A phase II study of nimotuzumab and CDDP concurrent with radiation in locally advanced squamous cell carcinoma of the head and neck (SCCHN).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e16024-e16024
Author(s):  
Wan-Teck Lim ◽  
Mei-Kim Ang ◽  
Quan Sing Ng ◽  
Lan-Ying Wang ◽  
Noan-Minh Chau ◽  
...  
Keyword(s):  
Function Analysis ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Normal Organ ◽  
Intention To Treat ◽  
Flat Dose ◽  
Grade 5 ◽  
Humanized Monoclonal Antibody ◽  
Acneiform Rash ◽  
Grade 3

e16024 Background: Nimotuzumab is a humanized monoclonal antibody (MAb) to EGFR. Concurrent cisplatin with radical radiotherapy (RT) is standard treatment for locally advanced SCCHN where it is unresectable or for organ-preservation. We explored the combination of nimotuzumab with concurrent CDDP and RT in these patients (pts). Methods: Pts with locally advanced stage III/IV SCCHN were eligible for study if: age > 18, ECOG 0-1, SCC, normal organ function. Analysis was by intention-to-treat (ITT). CDDP 100 mg/m2 on days 1, 22, and 43 was given with RT (70 Gy over 35 fractions). Nimotuzumab was given as a flat dose of 200 mg weekly on weeks 1 to 8 of treatment. Pts were followed up for RECIST response, progression free survival and toxicity. Results: Twenty-eight pts were available for analysis at the time of report. The median age was 58 (30-69). Most were Chinese (90%) and all ECOG 0-1. Twelve pts had oropharynx Ca, 16 had non-oropharyx Ca. Twenty-five pts were evaluable for response, 2 pts withdrew consent after 2 weeks, 1 pt died of undiagnosed Fanconi anemia. By ITT, the best overall response rate (CR/PR) was 78.6% (12 CR/10 PR), SD 3.6% (1), PD 7.2% (2). Pts with oropharynx Ca had higher PFS rate at 1 year than non-oropharynx (80% vs 48%). Major grade 3/4 toxicities were limited to mucositis, dysphagia, and fatigue. Grade 5 toxicity due to febrile pancytopenia occurred in 1 pt with undiagnosed Fanconi’s. Acneiform rash typical of EGFR inhibitors occurred in 1 pt. Conclusions: Nimotuzumab with concurrent CDDP/RT is feasible and there was minimal additional toxicity encountered. Final results will be updated at the meeting.

Randomized phase III study of adjuvant versus progression-triggered treatment with gemcitabine (G) after radical cystectomy (RC) for locally advanced bladder cancer (LABC) in patients not suitable for cisplatin-based chemotherapy (CBC) (AUO-trial AB22/00).

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 250-250 ◽  
Author(s):  
Jan Lehmann ◽  
Michael Kuehn ◽  
Claus Fischer ◽  
Bjoern Volkmer ◽  
Friedrich von Rundstedt ◽  
...  
Keyword(s):  
Adjuvant Therapy ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Intention To Treat ◽  
Kaplan Meier ◽  
Node Positive Disease ◽  
Secondary Endpoints ◽  
The Difference ◽  
Grade 3

250 Background: Cisplatin-based chemotherapy (CBC) has been widely used in trials of adjuvant therapy for LABC after RC. A high proportion of patients are unfit for CBC after RC for LABC. We therefore performed a prospective randomized phase III trial on G-monotherapy administered as adjuvant therapy (G-adj) vs in case of progression (G-prog) in pts not suitable for CBC. Methods: Between 7/2000 and 12/2008 120 of 178 planned pts with LABC unfit for CBC were randomized between 6 adjuvant cycles of G (q3w) starting within 12 wks after RC and G in case of disease progression. The primary endpoint of the trial was progression-free survival (PFS). Secondary endpoints included cancer-specific (CSS) and overall survival (OS) as well as treatment related toxicity. Results: The trial of 178 planned pts was closed early due to slow accrual. Of 120 randomized pts from 29 centers 114 were eligible for analysis. Median age of 81 male and 33 female pts was 72 (45-82) years. Lymph-node positive disease was found in 52/114 (47%) of pts at the time of surgery. The intention-to-treat analysis demonstrated a 10% difference in PFS after 3 years 50% (G-adj) vs 40% (G-prog) with a median PFS of 23 mo (G-adj) vs 17 mo (G-prog). The difference in PFS was not statistically significant (nss) (p= 0.335; HR 1.375, 95%CI 0.719 - 2.627). CSS at 3ys: 56% (G-adj) vs 50% (G-prog) with a median CSS of 49 mo (G-adj) vs 38 mo (G-prog). The difference in CSS was nss (p= 0.622; HR 1.166, 95%CI 0.632 - 2.149). OS at 3ys: 49% (G-adj) vs 48% (G-prog) with a median OS of 32 mo (G-adj) vs 31 mo (G-prog). The difference in OS was nss (p= 0.426; HR 1.225, 95%CI 0.743 - 2.018). Treatment with G was usually well tolerated, with less than 15% grade 3/4 toxicities..There was one treatment related death in the G-adj arm. Conclusions: The study-hypothesis of a 15% difference in PFS after 3 years in favor of G-adj vs G-prog could not be confirmed. Nevertheless a marked difference in survival in favor of G-adj was shown by Kaplan-Meier plots regarding PFS, CSS and OS within the first 24 months after RC. Clinical trial information: NCT00146276.

A phase 2 study of talimogene laherparepvec, nivolumab, and trabectedin (TNT) in advanced sarcoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 11567-11567
Author(s):  
Neal Shiv Chawla ◽  
Ted Kim ◽  
Travis Sherman ◽  
Jonathan Dang ◽  
Victoria S. Chua ◽  
...  
Keyword(s):  
Immune Response ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Intratumoral Injection ◽  
Spindle Cell Sarcoma ◽  
Talimogene Laherparepvec ◽  
Overall Response ◽  
Intention To Treat ◽  
Grade 3 ◽  
Advanced Sarcoma

11567 Background: Combination trabectidin (T) and nivolumab (N) has been shown to be a safe and effective therapy in soft tissue sarcoma (STS). Intratumoral injection of talimogene laherparepvec (TVEC) has a local oncolytic effect, and increases immune response via enhanced recruitment of antigen presenting cells, and thereby cytotoxic immune response. This study aims to determine if the addition of TVEC to combination trabectedin and nivolumab is effective and safe in advanced sarcoma. Methods: Eligible patients include patients ≥ 18 years of age with locally advanced unresectable or metastatic STS, measurable disease by RECIST v1.1, and at least one accessible tumor for TVEC intratumoral injection. N (3 mg/kg i.v. q 2 weeks), T (1.2 mg/m2 i.v. q 3 weeks) and TVEC (1x10e8 PFU/ml q 2 weeks depending on tumor size) were administered. A test dose of TVEC (1x10e6 PFU/ml) was initially given, followed three weeks later by full dose TVEC. Primary endpoint: Progression-free survival (PFS); Secondary endpoints: (1) Best overall response during treatment period, (2) PFS rate at 6 and 9 months, (3) Overall survival (OS) rate at 6, 9, and 12 months, (4) Incidence of conversion from unresectable to resectable tumor, and (5) Incidence of treatment-related adverse events. Interim. Results: There were 36 evaluable subjects under the Modified Intention-to-Treat (MITT) population, having completed the first cycle of TNT and a CT or MRI scan at the 6-week follow-up period. The most common histological subtypes include leiomyosarcoma (9), liposarcoma (5), spindle cell sarcoma (3), pleomorphic sarcoma (2), Ewing’s sarcoma (2), and other (5). Median number of prior lines of therapy was 4 (range 1-8). Best Overall Response by RECIST v1.1 = 3 PR, 27 SD, 5 PD. One patient, with previously unresectable disease was taken for resection and was found to have 100% necrosis on surgical pathology. Disease control rate (CR+PR+SD) was 86.1%. The median PFS was 5.5 (range: 1-18) months; 6-month PFS rate: 62.1%. Median PFS on therapy immediately preceding this trial was 2.0 months (range = 1-14 months). There were 47 evaluable subjects for OS analysis under the Intention-to-Treat (ITT) population having received at least one dose of T and N. The median OS was 9.0 (range 0-20) months; 6-month OS rate: 73%. Safety analysis: There were 47 evaluable subjects under the ITT population. 28% of these patients experienced ³1 SAE. The most common grade 3/4 TRAEs include anemia (12), increased ALT (8), fatigue (4), thrombocytopenia (4), neutropenia (4). There were no grade 3/4 TVEC injection site reactions. 22% of patients in the MITT cohort remain on study. Conclusions: These results suggest that combination therapy with TNT appears to be as effective as standard therapy, with no new safety signals seen. Furthermore, median PFS exceeded that of the immediately preceding lines of therapy in this heavily pre-treated cohort. As data matures, further data will be reported. Clinical trial information: NCT03886311.

Randomized Phase II Trial of First-Line Trastuzumab Plus Docetaxel and Capecitabine Compared With Trastuzumab Plus Docetaxel inHER2-Positive Metastatic Breast Cancer

2010 ◽  
Vol 28 (6) ◽  
pp. 976-983 ◽  
Author(s):  
Andrew M. Wardley ◽  
Xavier Pivot ◽  
Flavia Morales-Vasquez ◽  
Luis M. Zetina ◽  
Maria de Fátima Dias Gaui ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Response Rate ◽  
Performance Status ◽  
Locally Advanced ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
First Line ◽  
Her2 Positive ◽  
Grade 3

PurposeTo evaluate trastuzumab (H) and docetaxel (T) with or without capecitabine (X) as first-line combination therapy for human epidermal growth factor receptor 2 (HER2) -positive advanced breast cancer.Patients and MethodsPatients with HER2-positive locally advanced or metastatic breast cancer were randomly assigned to H (8 mg/kg loading; 6 mg/kg every 3 weeks) plus T (75 mg/m2in HTX arm, 100 mg/m2in HT arm, every 3 weeks) with or without X (950 mg/m2twice per day on days 1 to 14 every 3 weeks). The primary end point was overall response rate (ORR).ResultsIn 222 patients, median follow-up was approximately 24 months. ORR was high with both regimens (70.5% with HTX; 72.7% with HT; P = .717); complete response rate was 23.2% with HTX compared with 16.4% with HT. HTX demonstrated significantly longer progression-free survival: median 17.9 months compared with 12.8 months with HT (hazard ratio, 0.72; P = .045), which translates to a gain of around 5 months. Two-year survival probability was 75% with HTX compared with 66% with HT. Febrile neutropenia (27% v 15%) and grade 3/4 neutropenia (77% v 54%) incidences were higher with HT than HTX. Treatment-related grade 3 hand-foot syndrome (17% v < 1%) and grade 3/4 diarrhea (11% v 4%) occurred more commonly with HTX than HT. One case of congestive heart failure occurred in each arm.ConclusionHTX is an effective and feasible first-line therapy for HER2-positive locally advanced or metastatic breast cancer, although it should be reserved for patients with good performance status who are not receiving long-term steroids.

JUPITER-02: Randomized, double-blind, phase III study of toripalimab or placebo plus gemcitabine and cisplatin as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (NPC).

2021 ◽  
Vol 39 (18_suppl) ◽  
pp. LBA2-LBA2
Author(s):  
Rui-hua Xu ◽  
Hai-Qiang Mai ◽  
Qiu-Yan Chen ◽  
Dongping Chen ◽  
Chaosu Hu ◽  
...  
Keyword(s):  
Interim Analysis ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Phase Iii ◽  
Line Treatment ◽  
First Line ◽  
Double Blind ◽  
Grade 3 ◽  
First Line Treatment

LBA2 Background: Gemcitabine-cisplatin (GP) chemotherapy is the standard 1st line treatment for locally advanced, recurrent or metastatic (r/m) NPC. Toripalimab, a humanized IgG4K monoclonal antibody specific for PD-1, provided durable responses in patients (pts) with r/m NPC as monotherapy in the ≥2nd line setting (POLARIS-02 study). The results of JUPITER-02, a randomized, placebo-controlled, double-blinded Phase III trial of toripalimab in combination with GP chemotherapy as first-line treatment for r/m NPC are summarized. Methods: Pts with advanced NPC with no prior chemotherapy in the r/m setting were randomized (1:1) to receive toripalimab 240 mg or placebo d1 in combination with gemcitabine 1000 mg/m2 d1, d8 and cisplatin 80 mg/m2 d1 every 3 weeks (Q3W) for up to 6 cycles, followed by monotherapy with toripalimab or placebo Q3W until disease progression, intolerable toxicity, or completion of 2 years of treatment. Stratification factors were ECOG PS (0 vs. 1) and extent of disease (recurrent vs. primary metastatic) at enrollment. Progression-free survival (PFS) and response were assessed by independent review committee (IRC) per RECIST v1.1. The primary endpoint was PFS by IRC in the ITT population. Secondary end points included ORR, DOR and OS. There was one prespecified interim analysis of PFS at 130 PFS events with a planned final analysis at 200 PFS events. Results: 289 pts were randomized: 146 to the toripalimab arm and 143 to the placebo arm. By May 30, 2020 as the interim analysis cutoff date, the median treatment duration was 39 weeks in the toripalimab arm and 36 weeks in the placebo arm. A significant improvement in PFS was detected for the toripalimab arm compared to the placebo arm (HR = 0.52 [95% CI: 0.36-0.74] two-sided p = 0.0003), with median PFS of 11.7 vs. 8.0 months. The 1-year PFS rates were 49% and 28% respectively. An improvement in PFS was observed across relevant subgroups, including all PD-L1 subgroups. The ORR was 77.4% vs. 66.4% (P = 0.033) and the median DOR was 10.0 vs. 5.7 months (HR = 0.50 [95% CI: 0.33-0.78]). As of Jan 15, 2021, OS was not mature, with 25 deaths in the toripalimab arm and 35 in the placebo arm (HR = 0.68 [95% CI: 0.41-1.14], P = 0.14). The incidence of Grade ≥3 adverse events (AEs) (89.0% vs 89.5%); AEs leading to discontinuation of toripalimab/placebo (7.5% vs 4.9%); and fatal AEs (2.7% vs 2.8%) were similar between two arms; however, immune-related (irAEs) (39.7% vs. 18.9%) and Grade ≥3 irAEs (7.5% vs. 0.7%) were more frequent in the toripalimab arm. Conclusions: The addition of toripalimab to GP chemotherapy as 1st-line treatment for pts with advanced NPC provided superior PFS and ORR and longer DOR than GP alone with a manageable safety profile. These results support the use of toripalimab with GP chemotherapy as the new standard care for this population. Clinical trial information: NCT03581786.

Obinutuzumab (GA101) in Patients With Relapsed/Refractory Indolent Non-Hodgkin Lymphoma: Results From the Phase II GAUGUIN Study

2013 ◽  
Vol 31 (23) ◽  
pp. 2920-2926 ◽  
Author(s):  
Gilles A. Salles ◽  
Franck Morschhauser ◽  
Philippe Solal-Céligny ◽  
Catherine Thieblemont ◽  
Thierry Lamy ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Phase Ii ◽  
Group Versus ◽  
Progression Free Survival ◽  
Dose Schedule ◽  
Non Hodgkin Lymphoma ◽  
Flat Dose ◽  
End Of Treatment ◽  
Grade 3 ◽  
Anti Cd20

Purpose The phase II part of the phase I/II GAUGUIN study evaluated the efficacy and safety of two different doses of obinutuzumab (GA101), a type II, glycoengineered, humanized anti-CD20 monoclonal antibody, in patients with relapsed/refractory indolent non-Hodgkin lymphoma. Patients and Methods Patients were randomly assigned to receive eight cycles of obinutuzumab (GA101) as a flat dose of 400 mg on days 1 and 8 of cycle 1 and also on day 1 of cycles 2 to 8 (400/400 mg) or 1,600 mg on days 1 and 8 of cycle 1 and 800 mg on day 1 of cycles 2 to 8 (1,600/800 mg). Results Forty patients were enrolled, including 34 with follicular lymphoma; 38 of 40 patients had previously received rituximab and 22 of 40 were rituximab refractory. The overall response rate at the end of treatment was 55% (95% CI, 32% to 76%) in the 1,600/800-mg group (9% complete responders) and 17% (95% CI, 4% to 41%) in the 400/400-mg group (no complete responders). Five of 10 rituximab-refractory patients had an end-of-treatment response in the 1,600/800-mg group versus one of 12 in the 400/400-mg group. Median progression-free survival was 11.9 months in the 1,600/800-mg group (range, 1.8 to 33.9+ months) and 6.0 months in the 400/400-mg group (range, 1.0 to 33.9+ months). The most common adverse events were infusion-related reactions (IRRs) seen in 73% of patients, but only two patients had grade 3 to 4 IRRs (both in the 1,600/800-mg group). No IRRs were considered serious, and no patients withdrew for IRRs. Conclusion The 1,600/800-mg dose schedule of obinutuzumab (GA101) has encouraging activity with an acceptable safety profile in relapsed/refractory indolent non-Hodgkin lymphoma.

Docetaxel, oxaliplatin, and capecitabine (TEX regimen) for patients with metastatic gastric cancer: Interim results from a phase II trial by the German AIO Group

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4554-4554 ◽  
Author(s):  
M. H. Moehler ◽  
P. Thuss-Patience ◽  
D. Arnold ◽  
W. Grothe ◽  
A. Stein ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Phase Ii ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Distant Metastases ◽  
Response Assessment ◽  
Metastatic Gastric Cancer ◽  
Phase Ii Trials ◽  
Grade 3 ◽  
Ecog Ps

4554 Background: Combination regimens of 3 drugs have shown promising activity as treatment for patients (pts) with metastatic gastric cancer (GC). Docetaxel combined with cisplatin and 5-FU (CF) improved overall survival and response rates when compared to standard CF. However, the identification of less toxic and more convenient variants of this regimen is still important. We have previously established a regimen with docetaxel (T) combined with oxaliplatin (E) and capecitabine (X) in a phase I trial [Grothe et al., Proc. ASCO 2006]. Results of a preplanned interim analysis of subsequent multicenter phase II trials of the TEX regimen are presented here. Methods: Pts with metastatic or locally advanced GC, adequate organ function, ECOG PS 0–2, and no prior chemotherapy for advanced disease (adjuvant allowed) were enrolled. TEX regimen was administered as defined: T 35 mg/m2 and E 70 mg/m2 on days (d) 1 and 8, with X 800 mg/m2 bid on d1–14 every 22 days Toxicity assessment was done 3-weekly while CT scans were repeated 9-weekly. Results: 35 of 48 pts were enrolled until 06/08: 28 male / 7 female, median age 59 (36–81) years, ECOG PS 0/1/2 69%/31%/0%, gastric / gastroesophageal cancer 60%/40%, distant metastases 96%, tumor in situ 37%. The most common toxicities reported were (CTC grade [gr] 3/4): diarrhea 20%/3%, vomiting 11%/3%, asthenia and neurotoxicity each 9%/0%. Mucositis and hand-foot-syndrome were observed in (grade 1+2 / grade 3) 29%/0% and 26%/3%, respectively. Hematoxicity was mild with grade 3 anemia in 10% and no other grade 3/4 toxicity except one episode of febrile neutropenia . Of 25 pts evaluable so far, first tumor response assessment revealed (RECIST criteria) partial response in 36% and stable disease in 40% of patients. Conclusions: TEX is a safe and tolerable regimen for patients with metastatic gastric cancer. Preliminary efficacy results indicate promising activity. Mature data including progression free survival will be presented at the meeting. [Table: see text]

Gemcitabine-oxaliplatin combination (SEGEMOX) in anthracycline (A) and taxanes (T) pretreated metastatic breast cancer (MBC): Results from the GERCOR-SEGEMOX phase II trial

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 1108-1108
Author(s):  
J. Gligorov ◽  
L. Cals ◽  
C. Tournigand ◽  
Z. Merad ◽  
J. Dutel ◽  
...  
Keyword(s):  
Stable Disease ◽  
Response Rate ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Intention To Treat ◽  
Number Of Patients ◽  
Visceral Metastases ◽  
Toxicity Analysis ◽  
Grade 3 ◽  
Number Of Cycles

1108 Objectives: To evaluate efficacy and safety of SEGEMOX regimen for previously A and T pre-treated MBC patients. Methods: Forty-five women with MBC not eligible for A and/or T chemotherapy were enrolled on SEGEMOX study. SEGEMOX was delivered as follows: Gemcitabine was given at 1000 mg/m2/100min on day 1, followed by oxaliplatin at 100 mg/m2/120min iv on day 2 every 2 weeks. Efficacy results were analyzed and are presented in an intention to treat analysis and toxicity according to the total number of cycles regimen. Results: Forty-four of the 45 patients received at least 1 cycle of SEGEMOX. Fifty-eight perccent of the patients have received previous adjuvant chemo, 36% 1st line and 42% 2nd line for MBC before the protocol inclusion. Visceral metastases were dominant site of disease (44% liver; 36% lung; 44% bone). Median age of the population was 55.8 years (36–73). After a median of 7.7 cycles (3.5 months of treatment); the overall response rate (ORR) is 38% [95%CI; 23%-51%] [1 CR (2.2%) and 16 PR (35.6%)]; 33% of stable disease [95%CI; 17%-43%], 24.4% progressive disease with a clinical benefit (CB) of 71% [95%CI; 57%-85%]. The median progression free survival (PFS) is 7.1 months for responders and 4.8 months for patients with stable disease. The all population median overall survival (OS) is 21.4 months with 22.7 months MOS for responders. Concerning toxicity analysis: 339 cycles of gemcitabine and 312 of oxaliplatinum were delivered. Respectively, grade 3–4 neutropenia occurred in 43% of patients (febrile neutropenia in 7%), grade 3–4 thrombocytopenia in 41%, and anemia in 2.3%. The most frequent non hematologic toxicities were represented by grade 3 peripheral neuropathy (Levi Scale) in 11.4% of the patients and grade 2 alopecia in 11.4%. For the subgroup of hormone receptor negative MBC (n = 12) the ORR is 33% [95%CI; 2%-64%], CB 50% [95%CI; 16%-73%], PFS of 2.8 months and MOS of 12 months. Conclusions: The SEGEMOX combination has relevant activity in A and T not eligible MBC patients, with a manageable toxicity profile. In the limited number of patients with HRN MBC even if the response rate is close to the overall population the prognosis seems still worse. No significant financial relationships to disclose.

Cetuximab in combination with chemoradiotherapy prior to surgery in patients with resectable, locally advanced esophageal carcinoma: A prospective, multicenter phase lb-ll trial of the Swiss Group for Clinical Cancer Research (SAKK 75/06)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4570-4570
Author(s):  
T. Ruhstaller ◽  
M. Pless ◽  
J. C. Schuller ◽  
H. Kranzbühler ◽  
R. von Moos ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Phase Ii ◽  
Phase 1 ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiation ◽  
Thoracic Esophagus ◽  
Clinical Cancer Research ◽  
Intention To Treat ◽  
Grade 3

4570 Background: Cetuximab significantly enhances efficacy of radiotherapy and chemotherapy in head and neck cancer. We investigated the safety and feasibility of adding cetuximab to neoadjuvant chemoradiation of locally advanced esophageal cancer. Methods: Pts with resectable, locally advanced squamous cell carcinoma (SCC) or adenocarcinoma (AC) of the thoracic esophagus or gastroesophageal junction (staged by EUS, CT and PET scan) were treated with 2 cycles of induction chemotherapy (docetaxel 75mg/m2, cisplatin 75mg/m2 q3w and weekly cetuximab 250mg/m2), followed by concomitant chemo- immuno-radiation therapy (CIRT: docetaxel 20mg/m2, cisplatin 25mg/m2 and cetuximab 250mg/m2 weekly five times concomitant with 45 Gy radiotherapy in 25 fractions); followed by surgery 4–8 weeks later. The phase I part consisted of 2 cohorts of 7 patients each, without and with docetaxel during CIRT, respectively. Interpatient dose-escalation (adding docetaxel during CIRT) was possible if < 2 out of 7 pts of the 1st cohort experienced limiting toxicity. Having finished the phase 1 part, 13 additional patients were treated with docetaxel-containing CIRT in a phase II part. Pathological response was evaluated according to the Mandard classification. Results: 27 pts from 12 institutions were included. As of today, results from 20 pts are available (cohort 1: 7, cohort 2: 7, phase ll : 6). Median age was 64yrs (range 47–71). 11 AC; 9 SCC. 19 pts (95%) completed CIRT (1 pt stopped treatment during induction therapy due to sepsis). 17 pts underwent resection (no surgery: 1pt for PD, 1pt for cardiac reasons). Grade 3 toxicities during CIRT included anorexia 15%, dysphagia/esophagitis 15%, fatigue 10%, nausea 10%, pruritus 5%, dehydration 5%, nail changes 5% and rash 5% .1 pt suffered from pulmonary embolism. 13 pts (65%, intention-to-treat) showed a complete or near complete pathological remission (cohort 1: 5, cohort 2: 4, phase II: 4). Conclusions: Adding cetuximab to preoperative chemoradiation for esophageal cancer is safe and feasible in a community-based multicenter setting. Antineoplastic activity is encouraging with 65% pathological responders. [Table: see text]

E4201: Randomized phase II study of gemcitabine in combination with radiation therapy versus gemcitabine alone in patients with locally advanced, unresectable, pancreatic cancer (LAPC): Quality-of-life (QOL) analysis

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4627-4627
Author(s):  
H. R. Cardenes ◽  
M. Powell ◽  
P. J. Loehrer ◽  
L. I. Wagner ◽  
D. F. Cella ◽  
...  
Keyword(s):  
Overall Survival ◽  
Objective Response ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Subscale Score ◽  
Prior Therapy ◽  
Randomized Phase Ii ◽  
Grade 3 ◽  
Overall Survival Benefit

4627 Background: E4201 compared radiation and gemcitabine (RT+Gem) versus Gem alone in LAPC. The primary endpoint was overall survival; secondary objectives included: objective response rate (RR), progression-free survival (PFS), toxicity and QOL. We previously reported that RT+Gem was associated with improved overall survival compared with Gem alone [median survival time, 11 months and 9.2 months, respectively; p=0.034], without impact in RR or PFS. (ASCO 2008, abstract # 4506). We now report on QOL as measured by the Hep subscale from the FACT-Hepatobiliary [FACT-Hep] between both arms. Methods: Eligible patients had LAPC adenocarcinoma, PS <2, without prior therapy. They were randomized to Arm A: Gem alone (1,000 mg/m2/week x 3, every 4 weeks, 7 cycles), or Arm B: RT (50.4Gy/28 fractions) plus Gem (600 mg/m2/weekly x 6) followed by 5 cycles of Gem alone (1,000 mg/m2/weekly x 3 every 4 wks). The FACT-Hep was administered at baseline (before starting induction), 6 weeks (immediately after completing induction), week 16 (Arm A) or week 15 (Arm B) mid-consolidation, and at 9 months. Results: From April, 2003 to December, 2005, 74 patients were enrolled, 71 were eligible [37 Arm A; 34 Arm B]. Grade ≥3 was reported in 80% and 82.4% in ARM A and B, respectively (p=1.00). Grade IV toxicities, mainly gastrointestinal and hematologic, were more common in ARM B (41.2% vs 5.7%, p=<0.0001). QOL compliance declined over time, most commonly attributable to either patients or staff choosing not to complete or administer the instrument due to declining health (96%, 69%, 60%, and 40% at baseline, week 6, 15/16 weeks and 9 months, respectively). Within Arm B, QoL scores dropped significantly from baseline to 6 weeks. By week 15, QoL scores for patients on Arm B rebounded to levels similar to baseline. Two-sided Wilcoxon rank sum tests failed to suggest differences in median FACT-Hep subscale score between treatment arms at any of the four time-points (alpha = 0.10). Conclusions: RT+Gem is associated with an overall survival benefit without apparent long term adverse impact on QOL when compared with Gem alone. No significant financial relationships to disclose.

Activity of cabozantinib (XL184) in metastatic melanoma: Results from a phase II randomized discontinuation trial (RDT).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8531-8531 ◽  
Author(s):  
Michael S. Gordon ◽  
Harriet M. Kluger ◽  
Geoffrey Shapiro ◽  
Razelle Kurzrock ◽  
Gerald Edelman ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Braf Mutation ◽  
Tumor Regression ◽  
Progression Free Survival ◽  
Bone Lesions ◽  
Open Label ◽  
Grade 5 ◽  
Common Grade ◽  
Grade 3 ◽  
Tumor Types

8531 Background: MET and VEGF signaling are implicated in angiogenesis, invasion, and metastasis. Cabozantinib (cabo) is an oral, potent inhibitor of MET and VEGFR2. A RDT evaluated activity and safety in 9 tumor types. Here we report on the metastatic melanoma cohort, including the ocular subtype. Methods: Eligible patients (pts) were required to have progressive measurable disease per RECIST. Pts received cabo at 100 mg qd over a 12 wk Lead-in stage. Tumor response (mRECIST) was assessed q6 wks. Treatment ≥ wk 12 was based on response: pts with PR continued open-label cabo, pts with SD were randomized to cabo vs placebo, and pts with PD discontinued. Primary endpoint in the randomized phase was progression free survival (PFS). Results: Enrollment to this cohort is complete (n = 77); all pts are unblinded. Baseline characteristics: median age 66 years; melanoma subtype: cutaneous/mucosal 70% and ocular 30%; known BRAF mutation 32%; LDH ≥ 1.1 x upper limit normal 35%; bone metastases 19%; median prior lines of therapy 1 (range 0-5). Median follow-up was 2.8 months (range 0.3 - 25). 35 pts (45%) completed the open-label Lead-in stage with 25 pts randomized to continue cabo (n=12) or to placebo (n=13). Median PFS from randomization was 5.7 months for cabo vs. 3 months for placebo (HR=0.3, p =0.055). Median PFS from Study Day 1 was 4.4 months. The estimate of PFS at month 6 (PFS6) is 44%. Evidence of objective tumor regression was observed in 39/65 pts (60%) with ≥ 1 post-baseline tumor assessment including 11/23 pts (48%) with ocular melanoma. Two bone scan evaluable pts demonstrated partial resolution of bone lesions at wk 6 accompanied by pain relief. Most common Grade 3/4 AEs were fatigue (14%), HTN (9%), constipation (4%), and diarrhea (3%); one related Grade 5 AE of diverticular perforation and peritonitis reported during Lead-in stage. Conclusions: Cabo demonstrates activity in metastatic melanoma pts, regardless of subtypes or BRAF mutation status, with improvement in PFS relative to placebo, and high rates of PFS6 and objective tumor regression. The safety profile of cabo was comparable to that of other VEGFR TKIs.

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