A randomized phase II trial of fulvestrant with or without ribociclib after progression on aromatase inhibition plus cyclin-dependent kinase 4/6 inhibition in patients with unresectable or metastatic hormone receptor positive, HER2 negative breast cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS1112-TPS1112 ◽  
Author(s):  
Kevin Kalinsky ◽  
Prabhjot Singh Mundi ◽  
Codruta Chiuzan ◽  
Melissa Kate Accordino ◽  
Meghna S. Trivedi ◽  
...  
Keyword(s):  
Phase Ii ◽  
Controlled Trial ◽  
Objective Response ◽  
Estrogen Therapy ◽  
Progression Free Survival ◽  
Rank Test ◽  
Clinical Trial Registry ◽  
Eligibility Criteria ◽  
Double Blind ◽  
Pik3ca Mutations

TPS1112 Background: CDK4/6i, including palbociclib and ribociclib (R), have demonstrated remarkable benefit in progression free survival (PFS) in patients (pts) with HR+, HER2- MBC with anti-estrogen therapy. Switching between anti-estrogen therapies at disease progression is standard of care in the treatment of HR+ MBC. We evaluate the strategy of switching anti-estrogen therapy to fulvestrant (F) and maintaining CDK4/6 inhibition with R in pts with HR+, HER2- MBC who have progressed on an AI + CDK4/6i. Methods: Trial Design Phase II, multi-center, randomized, double-blind, placebo-controlled trial to evaluate F +/- R in pts with HR+, HER2- MBC who have previously progressed on any AI + CDK4/6i: Screened at 2 different scenarios: Scenario 1: Before receiving any CDK4/6i Scenario 2: Time of progression of disease (POD) while being treated with an AI + CDK4/6i Intervention At randomization, pts assigned 1:1 to either a) F + R or b) F + placebo, with treatment given in 4-week cycles. Major Eligibility Criteria 1, Metastatic BC, 2. HR+ HER2-, 3. Measurable or unmeasurable disease Specific Aims Primary: PFS. Secondary: Objective response rate, clinical benefit rate, overall survival, and duration of response. Biomarker assessment: amplification of cyclin D1 and cyclin E, phosphoRb and TK1 expression, Rb1 and p16 loss, and ctDNA for ESR1 and PIK3CA mutations. Statistical Methods Assuming a median PFS of 3.8 months with F alone, we predict that F + R will lead to a median PFS of at least 6.5 months. A one-sided log-rank test with a sample size of N = 120 and alpha = 0.025, achieves 80% power to detect a difference in PFS of 2.7. With a 10% dropout, n = 132. Clinical trial registry number NCT02632045.

Prospective randomized phase II trial of pazopanib versus placebo in patients with progressive carcinoid tumors (CARC) (Alliance A021202).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4005-4005 ◽  
Author(s):  
Emily K. Bergsland ◽  
Michelle R. Mahoney ◽  
Timothy R. Asmis ◽  
Nathan Hall ◽  
Priya Kumthekar ◽  
...  
Keyword(s):  
Phase Ii ◽  
Kinase Inhibitor ◽  
Treatment Options ◽  
Objective Response ◽  
Progression Free Survival ◽  
Rank Test ◽  
Double Blind ◽  
Upper Confidence Limit ◽  
Well Differentiated ◽  
Grade 3

4005 Background: Patients (pts) with progressive advanced well-differentiated neuroendocrine tumors arising outside of the pancreas have limited systemic treatment options. Pazopanib (PZ) is an oral multi-kinase inhibitor with activity against VEGFR-2,-3, PDGFR-α, and β, and c-KIT, with initial data suggesting efficacy in CARC. Methods: This was a multicenter, randomized, double-blind, phase II study of PZ (800 mg/day) versus placebo (PL) in progressive CARC. Key eligibility: low-intermediate grade CARC, radiologic progressive disease (PD) < 12 months (mo), and adequate end-organ function. Prior somatostatin analog (SSA) mandated for midgut tumors. Concurrent SSA allowed if previous PD on SSA documented. Primary endpoint was progression-free survival (PFS), defined as time from randomization to PD by central review or death. Secondary endpoints included overall survival (OS), objective response rate (ORR) and safety. The trial had 85% power to detect a difference in median PFS of 14 v 9 mo (hazard ratio [HR] 0.64) at one-sided alpha = 0.1. A stratified log-rank test based on the intend-to-treat (ITT) principle was used. Unblinding and crossover were allowed if PD confirmed by central review. Results: 171 (97 PZ, 74 PL) pts were randomized between 6/2013-10/2015: median age 63; 56% female; 66% small bowel primary; 87% concurrent SSA. Median follow-up of 31 mo; 112 (56 PZ, 56 PL) PFS events observed. 6 pts (4 PZ, 2 PL) remain on initial treatment. Median PFS was 11.6 and 8.5 mo in PZ and PL, respectively (HR = 0.53, 1-sided 90% upper confidence limit [UCL] 0.69, p = 0.0005) which crossed the pre-specified protocol efficacy boundary. 49 PL pts received PZ after PD. Median OS was 41 and 42 mo in PZ and PL, respectively (HR = 1.13, 1-sided 90% UCL 1.51, p = 0.70). RR data will be presented. Notable grade 3+ adverse events were (PZ v. PL %) hypertension (35 v. 8), fatigue (11 v. 4), ALT (10 v. 0), AST (10 v. 0), and diarrhea (7 v. 4). Conclusions: PZ compared to PL was associated with significant improvement in PFS in patients with progressive CARC. The results confirm that VEGF signaling pathway is a valid target for therapy in CARC. Support: U10CA180821, U10CA180882 https://acknowledgments.alliancefound.org . Clinical trial information: NCT01841736.

An international, randomized, placebo-controlled, double-blind phase III study (MONET1) of motesanib plus carboplatin/paclitaxel (C/P) in patients with advanced nonsquamous non-small cell lung cancer (NSCLC).

2011 ◽  
Vol 29 (18_suppl) ◽  
pp. LBA7512-LBA7512 ◽  
Author(s):  
G. Scagliotti ◽  
I. Vynnychenko ◽  
Y. Ichinose ◽  
K. Park ◽  
K. Kubota ◽  
...  
Keyword(s):  
Cox Model ◽  
Objective Response ◽  
Stage Iv ◽  
Progression Free Survival ◽  
High Rate ◽  
Phase Iii ◽  
Rank Test ◽  
Double Blind ◽  
Grade 3 ◽  
Nonsquamous Nsclc

LBA7512 Background: This study evaluated whether motesanib (a selective oral inhibitor of VEGFR 1, 2 and 3; PDGFR and Kit) plus C/P improved overall survival (OS) compared with placebo + C/P in patients (pts) with nonsquamous NSCLC and in a subset of pts with adenocarcinoma. Methods: Pts had stage IIIB/IV or recurrent nonsquamous NSCLC and no prior systemic therapy for advanced NSCLC. The study initially enrolled all histologies but was amended to exclude pts with squamous NSCLC owing to a high rate of hemoptysis. Pts were randomized 1:1 to receive up to six 3-wk cycles of C (AUC 6 mg/mL·min) and P (200 mg/m2) with either motesanib 125 mg QD (Arm A) or placebo QD (Arm B) orally continuously. The primary endpoint was OS; secondary endpoints included progression-free survival (PFS), adverse events (AEs), objective response rate (ORR) and association between placental growth factor (PLGF) change and OS. OS was evaluated using a stratified Cox model and 2-sided log-rank test (α=0.03 for nonsquamous pts and α=0.02 for adenocarcinoma pts). Results: 1090 pts with nonsquamous NSCLC were randomized (Arm A/B, n=541/549); 890 had adenocarcinoma (n=448/442). 61% were men; median age was 60 years (range 21–87); 83% had stage IV disease. At the time of analysis, 753 pts had died (608 pts with adenocarcinoma). Median follow-up was 10.6 mo. OS was not significantly improved in Arm A compared with Arm B (Table). In Arm A, PLGF analysis did not show an association with OS. The incidence of grade ≥3 AEs in Arms A/B was 73/59%. Grade ≥3 AEs occurring more frequently in Arm A than B included neutropenia (22/15%), diarrhea (9/1%), hypertension (7/1%) and cholecystitis (3/0%). The incidence of grade 5 AEs was 14/9% in Arms A/B. Conclusions: In pts with advanced nonsquamous NSCLC, treatment with motesanib + C/P did not significantly improve OS compared with C/P alone. [Table: see text]

Randomized phase II trial of TACE plus everolimus as first-line therapy in localized unresectable hepatocellular carcinoma (HCC): The TRACER trial.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS4149-TPS4149
Author(s):  
Ronnie Tung Ping Poon ◽  
Li-Tzong Chen ◽  
Hong-Ling Xue ◽  
Bayane Tannir ◽  
Jia Hua Wang ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Objective Response ◽  
Mammalian Target Of Rapamycin ◽  
Data Monitoring Committee ◽  
Preclinical Study ◽  
Clinical Trial Registry ◽  
Double Blind ◽  
First Line Therapy

TPS4149 Background: Transcatheter Arterial Chemoembolization (TACE) has shown benefit in improving survival and is a widely used treatment for unresectable HCC. However, TACE induces hypoxia leading to up-regulation of HIF-1α and VEGF signaling, and tumor progression. Everolimus is an oral inhibitor of mammalian target of rapamycin (mTOR) and its downstream signaling including HIF-1α. Everolimus has also been shown to increase chemosensitivity of HCC in preclinical study (Cancer Lett; 273(2):201-9). Combining everolimus with TACE may delay tumor progression. TRACER (Tace with Rad001 in Asian Centers for Evaluation and Research) aims to evaluate the efficacy and safety of everolimus plus TACE in patients with localised unresectable HCC. Methods: TRACER is a multinational, randomized, double-blind, placebo-controlled phase II trial. Patients aged ≥18 years newly diagnosed with localized unresectable Child A HCC; ECOG PS of <2; ≥1 unidimensional lesion measurable according to RECIST; and adequate bone marrow, liver, and renal function. Exclusion criteria include main portal vein invasion and/or extrahepatic spread; prior local or systemic treatment for HCC, or contraindications to TACE. Eligible patients who have successfully undergone the first TACE are randomized 1:1 to oral everolimus 7.5mg or matching placebo daily. TACE is repeated every 10 weeks or so. A short everolimus dose interruption of 48 hours before and after each TACE has been designed to allow recovery from complications of TACE. For standardization, doxorubicin-eluting beads are being used in every TACE. Patients shall exit the trial upon tumor progression, unacceptable toxicity, death, or trial discontinuation. All endpoints will be assessed on an ITT basis. The primary endpoint is time to progression base on Modified RECIST Criteria. Secondary endpoints include objective response rate, overall survival, and incidence of extrahepatic spread, safety and exploratory biomarkers. An independent data monitoring committee has been established to safeguard the trial subjects. Estimated total enrollment is 80, of which 12 subjects have been enrolled. (Clinical Trial Registry Number: NCT01379521.)

SPIRITT (study 20060141): A randomized phase II study of FOLFIRI with either panitumumab (pmab) or bevacizumab (bev) as second-line treatment (tx) in patients (pts) with wild-type (WT) KRAS metastatic colorectal cancer (mCRC).

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 454-454 ◽  
Author(s):  
J. Randolph Hecht ◽  
Allen Lee Cohn ◽  
Shaker R. Dakhil ◽  
Mansoor N. Saleh ◽  
Bilal Piperdi ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Eligibility Criteria ◽  
Grade 5 ◽  
Randomized Phase Ii ◽  
Secondary Endpoints ◽  
Previously Treated

454 Background: Pmab has demonstrated significant improvement in progression-free survival (PFS) in pts with WT KRAS mCRC as 2nd-line tx in a phase III trial comparing pmab + FOLFIRI vs FOLFIRI alone. Here, we describe the results of SPIRITT, a multicenter, randomized phase II study evaluating pmab + FOLFIRI and bev + FOLFIRI in pts with WT KRAS mCRC previously treated with a 1st-line bev + oxaliplatin (Ox)-based chemotherapy regimen. Methods: Pts were randomized 1:1 to pmab 6.0 mg/kg + FOLFIRI Q2W or to bev 5.0 or 10.0 mg/kg + FOLFIRI Q2W. Eligibility criteria included: WT KRAS mCRC, ECOG ≤ 1, no prior irinotecan or anti-EGFR tx, and tx failure of prior 1st-line bev + Ox-based therapy (≥ 4 cycles). The primary endpoint was PFS; secondary endpoints included overall survival (OS), objective response rate (ORR), and safety. No formal hypothesis was tested. Results: 182 pts with WT KRAS mCRC were randomized. All pts received tx. Efficacy results are shown (table). Worst grade of 3/4 adverse events (AE) occurred in 78% of pts in the pmab + FOLFIRI arm and 65% in the bev + FOLFIRI arm. Grade 5 AEs occurred in 7% of pts in the pmab + FOLFIRI arm and 7% in the bev + FOLFIRI arm. Tx discontinuation due to any AE was 29% in the pmab + FOLFIRI arm and 25% in the bev + FOLFIRI arm. Conclusions: In this estimation study of pts with WT KRAS mCRC that previously received bev + Ox-based tx, the PFS hazard ratio (HR) was 1.01 (95% CI: 0.68 - 1.50). The OS HR was 1.06 (95% CI: 0.75 - 1.49). The observed ORR was higher in the pmab + FOLFIRI arm. 54% of bev + FOLFIRI pts received subsequent anti-EGFR tx. The safety profile for both arms was similar to previously reported studies. Tx discontinuation rates due to AEs were similar between the arms. Clinical trial information: NCT00418938. [Table: see text]

Palbociclib plus cetuximab versus placebo plus cetuximab in platinum-resistant, cetuximab-naive, HPV-unrelated head and neck cancer: A double-blind randomized phase II trial (PALATINUS).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 6013-6013 ◽  
Author(s):  
Douglas Adkins ◽  
Jin-Ching Lin ◽  
Assuntina Gesualda Sacco ◽  
Jessica C. Ley ◽  
Peter Oppelt ◽  
...  
Keyword(s):  
Head And Neck ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Rank Test ◽  
Double Blind ◽  
Platinum Resistant ◽  
Randomized Phase Ii

6013 Background: Cetuximab monotherapy results in a median overall survival (OS) of approximately 6 months (mo) in platinum-resistant recurrent/metastatic head and neck squamous cell carcinoma (HNSCC). HNSCC unrelated to human papillomavirus (HPV) is driven by hyperactivation of the CDK4/6 and cyclin D1 (CD1) regulatory complex, resulting in cell cycle progression and tumor growth, suggesting that CDK4/6 inhibition can be a rational therapeutic strategy in this setting. Palbociclib (PAL) is a selective CDK4/6 inhibitor that may reverse cetuximab resistance by countering the actions of deregulated CD1. PAL plus an epidermal growth factor receptor inhibitor synergistically reduced cell viability of HPV-unrelated HNSCC cell lines. In a single-arm, multicenter trial of platinum-resistant, cetuximab-naive, HPV-unrelated HNSCC, PAL in combination with cetuximab resulted in a median OS of 9.5 mo. Methods: In a double-blind randomized phase II trial, patients (pts) with platinum-resistant, cetuximab-naïve, HPV-unrelated HNSCC were treated with cetuximab plus either PAL (arm A) or placebo (arm B). Pts were stratified by performance status (PS) and prior immunotherapy (IT). 120 pts were required for 1:1 randomization to have ≥ 80% power to detect a hazard ratio (HR) of 0.6 (corresponding to a median OS of 10 mo in arm A and 6 mo in arm B) using a 1-sided log-rank test P=0.10). Key secondary endpoints included progression-free survival (PFS), adverse events (AEs), and p16 status. Results: Pts (n=125) were randomized (arm A, 65; arm B, 60). PS and prior IT were balanced between the arms. Median (95% CI) follow-up for OS was 15.9 (15.0–19.4) mo. Median OS was 9.7 (7.3–13.9) mo in arm A and 7.8 (6.7–10.6) mo in Arm B (stratified by PS: HR=0.82 [95% CI, 0.54–1.25], P=0.18). Median PFS was 3.9 mo in arm A and 4.6 mo in arm B (stratified by PS: HR=1.00 [0.7–1.5], P=0.5). Hematologic AEs were more common in arm A. Only 11 pts (9%) received IT after being treated on the trial. Conclusions: Among pts with platinum-resistant, HPV-unrelated HNSCC, PAL plus cetuximab resulted in a trend of prolongation of median OS compared with cetuximab. Clinical trial information: NCT02499120.

scholarly journals Pimasertib Versus Dacarbazine in Patients With Unresectable NRAS-Mutated Cutaneous Melanoma: Phase II, Randomized, Controlled Trial with Crossover

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1727 ◽  
Author(s):  
Celeste Lebbé ◽  
Caroline Dutriaux ◽  
Thierry Lesimple ◽  
Willem Kruit ◽  
Joseph Kerger ◽  
...  
Keyword(s):  
Phase Ii ◽  
Cutaneous Melanoma ◽  
Controlled Trial ◽  
Objective Response ◽  
Progression Free Survival ◽  
Open Label ◽  
Serious Adverse Events ◽  
Unresectable Stage ◽  
Secondary Endpoints ◽  
Grade 3

This study investigated the efficacy and safety of pimasertib (MEK1/MEK2 inhibitor) versus dacarbazine (DTIC) in patients with untreated NRAS-mutated melanoma. Phase II, multicenter, open-label trial. Patients with unresectable, stage IIIc/IVM1 NRAS-mutated cutaneous melanoma were randomized 2:1 to pimasertib (60 mg; oral twice-daily) or DTIC (1000 mg/m2; intravenously) on Day 1 of each 21-day cycle. Patients progressing on DTIC could crossover to pimasertib. Primary endpoint: investigator-assessed progression-free survival (PFS); secondary endpoints: overall survival (OS), objective response rate (ORR), quality of life (QoL), and safety. Overall, 194 patients were randomized (pimasertib n = 130, DTIC n = 64), and 191 received treatment (pimasertib n = 130, DTIC n = 61). PFS was significantly improved with pimasertib versus DTIC (median 13 versus 7 weeks, respectively; hazard ratio (HR) 0.59, 95% confidence interval (CI) 0.42–0.83; p = 0.0022). ORR was improved with pimasertib (odds ratio 2.24, 95% CI 1.00–4.98; p = 0.0453). OS was similar between treatments (median 9 versus 11 months, respectively; HR 0.89, 95% CI 0.61–1.30); 64% of patients receiving DTIC crossed over to pimasertib. Serious adverse events (AEs) were more frequent for pimasertib (57%) than DTIC (20%). The most common treatment-emergent AEs were diarrhea (82%) and blood creatine phosphokinase (CPK) increase (68%) for pimasertib, and nausea (41%) and fatigue (38%) for DTIC. Most frequent grade ≥3 AEs were CPK increase (34%) for pimasertib and neutropenia (15%) for DTIC. Mean QoL scores (baseline and last assessment) were similar between treatments. Pimasertib has activity in NRAS-mutated cutaneous melanoma and a safety profile consistent with known toxicities of MEK inhibitors. Trial registration: ClinicalTrials.gov, NCT01693068.

An international phase II study of an all-oral combination of oral vinorelbine (NVBo) and capecitabine (X) in HER2-negative metastatic breast cancer (MBC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1056-1056 ◽  
Author(s):  
N. Tubiana-Mathieu ◽  
P. Bougnoux ◽  
D. Becquart ◽  
A. Chan ◽  
F. Majois ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Objective Response ◽  
Safety Data ◽  
Metastatic Breast ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
Eligibility Criteria ◽  
Good Tolerability ◽  
Oral Vinorelbine

1056 Background: Oral chemotherapy (CT) is attractive for patients (pts) with MBC. The all-oral regimen of NVBo and X is active with good tolerability in MBC. We report efficacy and safety data from an international phase II study of NVBo plus X. Methods: Main eligibility criteria included: measurable HER2-negative, CT-naive MBC, relapse ≥6 months after completing (neo)adjuvant CT, Karnofsky PS ≥70%, age ≥18 years. Study treatment: 3-weekly cycles of NVBo 60 mg/m2 (cycle 1) or 80 mg/m2 (from cycle 2) d1 and d8, plus X 1,000 (750 if ≥ 65 years) mg/m2 twice-daily d1–14. Treatment was continued until progression or unacceptable toxicity. Results: 55 pts were enrolled: median age: 58.5 years (41% ≥65); prior (neo)adjuvant CT in 63%; type of CT: anthracycline 67%, anthracycline + taxane 18%, CMF 15%; visceral involvement in 78%; >2 metastatic sites in 46%. Median 6 cycles; median relative dose intensity: NVBo 88%, X 87%; NVBo dose escalated to 80 mg/m2 in 94% of pts. G3/4 NCI CTC v2 adverse events (n=54): neutropenia 44% of pts, vomiting 9%, febrile neutropenia 7%, stomatitis 7%, asthenia 7%, infection with G3/4 neutropenia 4%, nausea 4%, diarrhea 4%, hand-foot syndrome 4%, thrombosis/embolism 4%. Efficacy (n=48 evaluable pts): objective response rate (RECIST) 44% (95% CI [29–59]), CR 2%, PR 42%, SD 35%, PD 21%, disease control (CR+PR+SD ≥6 months) 56%. Median time to objective response was 2.9 months. Because of short follow-up, progression-free survival, overall survival and duration of response data are not yet available. Conclusion: The all-oral combination of NVBo and X is an effective and well-tolerated first-line therapy for MBC. Based on these results and the high convenience of oral CT, evaluation of this regimen vs i.v. combinations in a randomized trial is ongoing. [Table: see text]

A phase II study of ABT-869 in hepatocellular carcinoma (HCC): Interim analysis

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4581-4581 ◽  
Author(s):  
H. Toh ◽  
P. Chen ◽  
B. I. Carr ◽  
J. J. Knox ◽  
S. Gill ◽  
...  
Keyword(s):  
Growth Factor ◽  
Ct Scan ◽  
Phase Ii ◽  
Tyrosine Kinases ◽  
Interim Analysis ◽  
Objective Response ◽  
Progression Free Survival ◽  
Open Label ◽  
Eligibility Criteria ◽  
Phase 2 Trial

4581 Background: ABT-869 is a novel orally active, potent and selective inhibitor of the vascular endothelial growth factor and platelet derived growth factor families of receptor tyrosine kinases. Results of an interim analysis of a phase 2 trial of ABT-869 in HCC are presented. Methods: An open-label, multicenter phase II trial (M06–879) of oral ABT-869 at 0.25 mg/kg daily in Child-Pugh A (C-PA) or QOD in Child-Pugh B (C-PB) patients (pts) until progressive disease (PD) or intolerable toxicity, is ongoing. Key eligibility criteria included unresectable or metastatic HCC; up to one prior line of systemic treatment; and at least one measurable lesion by computed tomography (CT) scan. The primary endpoint was the progression free (PF) rate at 16 weeks. Secondary endpoints included objective response rate (ORR), time to progression (TTP), progression free survival (PFS) and overall survival (OS). CT scans were assessed centrally and by the investigators; presented results are from central assessment. Results: 44 pts were enrolled from 09/07 to 08/08 at 6 centers internationally, with interim data available for 34 pts. There were 28 C-PA pts (median age, 63.5 y [range, 20- 81]) and 6 C-PB pts (median age, 64.5 y [range, 36–69]) and 73.5% received no prior systemic therapy. For the 19 evaluable C-PA pts included in the per-protocol interim analysis, 8 (42.1%) were progression free at 16 weeks [95% CI 20.3, 66.5]. The estimated ORR was 8.7% [95% CI, 1.1, 28] for the 23 C-PA pts and 0% for the 2 C-PB pts who had at least one post-baseline CT scan reviewed by central imaging. For all 34 pts, median TTP was 112 d [95% CI, 110, -], median PFS was 112 d [95% CI, 61, 168] and median OS was 295 d [95% CI, 182, 333]. The most common adverse events (AEs) for all pts were hypertension (41%), fatigue (47%), diarrhea (38%), rash (35%), proteinuria (24%), vomiting (24%), cough (24%) and oedema peripheral (24%). The most common grade 3/4 AEs for all pts were hypertension (20.6%) and fatigue (11.8%). Most AEs were mild/moderate and reversible with interruption/dose reductions/or discontinuation of ABT-869. Conclusions: ABT-869 appears to benefit HCC patients, with an estimated TTP of 112 days and an acceptable safety profile. Updated results from this ongoing study will be presented. [Table: see text]

Lapatinib in combination with ECF/x in EGFR1 positive first-line metastatic gastric cancer (GC): A phase II randomized placebo controlled trial (EORTC 40071).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS4140-TPS4140
Author(s):  
Markus Hermann Moehler ◽  
Arno Schad ◽  
Murielle E. Mauer ◽  
Michel Praet ◽  
Francisco J. Sapunar ◽  
...  
Keyword(s):  
Phase Ii ◽  
Controlled Trial ◽  
Cohort Analysis ◽  
Progression Free Survival ◽  
Metastatic Gastric Cancer ◽  
Phase Iii ◽  
Her2 Status ◽  
Clinical Activity ◽  
Curative Surgery ◽  
Double Blind

TPS4140 Background: Survival of HER2+ metastatic GC is prolonged by trastuzumab when administered with CF/X (VanCutsem, ASCO 2009). Lapatinib inhibits both EGFR1 and HER2, is active in HER2+ GC lines, and has shown clinical activity in uncontrolled phase II GC trials. A phase III trial of lapatinib with X + oxaliplatin in HER2+ (FISH) GC is closed to recruitment. Additional unaddressed questions include the efficacy and safety of lapatinib with ECF/X (epirubicin + cisplatin + 5-FU or capecitabine (X), which is a preferred chemotherapy (CT) regimen in GC), and its activity in patients (pts) with discordant FISH or IHC HER2 status or EGFR1+. Methods: This is a phase II, randomized, double- blind, placebo controlled, multicenter trial sponsored by the EORTC. About 480 pts with adenocarcinoma of the stomach or esophagogastric junction not amenable to curative surgery and without prior palliative CT are screened centrally for HER2/EGFR1 by FISH and IHC. Patients are enrolled into one of two strata: 1) HER2 FISH- and IHC 2/3+, or 2) HER2 IHC 0/+ and EGFR1 FISH+ or IHC 2/3+. Pts HER2 FISH+/IHC 2/3+ and pts without HER2/EGFR1 by FISH/IHC will be excluded. 168 pts are anticipated to be randomized to lapatinib 1,250 mg cont. until progression or placebo, administered 6 cycles of ECF or ECX (72/96 in stratum 1/2, respectively).The primary endpoint is progression-free survival (PFS) in stratum 2 and 77 events are needed for 80% power to detect an increase in PFS from 4 to 6.5 months with lapatinib (HR=0.615, one-sided alpha 10%). Secondary endpoints include PFS, toxicity, response rate, overall survival, and correlation of HER2/EGFR1 status with response. Currently, half of all screened patients (19/38) have been randomized. So far, 8/38 (21%) pts were HER2+ according TOGA criteria. By FISH or IHC, 14/38 were EGFR1+, with 4/14 pts double HER2/EGFR+. Enrolment continues in 5 centers with about 4-10 patients per month. A safety cohort analysis will be performed in the first 15 pts receiving lapatinib. Conclusions: This is the first trial to analyze prospectively and separately the role of lapatinib combined with chemotherapy in EGFR1+ GC pts stratified by FISH/ IHC.

Evofosfamide (TH-302) in combination with gemcitabine in previously untreated patients with metastatic or locally advanced unresectable pancreatic ductal adenocarcinoma: Primary analysis of the randomized, double-blind phase III MAESTRO study.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 193-193 ◽  
Author(s):  
Eric Van Cutsem ◽  
Heinz-Josef Lenz ◽  
Junji Furuse ◽  
Josep Tabernero ◽  
Volker Heinemann ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Objective Response ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Ductal Adenocarcinoma ◽  
Significant Prognostic Factor ◽  
Primary Analysis ◽  
Eligibility Criteria ◽  
Double Blind

193 Background: Pancreatic ductal adenocarcinoma (PDAC) is invariably diagnosed at an advanced stage and has poor clinical outcome. Hypoxia is a significant prognostic factor in PDAC progression and is associated with poor prognosis. Evofosfamide (Evo, previously known as TH-302) is a hypoxia-activated prodrug of bromo-isophosphoramide mustard (Br-IPM) that is preferentially activated under hypoxic conditions. The addition of Evo to gemcitabine (Gem) significantly improved progression-free survival (PFS) in a randomized phase II trial in advanced PDAC (NCT01144455). Methods: MAESTRO is an international, randomized, double-blind, placebo-controlled phase III trial of Evo/Gem vs Placebo/Gem in patients (pts) with measurable, locally advanced unresectable or metastatic PDAC (NCT01746979). Evo and Gem were administered intravenously at a dose of 340 mg/m2 and 1,000 mg/m2, respectively, on days 1, 8, and 15 of a 28-day cycle. Treatment continued until disease progression. Key eligibility criteria included ECOG PS 0/1 and no neoadjuvant or adjuvant chemotherapy <6 months prior to entry. The primary endpoint was overall survival (OS) with the study designed to detect a HR of 0.75 with 90% power. Secondary endpoints included PFS and objective response rate (ORR), employing a hierarchical testing procedure with a 2-sided α=0.05 at each level. Results: A total of 693 pts were randomized to treatment with Evo/Gem (n=xxx) or Placebo/Gem (n=yyy). Baseline pt characteristics were similar between treatment arms. The OS HR was X.XX (95% CI: Y.YY, Z.ZZ; p=A.AAA). Median OS was AA.A months (m) for Evo/Gem vs BB.B m for Placebo/Gem. Median PFS was C.C m and D.D m, respectively (HR E.EE [95% CI: F.FF, G.GG; p = H.HHH). ORR was JJ.J% with Evo/Gem vs KK.K% with Placebo/Gem (p = L.LLL). Grade ≥3 adverse events (AEs) occurring in >5% of pts in treated with Evo/Gem were: TBC. Conclusions: The data from the MAESTRO trial will make an important contribution to our understanding of PDAC treatment. Clinical trial information: NCT01746979.

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