Hi-STEP1 study
Overview
- Adult patients with peritoneal metastases from advanced gastric or colorectal cancer can participate in the Hi-STEP1 study.
- The prerequisite is that the tumour and peritoneal metastases can be completely removed during surgery, followed by chemotherapy in the abdominal cavity.
- In the study, researchers use the participants' tumour tissue to create miniature models of the tumours (known as tumour organoids) in the laboratory. They use these models to investigate how the tumours respond to different types of chemotherapy and what characteristics the cancer cells have. This data can help to plan chemotherapy more individually in the future and develop new treatment approaches.
Study status: The study is currently enrolling patients (recruitment open).
If stomach or colon cancer has spread to the peritoneum – forming what is known as "peritoneal carcinomatosis" – the prognosis for patients is usually poor.
Although current therapy can prolong the survival of those affected, curing the illness is often not possible. Even after successful initial treatment, the risk of relapse is very high.
The current standard treatment is to flush the abdominal cavity with a heated chemotherapy solution after surgical removal of the tumour and metastases. There are many different chemotherapy regimen(s) for this so-called HIPEC (hyperthermic intraperitoneal chemotherapy).
Laboratory tests with so-called organoid cultures could help to find a chemotherapy substance for HIPEC that is effective for the individual patient: Tumour organoids are "mini-tumours" that are grown in the laboratory from the tumour cells of study participants using special cell culture methods. In this study, they are produced from tissue samples of peritoneal metastases. Many laboratory studies have already shown that tumour organoids have similar properties to the patient's tumour that they come from. Researchers can use them to test whether and how well different drugs work in comparison. If the organoids are implanted in laboratory animals, it is also possible to obtain initial indications of the tumour's possible response to the selected drugs in a living organism.
What the Hi-STEP1 study aims to achieve: Researchers want to gain a better understanding of stomach and colon cancer with peritoneal carcinomas by conducting laboratory tests on the tumour cells of study participants. These findings could form the basis for tailoring HIPEC to individual patients in the future and developing new treatment approaches. This will be further investigated in a follow-up study.
- You can read more about the objectives of the Hi-STEP1 study in the section What is the aim of the Hi-STEP1 study?.
Which types of cancer are covered by Hi-STEP1?
Patients with peritoneal metastases (peritoneal carcinomatosis) from an advanced tumour in the digestive tract are eligible to participate in the Hi-STEP1 study. The following tumours of the digestive tract are being investigated in this study:
- Adenocarcinoma of the stomach
- Adenocarcinomas of the gastroesophageal junction (a type of cancer that develops in the area between the oesophagus and the stomach)
- Adenocarcinomas of the colon or rectum
For information on additional requirements, please refer to the section Who is the study suitable for?.
What is the aim of the Hi-STEP1 study?
Hi-STEP1 is derived from the English name of the study.
- The study title in English is: "Response Prediction of Hyperthermic Intraperitoneal Chemotherapy in Gastrointestinal Cancers".
In simple terms, researchers want to investigate whether it is possible to predict how well cancer in the abdominal cavity will respond to a special form of chemotherapy. In this treatment, the abdominal cavity is flushed with a heated chemotherapy solution. The technical term for this treatment is "hyperthermic intraperitoneal chemotherapy", abbreviated to HIPEC.
Objectives of the Hi-STEP1 study
Scientists want to achieve various objectives:
- First, they want to test how samples of peritoneal metastases (peritoneal carcinomatosis) from individual patients respond to different chemotherapy drugs: To do this, they use these tissue samples to create novel “mini-tumour” models, known as tumour organoids. The effectiveness of various drugs is then tested in the individual tumour organoid in the laboratory.
- In addition, tumour tissue is implanted into laboratory animals, which are then treated with drugs. This allows their effectiveness to be studied in an organism that is more similar to humans than a cell culture model.
- The researchers also examine the genetic material of the tumour to characterise its molecular properties more precisely and possibly find new targets for targeted therapy.
- Finally, they record the medical progress data of the patients after the operation and subsequent HIPEC treatment and compare that data with the laboratory results. This allows them to analyse whether these tests can be used to predict the success of the therapy.
Depending on the results of the Hi-STEP1 study, a larger clinical trial is planned. In this trial, researchers could further investigate whether patients with personalised HIPEC have better chances of recovery than with standard therapy.
Patients can participate in the study if ALL of the following requirements are met:
- The participant is 18 years of age or older.
- The tumour has spread to the peritoneum (peritoneal carcinomatosis) and originates in the stomach, intestine or the area between the oesophagus and stomach.
- The intraoperative peritoneal carcinomatosis index (PCI) must not exceed 15 for participants with stomach cancer or 20 for those with bowel cancer. This index is used by specialists to assess how far the cancer cells have spread in the peritoneum and whether surgical removal is advisable.
- It is possible to remove peritoneal carcinomatosis largely or completely through surgery. The aim of this surgery is to achieve a cure.
- There are no medical reasons that would argue against surgery and administering heated chemotherapy directly into the abdominal cavity (HIPEC).
- The patient's general state of health is not too severely impaired. Health care professionals rate their performance according to the Eastern Cooperative Oncology Group (ECOG) as less than or equal to 2.
- Participants have an estimated survival time of at least 6 months.
- The patient has been informed. He or she understands the content and possible individual risks of participation, and has agreed in writing to participate.
Patients cannot participate in the study if at least ONE of the following points applies:
- The patient does not meet the above requirements for the study.
- The patient has already received palliative chemotherapy or radiation therapy for the tumour – except for so-called neoadjuvant therapy or adjuvant cancer therapy treatments – i.e. therapies before or after surgery with the intention of curing the patient.
- The cancer has spread extensively throughout the body. There are many tumour metastases in several areas of the body, for example, many metastases in both lobes of the liver or simultaneously in the liver and lungs. Surgery with the aim of providing a cure is therefore not possible.
- Peritoneal metastases have reappeared after being surgically removed.
- A patient is pregnant, breastfeeding or wishes to become pregnant within 7 months of completing treatment.
- There is a second cancer that occurred less than 5 years ago – except for tumours that were detected very early and completely removed.
- The patient is housed in a closed facility.
Hi-STEP1 is a multicentre, single-arm pilot study.
- A multicentre study takes place at several study centres. Hi-STEP1 takes place at several study centres across Germany.
- Single-arm means that there is no control group in the study. All participants follow the same procedure within the study.
- A pilot study is conducted with only a few study participants prior to a larger clinical study. The aim is to determine whether the procedure can be implemented and whether the methods are suitable for larger studies.
(1) Presentation at the study centre
If the patient is suitable for the study and has registered, an informational meeting will take place in advance during a consultation at the oncological or surgical outpatient clinic of the study centre. There, the patient will learn what the study is about, what what procedures are involved and what the significance of participation is.
Anyone who wishes to participate in the study must sign a declaration of consent. Patients can also indicate whether they would like to be informed about any additional hereditary disease risks that may be found.
(2) Sample collection (biopsy), surgery and chemotherapy (HIPEC)
During the operation, the medical team removes the tumour (if still present) and all metastases in the peritoneum.
Some of the tissue removed is sent for routine pathology tests, while some is used for medically relevant laboratory tests (for more information see step (3)).
This is followed by irrigation of the abdominal cavity with heated chemotherapy (HIPEC) in accordance with the standards of the study centre.
During the hospital stay, doctors also take blood samples for other laboratory tests. The study doctors also collect clinical data for the study. This includes, for example, the date of the initial diagnosis, the tumour stage and information about the course of the operation including any complications, such as bleeding.
(3) Laboratory tests with tumour cells
The researchers use the collected tumour cells to grow special cell cultures in the laboratory – known as tumour organoids. These tumour organoids can then be transferred to mice for further examination.
The researchers perform various tests on the organoids and blood samples. These include
- Sensitivity tests: Researchers investigate which chemotherapy drugs commonly used for HIPEC in cases of peritoneal metastases best inhibit cell growth in the organoids.
- Molecular investigations: Among other things, molecular diagnostics are used to check whether there are cancer-causing changes in the genetic material of the cancer cells that can be treated with targeted therapy.
- Confirmatory tests: After implanting tumour tissue in laboratory animals, the effectiveness of relevant drugs or drug combinations is tested in living organisms.
(4) Follow-up: What happens after the end of treatment
Follow-up care as part of routine care usually lasts for 5 years from the initial diagnosis. Patients must come to the respective study centre for check-ups as part of routine follow-up care. The interval between check-ups depends on the respective study centre – these appointments are usually every 6 months.
The following examinations are part of follow-up care:
- a consultation with the doctor
- a physical examination
- if necessary, a computed tomography, CT scan
The medical procedure for surgery and HIPEC is the same as for patients who are not participating in the study. You therefore have a comparable chance of successful treatment and face comparable risks of complications and surgical consequences.
These are the potential advantages of participating in the Hi-STEP1 study:
By participating, patients support cancer research and contribute to gaining new insights that may help future patients with peritoneal metastases.
Participation in the Hi-STEP1 study may also have disadvantages:
Genetic testing may reveal hereditary predispositions to cancer or other diseases. Participants can then learn about future health risks for themselves and about potential health risks for related family members as well. If you do not wish to receive such results, you can specify this during the study information session.
Important to know: The study doctors will provide you with comprehensive information about the study procedure, the opportunities and the possible risks. They will provide support with the intention of enabling you to make a well-informed decision.
Where is the study being conducted?
The study is currently being conducted at the Comprehensive Cancer Centre of the NCT sites in Dresden, Berlin and Cologne. Participation at other NCT study centres is being planned.
What costs will participants incur?
Participation in the trial is free of charge for patients. However, you will not receive any expense allowance. Travel costs will not be reimbursed as part of the trial.
If you have any questions about the financing of the study, you can ask the study team. For example, during the informational meeting.
How many participants will the study accept? Where are there still places available?
A total of 48 patients can participate in the study.
You can find out whether there are still places available at the study centre of the Clinic for Visceral, Thoracic and Vascular Surgery at the Dresden University Hospital.
Interested cancer patients should first discuss with their attending oncologist whether they can participate in the study. They know best whether the medical criteria for participation have been met.
Afterwards, the attending physicians or cancer patients themselves can contact the study centre at the Clinic for Visceral, Thoracic and Vascular Surgery in Dresden via email at studienzentrum-vtg-at-uniklinikum-dresden.de. The study team will examine the possibility of your participation.
If participation is possible, the study centre will contact the patient after the consultation.
Further information is available from the study centre.
Scientific publications (selection)
Coccolini F, Cotte E, Glehen O, Lotti M, Poiasina E, Catena F, Yonemura Y, Ansaloni L. Intraperitoneal chemotherapy in advanced gastric cancer. Meta-analysis of randomised trials. Eur J Surg Oncol. 2014 Jan;40(1):12-26. doi: 10.1016/j.ejso.2013.10.019.
Drost J, Clevers H. Organoids in cancer research. Nat Rev Cancer. 2018 Jul;18(7):407-418. doi: 10.1038/s41568-018-0007-6.
Forsythe SD, Sasikumar S, Moaven O, Sivakumar H, Shen P, Levine EA, Soker S, Skardal A, Votanopoulos KI. Personalised identification of optimal HIPEC perfusion protocol in patient-derived tumour organoid platform. Ann Surg Oncol. 2020 Dec;27(13):4950-4960. doi: 10.1245/s10434-020-08790-2. Epub 2020 Jul 6.
Fujii M, Sato T. Somatic cell-derived organoids as prototypes of human epithelial tissues and diseases. Nat Mater. 2021 Feb;20(2):156-169. doi: 10.1038/s41563-020-0754-0.
Gill RS, Al-Adra DP, Nagendran J, Campbell S, Shi X, Haase E, Schiller D. Treatment of gastric cancer with peritoneal carcinomatosis by cytoreductive surgery and HIPEC: a systematic review of survival, mortality, and morbidity. J Surg Oncol. 2011 Nov 1;104(6):692-8. doi: 10.1002/jso.22017. Epub 28 June 2011. PMID: 21713780.
Quénet F, Elias D, Roca L, Goéré D, Ghouti L, Pocard M, Facy O, Arvieux C, Lorimier G, Pezet D, Marchal F, Loi V, Meeus P, Juzyna B, de Forges H, Paineau J, Glehen O; UNICANCER-GI Group and BIG Renape Group. Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy versus cytoreductive surgery alone for colorectal peritoneal metastases (PRODIGE 7): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2021 Feb;22(2):256-266. doi: 10.1016/S1470-2045(20)30599-4.
Ubink I, Bolhaqueiro ACF, Elias SG, Raats DAE, Constantinides A, Peters NA, Wassenaar ECE, de Hingh IHJT, Rovers KP, van Grevenstein WMU, Laclé MM, Kops GJPL, Borel Rinkes IHM, Kranenburg O. Organoids from colorectal peritoneal metastases as a platform for improving hyperthermic intraperitoneal chemotherapy. Br J Surg. 2019 Sep;106(10):1404-1414. doi: 10.1002/bjs.11206.
This study description was prepared by authors from the Cancer Information Service, under the direction of Dr. S. Weg-Remers, based on the study documentation.