A phase II study of combination epigenetic therapy in metastatic colorectal cancer (mCRC): A phase II consortium (P2C)/Stand Up 2 Cancer (SU2C) study.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3539-3539
Author(s):  
Nilofer Saba Azad ◽  
Anthony B. El-Khoueiry ◽  
Michelle R. Mahoney ◽  
Douglas Adkins ◽  
Patrick J. Flynn ◽  
...  
Keyword(s):  
Phase Ii ◽  
Urinary Tract Obstruction ◽  
Circulating Tumor Dna ◽  
In Vivo Studies ◽  
Epigenetic Therapy ◽  
Clinical Activity ◽  
Eligibility Criteria ◽  
Background Therapy ◽  
Ecog Ps

3539 Background: Therapy with decitabine and entinostat (ENT: HDAC inhibitor) shows synergistic effect in re-expression of tumor-suppressor genes and growth inhibition in CRC cell lines and in vivo studies. Methods: We conducted a phase II, multi-institutional study of SQ 5-azacitidine (AZA) and oral ENT in mCRC pts. A 28 day cycle included: AZA at 40 mg/m2 d1-5 and 8-10 with ENT 7 mg d3 and 10. Initial eligibility criteria included: ECOG PS 0-1, good end organ function, and biopsiable disease for cohort A (CoA). An interim analysis indicated that toxicity which crossed pre-specified safety boundary was secondary to disease. A 2nd cohort B (CoB) with eligibility restrictions: <2 prior regimens in KRAS-mutated CRC pts, <3 prior regimens if KRAS wild-type, and liver disease limited to <30% of volume was accrued. Serial tumor biopsies and research blood were collected to assess for methylation/expression changes in circulating tumor DNA and biopsies, respectively. The primary endpoint was response as measured by RECIST criteria using a 2-stage Simon design. Results: 47 pts were initially enrolled (24 CoA, 23 CoB). Pts received a median of 2 cycles on both cohorts (1-16 CoA, 2-6 CoB). Pts had a median of 4 prior therapies for CoA (range 2-9) and 3 for CoB (range 2-6). Gr 4 AEs attributable to treatment for CoA included hyperglycemia (1) and hypokalemia (1); other common Gr 3 AEs included anemia (3), decreased lymphocytes (7), fatigue (3), and nausea (3). CoB pts experienced grade 3 chest pain (1), neutropenia (2), leucopenia (2), urinary tract obstruction (1), and hypophosphatemia (1). No responses have been observed. Results of translational objectives will be presented at the meeting. Conclusions: SQ AZA and ENT therapy does not have clinical activity as defined by confirmed response in aCRC. Follow-up for survival, response to subsequent therapy, and correlative analysis are ongoing. Supported in part by N01-CM-2011-00099. Clinical trial information: NCT01105377. [Table: see text]

International multicenter phase II study of the HDAC inhibitor (HDACi) depsipeptide (FK228) in cutaneous T-cell lymphoma (CTCL): Interim report

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3063-3063 ◽  
Author(s):  
S. Whittaker ◽  
W. McCulloch ◽  
T. Robak ◽  
E. Baran
Keyword(s):  
T Cell ◽  
Clinical Activity ◽  
Open Label ◽  
Eligibility Criteria ◽  
Cell Counts ◽  
T Cell Lymphomas ◽  
The Uk ◽  
Ecog Ps

3063 Background: Depsipeptide, a unique bicyclic peptide histone deacetylase inhibitor (HDACi), has shown activity in a range of in vitro and in vivo tumor models and clinical activity in T-cell lymphomas and prostate cancer. This study seeks to confirm the CTCL activity previously reported by the NCI (Piekarz, et al., ASCO, 2004). Methods: Single-arm, open label study, in 25 centers in the UK, Germany, Poland and the US. Patients aged ≥18 years with biopsy-confirmed CTCL (centrally reviewed) who have failed at least one prior systemic treatment receive up to 6 cycles of depsipeptide as a 4-hour IV infusion on Days 1, 8 and 15 q 28 days. Eligibility criteria include: mycosis fungoides and Sézary syndrome plus variants, Stages IB - IVA, adequate organ function, ECOG PS ≤ 1. Patients with significant cardiovascular abnormalities are excluded in addition to those taking QTc-prolonging or CYP3A4-inhibiting drugs. The primary endpoint is overall reponse rate measured by a combination of imaging, circulating cell counts and a weighted skin average instrument, confirmed by standardized photography. A subset undergoes pharmacokinetic assessments. Correlative studies include acetylation status, apoptotic markers and proteomic analyses where possible. Target accrual is 76 to yield 64 evaluable patients. Results: 30 patients have received treatment with 17 evaluable for efficacy. Responses seen are 1 cCR, 4 PRs (duration 2+ to 6 months) 9 SD and 3 PD. 3 patients withdrew early for PD and 2 for other reasons. The remaining patients on study are too early to assess. Most frequent toxicities are: nausea/vomiting, fatigue, myelosuppression and asymptomatic ECG changes. No patient has withdrawn for toxicity and there have been no treatment-related deaths. Conclusions: The previously reported efficacy of depsipeptide in CTCL has also been seen in the present study. Duration of response is encouraging. Toxicity is manageable and the study continues to accrue. [Table: see text]

Pembrolizumab treatment of advanced neuroendocrine tumors: Results from the phase II KEYNOTE-158 study.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 190-190 ◽  
Author(s):  
Jonathan R. Strosberg ◽  
Nobumasa Mizuno ◽  
Toshihiko Doi ◽  
Enrique Grande ◽  
Jean-Pierre Delord ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Neuroendocrine Tumors ◽  
Phase Ii ◽  
Tumor Imaging ◽  
Unknown Primary ◽  
Clinical Activity ◽  
Eligibility Criteria ◽  
Biomarker Analysis ◽  
Ecog Ps

190 Background: Data from the KEYNOTE-028 study (NCT02054806) suggested that pembrolizumab (pembro) has clinical activity in a subset of patients (pts) with heavily pretreated neuroendocrine tumors (NET). The KEYNOTE-158 study (NCT02628067) is a phase II basket study investigating the antitumor activity of pembro in 10 specific cancer types. An analysis of the 107 pts included in the NET cohort is presented. Methods: Key eligibility criteria for this cohort included well- and moderately-differentiated NET of the lung, appendix, small intestine, colon, rectum, or pancreas; progression on or intolerance to ≥ 1 line of standard therapy; ECOG PS 0 or 1; and provision of a tumor sample for biomarker analysis. Pts received pembrolizumab 200 mg Q3W for 2 y or until progression, intolerable toxicity, or physician or patient decision. Tumor imaging was performed every 9 wks for the first 12 mo, and every 12 wks thereafter. PD-L1 positivity, defined as a combined positive score (CPS) ≥ 1, was evaluated retrospectively by IHC. Primary endpoint was ORR assessed per RECIST v1.1 by independent central radiology review. Secondary endpoints included DOR, PFS, OS, and safety. Results: 107 pts were treated. Median age was 59 (range, 29-80) y, 44.9% had ECOG PS 1, and 67.3% received ≥ 2 prior therapies for advanced disease. 15.9% of enrolled pts had PD-L1+ tumors. As of the January 15, 2018 data cutoff, the median follow-up duration was 18.6 (range, 0.2-22.7) mo. ORR was 3.7% (95% CI, 1.0-9.3), with 0 CR and 4 PR (3 pancreatic and 1 gastrointestinal [unknown primary]). 61 pts had SD as best response. The 4 responses were observed in pts with PD-L1 negative tumors. Median DOR had not been reached (range, 4.1-15.9+), with 3 of 4 responses ongoing after ≥ 9 mo follow-up. Median (95% CI) PFS was 4.1 (3.5-5.4) mo, and the 6-mo PFS rate was 38.2%. Median OS (95% CI) had not been reached (18.8-not reached), and the 6-mo OS rate was 84.6%. Treatment-related AEs occurred in 75.7% of pts, and the most common was fatigue (21.5%). 20.6% of pts had treatment-related grade 3-4 AEs. Conclusions: Pembrolizumab monotherapy showed limited antitumor activity and manageable safety in pts with previously treated advanced NET. Clinical trial information: NCT02628067.

A phase II trial of carboplatin (C) and nab-paclitaxel (ABI-007-nab-P) in patients with unresectable stage IV melanoma: Final data from N057E

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 9055-9055
Author(s):  
S. N. Markovic ◽  
V. J. Suman ◽  
L. A. Kottschade ◽  
T. Amatruda ◽  
R. R. McWilliams ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Stage Iv ◽  
Median Number ◽  
Clinical Activity ◽  
Eligibility Criteria ◽  
Unresectable Stage ◽  
Number Of Cycles ◽  
Ecog Ps ◽  
Stage Iv Melanoma

9055 Background: There is increasing evidence that paclitaxel and carboplatin are clinically active in the treatment of metastatic melanoma (MM). Nab-P is an albumin-bound paclitaxel with ability to bind SPARC (secreted protein acid rich in cysteine), that is overexpressed in MM and associated with poor prognosis. This study explores the clinical activity of the combination of nab-P and C in patients (pts) with stage IV melanoma and SPARC correlatives. Methods: A parallel phase II trial was conducted in pts with unresectable stage IV melanoma, who were either chemotherapy naïve (CN) or were previously treated (PT). A treatment regimen consisting of nab-P (100 mg/m2) and C (AUC 2) was administered on days 1, 8, and 15 of a 28 day cycle. The primary aim of this study was to assess whether tumor response rate (CR + PR by RECIST) was ≤15% vs ≥35% in the CN group and ≤5% vs ≥ 20% in the PT cohort. Major eligibility criteria: ≥18 years of age, ECOG PS ≤2, adequate organ function, platinum or taxane naive, peripheral neuropathy < grade 2, and no untreated brain metastasis; no pregnant and/or nursing women. Tumor tissue was tested for SPARC and level 3 immunohistochemical staining was considered positive. Results: 76 pts (41-CN and 35 PT) enrolled from 11/2006 - 7/2007, 3 pts (2-CN, 1-PT) cancelled prior to starting treatment. The median number of cycles administered was 4 (range 1–18-CN and 1–10-PT). There were 11 (28.2%) confirmed responses (1 CR and 10 PRs) in the CN cohort (90% CI: 16.7–42.3%) and 3 (8.8%) confirmed responses (3 PRs) in the PT cohort (90% CI: 2.5–21.3%). Median PFS was 4.5 months (CN) and 4.1 months (PT). Median OS was 11.1 months (CN) and 10.9 months (PT).The most common severe toxicities in both groups (CTCAE ≥ grade 3) included neutropenia, thrombocytopenia, neuro-sensory, fatigue, nausea, and vomiting. PFS was not affected by SPARC positivity; however, based on limited data there is some evidence that OS may be longer with tumoral SPARC positivity (10.0 vs 12.8 mo; SPARC negative vs SPARC positive). Conclusions: The weekly combination of nab-P and C appears to be well tolerated with promising clinical activity as front line or salvage therapy in pts with MM. SPARC positivity may be associated with improved OS. No significant financial relationships to disclose.

scholarly journals Medicinal Plants with Anti-Trichomonas vaginalis Activity in Iran: A Systematic Review

2019 ◽  
Author(s):  
Hajar ZIAEI HEZARJARIBI ◽  
Najmeh NADEALI ◽  
Mahdi FAKHAR ◽  
Masoud SOOSARAEI
Keyword(s):  
Systematic Review ◽  
Medicinal Plants ◽  
Trichomonas Vaginalis ◽  
Scientific Information ◽  
Medicinal Herbs ◽  
In Vivo Studies ◽  
Eligibility Criteria ◽  
Sexually Transmitted

Background: Trichomoniasis, due to Trichomonas vaginalis, is one of the most common sexually transmitted parasitic diseases in the world such as Iran. This systematic review aimed to explore the studies evaluating the medicinal herbs with anti- T. vaginalis activity which used in Iran. Methods: Articles published in 4 Persian and 4 English databases were obtained between 2000 and 2015 including Google Scholar, PubMed, Science Direct, Scopus, Magiran, Barakatkns (formerly IranMedex), Elm net, and SID (Scientific Information Database). Studies out of Iran, studies on animal models and articles on other parasite species than T. vaginalis were excluded from this review. Results: Twenty-one articles including in vitro experiments, met our eligibility criteria. Thoroughly, 26 types of plants were examined against T. vaginalis. Medicinal herbs such as Artemisia, Zataria multiflora, and Lavandula angustifolia are remarkably effective on T. vaginalis. As such, use of other parts of these plants in different concentrations and timelines is recommended for future in vivo studies. Conclusion: The present systematic review provides comprehensive and useful information about Iranian medicinal plants with anti-T. vaginalis activity, which would be examined in the future experimental and clinical trials and herbal combination therapy.

A phase I study of oral darinaparsin in patients (pts) with advanced solid tumors (AST).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e13040-e13040
Author(s):  
Luis H. Camacho ◽  
Neil N. Senzer ◽  
Wael A. Harb ◽  
John A Barrett ◽  
Christopher Charles Korth ◽  
...  
Keyword(s):  
Oral Formulation ◽  
Preliminary Evidence ◽  
Clinical Activity ◽  
Drug Discontinuation ◽  
Serum Trough ◽  
Grade 3 ◽  
Ecog Ps ◽  
Trough Levels

e13040 Background: Darinaparsin [Zinapar, ZIO-101(S-dimethylarsino-glutathione)], is a novel organic arsenic compound with in vitro and in vivo anticancer activity in tumor cell lines resistant to arsenic trioxide. An oral formulation is now available. Methods: This study used a 3+3 escalating design, dosing orally for 21 days followed by 7 days off (28 day cycle). Pts with AST refractory to standard therapy, ECOG performance score (PS) ≤ 2 and adequate organ function were treated. Study objectives were safety profile evaluation, pharmacokinetics (PK) and preliminary activity of oral darinaparsin. CTCAE v. 4.0 and RECIST 1.1 were used. Results: A total of 10 pts (8 males, 2 females), with ECOG PS 0=2, 1=8, mean age of 71 years (range: 60-81), median of prior therapies 3 (range: 1-4) were treated. A median of 2 cycles of darinaparsin was administered (range: 1-6). Dose limiting toxicities (DLT) were confusion (n=1; 400 mg), cognitive disturbance (n=1; 400 mg) and encephalopathic syndrome (n=1; 300 mg), reversible with drug discontinuation. The highest tolerable dose was 300 mg per day. Most frequent AEs were: hypokalemia, nausea (40% each), fatigue (30%), anemia, diarrhea, hypophosphatemia, pneumonia, vomiting (20% each). Most frequent grade ≥3 AEs were: hypokalemia, hypophosphatemia (20% each). Best overall response was stable disease (at 2 cycles), observed in 5 pts: adenocarcinoma of colon (2 pts), chordoma, adenocarcinoma of small bowel and carcinoma of tongue. PK analysis of 400 mg cohort (n=4) and 300 mg cohort (n=6) resulted in Tmax at 9 hr post treatment and Cmax slightly greater than dose proportional (p<0.05). Steady-state trough levels were achieved on or before Day 5. Approximately 40 % greater Cmax was observed on D15 compared to D1 for the 300 mg cohort (p<0.05) while unchanged at 400 mg. DLTs were observed when duration of exposure was more than 7 days and serum trough levels were 800 ng/ml or above. Conclusions: Oral darinaparsin is well tolerated at the dosage of 300 mg per day for 21days in a 28 day cycle in pts with AST. Preliminary evidence of clinical activity and a predictable PK profile justify further evaluation of darinaparsin in selected indications.

Phase II trial of the phosphatidyinositol-3 kinase (PI3K) inhibitor BKM120 in recurrent glioblastoma (GBM).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 2015-2015 ◽  
Author(s):  
Patrick Y. Wen ◽  
W. K. Alfred Yung ◽  
Ingo K. Mellinghoff ◽  
Kathleen Lamborn ◽  
Shakti Ramkissoon ◽  
...  
Keyword(s):  
Phase Ii ◽  
Pi3k Pathway ◽  
Homozygous Deletion ◽  
Recurrent Glioblastoma ◽  
Pi3k Inhibitor ◽  
Eligibility Criteria ◽  
Drug Concentrations ◽  
Recurrent Gbm

2015 Background: The PI3K pathway is activated in most GBMs and represents a potential therapeutic target. BKM120 is an oral, pan-Class I PI3K inhibitor that enters the brain at therapeutic concentrations demonstrated to inhibit PI3K pathway, and potently inhibits the growth of U87 GBM tumors and human glioma tumor spheres in vitro and in vivo. Methods: The Ivy Foundation Early Phase Clinical Trials Consortium is conducting a phase II study of BKM120 in recurrent GBM patients with activation of the PI3K pathway (mutation, homozygous deletion or loss of IHC of PTEN, PIK3CA or PIK3RI mutations, or detectable pAKT). Additional eligibility criteria included radiologic progression, 1st or 2nd relapse, > 18 yrs, KPS > 60, adequate bone marrow and organ function, controlled blood glucose, and no enzyme-inducing antiepileptic drugs. Patients received BKM120 100mg daily. The study consisted of 2 parts conducted concurrently. Part 1 involved up to 15 patients who received BKM120 daily for 8-12 days prior to surgery for recurrent disease. Patients underwent FDG PET, pharmacokinetic (PK) studies, and tumor was obtained for drug concentrations and pharmacodynamic effects. Part 2 consisted of up to 50 patients with unresectable GBM treated with BKM120. The primary endpoint for Part 2 was 6-month progression-free survival (p0 =15%; p1= 32%). Results: To date 7 patients have been enrolled into Part 1, 33 into part 2. There were 5 women and 35 men. Median age was 54 yrs (29-68). Treatment was fairly well-tolerated. Major grades 3/4 toxicities were asymptomatic lipase elevation (5), fatigue (3), hyperglycemia (3), rash (3) elevated AST (1), and depression (1). Analysis of tumor from Part 1 showed reduction of pAkt by IHC. Genotyping of tumor specimens is ongoing. To date 33 patients had positive pAkt, 21 had PTEN loss by IHC. Of the first 19 patients who underwent whole exome sequencing, 3 had PIK3Ca mutations and 6 had PTEN mutations. Conclusions: BKM120 is generally well tolerated in patients with recurrent GBM and achieves adequate tumor concentration to inhibit pAkt. Updated PK and efficacy data and correlation of the latter with tumor genotype will be presented. Clinical trial information: NCT01339052.

Bevacizumab (Bmab) in combination with uracil-tegafur (UFT) and oral leucovorin (LV) in elderly patients (≥ 75 years old) with metastatic colorectal cancer (mCRC): A multicenter phase II trial (J-BLUE study).

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 588-588
Author(s):  
Mitsuo Shimada ◽  
Tomohiro Nishina ◽  
Jun Higashijima ◽  
Toshikazu Moriwaki ◽  
Toshiki Masuishi ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Elderly Patients ◽  
Phase Ii ◽  
Performance Status ◽  
Progression Free Survival ◽  
Open Label ◽  
Effective Treatment Option ◽  
Ecog Performance Status ◽  
Eligibility Criteria ◽  
Ecog Ps

588 Background: Now fluoropyrimidine plus Bmab is considered a recommendable option to the majority of elderly mCRC patients who are deemed inappropriate for the standard doublet chemotherapy with biologics. Our previous phase II study of UFT/ LV in elderly mCRC patients (≥75 years old) had demonstrated acceptable safety and efficacy (overall response rate [ORR] 33%, progression-free survival [PFS] 5.3 months, overall survival [OS] 18 months). The aim of the present study was to investigate the efficacy and safety of Bmab in combination with UFT/LV for elderly mCRC patients. Methods: This study was designed as a single-arm, open-label, multicenter, cooperative group (SGOSG-TCTG) clinical trial (trial registration: UMIN000003515). Key eligibility criteria included age ≥75 years, ECOG performance status (PS) 0 or 1, first-line chemotherapy, measurable lesions, and preserved organ functions. Patients received UFT 300mg/m2/day and LV 75mg/body/day on days 1-21 followed by 7 days rest, and intravenous administration of Bmab 5mg/kg on days 1 and 15. Treatment repeated every 28 days. The primary endpoint was PFS, and secondary endpoints were ORR, OS, and safety. Results: A total of 55 patients were enrolled from 15 institutions between Aug 2008 and Mar 2012. Among them, 52 eligible patients were evaluated. Median age was 80 years (range: 75-87). ECOG PS 0 was 73%. Median PFS was 8.2 months (95% confidence interval [CI], 6.2-10.3, events in 86.5%). Confirmed ORR was 40.4% (95% CI, 27.0-54.9%). Median OS was 18.7 months (95% CI, 10.3-27.0, events in 48%). The most common grade ≥3 treatment-related adverse events were hypertension (11.5%), fatigue (7.7%), nausea (5.8%), and diarrhea (5.8%). The treatment-related death occurred in 2 (3.8%) patients. Main reasons for discontinuation of treatment were disease-progression (62.5%) and toxicity (27.1%). Conclusions: Bmab in combination with UFT/LV is tolerable and effective treatment option for elderly patients (≥75 years old) with mCRC. Further trial with Bmab plus UFT/LV targeting elderly mCRC patients would be warranted. Clinical trial information: 000003515.

MS201944-0170: A phase IIa study to investigate the clinical activity and safety of avelumab in combination with cetuximab plus gemcitabine and cisplatin in patients with advanced squamous NSCLC.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS9123-TPS9123
Author(s):  
Fortunato Ciardiello ◽  
Manuel Cobo Dols ◽  
Oscar Juan Vidal ◽  
Luis G. Paz-Ares ◽  
Javier de Castro Carpeño ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Stage Iv ◽  
Clinical Activity ◽  
Alk Rearrangement ◽  
Eligibility Criteria ◽  
Prior Therapy ◽  
Platinum Based Chemotherapy ◽  
Treatment Naïve ◽  
Ecog Ps ◽  
Gemcitabine And Cisplatin

TPS9123 Background: Preclinical studies have demonstrated that cetuximab plus chemotherapy results in immunogenic cell death and an increase in CD8+ T cells in the tumor microenvironment. Avelumab (an anti–PD-L1 antibody) has previously shown antitumor activity in NSCLC. We hypothesize that the combination of cetuximab with platinum-based chemotherapy and avelumab may have synergistic antitumor activity. Methods: This phase IIa, single-arm, multicenter study is investigating the clinical activity and safety of avelumab in combination with cetuximab plus gemcitabine and cisplatin in patients with advanced squamous NSCLC who are treatment naive in the advanced setting (NCT03717155). Eligibility criteria include histologically confirmed stage IV, metastatic or recurrent NSCLC with squamous histology, with no prior systemic therapy for metastatic NSCLC, no prior therapy with any antibody/drug targeting T-cell coregulatory proteins, and ECOG PS of 0 to 1. Patients with a tumor harboring an activating EGFR mutation or ALK rearrangement are excluded. Patients will receive doublet chemotherapy (cisplatin 75 mg/m2 on day 1, gemcitabine 1250 mg/m2 on days 1 and 8), cetuximab on days 1 (250 mg/m2) and 8 (500 mg/m2), and avelumab 800 mg on days 1 and 8 for a total of four 3-week cycles. Thereafter, avelumab (800 mg) and cetuximab (500 mg/m2) will be administered as maintenance treatment Q2W until disease progression, unacceptable toxicity, or withdrawal. Enrollment in a safety run-in, which will evaluate the safety and tolerability of avelumab in combination with cetuximab plus gemcitabine and cisplatin, is planned for the first 6 patients. Enrollment began on October 30, 2018. Study enrollment will continue until approximately 40 evaluable patients have been recruited. The primary endpoint is confirmed best overall response per RECIST 1.1 by investigator assessment. Secondary endpoints include safety (NCI CTCAE v5.0) and tolerability of the combination, duration of response, survival, and tumor biomarkers. The study is ongoing at sites in Hungary and Spain. Clinical trial information: NCT03717155.

Activity of irofulven (IROF) combined with capecitabine (CAPE) in patients (pts) with advanced thyroid carcinoma: Phase II international multicenter study (preliminary results)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 15511-15511
Author(s):  
J. Droz ◽  
E. Baudin ◽  
V. Medvedev ◽  
J. Delord ◽  
M. Kane ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Phase Ii ◽  
Objective Response ◽  
Median Number ◽  
Eligibility Criteria ◽  
Prior Chemotherapy ◽  
Advanced Thyroid Cancer ◽  
International Multicenter Study ◽  
Ecog Ps ◽  
International Multicenter

15511 Background: IROF, the first compound of the acylfulvene class to enter clinical trials, has demonstrated antitumor activity in a variety of chemoresistant tumors. Currently available chemotherapy offers limited benefit to pts with advanced thyroid cancer. A phase I trial of an IROF/CAPE combination showed confirmed partial responses in 2/4 pts (Alexandre, ASCO 2003). An international multicenter 2-stage, phase II trial was initiated to evaluate the objective response rate (RECIST) in pts with advanced thyroid cancer. Methods: Eligibility criteria included advanced Differentiated, Medullary or Anaplastic (D/M/A) thyroid cancer, ECOG PS 0–2, no benefit from prior I131 and ≤1 prior chemotherapy regimen. Pts received IROF 0.4 mg/kg (30 min IV infusion), days 1 and 15 and CAPE orally 2000 mg/m2 day 1 to 15 every 28 days. Results: As of Dec-05, 23 pts (D/M/A: 14/5/4) have been treated. Pt characteristics are (D/M/A); median age: 60/55/61 years (range 34–74), median PS: 1/1/1; prior chemotherapy in 4/1/2 pts; all had metastatic disease predominantly lung, bone and lymph nodes, with a median of 2/1/3 sites of metastasis. Median number of cycles given was 5/4/1. Efficacy: All pts are evaluable. No objective responses observed to date, SD was observed in 11 (79%)/ 3 (60%)/0 pts with median duration 4.8/5.2/0 months; 2/11 (D) pts with SD had 14% and 19% decreases in tumor size. Safety: Main adverse events were thrombocytopenia (grade [G] 1–2: 24% pts), neutropenia (G1–2: 17%; G3: 4%), nausea (G1–2: 41%), asthenia (G1–2: 41%); 1 pt had G3 asthenia. No pts discontinued due to toxicity. Conclusions: No objective responses were observed in pts with differentiated thyroid cancer treated with IROF/CAPE every 2 weeks, with 79% SD. Tolerance was acceptable and accrual is ongoing in the anaplastic cohort. [Table: see text]

Comparable safety and response rate with bevacizumab in combination with capecitabine/oxaliplatin (CapOx/Bev) versus capecitabine/irinotecan (CapIri/Bev) in advanced CRC (mCRC): A randomized phase II study of the AIO GI tumor study group

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4034-4034 ◽  
Author(s):  
W. H. Schmiegel ◽  
A. Reinacher-Schick ◽  
W. Freier ◽  
G. Dietrich ◽  
D. Arnold ◽  
...  
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Treatment Plan ◽  
Phase Iii ◽  
Tumor Control ◽  
Eligibility Criteria ◽  
Randomized Phase Ii ◽  
Hand Foot Syndrome ◽  
Ecog Ps ◽  
Unacceptable Toxicity

4034 Background: Bevacizumab (Bev) combined with 5-FU/FA and both, irinotecan or oxaliplatin are standard regimens for mCRC. Recently, a phase III trial has demonstrated that infusional 5-FU can be substituted by capecitabine (cape) when combined with oxaliplatin and Bev whereas conflicting data are available for feasibility and efficacy of cape/irinotecan combinations. This randomized phase II trial was to compare safety and efficacy of Bev with either CapOx or CapIri in untreated mCRC. Methods: Eligibility criteria: untreated mCRC pts, ECOG PS <= 2, measurable lesion(s), adequate hematologic and organ function. Primary endpoint was % of pts progression-free after 6 months. Treatment plan: Bev 7.5 mg/kg day (d)1 with either oxaliplatin (130 mg/m2 d1)/cape (1,000 mg/m2 bid d1–14; CapOx/Bev, arm A) or irinotecan (200 mg/m2 d1)/cape (800 mg/m2 bid d 1–14; CapIri/Bev, arm B), all q d22. Arm B doses were 20% lower for both, cape and irinotecan, compared to previous trials reporting an unacceptable toxicity profile (Köhne, ASCO 2005). Treatment was continued until progression or unacceptable toxicity. Results: So far, toxicity data are available on 228 (118/110 pts arm A/B) of total 240 pts. Baseline characteristics (arm A/B): median age 64/65 yrs, male 67%/68%. A total of 684/719 cycles (median 6/6 cycles) have been administered. Most common CTC grade 3/4 toxicities (% of pts): Diarrhea 17.0/15.5, hand-foot-syndrome 5.9/2.7, peripheral neuropathy 15.3/0.0. Specific AE′s such as thrombosis, 3° hypertension and GI perforation occurred in 3.4/4.5%, 3.4/0.9% and 0.9/0.9% of pts, respectively. Among 185 evaluable pts (96/89), tumor control rates (CR+PR+SD) in arm A/B were 81.4%/82.8%, overall response rates (CR+PR) were 49.0%/52.7%. Conclusions: Both regimens, CapOx/Bev and CapIri/Bev, are well tolerated without differences in toxicity (except neuropathy). Interestingly, despite the protocol defined dose reduction of CapIri there is seemingly no difference in efficacy as measured by tumor control and response rate. Meanwhile, the trial has finished accrual and data including PFS rate will be presented at the meeting. [Table: see text]

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