Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT04555473
Other study ID # TAILOR
Secondary ID
Status Recruiting
Phase
First received
Last updated
Start date May 12, 2020
Est. completion date May 4, 2023

Study information

Verified date April 2020
Source Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Contact Giuseppe Vizzielli, PhD
Phone 3403990822
Email giuseppe.vizzielli@policlinicogemelli.it
Is FDA regulated No
Health authority
Study type Observational [Patient Registry]

Clinical Trial Summary

This is a longitudinal observational phase II, single center, single arm study on the reliability of high grade serous ovarian carcinoma organoids obtained from primary debulking surgery (PDS)+adjuvant chemotherapy and neoadjuvant chemotherapy + interval debulking surgery (NACT+IDS) cases as model for the patients' response to treatments. Since organoids represent a model system comparable to patient-derived xenografts, the investigators tested the null hypothesis that the possibility of correctly identifying the drug-sensitivity could improve from 80%, as assessed by xenografts to at least 95%. The first step was planned to include 7 patients; if 5 or more patients do not respond, the trial will be terminated. If the trial goes on to the second stage, a total of 43 patients will be studied. Considering a patient dropout of approximately 10%, the study was planned to enroll at least 48 patients.


Description:

In this project, the investigators propose to employ the patients-derived organoid technology to test HGSOC organoids obtained from PDS+adjuvant chemotherapy and NACT+IDS cases to predict patients' response to treatments; moreover, the investigators aim to study genomic and phenotypic evolution of HGSOC organoids from PDS+adjuvant chemotherapy and NACT+IDS patients undergoing relapse. Finally, the investigators intend to investigate splicing-targeting technologies as new potential therapeutic treatments to increase vulnerability of HGSOCs. FIGO stage IIIC or IV ovarian, fallopian tube, or primary peritoneal cancer patients will be included if disease at metastatic sites is supposed to be completely resectable and they will be triaged for staging laparoscopy to obtain histologic diagnosis and to provide the tumor load assessment through the laparoscopic score. If PDS is chosen, open cytoreduction will be performed at the same time and bioptic tissue will be collected for organoids; otherwise, women will be submitted to NACT followed by IDS and tissue for organoids will be collected from both staging LPS biopsy (pre-) and subsequent surgery (post-NACT). Part of each surgical specimen will be used to obtain organoids, whereas part will be frozen for direct comparative analysis of the original tumor. 1-6 organoids from each patient will be prepared from PDS or NACT-IDS patients (pre- and post-NACT) and blood samples will also be collected to purify extracellular circulating RNA (cRNAs).


Recruitment information / eligibility

Status Recruiting
Enrollment 48
Est. completion date May 4, 2023
Est. primary completion date November 4, 2021
Accepts healthy volunteers No
Gender Female
Age group 18 Years to 75 Years
Eligibility Inclusion Criteria:

1. age between 18 and 75 years

2. estimated life expectancy of at least 4 weeks

3. performance status (PS) according to Eastern Cooperative Oncology Group (ECOG) < 2

4. adequate bone marrow, respiratory, hepatic, cardiologic medullary and renal function (creatinine clearance < 60 ml/min according to Cockroft formula)

5. histologic diagnose of epithelial ovarian cancer at frozen section and laparoscopic score = 8 or = 12 (considered HTL) with no evidence of mesenteric retraction

Exclusion Criteria:

1. Pregnancy or breast-feeding

2. History of concomitant or previous malignancy in the last 5 years

Study Design


Intervention

Procedure:
Tumor biopsy
Both interventions performed at baseline upon study enrolment (pre- and post-NACT for NACT+IDS patients) and at the time of recurrence. Part of each surgical specimen will be used to obtain organoids, whereas part will be frozen for direct comparative analysis of the original tumor (1-6 organoids from each patient). Blood samples will be collected to purify extracellular circulating RNA (cRNAs).

Locations

Country Name City State
Italy Fondazione Policlinico Universitario "A. Gemelli" IRCCS Rome

Sponsors (1)

Lead Sponsor Collaborator
Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Country where clinical trial is conducted

Italy, 

References & Publications (6)

Fagotti A, Ferrandina G, Vizzielli G, Fanfani F, Gallotta V, Chiantera V, Costantini B, Margariti PA, Gueli Alletti S, Cosentino F, Tortorella L, Scambia G. Phase III randomised clinical trial comparing primary surgery versus neoadjuvant chemotherapy in a — View Citation

Hill SJ, Decker B, Roberts EA, Horowitz NS, Muto MG, Worley MJ Jr, Feltmate CM, Nucci MR, Swisher EM, Nguyen H, Yang C, Morizane R, Kochupurakkal BS, Do KT, Konstantinopoulos PA, Liu JF, Bonventre JV, Matulonis UA, Shapiro GI, Berkowitz RS, Crum CP, D'And — View Citation

Petrillo M, Zannoni GF, Beltrame L, Martinelli E, DiFeo A, Paracchini L, Craparotta I, Mannarino L, Vizzielli G, Scambia G, D'Incalci M, Romualdi C, Marchini S. Identification of high-grade serous ovarian cancer miRNA species associated with survival and — View Citation

Ricci F, Bizzaro F, Cesca M, Guffanti F, Ganzinelli M, Decio A, Ghilardi C, Perego P, Fruscio R, Buda A, Milani R, Ostano P, Chiorino G, Bani MR, Damia G, Giavazzi R. Patient-derived ovarian tumor xenografts recapitulate human clinicopathology and genetic — View Citation

Tuveson D, Clevers H. Cancer modeling meets human organoid technology. Science. 2019 Jun 7;364(6444):952-955. doi: 10.1126/science.aaw6985. — View Citation

Vizzielli G, Costantini B, Tortorella L, Petrillo M, Fanfani F, Chiantera V, Ercoli A, Iodice R, Scambia G, Fagotti A. Influence of intraperitoneal dissemination assessed by laparoscopy on prognosis of advanced ovarian cancer: an exploratory analysis of a — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary Reliability (yes/no) of HGSOC organoids obtained from PDS+adjuvant chemotherapy and NACT+IDS cases as a model for the patient's response to treatments Part of each surgical specimen of eligible women will be used to obtain PDOs according to established protocols (Tuveson et al.), whereas part will be frozen for direct comparative analysis of the original tumor. At first passages, organoids will be characterized for histologic and cytologic features. PDOs maintaining HGSOC features will be analysed for genomic features and splicing-sensitive transcriptomic signatures by next generation sequencing (NGS). The identified transcriptomic signatures of PDOs will be compared to those of the original tumor by quantitative real time PCR (qPCR) analysis. PDOs will then be characterized for their response to specific drugs and the response will be compared to that of the patient undergoing chemotherapy. Dichotomic variable: Yes/No Up to 36 months
Secondary The genomic and phenotypic evolution of tumor cells in HGSOC organoids from PDS+ adjuvant chemotherapy and NACT+IDS patients undergoing relapse At time of relapse (if any), we will repeat NGS genomic and transcriptomic analysis of chemoresistant PDOs derived from selected patients who experienced relapse and underwent secondary surgery. Bioinformatics analyses will be applied to capture changes in the mutational status and in the transcriptional/splicing signature that accompany acquisition of chemoresistance in vitro. These features will then be compared to evolution of the tumor in vivo by sequencing (mutations) and qPCR (transcriptomics) of tissue obtained during surgery. Dichotomic variable: Yes/No Up to 36 months
Secondary Splicing dysregulation and splicing-targeting technologies as new potential therapeutic treatments to increase vulnerability of MYC-overexpressing HGSOCs HGSOCs often display amplification of MYC, an oncogene that dysregulates the splicing program. We will test if HGSOC PDOs are sensitive to splicing-targeting drugs (E7107, THZ531, PRMT5 inhibitor) administered either alone or in combination with chemotherapy. THZ531 renders BRCA1/2 proficient HGSOC cell lines sensitive to PARPi. We will extend this study to PDOs and analyze their sensitivity to splicing-targeting drugs during their evolution in vitro. Changes in splicing signatures will be evaluated and correlated with the response to combined treatments, to determine their potential as biomarkers. We will also silence splicing factors deregulated in HGSOCs by RNA interference to determine their impact on PDO response to chemotherapy in terms of survival, expansion potential and transcriptomic signatures. Dichotomic variable: Yes/No Up to 36 months
See also
  Status Clinical Trial Phase
Active, not recruiting NCT03393884 - Study of IMNN-001 (Also Known as GEN-1) With NACT for Treatment of Ovarian Cancer (OVATION 2) Phase 1/Phase 2
Recruiting NCT05200559 - T-regulatory Cell Depletion With E7777 Combined With Pembrolizumab in Recurrent or Metastatic Solid Tumors Phase 1/Phase 2
Completed NCT04546373 - Niraparib as Maintenance Therapy in Patients With Platinum Sensitive Recurrent Ovarian Cancer
Active, not recruiting NCT03371693 - Cytoreductive Surgery(CRS) Plus Hyperthermic Intraperitoneal Chemotherapy(HIPEC) With Lobaplatin in Advanced and Recurrent Epithelial Ovarian Cancer Phase 3
Completed NCT01442051 - Acute Normovolemic Hemodilution in Patients Undergoing Cytoreductive Surgery for Advanced Ovarian Cancer N/A
Not yet recruiting NCT04983550 - Efficacy and Safety of SG001 Combined With PLD in Patients With Platinum-resistant Relapsed EOC Phase 2
Completed NCT02480374 - Study of Safety & Biological Activity of IP IMNN-001 (Also Known as GEN-1) With Neoadjuvant Chemo in Ovarian Cancer Phase 1
Recruiting NCT01680575 - Study on Neutropenia Induced by Adjuvant Paclitaxel/Carboplatin Chemotherapy in Patients With Epithelial Ovarian Cancer N/A
Terminated NCT01202890 - Study of Revlimid With Doxil and Avastin for Patients With Platinum Resistant Ovarian Cancer Phase 1
Completed NCT00561795 - Feasibility Study of Pazopanib in Combination With Chemotherapy in Gynaecological Tumors Phase 2
Completed NCT00314678 - Cisplatin Induction With Paclitaxel Consolidation for Stage III-IV Epithelial Ovarian and Primary Peritoneal Cancer Phase 2
Not yet recruiting NCT04889495 - A Post-marketing Surveillance to Assess the Safety and Effectiveness of Zirabev in Domestic Patients With Various Cancer
Not yet recruiting NCT06010667 - A Prospective, Randomized Controlled Study of Cyclophosphamide, Bevacizumab With or Without Envafolimab in Recurrent Epithelial Ovarian Cancer (EOC), Fallopian Tube Cancer, and Primary Peritoneal Cancer
Recruiting NCT06085456 - Individualized Health Management of Epithelial Ovarian Cancer: A Retrospective Study
Completed NCT06366997 - Diagnosis of Epithelial Ovarian Cancer Using Ovarian Cancer Score (OCS) Test
Active, not recruiting NCT05212779 - Predicting the Risk of Ovarian Cancer Recurrence Using Circulating Tumor DNA to Assess Residual Disease
Recruiting NCT04620954 - Clinical Trial of Chemotherapy, Oregovomab and Nivolumab in Patients With Epithelial Cancer of Ovarian, Tubal or Peritoneal Origin Phase 1/Phase 2
Completed NCT02312661 - Study of Metformin With Carboplatin/Paclitaxel Chemotherapy in Patients With Advanced Ovarian Cancer Phase 1
Completed NCT01666444 - VTX-2337 and Pegylated Liposomal Doxorubicin (PLD) in Patients With Recurrent or Persistent Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Cancer Phase 2
Completed NCT01891344 - A Study of Rucaparib in Patients With Platinum-Sensitive, Relapsed, High-Grade Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer (ARIEL2) Phase 2