An open label, phase II trial of continuous low-irradiance photodynamic therapy (CLIPT) using verteporfin for the treatment of cutaneous breast cancer metastases.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS1121-TPS1121 ◽  
Author(s):  
Steven J. Isakoff ◽  
Gary S. Rogers ◽  
Samuel Hill ◽  
Patrick McMullan ◽  
Karleen R. Habin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Photodynamic Therapy ◽  
Systemic Therapy ◽  
Objective Response ◽  
Metastatic Breast ◽  
Open Label ◽  
Cutaneous Metastases ◽  
Normal Tissue Reaction ◽  
Open Label Phase ◽  
Modified Recist

TPS1121 Background: Cutaneous metastases occur in approximately 20% of patients (pts) with metastatic breast cancer (mBC) and can be highly symptomatic and distressing. Radiation is frequently offered, but progression often occurs quickly. Photodynamic therapy is a promising approach with encouraging results in small studies. Here we will evaluate a novel Continuous Low-Irradiance Photodynamic Therapy (CLIPT) system that emits 690nm LED via a handheld powerpack attached to a single-use sterile light patch to deliver a total energy level of 10J/cm2. Verteporfin (Visudyne) is a photosensitizer approved for ophthalmological use that when combined with CLIPT generates activated oxygen species which can destroy tumor cells with limited normal tissue reaction. Methods: This open label, phase 2 study will evaluate the efficacy and safety of CLIPT with verteporfin in 15 pts with cutaneous lesions from mBC. Pts will receive a single IV injection of verteporfin on day 1. The 9x9cm patch with an adhesive border is placed over the treatment site and attached to the CLIPT portable power pack. The pt turns the device on at home 6 hours after the verteprofin injection and it automatically turns off after 24 hours. The pt will remove the patch and return to clinic on day 3. The primary endpoint is objective response rate (RR) at 3 weeks following CLIPT using a modified RECIST which accounts for nodular or diffuse plaque-like lesions. Secondary endpoints include RR at 2, 8 and 12 weeks, toxicity, and quality of life (using FACT-B, a Participant Symptom Scale, and Brief Pain Inventory). Pts who derive clinical benefit may be retreated up to 3 times to the same or different region. Eligible pts will have: cutaneous metastases from mBC with measurable disease by protocol defined modified RECIST 1.1, ≥ 1 line of prior systemic or local therapy for mBC, ≥ 14 days from prior systemic therapy or 60 days from radiation to target lesion, and no expectation for systemic therapy for ≥ 14 days after CLIPT. RR will be reported with 95% CI. If ≥ 3 responses (RR ≥ 20%) are observed, the null hypothesis of RR ≤ 5% will be rejected. At the time of abstract submission, 1 patient has been accrued. Clinical trial information: NCT02939274.

A randomized, open-label, phase II study of lapatinib / capecitabine, lapatinib / vinorelbine, or lapatinib / gemcitabine in patients with ErbB2-amplified metastatic breast cancer progressing after taxane treatment: Results of an interim analysis (GLICO-0801 / EGF111792).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e11087-e11087
Author(s):  
Henry Leonidas Gomez ◽  
Silvia P. Neciosup ◽  
Celia Tosello ◽  
Patricia Xavier ◽  
Yeni Neron do Nascimento ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Phase Ii ◽  
Interim Analysis ◽  
Metastatic Breast ◽  
Primary Objective ◽  
Open Label ◽  
Open Label Phase ◽  
Hand Foot Syndrome ◽  
Number Of Cycles

e11087 Background: Lapatinib-capecitabine is approved for the treatment of ErbB2-amplified metastatic breast cancer (MBC) after failure to anthracyclines, taxanes and trastuzumab. GLICO-0801 evaluates different lapatinib-based chemotherapy combinations as 1st/2nd line treatment for ErbB2 amplified MBC progressing after taxane treatment. We present the results of a planned safety interim analysis. Methods: This is an open-label, randomized, international, phase II trial exploring lapatinib (L) 1250mg qd in combination with capecitabine 2000mg/m2 d 1-14 (Arm A) or vinorelbine 25mg/m2 d 1 and 8 (Arm B) or gemcitabine 1000mg/m2 d 1 and 8 (Arm C). Primary objective is to determine the clinical benefit rate (defined as CR+PR+SD for ≥24 weeks). This trial is registered at www.clinicaltrials.gov number: NCT01050322 Results: The first83 randomized patients (pts) (Arm A=29, B=28 and C=26) were included in this analysis. Of them, 65 (78%) have discontinued therapy with mean number of cycles of 4.7, 6.2 and 7.5 in arms A, B and C respectively. Eighteen (21%) pts are still on treatment. Median age was 52y (29-84); 80 pts (96%) had PS 0-1; 51 (61%) were postmenopausal. Fifty-six pts (67%) had visceral metastasis, 52 (63%) were treated as 2nd line therapy and 36 (43%) had received prior trastuzumab. Most reported adverse events (AE) (87%) were grade 1-2. The most common AE (any grade) in arm A: diarrhea 72%, hand-foot syndrome 45%, vomiting 39%, anemia 36%; in arm B: diarrhea 75%, neutropenia 68%, nausea 43%, vomiting 39%; in arm C: diarrhea 72%, neutropenia 60%, anemia 44%, increase in ALT 44%. The most frequent serious AE reported in arm A: diarrhea in 3 pts (10%) and thrombocytopenia in 2 pts (7%); in arm B: febrile neutropenia in 2 pts (7%) and in arm C: sepsis in 1 pt (4%). There was one toxic death related to chemotherapy in arm C. Conclusions: There were no unexpected toxicities so far in this trial with most AEs being mild to moderate and manageable. This interim analysis supports the continuation of the study.

LUX-breast 2: Phase II, open-label study of oral afatinib in HER2-overexpressing metastatic breast cancer (MBC) patients (pts) who progressed on prior trastuzumab (T) and/or lapatanib (L).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS651-TPS651 ◽  
Author(s):  
Tamas Hickish ◽  
Ling-Ming Tseng ◽  
Ajay O. Mehta ◽  
Janice Tsang ◽  
Nadezhda Kovalenko ◽  
...  
Keyword(s):  
Phase Ii ◽  
Objective Response ◽  
Xenograft Model ◽  
Metastatic Breast ◽  
Stage Iv ◽  
Response Duration ◽  
Open Label ◽  
Erbb Family ◽  
Erbb Signaling ◽  
Open Label Phase

TPS651 Background: Management of HER2-overexpressing MBC has improved over the past decade. However, pts still develop resistance to currently available HER2-targeted therapies and novel effective treatments are increasingly required as dual targeted combinations are given in early treatment lines already. Current therapies focus on targeting HER2 and do not inhibit all relevant ErbB Family dimers. Afatinib is an oral, irreversible ErbB Family Blocker that inhibits signaling through activated EGFR (ErbB1), HER2 (ErbB2) and ErbB4 receptors and transphosphorylation of ErbB3. Preclinical studies have demonstrated efficacy in T-sensitive and T-resistant human BC xenograft models dependent on ErbB signaling. Efficacy of afatinib in a T-resistant SUM 190 xenograft model has been shown to be increased by addition of IV vinorelbine (V). Afatinib monotherapy has shown promising clinical benefit in 46% of HER2-overexpressing MBC pts who progressed on prior T, with 10% of pts achieving PR. Methods: This open-label Phase II trial (NCT01271725) investigates efficacy and safety of afatinib alone (40 mg/d) followed by afatinib ‘beyond progression’ plus chemotherapy in 120 pts with HER2-overexpressing MBC, who progressed on prior neoadjuvant and/or adjuvant T and/or L. Pts who progress on afatinib monotherapy receive afatinib plus either weekly paclitaxel (P) 80 mg/m2 or V 25 mg/m2. Eligible pts have confirmed HER2-overexpressing BC, stage IV disease measurable by RECIST 1.1, progressed on T and/or L therapy in either neoadjuvant and/or adjuvant setting, are eligible for retreatment with P or V and should not have been pretreated with P (≤12 months) or V, respectively. Exclusion criteria: inadequate cardiac, renal, hepatic and hematological function, pre-existing gastrointestinal dysfunction, rapidly progressing visceral disease, ILD and active brain metastases. The primary endpoint is objective response (OR) and secondary endpoints include best overall response, duration of OR and PFS; safety will be assessed separately for afatinib mono- and combination therapy. Patient enrollment began in May 2011 in ~35 sites and 5 countries.

Phase II randomized, open-label study of YM155 (sepantronium bromide) plus docetaxel versus docetaxel alone as first-line treatment for HER2 negative metastatic breast cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 548-548
Author(s):  
Michael R. Clemens ◽  
Anne Therese Keating ◽  
Oleg Gladkov ◽  
Fei Jie ◽  
Joyce Steinberg ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Randomized Study ◽  
Objective Response ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Line Treatment ◽  
Open Label ◽  
Eligibility Criteria ◽  
Prior Therapy

548 Background: YM155 (YM) is a small molecule survivin suppressant. In a phase I/II study of YM plus docetaxel (D) in solid tumors evidence of anti-tumor activity was observed in women with human epidermal growth factor 2 non-overexpressing (HER2 negative) metastatic breast cancer (mBC). Methods: This was a randomized study of YM plus D versus D as 1st line treatment in subjects with HER2 negative mBC. Eligibility criteria were: ECOG < 1, no prior chemotherapy for mBC, and at least one measurable lesion. Primary endpoint was progression free survival (PFS); secondary endpoints were: objective response rate (ORR), overall survival (OS), duration of response (DOR), clinical benefit rate (CBR), time to response (TTR) and safety. YM was administered at 5 mg/m2/day as a 168 hr continuous infusion followed by 14 Day (d) observation and D was administered at 75 mg/m2over 1 hr on d1 every 21d. In the control arm, D was dosed per investigator choice q 21d. Results: 101 subjects were randomized (50 YM + D; 51 D). Median (m) age 55 (range: 25 – 79), 25% had triple negative disease, > 60% had bone and lymph mets, 86% had prior therapy for BC. mPFS (days) was 251 (95%CI: 176 – 333) YM + D vs 252 (95%CI: 202-433) D (p=0.34). ORR, CBR and TTR (YM+D; D): 26% vs. 25.5%; 82% vs. 84.3% and 45 vs 59 d. OS data are immature but showed no difference (p=0.911). Adverse events [AEs (> 25%)] [YM + D% vs D %]: neutropenia 83 vs 84, alopecia 62.5 vs 53, fatigue 50 vs 41.2, nausea 35.4 vs 41.2, leucopenia 27 vs 33 and dyspnoea 33 vs 14. Common (>10%) serious AEs [YM + D% vs D%]: febrile neutropenia 21 vs 8 and neutropenia 10 vs 8. Conclusions: Preclinical and clinical evidence suggested the combination of YM + D may offer additional benefit to D alone in subjects with mBC. This study showed no difference in efficacy, but the combination appeared to be well tolerated. Clinical trial information: NCT01038804.

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