Phase II trial of ixabepilone in patients with metastatic breast cancer (MBC) who are resistant to an anthracycline, a taxane and capecitabine

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 660-660 ◽  
Author(s):  
E. Thomas ◽  
E. A. Perez ◽  
P. Mukhopadhyay ◽  
G. Lerzo ◽  
X. Pivot ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Objective Response ◽  
Metastatic Breast ◽  
Cytotoxic Agents ◽  
Clinical Activity ◽  
Synthetic Analog ◽  
Primary Analysis ◽  
Metastatic Setting ◽  
Grade 3

660 Background: Patients (pts) with MBC previously treated with an anthracycline, a taxane and capecitabine have very limited treatment options. Ixabepilone is the first semi-synthetic analog in a new class of cytotoxic agents, the epothilones. It has shown activity in breast and other tumors. Methods: This single-arm Phase II trial was designed to assess the objective response rate (ORR) of ixabepilone in MBC pts resistant to an anthracycline, a taxane and capecitabine. Pts had to be resistant to each regimen as defined by progression within 8 wks in the metastatic setting or recurrence within 6 months (mo) of adjuvant anthracycline/taxane. Capecitabine must have been given in the metastatic setting. Response was assessed by an independent radiology review committee (IRRC; primary analysis) and by each investigator per RECIST. Ixabepilone was administered IV at 40 mg/m2 over 3 h every 3 wks. Results: A total of 126 pts were treated: median age 51 yrs (range 30–78), Karnofsky PS range 70–100% and 70% pts had baseline liver metastases. 88% pts had received ≥2 prior metastatic regimens. 113 pts were response evaluable (had target disease by IRRC and met eligibility criteria for prior therapy). Median duration of response was 5.3 mo. Stable disease (SD) was the best response in 50% pts and 14% pts had SD ≥6 mo duration. Median PFS was 3.1 mo. Pts received a median of 4 cycles (range 1–16). The most common Grade 3/4 treatment-related adverse events were sensory peripheral neuropathy (14%), fatigue (10%), myalgia (7%), and stomatitis (6%). The neuropathy was cumulative and reversible. Time to resolution (to Grade 1 or baseline) for Grade 3/4 neuropathy was 5.4 wks by Kaplan-Meier analysis. Grade 3/4 neutropenia and thrombocytopenia occurred in 54% and 7% of pts, respectively. Febrile neutropenia was reported in 3% pts. Conclusions: Ixabepilone demonstrates promising clinical activity and a manageable safety profile in patients highly resistant to standard chemotherapy. [Table: see text] [Table: see text]

Multicentric phase II trial of gemcitabine plus capecitabine combination in the treatment of previously anthracycline(An)-treated metastatic breast cancer (MBC): SOLTI 0301 study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1051-1051 ◽  
Author(s):  
E. M. Ciruelos ◽  
J. Baselga ◽  
H. Cortes-Funes ◽  
A. Lluch ◽  
J. I. Mayordomo ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Objective Response ◽  
Metastatic Breast ◽  
Hematological Toxicity ◽  
Clinical Activity ◽  
Her2 Overexpression ◽  
Group 2 ◽  
Grade 3 ◽  
Group 1

1051 Background: Based on clinical activity of capecitabine(C) and gemcitabine (G) on the treatment of MBC, we performed a multicentric phase II trial of the combination to test its efficacy and safety profile. Methods: Sample size of 72 evaluable MBC patients (pts) previously An-treated (neoadjuvant 8%, adjuvant 69%, advanced 30%). Median age: 59 years (35–76 years). Estrogen Receptor positive: 47 (65%). HER2 overexpression: 16 (22%). Prior hormonal/trastuzumab allowed. Soft tissue/ganglionar/pleural/bone disease: 19 (26%); visceral metastasis: 53(74%). Stratification: previous chemotherapy (CT) for advanced disease (none: group 1; any: group 2). Study treatment: oral bid C 1,660 mg/m2/day (d) (d1–14) + iv G 1,000 mg/m2/d (d1&8). Cycles repeated every 3 weeks. RECIST/NCI-CTC 2.0 criteria. Primary end point: Objective Response Rate. Results: Response Rates and Clinical Benefit (CB) are detailed in the table . Median follow-up 7.2 months (m) (0.2–18.4). Median time to progression 11.2 m: group 1, 12 m (95%CI: 6.4–14.5); group 2, 8.9 m (95%CI: 6.9–14).Total and median administered cycles/pt: 479 and 8. Delayed cycles: 103(21.5%): 27% due to hematological toxicity, 11% due to non-hematological toxicity, 62% due to other causes. C dose reduced in 27 cycles (5.6%), 12 of them due to non- hematological toxicity. G dose reduced in 169 cycles (35%), mostly on day 8, and due to hematological toxicity (80% of reduced cycles). Grade 3–4 neutropenia: 32 pts (56%), 1 case of febrile neutropenia. Grade 3–4 non-hematological toxicities: asthenia 8 pts (14%), hand- foot syndrome 6 pts (10.5%), mucositis 3 pts (5%), diarrhea 2 pts (3.5%). Conclusions: Combination of C+G in the treatment of previously anthracycline-treated MBC is safe and active, with a manageable toxicity profile and a good clinical activity. [Table: see text] No significant financial relationships to disclose.

scholarly journals Ramucirumab in Combination with Pembrolizumab in Treatment-Naïve Advanced Gastric or GEJ Adenocarcinoma: Safety and Antitumor Activity from the Phase 1a/b JVDF Trial

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2985
Author(s):  
Ian Chau ◽  
Nicolas Penel ◽  
Andres O. Soriano ◽  
Hendrik-Tobias Arkenau ◽  
Jennifer Cultrera ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Progression Free Survival ◽  
Clinical Activity ◽  
Metastatic Setting ◽  
Duration Of Response ◽  
Treatment Naïve ◽  
Combined Positive Score ◽  
Grade 3

Ramucirumab (anti-VEGFR2) plus pembrolizumab (anti-PD1) demonstrated promising antitumor activity and tolerability among patients with previously treated advanced cancers, supporting growing evidence that combination therapies modulating the tumor microenvironment may expand the spectrum of patients who respond to checkpoint inhibitors. Here we present the results of this combination in first-line patients with metastatic G/GEJ cancer. Twenty-eight patients (≥18 years) with no prior systemic chemotherapy in the advanced/metastatic setting received ramucirumab (8 mg/kg days 1 and 8) plus pembrolizumab (200 mg day 1) every 3 weeks as part of JVDF phase 1a/b study. The primary endpoint was safety. Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and overall survival (OS). Tumors were PD-L1-positive (combined positive score ≥ 1) in 19 and -negative in 6 patients. Eighteen patients experienced grade 3 treatment-related adverse events, most commonly hypertension (14%) and elevated alanine/aspartate aminotransferase (11% each), with no grade 4 or 5 reported. The ORR was 25% (PD-L1-positive, 32%; PD-L1-negative, 17%) with duration of response not reached. PFS was 5.6 months (PD-L1-positive, 8.6 months; PD-L1-negative, 4.3 months), and OS 14.6 months (PD-L1-positive, 17.3 months; PD-L1-negative, 11.3 months). Acknowledging study design limitations, ramucirumab plus pembrolizumab had encouraging durable clinical activity with no unexpected toxicities in treatment-naïve biomarker-unselected metastatic G/GEJ cancer, and improved outcomes in patients with PD-L1-positive tumors.

Efficacy and Safety of Ixabepilone (BMS-247550) in a Phase II Study of Patients With Advanced Breast Cancer Resistant to an Anthracycline, a Taxane, and Capecitabine

2007 ◽  
Vol 25 (23) ◽  
pp. 3407-3414 ◽  
Author(s):  
Edith A. Perez ◽  
Guillermo Lerzo ◽  
Xavier Pivot ◽  
Eva Thomas ◽  
Linda Vahdat ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Objective Response ◽  
Sensory Neuropathy ◽  
Efficacy And Safety ◽  
Peripheral Sensory Neuropathy ◽  
Metastatic Setting ◽  
Grade 3 ◽  
Peripheral Sensory

PurposeTo evaluate the efficacy and safety of ixabepilone in patients with metastatic breast cancer (MBC) resistant to anthracycline, taxane, and capecitabine, in this multicenter, phase II study.Patients and MethodsPatients with measurable disease who had tumor progression while receiving prior anthracycline, taxane, and capecitabine were enrolled. Ixabepilone 40 mg/m2monotherapy was administered as a 3-hour intravenous infusion on day 1 of a 21-day cycle. The primary end point was objective response rate (ORR), assessed by an independent radiology facility (IRF).ResultsA total of 126 patients were treated and 113 were assessable for response. Patients were heavily pretreated: 88% had received at least two lines of prior chemotherapy in the metastatic setting. IRF-assessed ORR was 11.5% (95% CI, 6.3% to 18.9%) for response-assessable patients. Investigator-assessed ORR for all treated patients was 18.3% (95% CI, 11.9% to 26.1%). Fifty percent of patients achieved stable disease (SD); 14.3% achieved SD ≥ 6 months. Median duration of response and progression-free survival were 5.7 and 3.1 months, respectively. Median overall survival was 8.6 months. Patients received a median of 4.0 treatment cycles (range, one to 16 cycles), and 25% of patients received ≥ eight cycles. Grade 3/4 treatment-related events included peripheral sensory neuropathy (14%), fatigue/asthenia (13%), myalgia (8%), and stomatitis/mucositis (6%). Resolution of grade 3/4 peripheral sensory neuropathy occurred after a median period of 5.4 weeks.ConclusionIxabepilone demonstrated clear activity and a manageable safety profile in patients with MBC resistant to anthracycline, taxane, and capecitabine. Responses were durable and notable in patients who had not previously responded to multiple prior therapies.

Phase II trial of carboplatin in the management of malignant mesothelioma.

1990 ◽  
Vol 8 (1) ◽  
pp. 151-154 ◽  
Author(s):  
D Raghavan ◽  
P Gianoutsos ◽  
J Bishop ◽  
J Lee ◽  
I Young ◽  
...  
Keyword(s):  
Phase Ii ◽  
Malignant Mesothelioma ◽  
Phase Ii Trial ◽  
Objective Response ◽  
World Health ◽  
Hematological Toxicity ◽  
Who Grade ◽  
Life Threatening ◽  
Grade 3 ◽  
Health Organization

Thirty-one patients with advanced malignant mesothelioma, previously untreated or having received only one prior cytotoxic regimen, were treated in a prospective, single-arm phase II trial with carboplatin (NSC 241240) at a dose of 150 mg/m2 per day intravenously (IV) for 3 days (450 mg/m2/course). One complete remission and four partial remissions were achieved, yielding an overall objective response rate of 16% (95% confidence interval [CI], 5.4% to 34%). The median duration of remission was 8 months (range, 5 to 17). Nonhematological toxicity was mild (only 12% with World Health Organization [WHO] grade 3 vomiting); 16% suffered WHO grade 3 to 4 hematological toxicity, but there were no life-threatening episodes and no treatment-related deaths. Carboplatin has modest activity against malignant mesothelioma and, because of its low toxicity, has a role in the management of this disease.

A phase II trial of irinotecan, 5-fluorouracil and leucovorin in patients with previously untreated advanced colorectal cancer (CRC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14599-14599
Author(s):  
N. Lee ◽  
S. Bae ◽  
S. Lee ◽  
D. Kim ◽  
K. Kim ◽  
...  
Keyword(s):  
Continuous Infusion ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Objective Response ◽  
Tumor Control ◽  
Ecog Performance Status ◽  
Grade 3 ◽  
Ecog Ps

14599 Background: We prospectively conducted a phase II trial to test the efficacy and safety of irinotecan, 5-fluorouracil and leucovorin (FOLFIRI) regimens for the first-line treatment of previously untreated patients with recurrent or metastatic advanced CRC. Methods: Thirty-four previously untreated patients with advanced CRC were enrolled in this study from June 2001 to December 2006. Eligible patients had histologically confirmed adenocarcinoma, no prior systemic therapy in palliative setting, ECOG PS = 2, adequate organ function, written informed consent and at least one measurable disease. The patients received either irinotecan 180 mg/m2 on day 1 with a LV bolus of 200 mg/m2 and a FU bolus of 400 mg/m2, and this was followed by a FU continuous infusion of 600 mg/m2 on day 1 and day 2 (the classic FOLFIRI regimen), or they were treated with a LV bolus of 400 mg/m2 and a FU bolus of 400 mg/m2 followed by a FU continuous infusion of 2,400 mg/m2 for 46 hours (the simplified FOLFIRI regimen), and these treatments were repeated every 2 weeks until disease progression. Results: There were 13 females and 21 males with median age of 54 years (range: 41–79). The most common metastatic sites were lung and liver. A total of 262 cycles were administrated with median 6 cycles per patient (range: 1–22). All pts were evaluable for toxicity, and 30 pts for response to the treatment. The objective response rate was 26.4% with 2 complete responses respectively. Sixteen (47%) pts had stable disease and 7 (20.5%) had a progression. The tumor control rate was 73.4%. The median TTP was 5.3 months, and the overall survival was 10.1 months. The prognostic factor for longer TTP and survival was the ECOG performance status (PS). The type of regimens was not affected on response rate, TTP and survival. The chemotherapy was generally well tolerated and the most common grade 3–4 toxicities were neutropenia, diarrhea. The non- hematological toxicities were similar for both treatment groups, with more frequent grade =3 neutropenia being noted for the simplified FOLFIRI regimen. Conclusions: The FOLFIRI regimen was demonstrated to have a moderate antitumor activity with acceptable toxicity profiles, and tend to show more favorable outcome for patients with good ECOG PS. No significant financial relationships to disclose.

A phase II study of GW786034 (pazopanib) in patients with recurrent or metastatic invasive breast carcinoma: Results after completion of stage I: A trial of the Princess Margaret Hospital Phase II Consortium

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 1133-1133 ◽  
Author(s):  
S. K. Taylor ◽  
S. Chia ◽  
S. Dent ◽  
M. Clemons ◽  
P. Grenci ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adverse Events ◽  
Phase Ii ◽  
Progressive Disease ◽  
Single Agent ◽  
Objective Response ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Lesion Size ◽  
Grade 3

1133 Background: Pazopanib, an oral small molecule inhibitor of VEGFR, PDGFR, and KIT, has demonstrated activity in phase I, with a recommended phase II dose of 800 mg/d (Hurwitz H et al, J Clin Oncol. 2005;23[16 suppl]:3012.1). We evaluated the activity of single agent pazopanib in recurrent or metastatic breast cancer (MBC). Methods: In this 2-stage design, patients with recurrent or MBC received pazopanib 800 mg/d. The primary endpoint was objective response rate (ORR) of 20%. Response in 3 out of 18 patients was required to go to stage 2. Treatment was continued until progression. Results: 21 patients entered stage 1; 67% were ER positive and all were HER-2-negative. Prior lines of chemotherapy were 1 in 76% and 2 in 14%. Of the 19 evaluable patients, 2 patients remain on treatment. 14 (74%) stopped due to progressive disease, 2 (10%) due to adverse events, and 1 (5%) due to patient request. Best response was partial response (PR) in 1 (5%), stable disease (SD) in 11 (58%), and progressive disease in 7 (37%). Clinical benefit rate (CR, PR, or SD for ≥ 6 months) was 26%. Median time to progression (TTP) was 3.7 months (95% C.I. 1.7 months - not reached). 9 out of 18 patients (50%) with measurable target lesions had some decrease in target lesion size. Estimated progression-free survival at 3 months was 55%, and 28% at 6 months. Adverse events were grade 3/4 elevations in AST (14%) and ALT (10%), and grade 3 hypertension and neutropenia (14% each). Other common events were grade 1/2 lymphopenia, neutropenia, diarrhea, fatigue, skin hypopigmentation, hypertension, nausea, vomiting, anorexia, and headache. Conclusions: Pazopanib is well tolerated and demonstrates activity in pretreated breast cancer. While the target ORR of 20% has not been met, rates of SD and TTP are comparable to other active agents in this setting, and therefore pazopanib may be an interesting agent for future studies in breast cancer. [Table: see text]

A phase II trial of the CDK4/6 inhibitor palbociclib (P) as single agent or in combination with the same endocrine therapy (ET) received prior to disease progression, in patients (pts) with hormone receptor positive (HR+) HER2 negative (HER2−) metastatic breast cancer (mBC) (TREnd trial).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1002-1002 ◽  
Author(s):  
Luca Malorni ◽  
Giuseppe Curigliano ◽  
Alessandro Marco Minisini ◽  
Saverio Cinieri ◽  
Carlo Tondini ◽  
...  
Keyword(s):  
Phase Ii ◽  
Clinical Data ◽  
Single Agent ◽  
Objective Response ◽  
Endocrine Resistance ◽  
Metastatic Breast ◽  
Complete Response ◽  
Clinical Activity ◽  
P Value ◽  
Open Label

1002 Background: P is approved for treatment of HR+/HER2− mBC combined with ET. There is paucity of clinical data of single-agent P in ET resistant pts. Pre-clinical data suggest P may partially reverse endocrine resistance, though this is yet to be tested in pts. Methods: This Phase II, open-label, multicenter study enrolled post-menopausal pts with HR+ HER2− mBC who progressed on 1 or 2 prior ETs. Pts were randomized to P (125 mg/d 3 w on/1 w off) alone or to continue their current ET (aromatase inhibitor or fulvestrant) in combination with P (same schedule as P arm). The primary endpoint was clinical benefit rate (CBR) [complete response (CR), partial response (PR) and stable disease (SD) for > 6 months (mo)]. Secondary endpoints were adverse events (AE) and additional measures of efficacy. A two-stage optimal design assessed treatment activity in each arm assuming activity as CB≥40% (α and β = 10%). Exploratory comparisons were planned for safety and efficacy endpoints. Results: 115 pts were enrolled (ITT population) 58 in the P arm and 57 in the P+ET arm. In both arms, 67% of pts had the study treatment as second line ET, 33% as third line, and about 1/3 of pts also received 1 prior chemotherapy for mBC. CBR was similar in both arms: 54% (95% CI 42 - 67%) with P+ET, and 60% (95% CI 48 -73%) with P alone. Median duration of CB was longer with P+ET (11.5 mo; 95% CI 8.6 – 17.8) than with P (6 mo; 95% CI 3.9 - 9.9) (HR 0.31, 95% CI 0.1 - 0.7, p-value 0.001, exploratory). Objective response rate (ORR; CR, PR) was 11% (95% CI 3 - 19%) and 7% (95% CI 0.4 -13%) with P+ET and P, respectively. PFS was 10.8 mo (95% CI 5.6 - 12.7) with P+ET and 6.5 mo (95% CI 5.4 - 8.5) with P alone (HR 0.69, 95% CI 0.4 - 1.1, p-value 0.13, exploratory). AEs were in line with previous data. Conclusions: Single agent P has clinical activity in ET pre-treated HR+/HER2– mBC pts. The observed increase in PFS and duration of CB with P+ET may suggest that P could reverse resistance to the prior line of ET. Translational studies are ongoing to explore potential biomarkers in this setting. Clinical trial information: NCT02549430.

Phase II trial of the c-Met inhibitor tepotinib in advanced lung adenocarcinoma with MET exon 14 skipping mutations.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20541-e20541
Author(s):  
Paul K. Paik ◽  
Enriqueta Felip ◽  
Remi Veillon ◽  
Jürgen Scheele ◽  
Rolf Bruns
Keyword(s):  
Lung Adenocarcinoma ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Objective Response ◽  
Elevated Serum ◽  
Stage Iiib ◽  
Met Inhibitor ◽  
Grade 3 ◽  
Lung Adenocarcinomas ◽  
Platinum Doublet

e20541 Background: Approximately 3-4% of lung adenocarcinomas express a truncated form of c-Met (c-Metex14) due to mutation-induced exon 14 skipping. c-Metex14 accumulates on the cell surface and is constitutively active with the ability to drive NSCLC. Data suggest that lung adenocarcinomas harboring c-METex14 are sensitive to c-Met kinase inhibitors. The highly selective c-Met inhibitor tepotinib is well tolerated and active at an oral dose of 500 mg QD. This single-arm phase II trial (NCT02864992) is investigating the efficacy and safety of tepotinib in patients (pts) with advanced lung adenocarcinoma harboring METex14. Methods: Adults with stage IIIB/IV lung adenocarcinoma who have failed 1 or 2 lines of systemic therapy, including a platinum doublet-containing regimen, are eligible. Tumors must harbor mutations that are known to cause exon 14 skipping, confirmed by a central laboratory, but not activating EGFR mutations or ALK rearrangements. Pts receive tepotinib 500 mg QD until disease progression, intolerable toxicity, or withdrawal from treatment for other reasons. The primary endpoint is objective response rate. Secondary endpoints include progression-free and overall survival, safety, pharmacokinetics, and quality of life. Recruitment of 60 patients in Europe, USA, and Japan is planned. Results: Four pts (age 64–77 years; 3 stage IV, 1 stage IIIB, all Caucasian males) have been enrolled. All had received two prior chemotherapy regimens including a platinum doublet. Pts have currently completed 1–5 cycles of tepotinib therapy. The majority of adverse events observed to date have been grade 1/2 in severity; grade 3 disease-related dyspnea, pulmonary embolism, and pleural effusion were observed in one patient and grade 3 tepotinib-related elevated serum amylase in another. Of the 3 pts with post-baseline tumor evaluations, two have had an unconfirmed partial response and the third (with only one post-baseline assessment) stable disease. Conclusions: These initial data suggest that the efficacy of tepotinib 500 mg QD is comparable to that of less selective c-Met inhibitors in pts with c-METex14 NSCLC (ORR > 40%). Tepotinib is also well tolerated. Recruitment to the trial is ongoing. Clinical trial information: NCT02864992.

Phase II trial of afatinib in patients with advanced/metastatic urothelial carcinoma (UC) with genetic alterations in ERBB receptors 1-3 who failed on platinum-based chemotherapy (CT).

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. TPS540-TPS540 ◽  
Author(s):  
Albert Font Pous ◽  
Javier Puente ◽  
Daniel E. Castellano ◽  
Francisco X. Real ◽  
Miguel A. Climent ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Genetic Alterations ◽  
Erbb Receptors ◽  
Clinical Activity ◽  
Erbb Family ◽  
Platinum Based Chemotherapy ◽  
Biomarker Analysis

TPS540 Background: First-line treatment of patients (pts) with advanced/metastatic UC consists of platinum-based CT, with no well-established subsequent therapy for platinum-refractory disease. Although checkpoint inhibitors have shown promising results recently, targeted agents have generally not demonstrated significant clinical activity in this setting. Around 20% of UC harbor ERBB family genetic alterations, as such it may be a suitable therapeutic target (Knowles, Nat Rev Cancer 2015;15:25–41). The irreversible ERBB family blocker, afatinib, has shown activity in a Phase II trial in a subset of pts with UC who had ERBB2/ERBB3 aberrations (Choudhury, J Clin Oncol 2016;34:2165–71). This Phase II trial will evaluate afatinib in pts with UC molecularly selected for ERBB receptor alterations. Methods: This single-arm trial will assess the efficacy and safety of afatinib in pts with UC harboring ERBB2/ERBB3 mutations or ERBB2 amplification (Cohort A), or EGFR (ERBB1) amplification (Cohort B). Eligible pts are ≥18 years of age with ECOG PS 0–1, histologically confirmed advanced/metastatic UC of the bladder, upper tract or urethra, not amenable to surgery and progressing during or after platinum-based CT, with available archival tissue samples for pre-screening biomarker analysis. Pts will receive oral afatinib 40 mg/day until disease progression or discontinuation. Cohort A is enrolling in two stages, with Stage 2 enrollment based on anti-tumor activity observed. The primary endpoint is progression-free survival (PFS) rate at 6 months; secondary endpoints include objective response rate, PFS, overall survival, disease control rate, duration of response and tumor shrinkage. Trial objectives will be analyzed separately for the two cohorts. Safety and biomarker assessments will also be performed. The trial commenced in June 2016; as of October 4, 2017, 201 samples have been analyzed, with 24.3% and 8% of pts with genetic alterations potentially eligible for inclusion in Cohort A and B, respectively. To date, 12 pts have received study treatment in Cohort A and 6 in Cohort B; recruitment is ongoing. Clinical trial information: NCT02780687.

Phase I/II trial in patients with metastatic breast cancer (MBC) previously treated with a taxane and an anthracycline: Final safety data

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10528-10528 ◽  
Author(s):  
L. T. Vahdat ◽  
J. Klimovsky ◽  
C. A. Bunnell
Keyword(s):  
Breast Cancer ◽  
Phase I ◽  
Phase Ii ◽  
Safety Data ◽  
Metastatic Breast ◽  
Synthetic Analog ◽  
Metastatic Setting ◽  
Previously Treated ◽  
Phase Ii And Iii ◽  
Anti Tumor Activity

10528 Background: Ixabepilone, a semi-synthetic analog of the natural product epothilone B, has shown anti-tumor activity in a broad range of tumor types including breast cancer. Preclinical studies suggest synergy between ixabepilone and capecitabine in breast cancer models and has fuelled interest in the clinical setting. Methods: This open-label Phase I/II study was conducted to determine the recommended Phase II (and III) doses of ixabepilone and capecitabine using a 3-hour infusion of ixabepilone given on Day 1 (Schedule A) or a 1-hour infusion of ixabepilone given for 3 days (Schedule B) in combination with capecitabine given orally on Days 1–14 every 21 days in patients (pts) with MBC previously treated with a taxane and an anthracycline. Eligible pts were aged ≥18 years with pathologic diagnosis of breast cancer and evidence of MBC, who had received prior treatment with a taxane and an anthracycline in the adjuvant or metastatic setting. Pts were excluded if they had received >3 prior chemotherapy regimens in the metastatic setting or had ≥Grade 2 neuropathy. Toxicity was continuously monitored using NCI CTC v2. Results from the 62 pts treated with 40 mg/m2 as a 3 hr-infusion ixabepilone and 2000 mg/m2 capecitabine are shown here. Results: 56 of the 62 pts (90%) were aged <65 years. 80% of pts had visceral disease; 44% were ER/PR/HER-2 negative. 44% of pts had received ≥ two prior chemotherapies in the metastatic setting. Grade 3 neuropathy (sensory and motor) was reported in 12 pts and 1 pt (19%, 2%), respectively. Hand-foot syndrome, reported in 39 pts (63%), was primarily Grade 2 (26%) or 3 (34%). Hematologic toxicities included Grade 4 leukopenia (7 pts, 12%) and Grade 4 neutropenia (16 pts, 26%). Dose reductions were used to manage sensory neuropathy and hematologic abnormalities. Conclusions: The recommended Phase II (and III) doses are 40 mg/m2 ixabepilone (3-hour infusion on Day 1 every 21 days) and 2000 mg/m2 capecitabine (divided BID on Days 1–14 every 21 days). This ixabepilone/capecitabine combination demonstrated a manageable safety profile and promising clinical anti-tumor activity in pts with MBC previously treated with a taxane and an anthracycline. [Table: see text]

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