CLO19-023: Induction Chemotherapy Followed by Chemoradiation and Trans-Anal Full Thickness Local Excision or Total Mesorectal Resection in Patients With T2-T3/NO-N+ Adenocarcinoma of the Rectum; Preliminary Results of Phase 2 Prospective Clinical Trial

2019 ◽  
Vol 17 (3.5) ◽  
pp. CLO19-023
Author(s):  
Ahmed Abdalla ◽  
Amr Aref ◽  
Amer Alame ◽  
Mohamad Barawi ◽  
Danny Ma ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Neoadjuvant Therapy ◽  
Local Excision ◽  
Pathological Response ◽  
Phase Iii ◽  
Prospective Clinical Trial ◽  
Phase 2 ◽  
Full Thickness ◽  
Complete Pathological Response ◽  
Mesorectal Resection

Background: The National Comprehensive Cancer Network (NCCN) Guidelines recently recognized total neoadjuvant therapy (TNT) as an acceptable option in patients with T3 and any N rectal cancer. Previous studies suggested that patients who received chemotherapy prior to conventional preoperative chemoradiation (CRT) and surgery allowed patients to receive more of their planned treatment with a better toxicity profile and increase in pathological response. However, those studies used a long course of FOLFOX or used capecitabine and oxaliplatin as an induction regimen. We are conducting a phase 2 prospective clinical trial to evaluate the use of 6 cycles of FOLFOX as TNT in patients with T2-T3/N0-N+. Patients and Methods: Patients with T2-T3/N0-N+ enrolled on our phase 2 prospective trial were included for this analysis. Patients received 6 cycles of FOLFOX (infusional fluorouracil, leucovorin, and oxaliplatin), which was administered every 2 weeks. After 3 weeks of recovery period, patients then received conventional CRT with 5FU or capecitabine. All patients got MRI and endorectal ultrasound (ERUS) at baseline, after completing FOLFOX 3-months regimen and after finishing conventional CRT. Patients underwent either full-thickness local excision or total mesorectal resection depending on their tumor response to neoadjuvant therapy. The time interval between completion of radiation therapy and surgery ranged between 7and 12 weeks. Results: A total of 10 patients completed the chemotherapy and CRT treatment regimen. 9 patients proceeded to surgery and the 10th patient is scheduled for surgery. Clinical downstaging by MRI or ERUS was shown in 9 of 10 patients with only 6 cycles of FOLFOX. Complete clinical response was achieved in 6 patients as evident by ERUS/MRI of the pelvis after 3 months of FOLFOX before CRT. Complete pathological response was found in 4 of 9 patients (44%). In addition, 4 other patients had significant albeit not complete pathological response. Conclusions: This study suggests that adding only 6 cycles of neoadjuvant FOLFOX before CRT improved clinical and pathological downstaging of T2-T3/N0-N+ rectal adenocarcinoma and may facilitate organ preservation surgery. This is strategy needs to be investigated in larger phase III trials to validate these findings.

scholarly journals Blood biomarkers associated to complete pathological response on NSCLC patients treated with neoadjuvant chemoimmunotherapy included in NADIM clinical trial

2021 ◽  
Vol 11 (7) ◽  
Author(s):  
Raquel Laza‐Briviesca ◽  
Alberto Cruz‐Bermúdez ◽  
Ernest Nadal ◽  
Amelia Insa ◽  
María del Rosario García‐Campelo ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Pathological Response ◽  
Blood Biomarkers ◽  
Complete Pathological Response ◽  
Nsclc Patients

Camrelizumab plus chemotherapy as neoadjuvant therapy for resectable, locally advanced esophageal squamous cell carcinoma (NIC-ESCC2019): A multicenter, open-label, single-arm, phase 2 study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4028-4028
Author(s):  
Jingpei Li ◽  
Jun Liu ◽  
Zhuoyi Li ◽  
Fei Cui ◽  
Yuan Zeng ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Squamous Cell Carcinoma ◽  
Neoadjuvant Chemotherapy ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Primary Tumor ◽  
Pathologic Response ◽  
Pathological Response ◽  
Phase 2 ◽  
Phase 2 Study

4028 Background: Despite multidisciplinary therapies, prognosis of pts with resectable esophageal squamous cell carcinoma (ESCC) remains poor. Combining PD-1 blockade to neoadjuvant chemotherapy might be a feasible and effective strategy. Camrelizumab (an anti-PD-1 antibody) was approved for advanced or metastatic ESCC in the second-line setting and showed improved anti-tumor activity and survival benefit when combined with chemotherapy in multiple advanced tumors. Methods: In this NIC-ESCC2019 phase 2 study, histologically or cytologically confirmed ESCC pts (stage II-IVA) were enrolled to receive two cycles of neoadjuvant chemoimmunotherapy (NIC) with camrelizumab (200 mg on day 1) plus nab-paclitaxel (260 mg/m² in total on day 1 and day 8) and cisplatin (75 mg/m² in total on days 1-3) of each 21-day cycle, followed by esophagectomy. The primary endpoint was complete pathologic response (CPR) rate in the primary tumor. Besides, we also explored the relationship between the tumor genomic profile or primary-tumor microenvironment and the pathological response. Results: Between Jan 17, 2020 and Dec 8, 2020, 56 pts were enrolled. 51 pts underwent surgical resection, and all had complete tumor resection. CPR was achieved in 18 (35.3%; 95% CI, 21.7%-48.9%) pts; 12 (23.5%) pts had major pathologic response (MPR), and 21 (41.2%) had incomplete pathological response (IPR). Of note, 16 (31.4%) pts achieved CPR in both primary tumor and lymph nodes. The objective response rate was 66.7% (95% CI, 40.0-70.4). No in-hospital mortality occurred. The most common treatment-related adverse events (TRAEs) were decreased WBC (20 [36%] of 56 pts), vomiting (19 [34%]), and alopecia (18 [32%]). Grade 3 TRAEs only occurred in 6 (11%) pts, and there were no grade 4 or 5 TRAEs. The most common immune-related AEs included grade 1-2 rash maculo-papular (7 [13%]) and reactive cutaneous capillary endothelial proliferation (5 [9%]). Presence of mutations in CREBBP and KMT2D at treatment-naïve time-point was correlated with non-response group (IPR and stable disease) (CREBBP, p = 0.046; KMT2D, p = 0.047). Among the immune populations, CD8+, CD8+PD-1+ and CD8+PD-L1+ T cells increased significantly after two doses of NIC, especially in the CPR+MPR group (CD8+, p = 0.013; CD8+PD-1+, p < 0.001; CD8+PD-L1+, p = 0.068). Conclusions: The addition of camrelizumab to neoadjuvant chemotherapy in ESCC demonstrated promising efficacy with acceptable toxicity, supporting the further investigation in a randomized phase 3 clinical trial. Clinical trial information: NCT04225364. [Table: see text]

A randomized phase II clinical trial of enzalutamide in combination with the therapeutic cancer vaccine, PSA tricom, in metastatic, castration resistant prostate cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. TPS5104-TPS5104
Author(s):  
Nishith K. Singh ◽  
Joseph W. Kim ◽  
Christopher Ryan Heery ◽  
William L. Dahut ◽  
Anna Couvillon ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
T Cells ◽  
T Cell ◽  
Cancer Vaccine ◽  
Phase Iii ◽  
Cytotoxic T Cell ◽  
Phase 2 ◽  
Therapeutic Cancer Vaccine ◽  
Randomized Phase 2

TPS5104 Background: There is a strong rationale to combine therapeutic cancer vaccines with hormonal abrogation in prostate cancer. Androgen abrogation augments T-cell trafficking to prostate, decreases immune tolerance, increases production of naïve thymic T-cells, enhances cytotoxic T-cell repertoire. PSA TRICOM (PROSTVAC) is a therapeutic, viral-vector based, off-the-shelf, cancer vaccine of PSA & 3 co-stimulatory molecules in phase III testing. This was developed at the NCI in collaboration with Bavarian Nordic Immunotherapeutics. It has demonstrated safety and survival benefit in a randomized phase 2 trial of metastatic castrate resistant prostate cancer (mCRPC). Enzalutamide is a modern androgen receptor inhibitor (ARI) approved for the treatment of mCRPC. Data from the clinical trials with these therapies suggest good individual tolerability without any overlapping toxicities. Analysis of previous trials suggests that vaccines may enhance clinical outcomes with ARI. These data form the scientific basis for a combination approach of a cancer vaccine with ARI to control tumor progression in mCRPC. Methods: A randomized, phase 2, open-label clinical trial at the NCI will enroll 72 chemo-naïve, minimally symptomatic patients with mCRPC. They will be randomized (1:1) to enzalutamide (160 mg daily) alone, or enzalutamide with PSA TRICOM for treatment until radiographic progression. PSA-TRICOM will be administered in a core phase (with day 1, 15 and 29 then 4 additional monthly boosts) followed by continued boosts every 3 months. The primary end point will evaluate time to progression in each arm with secondary endpoints including overall survival and systemic immune responses (lymphocyte subsets, regulatory T-cells, regulatory T-cell function, cytokines, naïve thymic emigrants). If a therapeutic cancer vaccine can enhance the clinical efficacy of a hormonal agent such as enzalutamide, it may help define a new role for vaccines as an adjuvant to standard therapies. We will also evaluate this combination in a second trial in non-metastatic, castration-sensitive patients where this combination may yield its greatest clinical impact.

scholarly journals Complete pathological response after neoadjuvant therapy in patients with rectal adenocarcinoma

2017 ◽  
Vol 80 (4) ◽  
pp. 212-217
Author(s):  
E.A. Sánchez-Pérez ◽  
J.A. Villanueva-Herrero ◽  
M.D. Sandoval-Martínez ◽  
B. Jiménez-Bobadilla
Keyword(s):  
Neoadjuvant Therapy ◽  
Rectal Adenocarcinoma ◽  
Pathological Response ◽  
Complete Pathological Response

scholarly journals Prospective Clinical Trial of 18 F-Fluciclovine PET/CT for Determining the Response to Neoadjuvant Therapy in Invasive Ductal and Invasive Lobular Breast Cancers

2016 ◽  
Vol 58 (7) ◽  
pp. 1037-1042 ◽  
Author(s):  
Gary A. Ulaner ◽  
Debra A. Goldman ◽  
Adriana Corben ◽  
Serge K. Lyashchenko ◽  
Mithat Gönen ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Neoadjuvant Therapy ◽  
Prospective Clinical Trial ◽  
Breast Cancers ◽  
Pet Ct

Neoadjuvant and adjuvant, floxuridine, leucovorin, oxaliplatin, and docetaxel (FLOD) in patients with locally advanced operable gastroesophageal adenocarcinoma: A phase II study with pathologic responses and long term follow-up.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 124-124
Author(s):  
Bach Ardalan ◽  
Miriam Gombosh ◽  
Dido Franceschi ◽  
Eli Avisar ◽  
Danny Yakoub ◽  
...  
Keyword(s):  
Adjuvant Chemotherapy ◽  
Neoadjuvant Therapy ◽  
Residual Disease ◽  
Locally Advanced ◽  
Pathological Response ◽  
Complete Pathological Response ◽  
Term Survival ◽  
Chemotherapy Patients

124 Background: A complete pathological response to neoadjuvant chemotherapy without the use of radiation has infrequently been reported in operable chemo-naïve stage III gastro esophageal adenocarcinoma patients. Methods: Twenty-nine patients were enrolled in this study. Neoadjuvant therapy consisted of Floxuridine, Leucovorin, Oxaliplatin, and Docetaxel and was administered in 2, four week cycles. Chemotherapy consisted on day one and day fifteen; Oxaliplatin, Docetaxel, FUDR, and Leucovorin. The latter two drugs were given concurrently over twenty four hours. On day eight, chemotherapy consisted of Docetaxel, FUDR, and Leucovorin. Following therapy, patients underwent surgical resection. Those patients having residual disease were offered adjuvant chemotherapy. Patients having a complete pathological response were not offered any further therapy. Results: Twenty-four out of twenty-nine patients completed neoadjuvant therapy and underwent esophagectomy. Two were declared inoperable after treatment. Three patients died prior to surgery. The median follow-up of all patients is now sixty months. The median overall survival has not been reached at sixty months. Five yr actual OS is 51%. Clinical response to neoadjuvant therapy was seen in (72.4%) patients. Complete pathological response to neoadjuvant therapy was seen in (16.7%) who are disease free at sixty month follow-ups. Seven out of twenty-four patients achieved partial pathological response (29.1%) and received adjuvant chemotherapy. They are all alive (100%). Eight patients achieved less than partial pathological response and received adjuvant chemotherapy, four out of eight are alive at sixty months (50%). Grade three and four toxicities were seen in sixteen out of twenty nine patients during neoadjuvant therapy. Grade three and four toxicities were seen in six out of fourteen patients during adjuvant therapy. Conclusions: Our chemotherapy regimen of Floxuridine, Leucovorin, Oxaliplatin and Docetaxel (FLOD) has resulted in long term survival in patients with adenocarcinoma of the esophagus. Clinical trial information: NCT00448760.

Total mesorectal excision compared to local excision in locally advanced rectal cancer achieving complete pathological response with neoadjuvant therapy: A National Cancer Database Analysis.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4107-4107
Author(s):  
Ahmed Abdalla ◽  
Sindhu Janarthanam Malapati ◽  
Sunny R K Singh ◽  
Susan Szpunar ◽  
Tarik H. Hadid ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Overall Survival ◽  
Neoadjuvant Therapy ◽  
Locally Advanced ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Pathological Response ◽  
National Cancer Database ◽  
Mesorectal Excision ◽  
Complete Pathological Response

4107 Background: Total mesorectal excision (TME) is the standard surgical intervention for patients with locally advanced rectal cancer (LARC) regardless of response to neoadjuvant therapy. In this study, we perform a comprehensive review of the National Cancer Database (NCDP) to compare the clinical and surgical outcomes of TME to local excision (LE) in patients with LARC. Methods: NCDP was systematically researched to abstract all patients with stage II and III rectal adenocarcinoma between the years 2004 and 2015. We subsequently excluded all the patients who did not achieve complete pathological response (pT0) after neoadjuvant therapy. The patients were then divided into two groups; those who underwent TME and those who underwent LE. Data were analyzed using SPSS v. 26.0, SAS v. 9.4. Results: A total of 4,705 were included in the study; 4,589 in the TME group and 116 in the LE group. Baseline characteristics were similar between the groups except for age. A total of 81(1.8%) of patients in the TME group and 8(6.9%) of patients in the LE group did not receive radiation (p=0.006) and 19(0.4%) of patients the TME group and 4(3.4%) of patients in the LE group did not receive chemotherapy. There was no difference in median overall survival between TME and LE groups. The median length of hospital stay was remarkably shorter in the LE group compared to the TME group (1 day vs 6 days, p<0.0001). The rate of 30-day and 90-day postoperative mortality were similar between the two groups (p-value=0.334 and 0.06, respectively). In the LE group, 4 (3.4%) of patients were readmitted within 30 days of the resection compared to 374 (8.5%) in the TME group but was not a statistically significant difference (p=0.059). Conclusions: In this study, TME and LE had similar overall survival and time to 25% mortality in patients with LARC who achieved complete pathological response after neoadjuvant therapy. Also, LE had a shorter hospital stay compared to the TME group. This study is limited by its retrospective nature, however these interesting observations warrant further investigation in randomized clinical trials. [Table: see text]

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