Randomized phase II study of vandetanib (VAN) alone or in combination with carboplatin and paclitaxel (CP) as first-line treatment for advanced non-small cell lung cancer (NSCLC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7544-7544 ◽  
Author(s):  
J. Heymach ◽  
L. Paz-Ares ◽  
F. De Braud ◽  
M. Sebastian ◽  
D. J. Stewart ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Objective Response ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Circulating Endothelial Cells ◽  
Once Daily ◽  
Randomized Phase Ii ◽  
Biomarker Analysis

7544 Background: VAN (ZD6474) is a once-daily oral agent that selectively inhibits VEGFR, EGFR and RET signaling. This randomized phase II trial investigated VAN alone or in combination with CP vs CP. Methods: Eligible patients (pts) had previously untreated locally advanced or metastatic (IIIB-IV) NSCLC. The primary objective was to determine whether VAN (300 mg/day) ± CP (C, target AUCss = 6 mg/ml·min; P; 200 mg/m2 iv) prolonged progression-free survival (PFS) vs CP (75% power to detect 30% prolongation; 1-sided P=0.2). An initial run-in phase had established VAN 300 mg/day as an appropriate dose to be given with CP. Results: A total of 181 pts (median age 61 yrs, range 27–83) received VAN (n=73), VAN + CP (n=56) or CP (n=52). The primary objective was met, with VAN + CP prolonging PFS vs CP (HR = 0.76, 95% CI 0.50–1.15; P=0.098): median PFS = 24 wks (VAN + CP) and 23 wks (CP). The VAN monotherapy arm was stopped early after a planned interim PFS analysis met the criterion for discontinuation (HR > 1.33 vs CP). The objective response rates were 32%, 25% and 7% for VAN + CP, CP and VAN, respectively. Overall survival (OS), a secondary endpoint, was not significantly different between pts receiving VAN + CP or CP (HR = 1.07, 95% CI 0.63–1.81; P=0.595). Exploratory subgroup analyses suggest advantages in PFS and OS for VAN + CP vs CP for the 56 female pts. There was a higher incidence of some adverse events with VAN + CP vs CP, including rash (64% vs 33%), diarrhea (53% vs 32%), asymptomatic QTc-related events (22% vs 4%) and hypertension (32% vs 4%). Pts receiving VAN + CP, including 7 who entered with CNS metastases and 11 with squamous histology, did not experience any intracranial bleeding, or hemoptysis of CTC grade 2 or higher. A biomarker analysis, including circulating endothelial cells and 35 plasma angiogenic factors and cytokines, suggests several potential markers predictive of clinical outcome and will be reported separately. Conclusions: In this randomized phase II trial of 1st-line advanced NSCLC, VAN + CP met the primary endpoint of prolonging PFS vs CP alone but did not provide a detectable survival advantage. No significant financial relationships to disclose.

A randomized phase II trial of weekly docetaxel plus either cisplatin or oxaliplatin in patients with previously untreated advanced gastric cancer: Preliminary results

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4566-4566
Author(s):  
S. Sym ◽  
S. Park ◽  
J. Park ◽  
K. Kwon ◽  
I. Jung ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Objective Response ◽  
Progression Free Survival ◽  
Tolerability Profile ◽  
Preliminary Results ◽  
Weekly Docetaxel ◽  
Randomized Phase Ii ◽  
Significant Difference

4566 Background: Docetaxel, in combination with cisplatin or oxaliplatin, has demonstrated efficacy against AGC. This randomized phase II trial evaluated two weekly docetaxel-based regimens to see which would be most promising according to objective response rate (ORR) as first-line therapy in AGC. Methods: Chemotherapy-naïve patients with measurable unresectable and/or metastatic gastric adenocarcinoma and a performance status ≤2 were randomly assigned to receive docetaxel (35 mg/m2) weekly on days 1 and 8 of a 21-day cycle plus either cisplatin (60 mg/m2 on day 1) (arm A) or oxaliplatin (120 mg/m2 on day 1) (arm B). Toxicity was assessed on days 1, 8, and 21 of each cycle, and response was evaluated every 2 cycles. Results: Between March 2007 and December 2008, 61 eligible patients entered. In Arm A, 29 patients were evaluable for objective response and 31 for safety. In Arm B, 28 patients were evaluable for objective response and 30 for safety. Median age was 52 years and disease status was comparable for both arms. Ten of 29 (34.5%) patients had a confirmed objective response in the arm A (95% confidence interval [CI] 17.1–51.8%) and 11 of 28 (39.2%) patients had a confirmed objective response in the arm B (95% CI 21.1- 57.2%). No significant difference was noted between the arms both for ORR (p=0.202) or for disease control (58.6% and 82.1%, respectively, p=0.082). Median progression free survival time was 4.4 month in the arm A and 4.3 months in the arm B (Hazard ratio = 0.936; 95% CI, 0.503–1.744; p = 0.836). There was no relevant difference in the occurrence of overall grade ¾ toxicity between the two arms (51.6% vs. 46.6%, respectively; p=0.800). Neutropenia was the most common grade 3/4 toxicity (32.3% vs. 36.6%, respectively). There was one treatment related death in Arm B. Conclusions: The preliminary results showed that both treatment arms have similar clinical efficacy as front-line treatment in AGC. Each regimen has a manageable tolerability profile. The accrual is ongoing. No significant financial relationships to disclose.

Hcrn GU15-215: A phase II trial of atezolizumab (atezo) and bevacizumab (bev) in cisplatin-ineligible patients (pts) with advanced/unresectable urothelial cancer (UC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS5098-TPS5098
Author(s):  
Arjun Vasant Balar ◽  
Samuel Aaron Funt ◽  
Shilpa Gupta ◽  
Arkadiusz Z. Dudek ◽  
Alejandro Recio Boiles ◽  
...  
Keyword(s):  
Phase Ii ◽  
Nyha Class ◽  
Objective Response ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Solitary Kidney ◽  
Cross Sectional ◽  
Biomarker Analysis ◽  
Pre Treatment

TPS5098 Background: Atezolizumab is a standard of care in selected cisplatin-ineligible pts with advanced UC. VEGF targeted therapies have activity in advanced UC and may lead to immune synergy when combined with anti-PD-1/L1 therapy. This phase II study is investigating the combination of bevacizumab and atezolizumab in untreated cisplatin-ineligible pts with advanced UC. Methods: HCRN GU15-215 (NCT03272217) is a phase 2, multicenter single arm trial to evaluate the efficacy and safety of atezolizumab and bevacizumab in pts with advanced UC. Cisplatin-ineligible pts (defined as any of estimated CrCl < 60 cc/min, Grade ≥ 2 hearing loss or neuropathy, ECOG PS 2 or solitary kidney) with untreated, histologically confirmed locally advanced or metastatic UC irrespective of PD-L1 expression status and with sufficient pre-treatment tumor tissue available for biomarker analysis are eligible. Pts who have received perioperative chemotherapy are eligible, however prior treatment with a checkpoint inhibitor is excluded. Pts with NYHA Class II or greater heart failure, significant cerebrovascular or cardiac disease within 3 months, uncontrolled HTN, persistent gross hematuria, and GI obstruction or perforation within 6 months are excluded. 70 pts will receive treatment with atezolizumab 1200 mg IV plus bevacizumab 15 mg/kg IV every 21 days. All pts will undergo an on-treatment biopsy before cycle 2 if safe and feasible. Peripheral blood samples and stool samples will be collected before treatment and on-treatment for immune-relevant biomarker analyses. Cross-sectional imaging will be performed every 9 weeks on therapy for the first 12 months and then every 12 weeks thereafter to assess for response. Subjects will be eligible to continue treatment until RECIST v1.1 defined progression or unacceptable toxicity for up to 24 months. The primary endpoint is overall survival rate at 1 year and will be analyzed by the Kaplan Meier method. Key secondary endpoints include objective response rate, duration of response, disease control rate, progression-free survival and safety and toxicity as defined by CTCAE version 4.0. Clinical trial information: NCT03272217 .

Final efficacy results of NCIC CTG IND.202: A randomized phase II study of recombinant interleukin-21 (rIL21) in patients with recurrent or metastatic melanoma (MM).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 9032-9032 ◽  
Author(s):  
Teresa M. Petrella ◽  
Catalin Liviu Dragos Mihalcioiu ◽  
Elaine McWhirter ◽  
Karl Belanger ◽  
Kerry J. Savage ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Lesion Size ◽  
Primary Objective ◽  
Effector Memory ◽  
Prior Therapy ◽  
Randomized Phase Ii ◽  
Elevated Liver Enzymes ◽  
Biomarker Analysis

9032 Background: rIL21 is a T-cell derived cytokine with antitumor activity dependent on NK cells or CD8+ T cells through induction of central and effector memory cells. A previous phase II study demonstrated an ORR of 22.5% in previously untreated patients with MM. We conducted a multicentre randomized phase II study of MM evaluating the efficacy, toxicity, pharmacokinetics, immunogenicity, and biomarkers of rIL21 versus dacarbazine (DTIC). Methods: Eligible patients: Recurrent or MM, with either maximum tumour lesion size of < 50 mm or LDH < 2.5 x ULN and prior therapy with BRAF/MEK inhibitors allowed. Patients were treated with either rIL-21, 30 µg /kg/day dose IV daily x 5 days weeks 1, 3, 5 q 8 weeks or dacarbazine (DTIC) 1000 mg/m2 IV q 3 weeks. The primary objective was to compare progression free survival (PFS). The trial was designed to detect a hazard ratio of 1.75 with one-sided alpha of 0.1; 58 progression events were required to provide 80% power. Results: 64 patients were randomized, 32 in the rIL-21 arm and 32 in the DTIC arm. The Table summarizes key demographic and efficacy endpoints. Common rIl21 related adverse events were fatigue, rash, diarrhea, nausea, myalgia and elevated liver enzymes. At least one dose reduction/ interruption or discontinuation occurred in 32 (100%) and 27 (96.4%) of rIL21 and DTIC patients. Conclusions: Despite encouraging efficacy in prior phase I/II studies, the results suggest that rIL-21 is comparable to DTIC in this patient population. Additional biomarker analysis from this study is pending and combination studies are currently ongoing. Clinical trial information: NCT00514085. [Table: see text]

Evolve: A post PARP inhibitor clinical translational phase II trial of cediranib-olaparib in ovarian cancer—A Princess Margaret Consortium – GCIG Phase II Trial.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5521-5521 ◽  
Author(s):  
Stephanie Lheureux ◽  
Ana Oaknin ◽  
Swati Garg ◽  
Jeffrey Bruce ◽  
Neesha C. Dhani ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Clinical Trial ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Parp Inhibitor ◽  
Objective Response ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Tumor Biopsy ◽  
Ps Ii

5521 Background: PARP inhibitors (PARPi) are approved therapies in high grade serous ovarian cancer (HGSOC). There are few studies after PARPi progression and correlation with dynamic changes in resistance. We hypothesized that PARPi resistance could be overcome by adding an anti-angiogenic. Methods: We report the first phase 2 trial assessing the combination of olaparib and cediranib after PARPi failure in HGSOC. This investigator initiated study included three cohorts of 10 evaluable patients (pts): i) platinum sensitive post PARPi (PS), ii) platinum resistant post PARPi (PR) and iii) exploratory cohort of pts re-challenged with chemotherapy post PARPi progression (PE) (NCT02681237). The primary objective was to determine objective response rate by RECIST v1.1 and progression free survival (PFS) at 16 weeks. Secondary objectives were to evaluate safety, PFS, overall survival (OS) and mechanisms of PARPi resistance. Pts who had radiographic progression on any PARPi were eligible. Archival tumor at initial diagnosis and baseline tumor biopsy at PARPi progression were mandatory. Pts received olaparib tablets 150mg BID with cediranib 20mg QD until progression or unacceptable toxicity. CT scans were performed every 8 weeks. Whole exome and RNA sequencing were performed on paired tumors tissues. Results: Thirty-four pts were enrolled. BRCA1/2 mutations were found in 9/11 PS, 8/10 PR and 7/13 PE pts. By RECIST1.1, four partial responses were observed (2 in PR and 2 in PE cohorts) and 18 stable disease. The 16−week PFS was 54.5% (31.8−93.6) in PS, 50% (26.9−92.9) in PR and 36% (15.6−82.8) in PE, respectively. OS at 1 year was 81.8% (61.9−100) in PS, 64.8% (39.3−100) in PR and 39.1% (14.7−100) in PE. Main related adverse events were anemia, hypertension, diarrhea and fatigue, grade 3 < 10%. Molecular analyses identified different mechanisms of PARPi resistance in ~77% of evaluable pts with matched pre-post PARPi progression biopsies such as reversion mutations in BRCA1/2 and other homologous repair (HR) genes; BRCA, HR and MDR upregulation, CCNE amplification and RIG-I like receptor downregulation. Conclusions: Treatment with olaparib-cediranib after PARPi failure was feasible and met the predefined bar for efficacy in each cohort. This is the largest clinical trial prospectively evaluating PARPi failure and correlating tissue genomic mechanisms of resistance. Clinical trial information: NCT02681237.

Randomized, phase II study of ficlatuzumab with or without cetuximab in patients with pan-refractory, recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS6594-TPS6594
Author(s):  
Julie E. Bauman ◽  
Denise Roe ◽  
Nabil F. Saba ◽  
Jessica Ruth Bauman ◽  
John M. Kaczmar ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Resistance Mechanism ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Platinum Resistance ◽  
Intrinsic Resistance ◽  
Eligibility Criteria ◽  
Randomized Phase Ii ◽  
Clinical Resistance

TPS6594 Background: Patients with pan-refractory R/M HNSCC, with clinical resistance to cytotoxic therapy, anti-EGFR molecular targeting, and immunotherapy, have poor survival. An established tumor-intrinsic resistance mechanism to cetuximab, an anti-EGFR IgG1 monoclonal antibody (mAb), is activation of the hepatocyte growth factor (HGF)/cMet pathway, which converges with the EGFR network at both the PI3K/Akt and MAPK nodes allowing for reciprocal compensation. Moreover, over-expression of HGF in the tumor microenvironment is immunosuppressive. Convergent data suggest that HGF/cMet pathway inhibition concurrent with EGFR blockade may overcome cetuximab resistance. We previously reported a Phase I study of ficlatuzumab, a humanized anti-HGF IgG1 mAb, with cetuximab in cetuximab-resistant R/M HNSCC. The combination showed promising safety, overall response rate (ORR) and progression-free survival (PFS). Preliminary biomarker analyses showed that high circulating cMet was associated with poor PFS whereas serum Veristrat, a proteomic classifier associated with worse prognosis in the setting of anti-EGFR monotherapy, was not. An increase in total peripheral T cells, particularly the CD8+ subset, was associated with treatment response while progression was associated with expansion of a unique myeloid population. We designed a follow-on randomized phase II trial evaluating ficlatuzumab with or without cetuximab in pan-refractory, R/M HNSCC with signaling and immune correlatives. Methods: This is a multicenter phase II trial with a randomized, non-comparative, two-arm design (ficlatuzumab 20 mg/kg with or without cetuximab 500 mg/m2 every 2 weeks) in patients with pan-refractory R/M HNSCC. Key eligibility criteria include: R/M HNSCC; cetuximab resistance (progression during or within 6 months of cetuximab-radiation or palliative cetuximab); platinum resistance; prior exposure to anti-PD1 mAb; ECOG 0-1; consent to baseline research biopsy. The primary objective is to evaluate the efficacy of each arm as measured by PFS. To test the hypothesis that either regimen improves historical PFS from 2 to 3.33 months requires 66 eligible patients. Key secondary endpoints are ORR and survival. Mechanistic biomarkers include tumor HGF/cMet pathway activation, tumor and peripheral immune profiles, soluble cMet, and serum Veristrat. Thirty-five of 66 subjects have enrolled at 6 centers. A Bayesian continuous monitoring rule for futility has not been triggered for either arm. Clinical trial information: NCT03422536 .

Randomized Phase II Trial of Ridaforolimus in Advanced Endometrial Carcinoma

2015 ◽  
Vol 33 (31) ◽  
pp. 3576-3582 ◽  
Author(s):  
Amit M. Oza ◽  
Sandro Pignata ◽  
Andres Poveda ◽  
Mary McCormack ◽  
Andrew Clamp ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Objective Response ◽  
Progression Free Survival ◽  
Mtor Pathway ◽  
Clinical Activity ◽  
Open Label ◽  
End Point ◽  
Randomized Phase Ii

Purpose The prognosis for women with recurrent and metastatic endometrial cancer is poor, and improved therapies are needed. The mammalian target of rapamycin (mTOR) pathway is an important target, and mTOR inhibitors show clinical activity in endometrial cancer. Patients and Methods An open-label, multicenter, randomized, phase II trial of oral ridaforolimus compared with progestin or investigator choice chemotherapy (comparator) was undertaken in women with metastatic or recurrent endometrial cancer who had progressive disease following one or two lines of chemotherapy and no hormonal therapy. The primary end point was progression-free survival (PFS) assessed by independent radiologic review. Results One hundred thirty patients were enrolled (64 received ridaforolimus and 66 received the comparator), and median age was 66 years. Treatment discontinuation as a result of adverse events was 33% with ridaforolimus versus 6% with the comparator, with common (> 10%) grade 3 toxicities being hyperglycemia, anemia, and diarrhea. Thirty-eight percent (ridaforolimus) versus 71% (comparator) of patients discontinued treatment as a result of disease progression. Median PFS at the protocol prespecified interim analysis with 58 PFS events (primary end point) was 3.6 months (95% CI, 2.7 to 7.3 months) for ridaforolimus and 1.9 months (95% CI, 1.9 to 2.3 months) for the comparator (hazard ratio, 0.53; 95% CI, 0.31 to 0.90; P = .008). PFS rate for ridaforolimus versus comparator was 48% versus 18% at 16 weeks and 38% versus 15% at 24 weeks. Objective response rate for ridaforolimus versus comparator was 0% versus 4% (P = .925), and stable disease was achieved in 35% versus 17% of patients (P = .021). Conclusion Oral ridaforolimus shows encouraging activity in advanced endometrial cancer but is associated with significant toxicity. Inhibition of the PI3K/Akt/mTOR pathway may be a viable therapeutic target.

RAS mutations in EXPERT-C, a randomized phase II trial of neoadjuvant capecitabine and oxaliplatin (CAPOX) and chemoradiotherapy (CRT) with or without cetuximab (C) in MRI-defined, high-risk rectal cancer (RC).

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 489-489 ◽  
Author(s):  
Francesco Sclafani ◽  
David Gonzalez ◽  
David Cunningham ◽  
Sanna Hullki Wilson ◽  
Clare Peckitt ◽  
...  
Keyword(s):  
High Risk ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Ras Mutations ◽  
Randomized Phase Ii ◽  
Exon 4 ◽  
The Impact ◽  
Kras Exon

489 Background: Studies indicate that RAS mutations beyond KRAS exons 2-3 may predict anti-EGFRs benefit. EXPERT-C was a randomized phase II trial of neoadjuvant CAPOX and CRT ± C in MRI-defined, high-risk RC. We have previously shown that adding C in KRAS (exons 2-3)/BRAF wild type (WT) patients did not improve complete response (CR) and was associated with a non-significant improvement in progression-free survival (PFS) (HR 0.62, p=0.23) and overall survival (OS) (HR 0.56, p=0.20). The aim of this study was to analyse the impact of RAS mutations on the outcome of C-treated patients in this trial. Methods: Between October 2005 and July 2008, 164 eligible patients were randomly assigned to 4 cycles of CAPOX followed by CRT, surgery, and 4 cycles of adjuvant CAPOX (n=81) or the same regimen plus C (CAPOX-C, n=83). KRAS (exons 2-3) and NRAS (exon 3) mutations were prospectively analysed. Of 90 KRAS/NRAS WT patients, 84 were retrospectively analysed for additional KRAS (exon 4) and NRAS (exons 2/4) mutations by using bi-directional Sanger sequencing. The effect of C on CR, PFS, and OS in patients with RAS WT tumors was analyzed. PFS and OS were estimated with the Kaplan-Meier method and treatment arms compared using a log-rank analysis. Results: Eleven (13%) of 84 patients initially classified as KRAS/NRAS WT were found to have tumours harbouring a mutation in KRAS exon 4 (11%) or NRAS exons 2/4 (2%). Overall, after this retrospective mutation analysis, 78/149 (52%) assessable patients were RAS WT (CAPOX, n=40; CAPOX-C, n=38). After a median follow-up of 63.8 months, in line with the initial analysis, the addition of C in the group of RAS WT patients, was associated with numerically higher, but not statistically significant, rates of CR (15.8% vs. 7.5%, p=0.31), 5-year PFS (78.4% vs. 67.5%, p=0.17) and 5-year OS (83.8% vs. 70%, p=0.20). Conclusions: Although the results of our analysis are potentially affected by the small numbers, in our locally advanced RC population the status of RAS did not appear to significantly improve the selection of patients who may benefit from the use of an anti-EGFR therapy.

PRECEDENT: A Randomized Phase II Trial Comparing Vintafolide (EC145) and Pegylated Liposomal Doxorubicin (PLD) in Combination Versus PLD Alone in Patients With Platinum-Resistant Ovarian Cancer

2013 ◽  
Vol 31 (35) ◽  
pp. 4400-4406 ◽  
Author(s):  
R. Wendel Naumann ◽  
Robert L. Coleman ◽  
Robert A. Burger ◽  
Edward A. Sausville ◽  
Elzbieta Kutarska ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase Ii ◽  
Liposomal Doxorubicin ◽  
Phase Ii Trial ◽  
Folate Receptor ◽  
Pegylated Liposomal Doxorubicin ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Platinum Resistant ◽  
Randomized Phase Ii

Purpose Vintafolide (EC145) is a folic acid–desacetylvinblastine conjugate that binds to the folate receptor (FR), which is expressed on the majority of epithelial ovarian cancers. This randomized phase II trial evaluated vintafolide combined with pegylated liposomal doxorubicin (PLD) compared with PLD alone. The utility of an FR-targeted imaging agent, 99mTc-etarfolatide (EC20), in selecting patients likely to benefit from vintafolide was also examined. Patients and Methods Women with recurrent platinum-resistant ovarian cancer who had undergone ≤ two prior cytotoxic regimens were randomly assigned at a 2:1 ratio to PLD (50 mg/m2 intravenously [IV] once every 28 days) with or without vintafolide (2.5 mg IV three times per week during weeks 1 and 3). Etarfolatide scanning was optional. The primary objective was to compare progression-free survival (PFS) between the groups. Results The intent-to-treat population comprised 149 patients. Median PFS was 5.0 and 2.7 months for the vintafolide plus PLD and PLD-alone arms, respectively (hazard ratio [HR], 0.63; 95% CI, 0.41 to 0.96; P = .031). The greatest benefit was observed in patients with 100% of lesions positive for FR, with median PFS of 5.5 compared with 1.5 months for PLD alone (HR, 0.38; 95% CI, 0.17 to 0.85; P = .013). The group of patients with FR-positive disease (10% to 90%) experienced some PFS improvement (HR, 0.873), whereas patients with disease that did not express FR experienced no PFS benefit (HR, 1.806). Conclusion Vintafolide plus PLD is the first combination to demonstrate an improvement over standard therapy in a randomized trial of patients with platinum-resistant ovarian cancer. Etarfolatide can identify patients likely to benefit from vintafolide.

Paclitaxel Given Once Per Week With or Without Bevacizumab in Patients With Advanced Angiosarcoma: A Randomized Phase II Trial

2015 ◽  
Vol 33 (25) ◽  
pp. 2797-2802 ◽  
Author(s):  
Isabelle L. Ray-Coquard ◽  
Julien Domont ◽  
Emmanuelle Tresch-Bruneel ◽  
Emmanuelle Bompas ◽  
Philippe A. Cassier ◽  
...  
Keyword(s):  
Phase Ii ◽  
De Novo ◽  
Phase Ii Trial ◽  
Clinical Investigation ◽  
Performance Status ◽  
Survival Rates ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Randomized Phase Ii ◽  
Radiation Induced

Purpose The aim of this randomized, phase II trial was to explore the activity and safety of adding bevacizumab to paclitaxel once per week in treatment of angiosarcomas (AS). Methods Patients were treated with paclitaxel alone (90 mg/m2 per week for six cycles of 28 days each; arm A) or with paclitaxel combined with bevacizumab (10 mg/kg once every 2 weeks; arm B). In the combination treatment arm, bevacizumab was administered after the six cycles of chemotherapy as maintenance therapy (15 mg/kg once every 3 weeks) until intolerance or progression occurred. Stratification factors were superficial versus visceral AS and de novo versus radiation-induced AS. The primary end point was the 6-month progression-free survival (PFS) rate, which was based on RECIST, version 1.1. Statistical assumptions were P0 = 20%, P1 = 40%, a = 10%, and b = 20%. P0 was the PFS rate at 6 months defining inactive drug, and P1 was the PFS rate at 6 months defining promising drug. Results A total of 52 patients were enrolled, and 50 were randomly assigned in 14 centers. The most common primary sites were the breast (49%) and skin (12%). There were 17 (34%) visceral and 24 (49%) radiation-induced AS. The performance status was 0 in 24 patients (49%) and 1 in the remaining 25 patients (51%). The median follow-up time was 14.5 months. Both treatment regimens were considered active, with 6-month PFS rates of 54% (14 of 26) in arm A and 57% (14 of 24) in arm B. The median overall survival rates were 19.5 months in arm A and 15.9 months in arm B. Toxicity was higher with the combination arm and included one fatal drug-related toxicity (intestinal occlusion). Conclusion The primary objective was met in both treatment arms. However, the present data do not support additional clinical investigation of combined paclitaxel/bevacizumab for the treatment of advanced AS.

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