The basal subtype to predict clinical benefit from neoadjuvant chemotherapy: Final results from a phase II clinical trial of DDMVAC + bevacizumab.

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. 4531-4531
Author(s):  
Arlene O. Siefker-Radtke ◽  
Woonyoung Choi ◽  
Sima Porten ◽  
Yu Shen ◽  
Ashish M. Kamat ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Neoadjuvant Chemotherapy ◽  
Phase Ii ◽  
Clinical Benefit ◽  
Phase Ii Clinical Trial ◽  
Basal Subtype

A randomized, phase II clinical trial of preoperative stereotactic body radiation therapy versus conventionally fractionated chemoradiation for resectable, borderline-resectable, or locally advanced type a pancreatic adenocarcinoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS4167-TPS4167
Author(s):  
William Adrian Hall ◽  
Susan Tsai ◽  
Anjishnu Banerjee ◽  
Ben George ◽  
Paul S. Ritch ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Radiation Therapy ◽  
Neoadjuvant Chemotherapy ◽  
Pancreatic Adenocarcinoma ◽  
Phase Ii ◽  
Stereotactic Body Radiation Therapy ◽  
Locally Advanced ◽  
Phase Ii Clinical Trial ◽  
Borderline Resectable ◽  
Conventionally Fractionated

TPS4167 Background: There is growing consensus for the use of neoadjuvant therapy in patients with potentially operable pancreatic adenocarcinoma (PC). However, there is not consensus on the type and duration of chemotherapy or radiation therapy (RT) dose. Stereotactic body radiation therapy (SBRT) has gained popularity despite the absence of prospective data for its use in the preoperative setting. Furthermore, SBRT preoperatively has not been standardized. At present, there exists no randomized data comparing preoperative SBRT with conventionally fractionated concurrent chemo-RT. We designed this trial to examine differences between pre-op RT dose and fractionation schedules. Methods: This study is a prospective, randomized, two-arm, phase II clinical trial. Eligible patients must have cytologically confirmed PC and be deemed suitable for surgical resection with resectable, borderline resectable, or locally advanced type A disease, based on cross-sectional imaging. Before randomization patients are stratified by clinical node positivity, neoadjuvant chemotherapy, and stage of disease. Patients are then randomized to either 50.4 Gy over 28 fractions with concurrent weekly Gemcitabine vs SBRT to a total dose of 25-35 Gy over 5 fractions. The primary endpoint of the study is pathologic node positivity. We hypothesize that patients treated with neoadjuvant chemotherapy followed by conventionally fractionated chemo-RT will have a lower rate of pathologic node positivity as compared to those patients treated with neoadjuvant chemotherapy followed by SBRT. Secondary endpoints include patient reported quality of life, local recurrence, primary tumor pathologic response, margin status, surgical complications, MR based treatment response, and overall survival. We anticipate a node positivity rate of 37% when using preoperative chemotherapy followed by SBRT. We hypothesize that treatment with chemotherapy followed by conventionally fractionated chemo-RT will reduce the rate of node positivity to 17%. Using a one-sided Type I error rate of 0.1, approximately 88 total patients (44 per arm) provide an 80% power to detect the hypothesized difference in pathologic node positivity between the two arms. To address patient dropout, an additional 14 patients (about 15%) will be enrolled for a total target accrual of 102 patients. The trial opened in November 2018 and 8 of the planned 102 patients have been enrolled. Clinical trial information: NCT03704662.

Clinical and Immunological responses in patients with malignant melanoma treated with a dendritic cell-based vaccine. Preliminary report from a multi-institutional phase II clinical trial

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 3004-3004
Author(s):  
M. Ross ◽  
L. H. Camacho ◽  
E. M. Hersh ◽  
C. K. Brown ◽  
J. Richards ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Immune Response ◽  
T Cells ◽  
Metastatic Melanoma ◽  
Phase Ii ◽  
Clinical Benefit ◽  
Therapeutic Vaccine ◽  
Phase Ii Clinical Trial ◽  
Age Related Macular Degeneration ◽  
Ifn Γ

3004 Background: We have previously reported that vaccination with IDM therapeutic vaccine (IDD-3/Uvidem [Uvidem is co-developed with SANOFI-AVENTIS]) composed of dendritic cells (DC) loaded with three allogeneic lysates from tumor cell lines can elicit immune and anti-tumor responses. We describe here the preliminary results from a phase II clinical trial in metastatic melanoma patients. Methods: DC-MEL-202 is a single arm, two-stage phase II trial designed to evaluate clinical and immunological activities and the safety of a multivalent DC vaccine in patients with in-transit or low volume metastatic melanoma. There was no HLA restriction. Autologous DC were generated, under GMP conditions, from monocytes cultured in GM-CSF and IL-13, loaded with three allogeneic melanoma tumor lysates (M44, SK-MEL 28 and COLO 829) and matured with a combination of bacterial extract (FMKP) and IFN-γ, generating up to 15 doses of the vaccine containing 25x106 DC. Patients received six bi-weekly and two 6-weekly injections (id and sc). Clinical responders were eligible to receive additional doses. Immune response against tumor-associated antigens (TAA) peptides was assessed, at several time points, by detection of IFN-γ producing cells by flow cytometry Results: 33 patients were treated. To date: Vaccination is well tolerated with toxicity limited to mild events (only one possibly related SAE, age-related macular degeneration, was reported). Clinical response (RECIST): 6 patients showed evidence of clinical benefit (1CR, 1PR and 4 SD) with duration of response ranging from 7.5 to 22 months. Assessment of pathological response in target sites in 2 pts (1 PR, 1 SD) showed no residual disease.. 23/33 patients are still alive with a mean follow-up of 11mo (range 3–22mo). Mature data of PFS and OS will be presented. Immune response: 21 (84 %) out of 25 evaluated patients showed detectable TAA-specific CD8+ T cells with ten showing boosted or appearance of anti-TAA specific CD8+ T cells. Conclusions: Vaccination with IDD-3/Uvidem is safe and can elicit tumor specific CD8+ T cells not limited to HLA-A2+ patients. Substantial clinical benefit warrants further development of IDD3. No significant financial relationships to disclose.

scholarly journals Phase II Clinical Trial of Pembrolizumab in Patients with Progressive Metastatic Pheochromocytomas and Paragangliomas

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2307 ◽  
Author(s):  
Camilo Jimenez ◽  
Vivek Subbiah ◽  
Bettzy Stephen ◽  
Junsheng Ma ◽  
Denai Milton ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Adverse Events ◽  
Phase Ii ◽  
Primary Endpoint ◽  
Clinical Benefit ◽  
Primary Tumor ◽  
Objective Response ◽  
Inflammatory Cells ◽  
Phase Ii Clinical Trial ◽  
Survival Duration

Metastatic pheochromocytomas and paragangliomas (MPPGs) are rare endocrine malignancies that are associated with high rates of morbidity and mortality because of their large tumor burden and location, progression, and release of catecholamines. Systemic therapies for MPPGs are limited. MPPGs are characterized by pseudohypoxia that may prevent immune system recognition. We conducted a phase II clinical trial of pembrolizumab in patients with progressive MPPGs. The primary endpoint was the non-progression rate at 27 weeks. The secondary endpoints included the objective response and clinical benefit rates, progression free and overall survival duration, and safety. We also determined whether PDL-1 expression and the presence of infiltrating mononuclear inflammatory cells in the primary tumor were associated with clinical response and hereditary background. Eleven patients were included in this trial, four (36%) with germline mutations and seven (64%) with hormonally active tumors. Four patients (40%, 95% confidence interval (CI) 12–74%) achieved the primary endpoint. The objective response rate was 9% (95% CI: 0–41%). The clinical benefit rate was 73% (95% CI: 39–94%). Four patients had grade 3 adverse events related to pembrolizumab. No patients experienced grade 4 or 5 adverse events or a catecholamine crisis. Progression free survival time was 5.7 months (95% CI: 4.37—not reached). The median survival duration was 19 months (95% CI: 9.9—not reached). PDL-1 expression and the presence of infiltrating mononuclear inflammatory cells in the primary tumor did not seem to be associated with disease response. Single-agent pembrolizumab has modest treatment efficacy in patients with progressive MPPGs. Positive responses seemed to be independent of patients’ hereditary backgrounds, tumor hormonal status, and the presence of infiltrating mononuclear inflammatory cells or PDL-1 expression in the primary tumor.

scholarly journals Phase II Clinical Trial of Neoadjuvant Alternating Doublet Chemotherapy With Ifosfamide/Doxorubicin and Etoposide/Cisplatin in Small-Cell Urothelial Cancer

2009 ◽  
Vol 27 (16) ◽  
pp. 2592-2597 ◽  
Author(s):  
Arlene O. Siefker-Radtke ◽  
Ashish M. Kamat ◽  
H. Barton Grossman ◽  
Dallas L. Williams ◽  
Wei Qiao ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Neoadjuvant Chemotherapy ◽  
Brain Metastases ◽  
Phase Ii ◽  
Urothelial Cancer ◽  
Small Cell ◽  
Phase Ii Clinical Trial ◽  
Disease Stage ◽  
Maximal Response ◽  
Doublet Chemotherapy

Purpose Currently, treatment recommendations for small-cell urothelial cancer (SCUC) are based on anecdotal case reports and small retrospective series. We now report results from the first phase II clinical trial developed exclusively for SCUC, to our knowledge. Patients and Methods From 2001 to 2006, 30 patients with SCUC provided consent and were treated with alternating doublet chemotherapy. Patients with surgically resectable disease (≤ cT4aN0M0) received a total of four cycles of neoadjuvant chemotherapy, whereas those with unresectable disease (≥ cT4b, N+, or M+) received two cycles beyond maximal response. Results Eighteen patients with surgically resectable SCUC received neoadjuvant treatment with a median overall survival (OS) of 58 months; 13 of these patients remain alive and cancer free. For patients with cT2N0M0 SCUC, the 5-year OS rate is 80%; only one of four patients with cT3b-4aN0M0 remains alive (median OS, 37.8 months). For 12 patients with unresectable or metastatic SCUC, the median OS was 13.3 months. Chemotherapy was well tolerated, with transfusion, neutropenic fever, and infection remaining the most frequent grade 3 and 4 toxicities. There was only one postsurgical death. Brain metastases were strongly associated with more advanced-stage disease, developing in eight of 16 patients with either bulky tumors (≥ cT3b) or metastatic disease (P = .004). Conclusion These clinical trial results are consistent with previously reported retrospective data demonstrating long-term survival with four cycles of neoadjuvant chemotherapy for surgically resectable SCUC. Once metastases develop, the prognosis remains poor. The strong positive association between disease stage and brain metastases highlights a patient subset that may potentially benefit from prophylactic cranial irradiation.

Sign in / Sign up

Export Citation Format

Share Document