scholarly journals Rational Study Endpoint(s) for Preoperative Trials in Pancreatic Cancer: Pathologic Response Rate, Margin Negative Resection, Overall Survival or ‘All of the Above’?

2013 ◽  
Vol 20 (12) ◽  
pp. 3712-3714 ◽  
Author(s):  
Gauri R. Varadhachary ◽  
Douglas B. Evans
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Response Rate ◽  
Pathologic Response ◽  
Study Endpoint ◽  
Pathologic Response Rate

Short-course radiation followed by mFOLFOX-6 plus avelumab for locally advanced rectal adenocarcinoma.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 139-139
Author(s):  
Ali Shamseddine ◽  
Youssef Zeidan ◽  
Ibrahim Moustafa Khalifeh ◽  
Joseph Gergi Kattan ◽  
Rim Turfa ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Interim Analysis ◽  
Response Rate ◽  
Locally Advanced ◽  
Rectal Adenocarcinoma ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Pathologic Response ◽  
Short Course ◽  
Pathologic Response Rate

139 Background: Total neoadjuvant treatment (TNT) for locally advanced rectal cancer is becoming an accepted approach over the last few years with increasing pathologic complete response (pCR) and compliance of patients for chemotherapy in comparison with the current standard of care i.e., fluoropyrimidine based chemoradiation followed by surgery and adjuvant chemotherapy. Sequential use checkpoint inhibitors after radiation therapy (RT) has demonstrated synergistic effect in vivo leading to decrease in size of irradiated and non-irradiated secondary tumors outside the radiation field (abscopal effect). Methods: This is an investigator initiated; open-label, single-arm multicenter phase II study, adopting Simon’s two-stage aiming at evaluating the pCR rate and safety of using short-course radiation therapy (25 Grays in 5 fractions), followed by 6 cycles of mFOLFOX-6 plus Avelumab (anti PDL1), then total mesorectal excision(TME) in patients with locally-advanced, potentially resectable rectal adenocarcinoma. Results: 13 out of 44 patients were accrued from 20, July till 28, Dec 2018 in the first stage of the study (30% from total sample size). They all met the inclusion criteria and received full protocol treatment. 12 out of the 13 completed TME. 1 of the 13 had progression of disease, so surgery was aborted and patient was dropped out the study. The sample consisted of 9 (69%) males and 4 (31%) females with median age of 62 (33.0, 73.0) years. The first interim analysis revealed 3 patients (25%) achieved pCR (tumor regression grade: TRG = 0) out of 12 as compared to the historical control group with pCR of 16%. For the rest of the patients, 3 (25%) had major pathologic response rate (pRR) with TRG = 1 (< 10% viable cells is tumor bed).In total, 6 out of 12 patients (50%) had major pathologic response rate. As for safety, no serious adverse events of grade 3 and 4 were reported. Conclusions: Based on the first interim analysis results, incorporation of Avelumab and short course radiotherapy is tolerable in patients with locally advanced rectal cancer treated with TNT. The study will resume recruitment to reach the target accrual. Clinical trial information: NCT03503630.

scholarly journals Association between neutropenia and survival to nab-paclitaxel and gemcitabine in patients with metastatic pancreatic cancer

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Giandomenico Roviello ◽  
Monica Ramello ◽  
Martina Catalano ◽  
Alberto D’Angelo ◽  
Raffaele Conca ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Response Rate ◽  
Progression Free Survival ◽  
Metastatic Pancreatic Cancer ◽  
Common Side Effect ◽  
First Line ◽  
Free Survival ◽  
Grade 3 ◽  
Toxicity Criteria

Abstract Neutropenia is a common side effect associated with nab-paclitaxel gemcitabine (Nab-Gem) therapy. We retrospectively investigated the association between neutropenia induced by first-line Nab-Gem and survival in metastatic pancreatic carcinoma patients. Metastatic pancreatic patients treated with first-line Nab-Gem were included in this retrospective analysis. Neutropenia was categorized using the National Cancer Institute Common Toxicity Criteria scale. Outcome measures were overall survival (OS), progression-free survival (PFS) and response rate. 115 patients were analyzed. Median PFS was 7 months (95% CI 5–8) for patients with grade ≥ 3 neutropenia and 6 months (95% CI 5–6) for patients with grade < 3 neutropenia [p = 0.08; hazard ratio (HR 0.68)]. Median OS was 13 months (95% CI 10–18) for patients with grade ≥ 3 neutropenia and 10 months (95% CI 8–13) for patients with grade < 3 neutropenia (p = 0.04; HR 0.44). In multivariate analysis, the occurrence of grade ≥ 3 neutropenia showed a statistically significant association with OS (HR 0.62; 95% CI 0.09–0.86; p = 0.05). Nab-Gem-induced neutropenia is associated with longer survival in metastatic pancreatic cancer patients.

A phase 2 clinical trial of neoadjuvant anti-PD-1 ab (Toripalimab) plus axitinib in resectable mucosal melanoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9512-9512
Author(s):  
Chuanliang Cui ◽  
Xuan Wang ◽  
Bin Lian ◽  
Lu Si ◽  
Zhihong Chi ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Tumor Cells ◽  
Response Rate ◽  
Mucosal Melanoma ◽  
Pathologic Response ◽  
Phase 2 ◽  
Viable Tumor ◽  
Pathologic Response Rate ◽  
Clinical Trial Information

9512 Background: The outcome of patients (pts) with resectable mucosal melanoma (MM) is still poor. Toripalimab combined with axitinib has shown impressive results in metastatic MM with an ORR of 48.3% and a median PFS of 7.5 months in a phase 1b trial. It was hypothesized that this combination therapy might cause pathologic response in neoadjuvant setting for resectable MM, so we conducted this single arm phase 2 trial. Methods: Eligible pts were adults (aged 18 to 75) with histologically confirmed resectable (localized or regional lymph node metastasis) MM disease. Exclusion criteria included ocular or unknown primary melanoma, distant metastatic disease or previous use of anti PD-1 ab. Pts received toripalimab 3 mg/kg Q2W plus axitinib 5 mg BID for 8 weeks as neoadjuvant therapy, then surgery and the adjuvant toripalimab 3 mg/kg Q2W starting 2±1week after surgery for totally 52 weeks. The primary end point is pathologic response rate according to the International Neoadjuvant Melanoma Consortium (pCR+pPR, pCR is defined as the complete absence of residual viable tumor and pPR ≤ 50% of viable tumor cells). The secondary end point is RFS in the ITT population. Clinical trial information: NCT04180995. Results: From Aug 2019 to Dec 2020, 21 pts have been eligible and enrolled. Basic characteristics: median age 62 years; M: F 28.6% : 71.4%; primary sites 8 femal genital(1urethra, 7vagina), 5 esophagus, 4 ano-rectal, 4 head & neck(3 nasal,1 oral), in which 47.6% localized disease (T3/4 60%), 52.4% regional lymphatic disease; Gene mutation: 4 cKit (1 amplification), 2 Nras,1 Braf (N581), 1mTOR. This therapy was tolerable with grade 3-4 treatment related AEs of 23.8% (liver dysfunction 14.3%, hyperglycemia 9.5% and hypertension 4.8%). 13 pts had received surgeries (local excision 30.8%, wide excision ± CLND72.7%)and 5 pts still in neoadjuvant treatment. One patient was inoperable for bone metastasis, and 2 pts withdrew for covid 19 epidemic. At a median follow up time of 59 weeks, the pathologic response rate was 28.6% (4/14, 2 pCR, 2pPR). Of the post-surgical specimens, 61.5% (8/13) showed significant TIL infiltration, with 38.5% Brisk and 23.1% Nonbrisk according to the definition of AJCC 8th edition. Plenty of plasma cells, histiocyte and pigment with hyaline fibrosis were also found in responders. No recurrence or metastasis was observed in responders until now, with a RFS reaching more than 58weeks. 5 pts with pNR( > 50% viable tumor cells) got disease progression, with 1 local recurrence, 1 regional lymphatic metastasis, and 3 distant metastases. The median RFS has not been reached. Conclusions: Neoadjuvant toripalimab plus axitinib in resectable MM has shown promising pathologic responses with good tolerance, which supports further investigation of neoadjuvant therapies in MM. Survival is still in follow-up. Clinical trial information: NCT04180995.

scholarly journals Efficacy and safety-in analysis of short-course radiation followed by mFOLFOX-6 plus avelumab for locally advanced rectal adenocarcinoma

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Ali Shamseddine ◽  
Youssef H. Zeidan ◽  
Ziad El Husseini ◽  
Malek Kreidieh ◽  
Monita Al Darazi ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Pathologic Response ◽  
Cytotoxic T Cell ◽  
Short Course ◽  
Pathologic Response Rate

Abstract Background Neoadjuvant chemotherapy and short-course radiotherapy followed by resection has been gaining recognition in the treatment of rectal cancer. Avelumab is a fully human immunoglobulin that binds Programmed Death-Ligand 1 (PD-L1) and prevents the suppression of the cytotoxic T cell immune response. This phase II trial evaluates the safety and pathologic response rate of short-course radiation followed by 6 cycles of mFOLFOX6 with avelumab in patients with locally advanced rectal cancer (LARC). Methods This study is prospective single-arm, multicenter phase II trial adopting Simon’s two-stage. Short-course radiation is given over 5 fractions to a total dose of 25 Gy. mFOLFOX6 plus avelumab (10 mg/kg) are given every 2 weeks for 6 cycles. Total mesorectal excision is performed 3–4 weeks after the last cycle of avelumab. Follow up after surgery is done every 3 months to a total of 36 months. Adverse event data collection is recorded at every visit. Results 13 out of 44 patients with LARC were enrolled in the first stage of the study (30% from total sample size). All patients met the inclusion criteria and received the full short-course radiation course followed by 6 cycles of mFOLFOX6 plus avelumab. 12 out of the 13 patients completed TME while one patient had progression of disease and was dropped out of the study. The sample consisted of 9 (69%) males and 4 (31%) females with median age of 62 (33–73) years. The first interim analysis revealed that 3 (25%) patients achieved pathologic complete response (pCR) (tumor regression grade, TRG 0) out of 12. While 3 (25%) patients had near pCR with TRG 1. In total, 6 out of 12 patients (50%) had a major pathologic response. All patients were found to be MMR proficient. The protocol regimen was well tolerated with no serious adverse events of grade 4 reported. Conclusion In patients with LARC, neoadjuvant radiation followed by mFOLFOX6 with avelumab is safe with a promising pathologic response rate. Trial Registration Number and Date of Registration ClinicalTrials.gov NCT03503630, April 20, 2018. https://clinicaltrials.gov/ct2/show/NCT03503630?term=NCT03503630&draw=2&rank=1.

Australasian Gastro-Intestinal Trials Group (AGITG) MASTERPLAN: Randomized phase II study of modified neoadjuvant FOLFIRINOX alone or in combination with stereotactic radiotherapy (SBRT) for patients with high-risk and locally advanced pancreatic cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS4172-TPS4172
Author(s):  
Andrew Oar ◽  
Andrew Kneebone ◽  
Mark Lee ◽  
David Goldstein ◽  
Katrin Marie Sjoquist ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
High Risk ◽  
Phase Ii ◽  
Response Rate ◽  
Locally Advanced ◽  
Resection Rate ◽  
Free Survival ◽  
Randomized Phase Ii

TPS4172 Background: Eighty per cent of patients with non-metastatic pancreatic cancer have high-risk, borderline resectable (BRPC) or locally advanced pancreas cancer (LAPC), conferring a 5-year overall survival of only 12%. MASTERPLAN evaluates the safety and activity of stereotactic body radiotherapy (SBRT) added to neoadjuvant chemotherapy in these patient cohorts. Methods: MASTERPLAN is an investigator-initiated prospective multi-centre randomized phase II trial. Inclusion criteria include histologically confirmed high-risk, BRPC or LAPC. High risk is defined as tumour > 4cm, extrapancreatic extension or node positive. Randomisation is 2:1 to chemotherapy + SBRT (investigational arm) or chemotherapy (control arm) by minimisation with stratification by operability (potentially operable - high risk; BRPC versus inoperable – LAPC; medically inoperable), planned chemotherapy and institution. Both treatment arms receive 6 x 2 weekly cycles of modified FOLFIRINOX (mFOLFIRINOX). Gemcitabine and nab-paclitaxel is permitted if mFOLFIRINOX is unsuitable. The investigational arm receives SBRT (40Gy in 5 fractions) with real time quality assurance. Resectability will be evaluated following initial chemotherapy +/- SBRT. Adjuvant chemotherapy is 6 cycles (12 weeks) of mFOLFIRINOX, or the same duration of gemcitabine and capecitabine (GEMCAP) if neoadjuvant gemcitabine/ nab-paclitaxel given. SBRT adverse events (AEs) will be recorded until study cessation. The primary endpoint is 12-month locoregional control. Secondary endpoints: safety, surgical morbidity and mortality, radiological response rate, progression free survival, pathological response rate, surgical resection rate, R0 resection rate, quality of life, deterioration free survival and overall survival. Biospecimens are collected for translational research for potential prognostic/predictive biomarkers of clinical endpoints and include serial tumour tissue collection from patients undergoing fiducial marker insertion and/or surgery, biopsy at disease progression, serial blood collection and serial buccal and faecal sample collection. An interim analysis will review locoregional failure, distant metastasis and rate of death on the first 40 patients after completion of 12 months follow up. The sample size is 120 patients (80 intervention:40 control), balanced for BRPC/LAPC (60 in each cohort). The minimum follow up is 12 months. The first site opened in October 2019 and 10 patients have been recruited from five sites at 17 Feb 2021. Overall 15 sites in Australia and New Zealand are planned to open to recruitment. Australian Clinical Trials Registry Number: ACTRN12619000409178. Clinical trial information: ACTRN12619000409178.

Phase II trial of gemcitabine and cisplatin as neoadjuvant chemotherapy for invasive bladder cancer: Preliminary results

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14590-14590 ◽  
Author(s):  
R. Dienstmann ◽  
D. Herchenhorn ◽  
F. A. Peixoto ◽  
F. Campos ◽  
V. O. Santos ◽  
...  
Keyword(s):  
Overall Survival ◽  
Bladder Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Pathologic Response ◽  
Complete Pathologic Response ◽  
Muscle Invasive ◽  
Gemcitabine And Cisplatin

14590 Background: Gemcitabine and cisplatin (GC) is an active and well tolerated combination in the treatment of metastatic bladder cancer (BC). Studies of neoadjuvant chemotherapy in BC suggest improved survival, especially for patients with complete pathologic response. We have prospectively analyzed the tolerability and efficacy of GC as neoadjuvant treatment of invasive BC. Methods: in this single-institution, one-stage phase II trial, patients (pts) with histologically verified muscle-invasive transitional cell carcinoma received 3 cycles of gemcitabine 1200 mg/m2 on days 1 and 8 with cisplatin 75 mg/m2 on day 1 prior to surgery. Radiologic response was evaluated with computed tomography and magnetic resonance imaging. Planned accrual was 35 pts. Primary endpoint was clinical and pathological response rate. Results: between Jun 2002 and Mar 2005, 22 pts (19 males) were enrolled. Accrual was poor due to a higher percentage of superficial tumors than expected. Median age was 61 years. All pts had Performance Status 0 or 1. Initial stage was II (T2) in 11 and III (T3–4) in 11 pts. Chemotherapy was well tolerated with infrequent grade III/ IV toxicity (nausea/ vomiting in 27%, neutropenia in 23% and neutropenic fever in 1 patient). Median follow-up is 26 months (6–40). Partial radiologic response rate was documented in 15 out of 19 assessable pts (79%). One patient was excluded due to renal toxicity in the first chemotherapy cycle and other had sarcomatoid carcinoma at definitive pathologic examination. By Dec 2005, 14 pts underwent radical cystectomy, 4 pts pelvic radiotherapy, 1 is waiting surgery and 1 had systemic progression before surgery. Nine out of 20 pts (45%) relapsed (8 systemic and 1 local) and 4 (20%) are dead (3 with confirmed disease progression). Complete pathologic response was observed in 3 pts (21.5% of 14) and local progression during chemotherapy in another 3 pts. Median estimated progression-free survival by Kaplan-Meier is 27 months (CI 95% 20.5–33.5) with median overall survival not reached. Conclusions: the combination of gemcitabine and cisplatin is effective and tolerable when used as neoadjuvant therapy in muscle-invasive bladder cancer. Longer follow-up is necessary to evaluate its impact in the overall survival of these pts. [Table: see text]

A pilot study of local injection of TNFerade biologic in addition to neo-adjuvant chemoradiation for the treatment of primary and recurrent rectal cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14585-14585
Author(s):  
K. A. Camphausen ◽  
M. Quezado ◽  
D. Citrin ◽  
J. F. Pingpank ◽  
B. Wood ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Local Recurrence ◽  
Response Rate ◽  
External Beam Radiotherapy ◽  
Inducible Promoter ◽  
Sphincter Preservation ◽  
Pathologic Response ◽  
Entire Area ◽  
Viable Tumor ◽  
Pathologic Response Rate

14585 Background: Rectal cancer presents unique therapeutic considerations due to competing concerns regarding sphincter preservation and local recurrence. Treatments using pre-operative chemoradiation are employed to decrease local recurrence and improve the probability of sphincter preservation. Agents, which improve the pathologic response rate may be of further benefit. Methods: TNFerade biologic is a replication deficient adenovirus expressing human TNF-alpha driven by a radiation inducible promoter. TNFerade biologic (4X10e10 pfu) is injected locally into rectal tumors once a week for 5 weeks. Patients receive concurrent chemoradiation utilizing oral capecitabene (937.50 mg/m2 BID, Monday-Friday) and external beam radiotherapy (1.8 Gy/day, 5 days per week to a total dose of 45 Gy). A boost dose of 5.4–9 Gy is delivered to sites of gross disease. After treatment, patients recover for 6–9 weeks before surgery. Patients are scored prior to the start of neo-adjuvant therapy for the feasibility of a sphincter preserving operation versus an abdominal perineal resection (APR). Following surgery the specimen (entire area submitted for processing) is examined for the percent of viable tumor remaining. The goal of the study is to show a target pathologic response rate of <10% viable tumor in more than 30% of patients treated. Results: Six patients have been treated (4M, 2F). There has been no toxicity attributable to the TNFerade biologic, and the chemoradiation has been well tolerated with only mild, expected toxicities. Five of the six patients have undergone surgery (one is awaiting surgery). Three of these five patients were thought to require an APR prior to treatment due to the size and location of their tumor. All five patients have successfully undergone sphincter- preserving operations. On examination of the five specimens, 3 had less than 5% viable tumor while 2 had greater than 50% viable tumor. All resections were margin negative. The target pathologic response rate of <10% viable tumor was achieved in 60% of the patients evaluated. Conclusion: The addition of TNFerade biologic to pre-operative chemoradiation was well tolerated and a prospective randomized trial comparing the addition of this agent to chemoradiation is warranted. No significant financial relationships to disclose.

Pathologic response rate (pCR) and near-pathologic response rate (near-pCR) with docetaxel-carboplatin (TCarb) in early triple-negative breast cancer.

2011 ◽  
Vol 29 (27_suppl) ◽  
pp. 277-277 ◽  
Author(s):  
P. Kern ◽  
H. C. Kolberg ◽  
A. Kalisch ◽  
C. Liedtke ◽  
F. Otterbach ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clin Oncol ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Response Rate ◽  
Pathological Complete Response ◽  
Complete Response ◽  
Pathologic Response ◽  
Term Survival ◽  
Pathologic Response Rate

277 Background: Triple-negative breast cancer (TNBC) is associated with a poor prognosis unless a pathological complete response is achieved (Liedtke C et al. 2008: J Clin Oncol 26:1275-1281) or almost achieved (Symmans WF. 2007: J Clin Oncol 25:4414-4422). Sensitivity to platin compounds has been demonstrated in BRCA1-positive settings (Byrski T et al. 2010: J Clin Oncol 20:28:375-9; Silver DP. 2010: J Clin Oncol 28:1145-1153) with only limited numbers of patients (Byrski T et al. 2010: J Clin Oncol 20:28:375-9) or in sporadic breast cancer with heterogeneous cohorts (Sikov WM et al 2009: J Clin Oncol 27:4693-4700; Chang HR et al. 2010: Cancer 15; 116:4227-4237). Methods: This pivotal trial was to assess the efficacy of platinum and taxane-based combination therapy without the use of anthracyclines. 27 patients with primary TNBC (majority of them cT2, two cT3 and one cT4a) had to be unsuitable for standard anthracycline-based chemotherapy. They received 6 cycles, respectively in two cases only 5 cycles, of carboplatin AUC 6 and docetaxel 75 mg/m2 q3w. The primary endpoint was the pCR-rate, secondary endpoint toxicity. Results: 20 out of 27 (74%) patients had pathological complete response (52%) or near-complete response (22%)—ypT1mic and ypT1a—both being associated with a good prognosis. Seven remaining patients had still good partial response, leaving only low residual cancer burden, which was defined as ypT1. Treatment was well-tolerated: grade III and IV toxicities were neutropenia, thrombopenia, oedema, nausea, joint pain, nail changes, fatigue, hypertension, and alopecia. Conclusions: These results show a high efficacy of carboplatin AUC6 and docetaxel 75 mg/m2 q3w and good feasibility as primary chemotherapy for TNBC with a pCR- and near-pCR-rate of 74% and total response rate of 100%. The incorporation of anthracyclines and parp-inhibitors into further trial designs could enhance the efficacy of these compounds. The omission of exposure to anthracyclines in patients with considerable heart disease risks seems to be feasible with a good pCR-rate, the latter being a surrogate-marker for long-term survival.

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