Survival of patients (pts) with metastatic melanoma treated with the anti-CTLA4 monoclonal antibody (mAb) CP-675,206 in a phase I/II study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8524-8524 ◽  
Author(s):  
J. Gomez-Navarro ◽  
S. Antonia ◽  
J. Sosman ◽  
J. M. Kirkwood ◽  
B. Redman ◽  
...  
Keyword(s):  
Phase I ◽  
Metastatic Melanoma ◽  
Median Survival ◽  
Phase Ii ◽  
Survival Data ◽  
Phase I Study ◽  
Objective Response ◽  
Phase Iii ◽  
Open Label ◽  
Expansion Cohort

8524 Background: The fully human anti-CTLA4 mAb CP-675,206 has demonstrated clinical activity in pts with metastatic melanoma. Prolonged survival was observed in a prior single-dose phase I study, even in pts who did not achieve objective tumor responses. Methods: A multidose phase I/II trial was conducted in pts (N = 119) with histologically confirmed stage IIIc (unresectable) or stage IV recurrent metastatic melanoma and ECOG PS = 1. The study consisted of a phase I, open-label, multidose study (3, 6, and 10 mg/kg) and a phase I expansion cohort for HLA-A2.1+ pts (10 mg/kg monthly [Q1M]), followed by a phase II open-label study of 2 dosing regimens: 10 mg/kg Q1M and 15 mg/kg every 3 months (Q3M). The primary endpoint was safety in phase I, immune monitoring in the expansion cohort, and response in phase II. Survival was analyzed as a secondary endpoint. Results: In the phase I study, Kaplan-Meier estimates of median overall survival were 17.6 months for all dose groups combined (n = 28). In the phase II study, median survival was 10.3 months in the 10 mg/kg arm and 11.0 months in the 15 mg/kg arm. Survival outcomes were favorable, compared with historical median survival of 7 months, independent of whether pts achieved an objective response. Updated survival data will be presented. Conclusions: Patients participating in a multiple dose study of CP-675,206 showed a survival time that was greater than expected on historic controls. These observations support the endpoints of an ongoing randomized phase III study in melanoma to further evaluate survival in the frontline setting. [Table: see text] [Table: see text]

CA184-161: A phase I/II trial of vemurafenib and ipilimumab in patients with BRAF V600 mutation-positive metastatic melanoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS8603-TPS8603 ◽  
Author(s):  
Antoni Ribas ◽  
F. Stephen Hodi ◽  
John F. Kurland ◽  
Vafa Shahabi ◽  
Stephen Francis ◽  
...  
Keyword(s):  
Phase I ◽  
Metastatic Melanoma ◽  
Phase Ii ◽  
Treatment Guidelines ◽  
Human Monoclonal Antibody ◽  
Objective Response ◽  
Braf Inhibitor ◽  
Maximum Tolerated Dose ◽  
Braf V600e ◽  
Phase Iii

TPS8603 Background: Ipilimumab (ipi) is a fully human monoclonal antibody that blocks cytotoxic T-lymphocyte antigen-4 (CTLA-4) to augment antitumor immune responses. Ipi significantly improved overall survival (OS) in two separate phase III trials of metastatic melanoma (MM): (1) at 3 mg/kg as monotherapy in previously treated patients and (2) at 10 mg/kg combined with dacarbazine in previously untreated patients. The most common drug-related adverse events with ipi were immune-related, and were generally reversible using treatment guidelines. Vemurafenib (vem) is a potent inhibitor of BRAF V600E-mutated kinase, which occurs in ~50% of MM. In clinical studies, vem produced objective response rates of ~50% with a significant improvement in the rate of OS in patients with previously untreated BRAF V600-positive MM. The purpose of this phase I/II study is to determine the safety and feasibility of ipi plus vem in patients with BRAF V600-positive MM, and to evaluate the efficacy of the combination in comparison to historical results observed with each agent alone. Methods: In phase I, an escalating dose design is used to assess safety/tolerability and to determine the maximum tolerated dose (MTD) of each agent. Vem will initially be given alone for 28 days at 960 mg p.o. BID, followed by vem in combination with ipi i.v. at 3 mg/kg [induction (q3w x 4) and maintenance (q12w)]. The next cohort will receive vem at 960 mg plus ipi increased to a dose of 10 mg/kg. Phase I will enroll an estimated 20 patients who have not previously received a CTLA-4 antagonist or BRAF inhibitor. If new or heightened frequency or severity of toxicities is not observed, a phase II single-arm extension at the MTD of each agent will be conducted in patients with previously untreated MM. The primary objectives of phase II (estimated enrollment of 30 patients) are to obtain preliminary evidence of efficacy (OS, 1- and 2-year survival rates) and to evaluate safety of the combination. Major inclusion criteria are ≥ 18 years of age, BRAF V600-positive MM, measurable tumor, no active brain metastasis, and an ECOG PS of 0-1. The first patient was enrolled in November 2011 and enrollment is ongoing (ClinicalTrials.gov identifier: NCT01400451).

Overall survival results from the randomized phase II study of palbociclib (P) in combination with letrozole (L) vs letrozole alone for frontline treatment of ER+/HER2– advanced breast cancer (PALOMA-1; TRIO-18).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1001-1001 ◽  
Author(s):  
Richard S. Finn ◽  
John Crown ◽  
Istvan Lang ◽  
Katalin Boer ◽  
Igor Bondarenko ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Phase Ii ◽  
Survival Data ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Open Label ◽  
Frontline Treatment ◽  
Open Label Phase

1001 Background: Preclinical data identified a synergistic role for P and hormone blockade in blocking growth of ER+ breast cancer (BC) cell lines. PALOMA-1 was an open-label phase II trial comparing progression-free survival (PFS) in patients (pts) with advanced ER+/HER2– BC treated with P+L or L alone. Median PFS increased with addition of P to L to 20.2 mos (vs 10.2 mos with L alone; HR = 0.488), with an acceptable safety profile, leading to accelerated approval by the US FDA. These results were confirmed in the phase 3 PALOMA-2 trial. At the time of the final PFS analysis, overall survival (OS) data were immature with only 61 events in both arms and a median follow-up of < 30 mos with a trend in favor of P+L vs L (37.5 vs 33.3 mos; HR = 0.813; P= 0.211). Here we present final OS results. Methods: PALOMA-1 was a 2-part study evaluating P+L in ER+/HER2– advanced BC. Part 1 enrolled postmenopausal pts with this subtype using only ER+/HER2– while Part 2 enrolled pts of this subtype additionally screened for CCND1 amplification and/or loss of p16. The primary endpoint was investigator-assessed PFS. Secondary endpoints included objective response rate, OS, safety, and correlative biomarker studies. A total of 165 pts were randomized; 66 in Part 1 and 99 in Part 2. Baseline characteristics were balanced between treatment arms. In both parts, pts were randomized 1:1 to receive P+L or L alone. OS data were collected as well as post-study therapy. Results: As of Dec 2016, there were 116 OS events. Median OS was 37.5 mos (95% CI: 31.4, 47.8) with P+L vs 34.5 mos (95% CI: 27.4, 42.6) for L (HR = 0.897 [95% CI: 0.623, 1.294]; P= 0.281). Median OS was 37.5 vs 33.3 mos (HR = 0.837; P= 0.280) for Part 1 and 35.1 vs 35.7 mos (HR = 0.935; P= 0.388) for Part 2. 78.6% of pts in the P+L arm received post-study systemic therapy vs 86.4% in the L arm. More pts in the L arm received ≥3 lines of therapy (37% vs 18%). Further subgroup analyses and details on post-study therapies will be presented. Conclusions: In PALOMA-1, P+L provided a statistically non-significant trend towards an improvement in OS. Survival data from the phase III, PALOMA-2 study is awaited. Sponsor: Pfizer; Clinical trial information: NCT00721409.

Open-label study of pemetrexed alone for chemonaive patients and pre-treated patients with malignant pleural mesothelioma: Outcomes of the International Expanded Access Program (EAP)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7709-7709
Author(s):  
P. Taylor ◽  
J. von Pawel ◽  
B. Castagneto ◽  
G. Dark ◽  
M. Marangolo ◽  
...  
Keyword(s):  
Median Survival ◽  
Phase Ii ◽  
Malignant Pleural Mesothelioma ◽  
Survival Data ◽  
Single Agent ◽  
Safety Data ◽  
Phase Iii ◽  
Pleural Mesothelioma ◽  
Open Label ◽  
Pretreated Group

7709 Background: In a previous phase II study of chemonaive malignant pleural mesothelioma (MPM) patients (pts), single-agent pemetrexed (P) resulted in a 14.1% response rate (RR) and median survival of 10.7 mos (95% CI 7.7–14.5) (Scagliotti 2003). Likewise, the P arm in a phase III study of pre-treated MPM pts yielded an 18.7% RR (40.7% with stable disease, SD) and median survival of 8.4 mos (95% CI 6.2–10.5) (Jassem 2006). The EAP provided 3311 MPM pts with access to P alone, P plus cisplatin, or P plus carboplatin in 13 countries. In this abstract we report on the safety and efficacy data of those MPM pts treated with P alone. Methods: Eligible pts had histologic or cytologic diagnosis of MPM and were either chemonaïve or previously treated with =1 line(s) of chemotherapy. Pts pre-treated with P were allowed if they had experienced clinical benefit from the prior P. Treatment consisted of P (500 mg/m2) once (day 1) every 21 days with standard pre-medication of vitamin B12, folic acid, and dexamethasone. Investigator-determined response (RR) and survival data (with censoring) were recorded at the end of study participation. Myelosuppression data (CTC) were also collected. Results: 812 MPM pts (319 chemonaïve; 493 pre-treated) received =1 dose of P and were evaluated for safety, and 643 pts (247 chemonaïve; 396 pre-treated) were evaluated for efficacy (RR and survival). In chemonaïve pts with MPM, the median age was 69 yrs (range: 39–87 yrs), 78.1% were male, and 71.6% had a KPS ≥80 (of the 93% who had PS evaluated). In pre-treated pts with MPM, the median age was 63 yrs (range: 31–85 yrs), 75.9% were male, and 74.5% had a KPS ≥80 (of the 95% who had PS evaluated). Both groups received a median of 4 cycles (chemonaive group range 1–18; pretreated group range 1–23). See the table for efficacy and safety data. Conclusions: Results of the EAP confirm earlier phase II and phase III studies. No significant financial relationships to disclose. [Table: see text]

Cancer Research Campaign phase II trial of temozolomide in metastatic melanoma.

1995 ◽  
Vol 13 (4) ◽  
pp. 910-913 ◽  
Author(s):  
N M Bleehen ◽  
E S Newlands ◽  
S M Lee ◽  
N Thatcher ◽  
P Selby ◽  
...  
Keyword(s):  
Phase I ◽  
Total Dose ◽  
Metastatic Melanoma ◽  
Median Survival ◽  
Phase Ii ◽  
Lung Metastases ◽  
Interleukin 2 ◽  
Survival Duration ◽  
Median Response ◽  
Median Survival Duration

PURPOSE Sixty patients with metastatic melanoma were treated in a phase II study with the imidazotetrazine derivative temozolamide to assess further the efficacy demonstrated in previous phase I studies. PATIENTS AND METHODS Fifty-five of 56 eligible patients were assessable for toxicity and 49 for response. The patients received temozolomide 150 mg/m2/d over 5 successive days orally (total dose, 750 mg/m2) in the first course. Courses were repeated every 4 weeks and the dose was escalated to 200 mg/m2/d x 5 (total dose, 1 g/m2) after the first course if toxicity was acceptable. Patients were all chemotherapy-naive, except for two who had previously received interferon alfa and one who had received interleukin-2 (the latter patient had also received two phase I drugs some time previously). RESULTS A complete response (CR) was documented in three patients (all with lung metastases) and a partial response (PR) in nine patients (21% CR plus PR rate). Seven of 56 patients were not assessable for response because of early death or deterioration. The overall response rate excluding these patients is 12 of 49 (24%). The median response duration was 6 months (range, 2.5 to 22+). Toxicity of the regimen, which was mainly hematopoietic, was low. The median survival duration for all patients was 5.5 months (range, 0.5 to 29.5). For responders, the median survival duration was 14.5 months (range, 3 to 28+), with four patients still alive. CONCLUSION Temozolomide in the schedule used has as good activity in chemotherapy-naive metastatic melanoma as the other most active agents currently in use. Further studies of the drug on its own and in combination with other agents is recommended.

REACT: A phase II study of rindopepimut (CDX-110) plus bevacizumab (BV) in relapsed glioblastoma (GB).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS2103-TPS2103 ◽  
Author(s):  
David A. Reardon ◽  
James J. Vredenburgh ◽  
Annick Desjardins ◽  
Ronald G. Steis ◽  
Erin M. Dunbar ◽  
...  
Keyword(s):  
Immune Responses ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Objective Response ◽  
Peptide Sequence ◽  
Phase Iii ◽  
Open Label ◽  
Term Survival ◽  
Gm Csf ◽  
Phase Ii Studies

TPS2103 Background: EGFRvIII is a constitutively active tumorigenic deletion mutation of EGFR. It is expressed in ~30% of primary GB where it is linked to poor long-term survival (Pelloski 2007). The investigational vaccine rindopepimut consists of the unique EGFRvIII peptide sequence conjugated to keyhole limpet hemocyanin (KLH), delivered intradermally (500ug with 150ug GM-CSF as an adjuvant). Remarkably consistent and promising results across 3 phase II studies in newly diagnosed, resected EGFRvIII+ GB (Lai 2011) represent a statistically significant improvement over a historical control cohort matched for major eligibility criteria (median overall survival [OS] = 24.4 - 24.6 vs. 15.2 months from diagnosis [m] and median progression-free survival [PFS] = 12.3 - 15.3 vs. 6.4 m). ACT IV, a phase III trial in this population, is ongoing. The immunosuppressive influence of residual/advanced GB presents a challenge to activation of efficacious antitumor immune responses. Anecdotal evidence (compassionate use cases, Sampson 2008) suggests that rindopepimut may induce specific immune responses and regression in multifocal and bulky residual tumors. Rindopepimut with BV, which inhibits VEGF and its immunosuppressive properties (including impaired maturation of dendritic cells and disruption of tumoral T cell infiltration [Johnson 2007, Shrimali 2010]) may further optimize EGFRvIII-specific immune response and antitumor activity. Methods: ReACT is a Phase II study of rindopepimut plus BV in patients (pts) with 1st or 2nd relapse of EGFRvIII+ GB. BV-naïve pts will be enrolled to Group 1 (n=70: randomized 1:1 to BV plus either rindopepimut/GM-CSF or control injection [low-dose KLH]) while BV-refractory patients will enter Group 2 (n=25: to receive BV plus open-label rindopepimut/GM-CSF). Concurrent with BV (10 mg/kg, q 2 wks), blinded treatment or open-label vaccine is given in priming phase (days 1, 15 and 29), then monthly until PD. Tumor response is assessed every 8 weeks, and patients are followed for survival after PD. Objectives are PFS at 6 months (primary), objective response rate, PFS, OS, safety, immunogenicity and elimination of EGFRvIII. ReACT opened to accrual in December 2011 (NCT01498328).

A single-arm, open-label, multicenter phase I/II study of the combination of panobinostat (pan) and carfilzomib (cfz) in patients (pts) with relapsed/refractory multiple myeloma (RR MM).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS8115-TPS8115
Author(s):  
Jesus G. Berdeja ◽  
Joseph Mace ◽  
Ruth E. Lamar ◽  
Victor Gian ◽  
Patrick Brian Murphy ◽  
...  
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Histone Deacetylase Inhibitors ◽  
Standard Dose ◽  
Objective Response ◽  
Progression Free Survival ◽  
Response To Treatment ◽  
Current Status ◽  
Open Label ◽  
Starting Dose

TPS8115 Background: Despite novel therapies, MM remains an incurable disease. Changes in histone modification are commonly found in human cancers including MM. Preclinical studies demonstrate synergistic anti-MM activity with histone deacetylase inhibitors (HDACi) and proteasome inhibitors (PI) through the dual inhibition of the proteasome and aggresome pathways. Pan is an oral pan-HDACi which has shown synergy with bortezomib in clinical studies. Cfz is a 2nd generation PI which has shown marked anti-MM activity with an improved safety profile. In this trial we evaluate the safety and efficacy of the combination of pan and cfz in pts with RR MM. Methods: This multi-center US study plans to enroll up to 52 adults with RR MM. The phase I study will determine the MTD of the combination of cfz and pan and follow a standard dose escalation design. Pan will be administered orally three times weekly during weeks 1 and 3 of each 28-day cycle (Days 1, 3, 5, 15, 17, 19) at a starting dose of 20 mg. Cfz will be administered intravenously on Days 1, 2, 8, 9, 15, and 16 of each 28-day cycle. Cfz starting dose will be 20mg on days 1,2 of cycle 1 with escalation to the corresponding dose level beginning at 27 mg , if well tolerated. Dose modifications will not be permitted during cycle 1 unless a pt experiences a DLT. A maximum of four dose levels will be evaluated. Approximately 24 pts will be enrolled during the phase I portion to establish the MTD. In the phase II portion of this study, pts with RR MM will receive treatment with the optimal dose of pan and cfz established during phase I. Pts will be assessed for response to treatment after each cycle (4 weeks). Pts with objective response or stable disease will continue treatment until disease progression or unacceptable toxicity occurs. The primary endpoint is to establish the optimal doses of cfz and pan that can be administered to pts with RR MM (phase I) and to evaluate the overall response rate (phase II). Secondary endpoints include time-to-progression, progression-free survival, overall survival and safety. Approximately 25 pts are planned for the phase II portion. Current status: As of 1/27/12 3 patients have been enrolled.

Epacadostat plus pembrolizumab in patients with advanced urothelial carcinoma: Preliminary phase I/II results of ECHO-202/KEYNOTE-037.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4503-4503 ◽  
Author(s):  
David C. Smith ◽  
Thomas Gajewski ◽  
Omid Hamid ◽  
Jeffrey S. Wasser ◽  
Anthony J. Olszanski ◽  
...  
Keyword(s):  
Phase I ◽  
Urothelial Carcinoma ◽  
Phase Ii ◽  
Advanced Disease ◽  
Alternative Therapy ◽  
Phase Iii ◽  
Open Label ◽  
Advanced Urothelial Carcinoma ◽  
Grade 3 ◽  
Line Of Therapy

4503 Background: Pembrolizumab (P), a PD-1 inhibitor, is active and well tolerated in platinum-treated, advanced urothelial carcinoma (UC). Epacadostat (E) potently and selectively inhibits indoleamine 2,3-dioxygenase 1 (IDO1), a tryptophan-catabolizing enzyme that suppresses T-cell–mediated immune surveillance. IDO1 overexpression is associated with tumor progression and shortened patient (pt) survival. ECHO-202/KEYNOTE-037 is an open-label, phase I/II study of E + P in pts with advanced tumors. We report phase I/II efficacy and safety outcomes for the UC cohort at an October 29, 2016 data cutoff. Methods: Adult pts with advanced UC, prior platinum therapy (adjuvant or advanced disease setting) or alternative therapy (if platinum was not appropriate), and no prior checkpoint inhibitor therapy were eligible to participate. In phase I, pts received E (25, 50, 100, or 300 mg PO BID) + P (2 mg/kg or 200 mg IV Q3W); MTD was not exceeded. E (100 mg BID) + P (200 mg Q3W) dosing was selected for phase II. Response was assessed in RECIST 1.1–evaluable pts. Safety was assessed in pts receiving ≥1 E + P dose. Results: A total of 40 pts (phase I, n = 5; phase II, n = 35) were evaluated. Median age was 67 years, 75% were men, 88% were white, 100% had prior platinum therapy, and 75% had 0–1 prior line of therapy for advanced disease. Preliminary ORR (CR+PR) and DCR (CR+PR+SD) for all efficacy-evaluable pts were 35% (13/37; all PR) and 57% (21/37; 13 PR, 8 SD), respectively; for pts with 0–1 prior line of therapy for advanced disease, ORR and DCR were 37% (10/27) and 63% (17/27). At data cutoff, 12/13 responses were ongoing (range, 1+ to 652+ days). PFS and biomarker analyses are ongoing. The most common TRAEs (≥10% of 40 pts) were fatigue (28%), rash (18%), and increased amylase (10%; asymptomatic). Grade ≥3 TRAEs occurred in 20% of pts (rash was the only grade ≥3 TRAE to occur in > 1 pt [n = 3]). Three pts discontinued due to TRAEs (grade 3 rash [n = 1]; grade 3 COPD exacerbation [n = 1], grade 2 diarrhea [n = 1]). Conclusions: E + P was generally well tolerated and associated with increased response compared with previously reported PD-1 inhibitor monotherapy in pts with advanced UC. A phase III UC study is planned. Clinical trial information: NCT02178722.

Phase I study of NBTXR3 activated by radiotherapy in patients with advanced cancers treated with an anti-PD-1 therapy.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS3173-TPS3173 ◽  
Author(s):  
Colette Shen ◽  
Jessica Frakes ◽  
Jared Weiss ◽  
Jimmy J. Caudell ◽  
Trevor G Hackman ◽  
...  
Keyword(s):  
Phase I ◽  
Phase I Study ◽  
Response Rate ◽  
Checkpoint Inhibitors ◽  
Lung Metastases ◽  
Objective Response ◽  
Intratumoral Injection ◽  
Primary Objective ◽  
Open Label ◽  
Open Label Phase

TPS3173 Background: Despite the past decade of transformative advances in immuno-oncology, the response rate to checkpoint inhibitors (ICIs) remains low (~15%). There is significant interest in developing strategies to overcome resistance to these treatments, thus increasing response rate. Emerging evidence suggests that radiation therapy (RT) could potentially augment the antitumor response to ICIs through synergic effect. However, RT dose and ultimate efficacy are limited by toxicity related to exposure of healthy tissues. NBTXR3 is a first-in-class radioenhancer administered by direct intratumoral injection, designed at the nanoscale to increase RT dose deposition within tumor cells and RT-dependent tumor cell killing, without increasing surrounding normal tissue toxicity. Preclinical and early clinical data suggest NBTXR3 activated by RT can trigger an anti-tumor immune response, producing both local and systemic (abscopal) effects. We hypothesize that NBTXR3 activated by RT, in combination with anti-PD-1 therapy (R3/RT/PD-1), will act synergistically to maximize the local RT effect and produce a systemic response sufficient to increase the proportion of ICI responders or convert ICI non-responders to responders. Methods: This trial [NCT03589339] is a multicenter, open-label, phase I study to evaluate safety and tolerability of R3/RT/PD-1 in three cohorts: (1) Locoregional recurrent or recurrent and metastatic head and neck squamous cell carcinoma (HNSCC) amenable to re-irradiation of the HN field, (2) Lung metastases, or (3) Liver metastases, both from any primary cancer eligible for anti-PD-1 treatment. Approximately two-thirds of patients in each cohort will be anti-PD-1 non-responders. NBTXR3 injected volume is based on a percentage of gross tumor volume (GTV). The primary objective is to determine the R3/RT/PD-1 recommended phase 2 dose in each cohort. Secondary objectives are to evaluate anti-tumor response (objective response rate; ORR), safety and feasibility of NBTXR3 injection, and NBTXR3 body kinetic profile. Exploratory objectives will assess biomarkers of R3/RT/PD-1 response, including PD-L1 status by IHC, as well as mRNA and cytokine immune marker profiling. To date, three patients have been treated, one in cohort 1, two in cohort 2. Clinical trial information: NCT03589339 .

scholarly journals Safety and activity of IT-139, a ruthenium-based compound, in patients with advanced solid tumours: a first-in-human, open-label, dose-escalation phase I study with expansion cohort

ESMO Open ◽  
2017 ◽  
Vol 1 (6) ◽  
pp. e000154 ◽  
Author(s):  
Howard A Burris ◽  
Suzanne Bakewell ◽  
Johanna C Bendell ◽  
Jeffrey Infante ◽  
Suzanne F Jones ◽  
...  
Keyword(s):  
Phase I ◽  
Dose Escalation ◽  
Phase I Study ◽  
Solid Tumours ◽  
Open Label ◽  
Label Dose ◽  
Expansion Cohort

Final efficacy results of a phase I/II trial of ixabepilone in combination with capecitabine in patients with metastatic breast cancer (MBC) previously treated with a taxane and an anthracycline

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10511-10511 ◽  
Author(s):  
C. A. Bunnell ◽  
J. Klimovsky ◽  
E. Thomas
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Objective Response ◽  
Metastatic Breast ◽  
Complete Response ◽  
Open Label ◽  
Metastatic Setting ◽  
Previously Treated ◽  
Her 2 ◽  
Phase Ii And Iii

10511 Background: Ixabepilone is an epothilone B analog that has demonstrated efficacy in taxane-sensitive and taxane-resistant MBC. Differing mechanisms of action and minimally overlapping toxicities provide the potential for synergy between ixabepilone and other cytotoxics. Methods: This open-label Phase I/II study was conducted to determine the recommended Phase II (and III) doses of ixabepilone and capecitabine using a 3-hour infusion of ixabepilone given on Day 1 (Schedule A) or a 1-hour infusion of ixabepilone given for 3 consecutive days (Schedule B) in combination with capecitabine given orally on Days 1–14 every 21 days in patients (pts) with MBC previously treated with a taxane and an anthracycline in the adjuvant or metastatic setting. Pts were excluded if they had received >3 prior chemotherapy regimens in the metastatic setting. Tumor response was determined after every 2 cycles. Results from the 62 patients treated with ixabepilone 40 mg/m2 as a 3 hr-infusion and capecitabine 2000 mg/m2 are shown here. Results: 56/62 patients (90%) were aged <65 yrs. 80% of pts had visceral disease and 44% were ER/PR/HER-2 negative. 44% of pts had received ≥2 prior chemotherapies in the metastatic setting. Pts received a median of 4 cycles (range 1–20). The overall response rate was 30% (15/50; 95% CI = 17.9–44.6%) comprised of one (2%) complete response and 14 (28%) partial responses. All 15 of the responders had extensive tumor metastases at baseline. Four of the 15 responders were triple negative for ER/PR/HER-2. The median time to response was 6 weeks (range 5–14 weeks), with most responders achieving an objective response by the end of Cycle 2. The median duration of response was 6.9 months (95% CI = 4.3–9.7 months). Conclusions: The recommended Phase II (and III) doses were 40 mg/m2 ixabepilone (3-hour infusion on Day 1 every 21 days) and 2000 mg/m2 capecitabine (2 doses on Days 1–14 every 21 days). This ixabepilone/capecitabine combination demonstrated promising synergistic antitumor activity and a manageable safety profile in pts with MBC previously treated with a taxane and an anthracycline. [Table: see text]

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