanib + RT (2.2 Gy/d accelerated fractionation, 5 d/wk; total 66 Gy) for 6 wks. The primary objective was to determine the safety, tolerability and maximum tolerated dose (MTD) of vandetanib in both regimens. The first pt cohort received vandetanib 100 mg/day; escalation to 200 mg and 300 mg in subsequent cohorts was permitted providing <2/6 (33%) pts in the preceding cohort experienced a dose-limiting toxicity (DLT). Cohort expansion at the MTD of vandetanib was also planned. Results: As of Dec 1 2008, 24 pts (median age 53.5 yrs; 19 male; all M0) had received treatment with vandetanib + RT + cisplatin (n=18) or vandetanib + RT (n=6). In the triplet arm, no DLTs occurred in the initial vandetanib 100 mg cohort (n=6); an additional 6 pts were enrolled to receive vandetanib 200 mg but this dose was considered to exceed the MTD since DLTs were reported in 3/5 evaluable pts (Table). Vandetanib 100 mg was therefore declared the MTD with RT + cisplatin and cohort expansion at this dose continues. In regimen 2), 6 pts have received vandetanib 100 mg + RT and evaluation of this initial cohort is ongoing. Conclusions: This study, which continues to recruit, is the first to evaluate dual targeting of VEGFR/EGFR tyrosine kinases with chemoradiation or radiation alone in HNSCC pts. Among the 24 treated pts, 2 have completed the 2-year follow up, 1 death occurred that was causally related to cisplatin, and 21 remain in follow up or continue to receive treatment. [Table: see text] [Table: see text]

Neoadjuvant treatment of locally advanced GIST: Results of APOLLON, a prospective, open label phase II study in KIT- or PDGFRA-positive tumors.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10031-10031 ◽  
Author(s):  
Peter Hohenberger ◽  
Claus Langer ◽  
Clemens Martin Wendtner ◽  
Werner Hohenberger ◽  
Annette Pustowka ◽  
...  
Keyword(s):  
Disease Progression ◽  
Phase Ii ◽  
Adjuvant Treatment ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Progression Rate ◽  
Open Label ◽  
Open Label Phase ◽  
Prospective Phase

10031 Background: Imatinib may significantly downstage the metastatic GIST. This prospective, phase II, open-label trial of neoadjuvant imatinib evaluated the overall tumor response and progression rate of disease in locally advanced, non-metastic patients. Methods: Inclusion criteria were: KIT (n=39) or PDFRA (n=6) positive GIST, proven by biopsy and IHC. Tumors had to be locally advanced, potentially resectable, M0. Patients received 400 mg of imatinib daily (KIT exon 9 mutations: twice daily) for 6 months, in the absence of disease progression or unacceptable toxicity. At two months 18F-FDG-PET examination was performed to assess response in paralle to CT imaging. Adjuvant treatment postoperatively was not part of the study protocol (CST1571-BDE43, NCT00112632). Median follow-up is 36 months in 39 patients. Results: From 7/2005 to 10/ 2009, 41 patients (16f, 25 m, mean age 54 yrs) were recruited to the trial with an average tumor size of 10.8 cm. One patient died from myocardial infarction 3 weeks after start of treatment, all other patients completed the protocol. In two patients dose reduction/interruption due to toxicity was required. 34/41 patients underwent resection of the tumor after a median of 200 d (range 57-394), while two patients had to be operated early due to disease progression. R0 resections were performed in 30/34 patients, two patients showed M1 disease at resection. Five patients showed developed progression postop., resulting in a PFS rate at 3 years of 85.2%. No patient has died so far from the disease. Conclusions: Neoadjuvant treatment with imatinib for six months is a safe treatment in patients with locally advanced disease. The extent of the operation can be significantly downsized after pretreatment. Despite the fact that no adjuvant treatment was foreseen, the progression-free rate at 3 years postoperatively is promising.

A randomized, open-label phase II study of single-agent vintafolide versus vintafolide plus docetaxel versus docetaxel alone in second-line NSCLC patients with all target lesions expressing folate-receptor (TARGET).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. TPS8125-TPS8125
Author(s):  
Martin J. Edelman ◽  
Hong Ma ◽  
Wendy Perez ◽  
Alex A. Adjei ◽  
Nasser Hanna
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Folate Receptor ◽  
Single Agent ◽  
Primary Objective ◽  
Second Line ◽  
Open Label ◽  
Histologic Diagnosis ◽  
Potential Biomarker ◽  
Open Label Phase

TPS8125 Background: Folate receptor (FR) is frequently overexpressed in NSCLC and is a potential biomarker for therapy selection. Vintafolide (EC145) is designed to target FR expressing cells and consists of folate linked to desacetylvinblastinehydrazide. The FR targeted imaging agent, 99mTc-etarfolatide (EC20), consists of folate coupled to technetium and identifies lesions that overexpress FR which may respond to vintafolide treatment. A phase II study of single-agent vintafolide in heavily pre-treated lung adenocarcinoma patients (pts) showed promising activity in clinical benefit response (50% vs. 14.3%) and overall survival (OS, 47.2 wks vs. 14.9 wks), in pts whose target lesions all expressed FR [FR (100%)] vs pts whose target lesions were not all FR positive (Edelman et al, JTO 2012:7:1618-21). This trial assesses the benefit of vintafolide as second-line therapy in NSCLC FR (100%) pts. Methods: This is a randomized, open-label phase II study of vintafolide vs. vintafolide + docetaxel vs. docetaxel in second line NSCLC FR (100%) pts ( NCT01577654 ). Key eligibility criteria include: cytologic or histologic diagnosis of NSCLC, 1 prior systemic therapy for advanced disease, and PS 0-1. At baseline, pts undergo 99mTc-etarfolatide imaging to detect FR-positive lesions. FR (100%) pts are randomized 1:1:1 to vintafolide, vintafolide + docetaxel, or docetaxel. Vintafolide (2.5 mg) is administered on d 1, 4, 8, and 11 of a 3-wk cycle. Docetaxel (75 mg/m2) is given on d 1 of a 3-wk cycle. Treatment continues until disease progression or unacceptable toxicity. Pts receiving vintafolide + docetaxel who discontinue docetaxel due to toxicity may continue vintafolide alone. Disease status is evaluated by RECIST v1.1 criteria every 6 wks and adverse events are monitored throughout. The primary objective of this study compares PFS between the docetaxel control arm and each experimental arm with the goal of demonstrating a hazard ratio of ≤0.67 favoring the experimental arms. Secondary objectives include response rate, disease control rate, OS, and safety/tolerability. Enrollment to the study is ongoing. Clinical trial information: NCT01577654.

Anlotinib and irinotecan for advanced Ewing sarcoma after failure of standard therapy: A multicenter, two-cohort, single-arm, open label, phase Ib/II trial (NCT03416517).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 11012-11012
Author(s):  
Jie Xu ◽  
Lu Xie ◽  
Wei Guo ◽  
Xiaodong Tang ◽  
Rongli Yang ◽  
...  
Keyword(s):  
Phase Ii ◽  
Ewing Sarcoma ◽  
Initial Level ◽  
Objective Response ◽  
Complete Response ◽  
Fixed Dose ◽  
Open Label ◽  
Phase Ib ◽  
Open Label Phase ◽  
Grade 3

11012 Background: Both protracted irinotecan and anti-angiogenesis therapy have shown promising results in Ewing sarcoma. We did this phase Ib/II trial to first define the proper dose of irinotecan in combination with anlotinib in Ewing sarcoma and then evaluate efficacy. Methods: Patients diagnosed with recurrent or refractory Ewing sarcoma were enrolled and sub-classified into cohort A (≥16y) or cohort B ( < 16y). In the dose-defining phase Ib portion, anlotinib was given at a fixed dose of 12mg D1-14every 21 days, while the de-escalated 3+3 design was used to detect the recommended dose of irinotecan in each cohort from an initial level of 20mg/m2/d dx5x2. Recommended phase 2 dose (RP2D) was defined as the highest dose at which no more than 30% patients experience a DLT in the first two courses. In the next dose-expanding phase II portion, the primary endpoint was objective response rate at 12 weeks (ORR12w). A conventional two-stage study design model was used. Results: 41 patients were enrolled with 29 in cohort A and 12 in cohort B. For cohort A, first 5 patients were treated at initial level in phase Ib portion, two of whom subsequently experienced delayed diarrhea as dose-limiting toxicity (DLT). Additional six patients were then treated at a lower dose of 15mg/m2. Since no more DLT was recorded, it was used as RP2D. 23/24 patients in cohort A phase II were available for response evaluation at 12 weeks, with one complete response (CR), 14 partial response (PR) (including one CMR who has a negative PET/CT scan but still abnormal lesions in MR scan), 2 stable disease (SD) and 6 progressive disease (PD). ORR12wwas 62.5%. For cohort B, no DLT was noticed in the first six patients treated at the initial level which was used as RP2D later. Finally, 12 patients were included in cohort B. ORR12wwas 83.3% with two CR, 8 PR (including one CMR) and two PD. Although effective, cohort B were closed because of slow enrollment. Most common grade 3/4 adverse events were diarrhea, abdominal pain and neutropenia. The genotype of UGT1A1*1 and UGT1A1*28 were not associated with the risk of diarrhea. Conclusions: The combination of irinotecan and anlotinib demonstrated an acceptable toxicity profile with promising evidence of clinical efficacy in advanced Ewing sarcoma. Clinical trial information: NCT03416517.

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