A phase II multicenter trial of the multitargeted kinase inhibitor sulfatinib in advanced medullary thyroid cancer (MTC) and radioiodine (RAI)-refractory differentiated thyroid cancer (DTC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 6037-6037 ◽  
Author(s):  
Jiaying Chen ◽  
Qinghai Ji ◽  
Junning Cao ◽  
Dongmei Ji ◽  
Chunmei Bai ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Growth Factor ◽  
Disease Progression ◽  
Phase Ii ◽  
Kinase Inhibitor ◽  
Phase Ii Study ◽  
Objective Response ◽  
Growth Factor Receptor ◽  
Stage I ◽  
Grade 3

6037 Background: Sulfatinib is an oral tyrosine kinase inhibitor targeting Vascular Endothelial Growth Factor Receptor (VEGFR), Fibroblast Growth Factor Receptor 1 (FGFR 1), and Colony Stimulating Factor 1 Receptor (CSF1R). In a proof of concept (PoC) phase II study, sulfatinib showed promising efficacy in patients (pts) with neuroendocrine tumors (NETs). Methods: This is an open label, two cohorts phase II study using Simon's two-stage design. In stage I, 15 pts will be enrolled in each cohort (advanced MTC or iodine-refractory DTC), and 10 more pts will be enrolled in a cohort in stage II if at least 2 PR observed in that cohort in stage I. Pts are required to have progressive disease in the past 12 months, but could not have received > 1 prior anti-angiogenesis therapy. Pts are treated with oral sulfatinib 300 mg once daily until disease progression, death, or intolerable toxicity. Primary endpoint is Objective Response Rate (ORR) by investigator per RECIST 1.1. Results: As of Dec 31 2016,the studyenrolled 18 pts (MTC: 6, DTC: 12), amongst whom 17 pts were efficacy evaluable. There were a total of 4 confirmed PRs, 1 in the MTC cohort and 3 in the DTC cohort, respectively. The others best response was stable disease (SD). 11 pts (61.1%) had dose interruption due to adverse events (AEs) and 5 pts (27.8%) had dose reduction. Two pts discontinued therapy (1 patient due to disease progression, another due to subject's decision). The most commonly reported AEs were proteinuria 72.2% (Grade 3-4: 22.2%), hypertriglyceridemia 50.0% (Grade 3-4: 0%), hypertension 44.4% (Grade 3-4: 16.7%), blood bilirubin increased 44.4% (Grade 3-4: 5.6%), and diarrhea 33.3% (Grade 3-4: 0%). No Grade 5 AE was reported by the time of data cut-off. Conclusions: Sulfatinib appears to be well tolerated in the pts with advanced MTC and RAI refractory DTC. Safety profile seems to be consistent to previous report, with mostly manageable AEs. Efficacy is encouraging in both indications. Further investigation is warranted. Clinical trial information: NCT02614495.

scholarly journals NFB-08. PHASE II STUDY OF AXITINIB IN PATIENTS WITH NEUROFIBROMATOSIS TYPE 2 AND PROGRESSIVE VESTIBULAR SCHWANNOMAS

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii419-iii419
Author(s):  
Sheetal Phadnis ◽  
Mari Hagiwara ◽  
Anna Yaffe ◽  
Carole Mitchell ◽  
Theodore Nicolaides ◽  
...  
Keyword(s):  
Growth Factor ◽  
Phase Ii ◽  
Kinase Inhibitor ◽  
Phase Ii Study ◽  
Growth Factor Receptor ◽  
Neurofibromatosis Type ◽  
Neurofibromatosis Type 2 ◽  
Vestibular Schwannomas ◽  
Volumetric Response

Abstract INTRODUCTION Vascular endothelial growth factor receptor (VEGFR), platelet derived growth factor receptor (PDGFR), and c-KIT represent clinically and/or preclinically validated molecular targets in vestibular schwannomas. We conducted a single institution, prospective, open-label, two-stage phase II study (ClinicalTrials.gov identifier NCT02129647) to estimate the response rate to axitinib, an oral multi-receptor tyrosine kinase inhibitor targeting VEGFR, PDGFR and c-KIT, in neurofibromatosis type 2 (NF2) patients with progressive vestibular schwannomas (VS). METHODS NF2 patients older than 5 years with at least one volumetrically measurable, progressive VS were eligible. The primary endpoint was to estimate the objective volumetric response rates to axitinib. Axitinib was given continuously in 28-day cycles for up to of 12 cycles. Response was assessed every 3 months with MRI using 3-D volumetric tumor analysis and audiograms. Volumetric response and progression were defined as ≥20% decrease or increase in VS volume, respectively. RESULTS Twelve eligible patients (ages: 14–56 years) were enrolled on this study. Seven of twelve patients completed 12 cycles (range: 2 to 12 cycles). We observed two imaging and three hearing responses. Best volumetric response was -53.9% after nine months on axitinib. All patients experienced drug-related toxicities, the most common adverse events were diarrhea, hematuria and skin toxicity, not exceeding grade 2 and hypertension, not exceeding grade 3. CONCLUSIONS While axitinib has modest anti-tumor activity in NF2 patients, it is more toxic and appears to be less effective compared to bevacizumab. Based on these findings, further clinical development of axitinib for this indication does not appear warranted.

scholarly journals Cabozantinib As Salvage Therapy for Patients With Tyrosine Kinase Inhibitor–Refractory Differentiated Thyroid Cancer: Results of a Multicenter Phase II International Thyroid Oncology Group Trial

2017 ◽  
Vol 35 (29) ◽  
pp. 3315-3321 ◽  
Author(s):  
Maria E. Cabanillas ◽  
Jonas A. de Souza ◽  
Susan Geyer ◽  
Lori J. Wirth ◽  
Michael E. Menefee ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Targeted Therapy ◽  
Phase Ii ◽  
Differentiated Thyroid Cancer ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Evaluation Criteria ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Multikinase Inhibitor

Purpose Sorafenib and lenvatinib are oral multikinase inhibitors targeting vascular endothelial growth factor receptor (VEGFR) and approved for radioiodine (RAI)-refractory differentiated thyroid cancer (DTC). However, there are no approved second- or third-line therapies. MET is implicated in resistance to VEGFR inhibitors. Cabozantinib is an oral multikinase inhibitor targeting MET in addition to VEGFR and is approved for medullary thyroid cancer. In a phase I study of cabozantinib, five of eight patients with DTC previously treated with a VEGFR-targeted therapy had an objective response to cabozantinib. Patients and Methods Patients with RAI-refractory disease with Response Evaluation Criteria in Solid Tumor (RECIST) measurable disease and evidence of progression on prior VEGFR-targeted therapy were enrolled in this single-arm phase II study. The cabozantinib starting dose was 60 mg/day orally but could be escalated to 80 mg if the patient did not experience a response. Patients underwent tumor assessment according to RECIST v1.1 every 8 weeks. In this study, if at least five of 25 response-evaluable patients had an objective response, cabozantinib would be considered a promising agent in this patient population. Results Twenty-five patients were enrolled. The median age was 64 years, and 64% of patients were men. Twenty-one patients had received only one prior VEGFR-targeted therapy (sorafenib, pazopanib, or cediranib), and four patients had received two such therapies. The most common treatment-related adverse events were fatigue, weight loss, diarrhea, palmar-plantar erythrodysesthesia, and hypertension. One drug-related death was noted. Of the 25 patients, 10 (40%) had a partial response, 13 (52%) had stable disease, and two (8%) had nonevaluable disease. The median progression-free survival and overall survival were 12.7 months and 34.7 months, respectively. Conclusion Cabozantinib demonstrated clinically significant, durable objective response activity in patients with RAI-refractory DTC who experienced disease progression while taking prior VEGFR-targeted therapy.

A phase II study of sunitinib in recurrent or metastatic endometrial carcinoma: A trial of the PMH Phase II Consortium

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5576-5576
Author(s):  
S. Welch ◽  
H. J. Mackay ◽  
H. Hirte ◽  
G. F. Fleming ◽  
R. Morgan ◽  
...  
Keyword(s):  
Phase Ii ◽  
Kinase Inhibitor ◽  
Phase Ii Study ◽  
Objective Response ◽  
Progression Free Survival ◽  
Open Label ◽  
Second Stage ◽  
Best Response ◽  
Grade 3 ◽  
Ecog Ps

5576 Background: Endometrial cancer (EC) is the most common gynecologic malignancy. Vascular endothelial growth factor (VEGF) overexpression in EC correlates with poor outcome, thus targeting VEGF is a rational therapeutic approach. We have conducted a two-stage open-label phase II study in advanced EC with sunitinib, an oral tyrosine kinase inhibitor of multiple VEGF receptors. Methods: Eligible pts have recurrent or metastatic EC and have received up to 1 prior chemotherapy (CT) regimen for metastatic disease. Sunitinib is given at 50 mg daily (OD) for 4 consecutive weeks (wks) followed by 2 wks off. Dose could be reduced to 37.5 mg OD and then 25 mg OD in the setting of toxicity. Imaging is repeated every 12 wks. Primary objectives are objective response rate (ORR by RECIST) and rate of 6-month progression-free survival (PFS). If 1 or more responses occur in the first 15 evaluable pts, the study would continue to a second stage (total = 30 pts). Secondary objectives are time to progression (TTP), overall survival (OS), and safety. Results: We report the results of the first stage of this study. Sixteen pts have been treated (median age: 63; range 41–74) with 37 cycles of sunitinib (median 2; range: 1–7). Baseline ECOG PS was 0 (7 pts), 1 (8 pts), or 2 (1 pt). Histology was endometrioid (7 pts), serous (5 pts), clear cell (1 pt), or mixed/other (3 pts). Most pts had high-grade histology (G3: 8; G2: 4; G1: 2; GX: 2). Nine pts had prior adjuvant CT, 8 pts had 1 prior CT for advanced EC, 4 pts had prior hormones and 7 pts had prior radiotherapy. Partial response was achieved by 2 pts (ORR = 12.5%), and 2 other pts had a best response of stable disease; 3 of these pts remained progression-free > 6 months. Median TTP = 2.5 months (95% CI: 2.47-NR), and median OS = 6.2 months (95% CI: 5.1-NR). Grade 3/4 adverse events (AE) in >10% of pts were fatigue (7 pts, 44%) and hypertension (5 pts, 31%). Dose reduction was required for 11 of 16 pts (69%). Two pts were inevaluable after receiving <2 cycles due to AE (grade 4 hyponatremia; grade 3 fatigue) and 1 other pt has yet to complete 2 cycles. Conclusions: Sunitinib shows preliminary activity in EC. This trial will proceed to a second stage of accrual to further explore the efficacy and safety of sunitinib in advanced EC. [Table: see text]

Phase II study of PX-866 in recurrent glioblastoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 2051-2051
Author(s):  
Marshall W. Pitz ◽  
Mary Valeria MacNeil ◽  
David R. Macdonald ◽  
Ankineedu Saranya Kakumanu ◽  
Brian Thiessen ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Objective Response ◽  
Recurrent Glioblastoma ◽  
Pi3k Inhibitor ◽  
Stage I ◽  
Stage Ii ◽  
Response Data ◽  
Grade 3 ◽  
Recurrent Gbm

2051 Background: Glioblastoma (GBM) is the most aggressive malignancy of the central nervous system. The majority of GBM have genetic changes that increase the activity of the phosphatidylinositol-3-OH kinase (PI3K) signal transduction pathway, critical for cell motility, proliferation, and survival. We present the interim results of PX-866, an oral PI3K inhibitor, in patients (pts) with recurrent GBM. Methods: Pts with histologically confirmed GBM at first recurrence after treatment with chemoradiation and adjuvant temozolomide are given PX-866 8 mg daily on this single-arm phase II study. MRI and clinical exam are done every 8 weeks to determine treatment response. The trial has a 2-stage design with dual endpoints of objective response and early progression (within 8 weeks). In Stage I, 15 pts are evaluated and if 0 responses and 10 or more early progressions are seen, enrolment will stop. Otherwise, Stage II will enrol another 15 pts for efficacy analysis. Tumour tissue is collected for analysis of potential markers of PI3K inhibitory activity (PTEN, EGFRvIII, PIK3CA mutations). Results: Seventeen pts have been enroled to date: 14 evaluable for response and 15 for toxicity. Median age was 54 years (range 35-70), with 7 females and 10 males. No pts had received treatment for recurrent GBM, and median time between initial diagnosis and study enrolment was 300 days (range: 113-447 days). Pts have received a median of one 8-week cycle of PX-866 (range: 1-4). Twelve pts have discontinued therapy, 9 due to disease progression and 3 due to grade 3/4 liver enzyme abnormalities. Other adverse effects have included fatigue (10 pts/1 grade 3), diarrhea (6 pts/3 grade 3), nausea (7 pts/0 grade 3), vomiting (6 pts/0 grade 3), lymphopenia (14 pts/3 grade 3). Stage I response data are premature; it is not yet known if the trial will continue to Stage II. Archival tissue is available on all patients and is undergoing analysis. Conclusions: This is one of the first trials of a PI3K inhibitor in pts with recurrent GBM. PX-866 has been relatively well tolerated. Stage I response data are premature; while it is not yet known if the criteria will be met to continue to Stage II, prolonged SD has been observed in some pts. The correlative biomarker assays underway will be important to understand this observation.

scholarly journals Vandetanib (ZD6474) in the Treatment of Medullary Thyroid Cancer

2011 ◽  
Vol 5 ◽  
pp. CMO.S6197 ◽  
Author(s):  
Hari Deshpande ◽  
Sanziana Roman ◽  
Jaykumar Thumar ◽  
Julie Ann Sosa
Keyword(s):  
Thyroid Cancer ◽  
Growth Factor ◽  
Phase Ii ◽  
Medullary Thyroid Cancer ◽  
Kinase Inhibitor ◽  
Locally Advanced ◽  
Growth Factor Receptor ◽  
Good Choice ◽  
Phase Ii Trials ◽  
Medullary Thyroid

Vandetanib (ZD6474) is an orally bioavailable small molecule tyrosine kinase inhibitor of multiple growth factor receptors, including RET (Rearrange during transfection), vascular endothelial growth factor receptor-2 (VEGFR-2) and epidermal growth factor receptor (EGFR). The activity against RET and VEGF made it a good choice in the treatment of medullary thyroid cancer (MTC). As there is considerable cross talk between growth factor pathways, dual inhibition with such agents has become an attractive strategy, in the treatment of many malignancies with encouraging Phase II clinical trial data to date. Vandetanib was tested in two Phase II trials in the treatment of patients with medullary thyroid cancer at doses of 100 mg and 300 mg daily respectively. The encouraging results of these 2 trials led to a randomized phase II trial comparing this medication to placebo using a crossover design. More than 300 patients were included in this study, which ultimately showed a significant improvement in progression-free survival in patients taking vandetanib. Based on these results, the Oncology Drug Advisory Committee (ODAC) of the Food and Drug Administration (FDA) recommended that vandetanib be approved for the treatment of patients with unresectable locally advanced or metastatic medullary thyroid cancer.

Phase II study of FOLFOX, bevacizumab and erlotinib as initial therapy for patients with metastatic colorectal cancer (MCRC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3545-3545
Author(s):  
J. A. Meyerhardt ◽  
K. Stuart ◽  
A. Zhu ◽  
C. Fuchs ◽  
P. Bhargava ◽  
...  
Keyword(s):  
Growth Factor ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Performance Status ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Initial Therapy ◽  
Tolerability Profile ◽  
Egfr Inhibition ◽  
Grade 3

3545 Background: Cytotoxic chemotherapy with targeted therapy against the vascular endothelial growth factor (VEGF) or the epidermal growth factor receptor (EGFR) has become a standard approach in MCRC, though combining VEGF and EGFR inhibition with chemotherapy as initial treatment is not well established. We conducted a phase II study of the combination of infusional 5-fluorouracil (5-FU), leucovorin, oxaliplatin (FOLFOX), bevacizumab, and erlotinib in chemotherapy naïve patients with MCRC. Methods: Eligible patients had measurable MCRC, no prior systemic therapy for MCRC or at least one year since completion of adjuvant therapy (only 5-FU and leucovorin acceptable), performance status 0–1. The regimen consisted of 14-day cycles of FOLFOX started on day 1 (oxaliplatin 85 mg/m2, bolus 5-FU 400 mg/m2, leucovorin 400 mg/m2 and 46-hour infusion 5-FU 2.4 g/m2), day 1 bevacizumab 5 mg/kg and erlotinib 150 mg daily. This isa single stage trial with goal of 35 patients. The primary endpoint was progression-free survival (PFS). Results: Between Jan and Dec 2005, 31 patients have been enrolled with the following characteristics: male/female, 19/12; PS ECOG 0/1, 15/16; median age 58, range 38–81. Of the 28 patients who completed at least 1 cycle, the most common grade 3/4 adverse events include: 8/28 (29%) diarrhea, 8/28 (29%) neutropenia, 5/28 (18%) rash, 4/28 (14%) fatigue, 3/28 (11%) nausea/vomiting, 3/28 (11%) neuropathy. 22/28 (78%) of patients had at least 1 grade 3/4 toxicity. 14/31 patients remain on trial, 13/31 (42%) came off for toxicity or withdrew consent due to treatment-related toxicities, 4 withdrew consent for other reasons. Efficacy data is not available at time of submission but will be more mature by June 2006. Conclusions: The combination of FOLFOX, bevacizumab and erlotinib appears to have moderate toxicity, with ∼40% of patients coming off trial due to side effects. Further characterization of the tolerability profile will be necessary when interpreting the efficacy of the combination. We expect full accrual as well as reasonable point estimates of PFS by June 2006. Supported by: Sanofi-Synthelabo, a member of the Sanofi-Aventis group, Genentech [Table: see text]

A phase II study of dasatanib (BMS 354825) in recurrent or metastatic ckit-expressing adenoid cystic (ACC) and non-ACC malignant salivary glands tumors (MSGT).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 6022-6022
Author(s):  
Stuart J. Wong ◽  
Ezra E.W. Cohen ◽  
Theodore Karrison ◽  
David N. Hayes ◽  
Merrill S. Kies ◽  
...  
Keyword(s):  
Adverse Events ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Objective Response ◽  
Study Drug ◽  
Protein Product ◽  
Stage I ◽  
Stage Ii ◽  
Best Response ◽  
Grade 3

6022 Background: ACC is a rare disease, accounting for 1/3rd of MSGT, in which 90% of cases express the protein product of the ckit proto-oncogene. Dasatinib is a potent and selective inhibitor of five oncogenic PTKs/kinase families including ckit. We conducted a phase II study to determine the antitumor activity of dasatinib in ACC and non-ACC MSGT. Methods: In a two-stage design, adult patients (pts) with recent radiographic progressive, recurrent or metastatic ACC, + cKIT, were treated with dasatinib 70 mg PO BID. Pts with non-ACC MSGT of other histologic types, were treated as a separate cohort. Response was assessed every 8 wks by imaging using RECIST criteria. The study design stipulated enrollment of n=40 ACC patients (20 in stage I and 20 in stage II) and 25 non-ACC patients (14 in stage I and 11 in stage II). Results: Fifty-four pts were enrolled, 40 ACC and 14 non-ACC. One additional pt was a screen failure. Baseline data on 54 pts are: M:F = 28:26, median age 56.6 yrs (range 20-82), PS 0:1:2 = 24:28:2, prior radiation:chemotherapy = 44:21. The most frequent adverse events experienced (as % of pts, worst grade 2 or higher and at least possibly related to study drug) were: fatigue (28%), nausea (19%), headache (15%), lymphopenia (11%), dyspnea (11%), alanine aminotransferase increased (7%), anorexia (7%), vomiting (7%), alkaline phosphatase increased (6%), diarrhea (6%), and non-cardiac chest pain (6%). No grade 4 adverse events occurred and only 15 pts experienced a grade 3 adverse event (at least possibly attributed to study drug), primarily dyspnea (4 patients) and fatigue (3 patients). Significant cardiac toxicity was observed in one pt (grade 3 prolonged QT corrected interval). Among ACC pts, best response to dasatinib: 0 pts (0%) had PR, 21 pts (52%) had SD (range 2.8-13.8 months), 12 pts (30%) had PD, and 2 died prior to cycle 2. Median PFS was 4.8 mos. For 14 evaluable non-ACC pts, none had an objective response, triggering early stopping. 7 had SD (range 1.4-6.6 months), and 4 PD. Conclusions: Although there were no objective responses, dasatinib is well tolerated, with tumor stabilization achieved by 52% of ACC pts. Dasatinib demonstrated no activity in non-ACC MSGT. Clinical trial information: NCT00859937.

Dovitinib as second-line therapy in patients with fibroblast growth factor receptor 2 (FGFR2)-mutated or non-mutated advanced and/or metastatic endometrial cancer (EC): A single-arm, multicenter, phase II study.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. TPS5616-TPS5616
Author(s):  
Gottfried E. Konecny ◽  
Neil Finkler ◽  
Agustin Garcia ◽  
Francesco Raspagliesi ◽  
Carolina Muriel Lopez ◽  
...  
Keyword(s):  
Growth Factor ◽  
Phase Ii ◽  
Kinase Inhibitor ◽  
Phase Ii Study ◽  
Performance Status ◽  
Growth Factor Receptor ◽  
Second Line ◽  
Open Label ◽  
Second Line Therapy ◽  
Line Therapy

TPS5616 Background: Despite the use of combination chemotherapy and introduction of novel targeted agents, the prognosis for advanced and/or metastatic EC is challenging. The occurrence of somatic activating FGFR2 mutations in EC suggests an opportunity for testing FGFR inhibitors. Dovitnib (DOV) is a potent receptor tyrosine kinase inhibitor of vascular endothelial growth factor receptor, platelet-derived growth factor receptor and FGFR. The objective of the study is to investigate the efficacy and safety of DOV as second-line therapy in patients (pts) with advanced and/or metastatic EC. Methods: This multicenter, non-randomized, open label, single-arm, phase II study (NCT01379534) will enroll adult female pts (N~80) with either FGFR2 mutated (group 1) or non-mutated (group 2) histologically confirmed advanced and/or metastatic EC, who have documented radiological evidence of progressive disease (RECISTv1.1) after 1 prior line of chemotherapy, excluding adjuvant therapy. Eligible pts also need to have ≥1 measurable lesion (RECISTv1.1) and ECOG performance status ≤ 2. Pts will receive oral DOV of 500 mg/day, on a 5-days-on / 2-days-off dosing schedule until disease progression, unacceptable toxicity, death, or discontinuation due to any other reason. Primary endpoint is 18-week progression-free survival (PFS) rate (local review; RECIST v1.1) and secondary endpoints include overall response rate, disease control rate, duration of response, PFS, overall survival, safety, tolerability, pharmacokinetics, and pharmacodynamic effect of DOV on soluble plasma biomarker expression level. A 2-stage design with Bayesian interim monitoring (interim for futility analyses) will be used in each group. For stage 1, 20 pts will be enrolled into each group. If ≥ 8 of the first 20 pts with measurable disease at baseline in either group are progression-free after 18 weeks of treatment, 20 additional pts will be enrolled into that group in stage 2. Preliminary results for each group will be evaluated in the interim analysis. As of 20 January 2013, 43 pts have been enrolled (12 with and 31 without FGFR2 mutations). Clinical trial information: NCT01379534.

scholarly journals Camrelizumab Plus Apatinib in Patients With Advanced Cervical Cancer (CLAP): A Multicenter, Open-Label, Single-Arm, Phase II Trial

2020 ◽  
Vol 38 (34) ◽  
pp. 4095-4106
Author(s):  
Chunyan Lan ◽  
Jingxian Shen ◽  
Yin Wang ◽  
Jundong Li ◽  
Zhimin Liu ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Phase Ii ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Advanced Cervical Cancer ◽  
Open Label ◽  
Duration Of Response ◽  
Grade 3

PURPOSE Camrelizumab is an antibody against programmed death protein 1. We assessed the activity and safety of camrelizumab plus apatinib, a tyrosine kinase inhibitor of vascular endothelial growth factor receptor-2, in patients with advanced cervical cancer. METHODS This multicenter, open-label, single-arm, phase II study enrolled patients with advanced cervical cancer who progressed after at least one line of systemic therapy. Patients received camrelizumab 200 mg every 2 weeks and apatinib 250 mg once per day. The primary end point was objective response rate (ORR) assessed by investigators per RECIST version 1.1. Key secondary end points were progression-free survival (PFS), overall survival (OS), duration of response, and safety. RESULTS Forty-five patients were enrolled and received treatment. Median age was 51.0 years (range, 33-67 years), and 57.8% of patients had previously received two or more lines of chemotherapy for recurrent or metastatic disease. Ten patients (22.2%) had received bevacizumab. Median follow-up was 11.3 months (range, 1.0-15.5 months). ORR was 55.6% (95% CI, 40.0% to 70.4%), with two complete and 23 partial responses. Median PFS was 8.8 months (95% CI, 5.6 months to not estimable). Median duration of response and median OS were not reached. Treatment-related grade 3 or 4 adverse events (AEs) occurred in 71.1% of patients, and the most common AEs were hypertension (24.4%), anemia (20.0%), and fatigue (15.6%). The most common potential immune-related AEs included grade 1-2 hypothyroidism (22.2%) and reactive cutaneous capillary endothelial proliferation (8.9%). CONCLUSION Camrelizumab plus apatinib had promising antitumor activity and manageable toxicities in patients with advanced cervical cancer. Larger randomized controlled trials are warranted to validate our findings.

scholarly journals Report of a Multicenter Phase II Trial Testing a Combination of Biweekly Bevacizumab and Daily Erlotinib in Patients With Unresectable Biliary Cancer: A Phase II Consortium Study

2010 ◽  
Vol 28 (21) ◽  
pp. 3491-3497 ◽  
Author(s):  
Sam J. Lubner ◽  
Michelle R. Mahoney ◽  
Jill L. Kolesar ◽  
Noelle K. LoConte ◽  
George P. Kim ◽  
...  
Keyword(s):  
Growth Factor ◽  
Phase Ii ◽  
Kinase Inhibitor ◽  
Evaluation Criteria ◽  
Growth Factor Receptor ◽  
Primary Objective ◽  
Clinical Activity ◽  
Biliary Cancer ◽  
Vegf Inhibitor ◽  
Grade 3

Purpose Biliary cancers overexpress epidermal growth factor receptor (EGFR), and angiogenesis has been correlated with poor outcome. Erlotinib, an EGFR tyrosine kinase inhibitor, and bevacizumab, a vascular endothelial growth factor (VEGF) inhibitor have each been shown to have activity in biliary cancer. The primary objective of this study was to evaluate the response rate by Response Evaluation Criteria in Solid Tumors (RECIST). Secondary end points included overall survival (OS), time to progression (TTP), VEGF levels, and molecular studies of EGFR and k-ras. Patients and Methods Eligible patients had advanced cholangiocarcinoma or gallbladder cancer. Patients were treated with bevacizumab 5 mg/kg intravenously on days 1 and 15 and erlotinib 150 mg by mouth daily on days 1 through 28. Responses were evaluated by RECIST. VEGF levels were collected, and samples were analyzed for EGFR mutation by polymerase chain reaction. Results Fifty-three eligible patients were enrolled at eight sites. Of 49 evaluable patients, six (12%; 95% CI, 6% to 27%) had a confirmed partial response. Stable disease was documented in another 25 patients (51%). Rash was the most common grade 3 toxicity. Four patients had grade 4 toxicities. Median OS was 9.9 months, and TTP was 4.4 months. Low repeats (< 16) in EGFR intron 1 polymorphism and G>G k-ras Q38 genotype (wild type) were associated with improved outcomes. Conclusion Combination chemotherapy with bevacizumab and erlotinib showed clinical activity with infrequent grade 3 and 4 adverse effects in patients with advanced biliary cancers. On the basis of preliminary molecular analysis, presence of a k-ras mutation may alter erlotinib efficacy. The combination of bevacizumab and erlotinib may be a therapeutic alternative in patients with advanced biliary cancer.

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