Neoplasms

All Conditions

Digestive System Diseases

Rare Diseases

Adenocarcinoma

Esophageal Neoplasms

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Gastrointestinal Neoplasms

Digestive System Neoplasms

Head and Neck Neoplasms

Gastrointestinal Diseases

Esophageal Diseases

Esophageal Cancer

Antineoplastic Agents

All Drugs and Chemicals

Irinotecan

Fluorouracil

Oxaliplatin

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Topoisomerase I Inhibitors

Enzyme Inhibitors

Treatment with Fluorouracil, Oxaliplatin, and Irinotecan is given for 4 cycles pre- and postoperatively, in total 8 cycles.

In this clinical trial, patients with gastric and gastroesophageal junction adenocarcinoma will be included. Treatment with curative intent will be given with chemotherapy for 4 cycles with fluorouracil, oxaliplatin and irinotecan preoperatively followed by surgery, and then additionally 4 cycles of the same chemotherapy postoperatively. The standard treatment today is preoperative treatment with fluorouracil and oxaliplatin pre-and postoperatively. The rationale for this trial is, that the addition of irinotecan might improve treatments results.

Irinotecan-based Triplet (FOLFOXIRI) as Perioperative Treatment in Resectable Gastric and Gastroesophageal Junction Adenocarcinoma.

Assessment of histopathological response, ypTNM, resection margin and residual tumor status. If Laurén classification and mismatch repair (MMR) or microsatelite instability status (MSI) could not be assessed on pretreatment biopsies it should be assessed on the resected specimen. Results do not have to be awaited before start of chemotherapy.

Lund University Hospital

Symptoms and General Pathology

Neoplasm Metastasis

Colorectal Neoplasms

Intestinal Neoplasms

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Neoplastic Processes

Micronutrients

Bevacizumab

Leucovorin

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Patients will first undergo upfront staging laparoscopy with retrieval of tumor tissue for standard pathology.

Two to 4 weeks after initial surgical exploration, patients will receive 4 cycles of FOLFOXIRI + bevacizumab, q2w. The last chemotherapy cycle will be given without bevacizumab.

Five to 7 weeks after the last administration of bevacizumab (i.e., 3 to 5 weeks after completion of chemotherapy), patients will undergo surgery with the intent to perform complete surgical cytoreduction of all peritoneal tumor deposits. Further chemotherapy according to the currently available treatment guidelines, including intraperitoneal hyperthermic chemotherapy in patients where complete surgical cytoreduction has been achieved, will be given at the discretion of the investigator.

Upfront staging laparoscopy with biopsy of peritoneal tumor deposits, assessment of peritoneal cancer index and resectability.

Upfront staging laparoscopy + peritoneal biopsy

Patients will receive 4 cycles of FOLFOXIRI + bevacizumab; the last cycle will be given w/o bevacizumab

Dosage: Bevacizumab: 5 mg/kg via 30 min. IV infusion, day 1; Oxaliplatin: 85 mg/m2 via 2-hour IV infusion, day 1; Irinotecan: 165 mg/m2 via 1-hour IV infusion, day 1; Leucovorin: 200 mg/m2 via 2-hour IV infusion, day 1; 5-Fluorouracil: 3200 mg/m2 via 48-hour IV infusion, day 1;

Neoadjuvant chemotherapy with FOLFOXIRI + bevacizumab

Three to 5 weeks after completion of FOLFOXIRI + bevacizumab chemotherapy, patients will undergo surgical re-exploration with the intent to perform a complete surgical cytoreduction. Further chemotherapy according to the currently available treatment guidelines, including intraperitoneal hyperthermic chemotherapy in patients where complete surgical cytoreduction has been achieved, may be given at the discretion of the investigator. Systemic chemotherapy may be started beginning 4 weeks post-surgery and after complete wound healing.

Surgical re-exploration

Thomas Bachleitner-Hofmann, MD

Gerald Prager, MD

Anja Grah

Daniela Truzla

There is a paucity of data on the histopathological response of peritoneal tumor deposits from colorectal cancer to neoadjuvant chemotherapy. Particularly, no prospective assessment of chemotherapy-associated histopathological response within the peritoneum has been performed so far. Therefore, there is an urgent need to conduct a clinical trial aimed at prospectively assessing the histopathological response within the peritoneum in patients with peritoneal metastasis from colorectal cancer.

Recently, Loupakis et al. reported that the triplet regimen of 5-fluorouracil, oxaliplatin and irinotecan (FOLFOXIRI) in combination with bevacizumab significantly improved median progression-free survival in metastatic colorectal cancer patients from 9.7 to 12.1 months as compared with fluorouracil, leucovorin, and irinotecan (FOLFIRI) + bevacizumab. In view of these data, it is likely that FOLFOXIRI + bevacizumab will also lead to a significant improvement of the histopathological response within the peritoneum of patients with peritoneal metastasis from colorectal cancer (pcCRC) as compared with previous standard chemotherapy.

The investigators hypothesize that FOLFOXIRI + bevacizumab will induce a pCR or major response in peritoneal tumor deposits in \>30% of patients (taking the response rate to FOLFOX- or FOLFIRI-based neoadjuvant chemotherapy from the published literature as a reference).

Peritoneal carcinomatosis from colorectal cancer (pcCRC) has a dismal prognosis. In the era of 5-fluorouracil treatment and palliative surgery only, median survival ranged from 5.2 to 7.0 months. In patients with bowel obstruction due to peritoneal carcinomatosis outcome was even worse, with a median overall survival of less than 4 months and a 1-year survival rate of 17%. With the advent of modern chemotherapy regimens, survival has improved considerably. However, the presence of pcCRC is still associated with a significantly worse prognosis as compared with other manifestations of metastatic CRC (e.g. liver and/or lung metastasis). A recent retrospective analysis of 2095 patients from 2 prospective randomized trials showed that both median PFS and OS were significantly shorter for patients with pcCRC as compared with patients without pcCRC (PFS: 5.8 vs. 7.2 months, HR=1.2; 95% CI 1.1 to 1.3, p=0.001; OS: 12.7 vs. 17.6 months, HR=1.3; 95% CI 1.2 to 1.5, p\<0.001).

The combination of cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has led to a remarkable improvement of survival in selected patients with pcCRC as illustrated by a prospective randomized trial and several retrospective series. The concept of CRS + HIPEC has therefore recently been incorporated into national treatment guidelines and is being increasingly performed in pcCRC patients with promising long-term results. The subgroup who benefits most of this multimodal therapeutic approach are patients with limited pcCRC where a complete removal of all cancer deposits within the peritoneum can be achieved.

There is increasing evidence that the addition of neoadjuvant systemic chemotherapy to CRS + HIPEC may further improve the outcome of patients with pcCRC. Neoadjuvant chemotherapy, i.e., chemotherapy that is given upfront before CRS + HIPEC is performed, offers several possible advantages for patients: First, it can help to identify nonresponders to treatment who may be unsuitable candidates for CRS. Second, neoadjuvant chemotherapy may limit extraabdominal systemic spread of the disease. Third, upfront chemotherapy may help to reduce the extent of peritoneal metastasis, thus facilitating CRS and increasing the likelihood of a complete surgical cytoreduction.

Importantly, it has recently been shown that the efficacy of neoadjuvant chemotherapy can be easily quantified by assessing the chemotherapy-induced histopathological response within the peritoneum and that the histopathological response is an independent predictor of survival. In a retrospective analysis of 115 pcCRC patients who underwent neoadjuvant chemotherapy followed by CRS, patients were grouped into three distinct categories depending on the histopathological response to neoadjuvant chemotherapy:

1. patients with complete pathologic response (pCR; no remaining viable tumor cells in peritoneal tumor nodules),
2. patients with major response (1-49% remaining viable tumor cells) or
3. patients with minor/no response (≥50% remaining viable tumor cells).

The study was able to show that the cumulative 5-year survival rate was 75% for patients with a pCR (HR=1) as compared with 57% for patients with a major response (HR=4.91) and only 13% for patients with a minor or no response (HR=13.46) (p=0.01). Overall, approximately 30% of patients were considered to be responders to neoadjuvant chemotherapy (9.7% pCR + 20.2% major response), while about 70% of patients were considered non-responders to treatment. Treatment consisted of a FOLFOX- or FOLFIRI-based regimen in the majority of patients.

The primary objective of the study is to prospectively assess the histopathological response to neoadjuvant chemotherapy with FOLFOXIRI + bevacizumab in peritoneal tumor deposits of 30 patients with pcCRC by determining the percentage of viable tumor cells in the resected specimen after neoadjuvant chemotherapy. For patients with multiple peritoneal specimens, the median percentage of viable cells in all specimens will be used. Patients with 0-49% of viable cells will be considered as responders. The timepoint of the assessment of the primary objective will be during re-exploratory surgery/surgical cytoreduction between days 78 and 106 of the treatment phase of the study. The investigators hypothesize that there will be \>30% responders after neoadjuvant chemotherapy with FOLFOXIRI + bevacizumab.

Responders will be defined as patients with pCR (0% viable tumor cells) and major response (1-49% viable tumor cells) after FOLFOXIRI + bevacizumab chemotherapy.

Non-responders will be defined as patients with minor/no response (≥50% viable tumor cells) after FOLFOXIRI + bevacizumab chemotherapy.

The following patients will also be counted as non-responders:

* Patients who do not undergo surgical re-exploration
* Patients who develop extraabdominal metastases
* Deaths before surgical re-exploration

Histopathological Response to FOLFOXIRI + Bevacizumab in Peritoneal Metastasis From Colorectal Cancer

Assessment of Histopathological Response to Combination Chemotherapy With Oxaliplatin, Irinotecan, Fluorouracil and Bevacizumab in Patients With Peritoneal Metastasis From Colorectal Cancer

The percentage of viable cells within the resected specimen after completion of neoadjuvant chemotherapy will be determined. For patients with multiple peritoneal specimens, the median percentage of viable cells in all specimens will be calculated. Patients with 0-49 % of viable cells will be considered as responders.

In case of multiple specimens, the change in the median percentages of viable cells in peritoneal tumor deposits between baseline and after completion of neoadjuvant chemotherapy will be compared.

Medical University of Vienna

ao.Univ.-Prof.Dr.

Sarcoma

Osteosarcoma

Sarcoma, Ewing

Neoplasms, Connective and Soft Tissue

Soft Tissue Sarcoma

Ewing Sarcoma

Upon histopathological examination, the tumor response was assessed on the basis of the presence and extent of necrosis, which was assessed by a combination of gross and microscopic observations. Tumor necrosis was graded as per Picci et al. tumor histopathological response grading (Huvos classification), where grade I is 0% to 49%.

Upon histopathological examination, the tumor response was assessed on the basis of the presence and extent of necrosis, which was assessed by a combination of gross and microscopic observations. Tumor necrosis was graded as per Picci et al. tumor histopathological response grading (Huvos classification), where grade II is 50% to 89%.

Upon histopathological examination, the tumor response was assessed on the basis of the presence and extent of necrosis, which was assessed by a combination of gross and microscopic observations. Tumor necrosis was graded as per Picci et al. tumor histopathological response grading (Huvos classification), where grade III is 90% to 99%.

Upon histopathological examination, the tumor response was assessed on the basis of the presence and extent of necrosis, which was assessed by a combination of gross and microscopic observations. Tumor necrosis was graded as per Picci et al. tumor histopathological response grading (Huvos classification), where grade IV is 100% necrosis.

patients who routinely received neoadjuvant chemotherapy according to Peking University People's Hospital chemo-protocols (PKUPH-OS and PKUPH-ES)

first-line chemotherapy

Wei Guo, Ph.D. and M.D.

For bone lesions treated with chemotherapy or targeted therapy, particularly for sarcomas that originate in bones, Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 is spurious because bone lesions are typically located in irregularly shaped bones, are difficult to measure accurately, and usually respond more slowly to treatment than soft tissue lesions. Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) allows for response to be measured in the absence of anatomic changes through assessment of metabolic activity. It does not, however, account for morphologic changes. This study evaluated whether clinical imaging findings of sarcomas after preoperative chemotherapy correlate with tumor responses by pathological evaluation using the rate of necrosis to develop reliable and quantitative clinical response criteria.

We reviewed a total of 190 primary lesions by clinical imaging, including X-ray, computed tomography (CT), magnetic resonance imaging, and bone scan or PET/CT in patients who received neoadjuvant chemotherapy. All patients had curative surgery of those lesions at Peking University People's Hospital or Peking University Shougang Hospital. Pathological evaluation was completed by determination of the tumor necrosis rate following Huvos' description. We also performed statistical diversity analysis for different pathological groups and generated receiver operating characteristic curves (ROC) to define the thresholds to distinguish different pathological groups.

Clinical Evaluation of Neoadjuvant Chemotherapy for Primary Malignant Sarcomas That Originate in Bone

Clinical Evaluation of Neoadjuvant Chemotherapy for Primary Malignant Sarcomas That Originate in Bone: a Multi-center Retrospective Study for Standardization and Modification of Response Evaluation Criteria

We evaluated all surgical resection specimens and were blinded to the clinical status. Upon histopathological examination, the tumor response was assessed on the basis of the presence and extent of necrosis, which was assessed by a combination of gross and microscopic observations. Tumor necrosis was graded as per Picci et al. tumor histopathological response grading (Huvos classification), where grade I is 0% to 49%, grade II is 50% to 89%, grade III is 90% to 99%, and grade IV is 100% necrosis.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Irinotecan-based Triplet (FOLFOXIRI) as Perioperative Treatment in Resectable Gastric and Gastroesophageal Junction Adenocarcinoma.	NCT03773367	Resectable Gast...	Fluorouracil Oxaliplatin Irinotecan	18 Years -	Lund University Hospital
Histopathological Response to FOLFOXIRI + Bevacizumab in Peritoneal Metastasis From Colorectal Cancer	NCT02591667	Colorectal Canc... Peritoneal Meta...	Upfront staging... Neoadjuvant che... Surgical re-exp...	18 Years -	Medical University of Vienna
Histopathological Response to FOLFOXIRI + Bevacizumab in Peritoneal Metastasis From Colorectal Cancer	NCT02591667	Colorectal Canc... Peritoneal Meta...	Upfront staging... Neoadjuvant che... Surgical re-exp...	18 Years -	Medical University of Vienna
Clinical Evaluation of Neoadjuvant Chemotherapy for Primary Malignant Sarcomas That Originate in Bone	NCT03742063	Clinical Respon... Histopathologic... Prognosis	first-line chem...	-	Peking University People's Hospital
Irinotecan-based Triplet (FOLFOXIRI) as Perioperative Treatment in Resectable Gastric and Gastroesophageal Junction Adenocarcinoma.	NCT03773367	Resectable Gast...	Fluorouracil Oxaliplatin Irinotecan	18 Years -	Lund University Hospital

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