HIPECFLOT9 - Prevent

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Krankenhaus Nordwest GmbH

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

17 Dec 2020 → ongoing

Decision date (initial)

2024-10-29

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-517300-10-01

EudraCT number

2017-003832-35

ClinicalTrials.gov

NCT04447352

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy

The primary efficacy objective of the study is to compare progression/disease-free survival (PFS/DFS) in patients.

Conditions and MedDRA coding

Resectable diffuse type gastric and gastroesophageal junction Typ II/III adenocarcinoma

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Histologically confirmed, medically operable, resectable diffuse or mixed type (according to Lauren’s classification) adenocarcinoma of the gastroesophageal junction (AEG II-III) or the stomach (uT3, uT4a, any N category, M0), or any T N+ M0 patient.
2. Patient has received 3 to 6 cycles of neoadjuvant FLOT (de-escalation or dose modification allowed)
3. No preceding cytotoxic or targeted therapy other than neoadjuvant FLOT (including de-escalated or dose reduced schema) therapy
4. No prior partial or complete tumor resection
5. Female and male patient ≥ 18 and ≤ 75 years. Female patient with childbearing potential needs to have a negative pregnancy test within 7 days prior to study start. Males and females of reproductive potential must agree to practice highly effective contraceptive measures* during the study. Male patients must also agree to refrain from father a child during treatment and additionally to use a condom during treatment period. Their female partner of childbearing potential must also agree to use an adequate contraceptive measure. *highly effective (i.e. failure rate of <1% per year when used consistently and correctly) methods: intravaginal and transdermal combined (estrogen and progestogen containing) hormonal contraception; injectable and implantable progestogen-only hormonal contraception; intrauterine device (IUD); intrauterine hormone-releasing system (IUS); bilateral tubal occlusion; vasectomised partner; sexual abstinence (complete abstinence is defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments).
6. ECOG ≤ 1
7. Exclusion of distant metastases by CT or MRI of abdomen, pelvis, and thorax, bone scan or MRI (if bone metastases are suspected due to clinical signs). Exclusion of the infiltration of any adjacent organs or structures by CT or MRI
8. Laparoscopic exclusion of peritoneal carcinomatosis at initial staging, before start of FLOT chemotherapy
9. Hematological, hepatic and renal function parameters adequate to allow surgical procedure and HIPEC at investigator´s discretion.
10. Patient able and willing to provide written informed consent and to comply with the study protocol and with the planned surgical procedures

Exclusion criteria 16

1. Patient without neoadjuvant therapy or those who received a neoadjuvant therapy other than FLOT
2. Known hypersensitivity against 5-FU, leucovorin, oxaliplatin, or docetaxel
3. Other known contraindications against, 5-FU, leucovorin, oxaliplatin, or docetaxel
4. Clinically significant active coronary heart disease, cardiomyopathy or congestive heart failure, NYHA III-IV
5. Clinically significant valvular defect
6. Past or current history of other malignancies not curatively treated and without evidence of disease for more than 3 years, except for curatively treated basal cell carcinoma of the skin and in situ carcinoma of the cervix.
7. Criteria of primary unresectability, e.g.: Radiologically documented evidence of major blood vessel invasion or invasion of adjacent organs (T4b). Patients with involved retroperitoneal (e.g. para-aortal, paracaval or interaortocaval lymph nodes) or mesenterial lymph nodes (distant metastases!).
8. Other severe internal disease or acute infection
9. Patient has undergone major surgery within 28 days prior to enrollment.
10. Cirrhosis at a level of Child-Pugh B (or worse) or cirrhosis (any degree) and a history of hepatic encephalopathy or ascites.
11. On-treatment participation in another interventional clinical study in the period 30 days prior to inclusion and during the study.
12. Patient pregnant or breast feeding, or planning to become pregnant.
13. Patient in a closed institution according to an authority or court decision (AMG § 40, Abs. 1 No. 4)
14. Any other concurrent antineoplastic treatment including irradiation
15. Known intraabdominal adhesion situs
16. Pre-existing peritoneal seeding

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. PFS/DFS, defined as the time from randomization to disease progression or relapse after surgery or death from any cause. If no event is observed PFS/DFS is censored at the time of last tumor assessment.

Secondary endpoints 9

1. OS, defined as the time from randomization to death from any cause If no event is observed OS is censored at the day of last subject contact.
2. Rate of patients with peritoneal relapse at 2 and 3 years in both arms.
3. PFS/DFS rates at 2, 3 & 5 years defined as the percentage of patients without disease progression or relapse after surgery or death from any cause after 2, 3 and 5 years referring to the total number of patients randomized into the respective treatment arm.
4. OS rates at 3 & 5 years defined as the percentage patients known to be alive after 3 and 5 years referring to the total number of patients randomized into the respective treatment arm.
5. Rate of surgical serious adverse events, according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE Version 5.0) grade ≥ 3 adverse events and grade ≥ 3 laboratory toxicities.
6. OS and PFS/DFS (medians and rates) according to subgroup (diffuse vs. mixed and gastric vs. GEJ type II/III).
7. Quality of life (QoL) – EORTC QLQ C30 and EORTC QLQ STO22 questionnaire: The QoL analyses will include QoL mean values, QoL response and time to symptom deterioration (TTSD) defined as the time interval between randomization and the first decrease by ≥ 10-points. All randomly assigned patients with a baseline and at least one post-baseline assessment will be included in TTSD analyses. Patients without observed deterioration will be censored at the time of their last QoL assessment.
8. Post-operative morbidity/mortality at day 30 after surgery acc. to Clavien–Dindo classification.
9. Post-operative Pain according to VAS (visual analog scale): The patient´s assessment of their current level of pain on a 100-mm horizontal VAS. The left-hand extreme of the line should be described as “no pain” and the right-hand as “unbearable pain”.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Krankenhaus Nordwest GmbH

Sponsor organisation

Krankenhaus Nordwest GmbH

Address

Steinbacher Hohl 2-26, Praunheim Praunheim

City

Frankfurt Am Main

Postcode

60488

Country

Germany

Scientific contact point

Organisation

Krankenhaus Nordwest GmbH

Contact name

Prof. Dr. Thorsten Götze

Public contact point

Organisation

Krankenhaus Nordwest GmbH

Contact name

Prof. Dr. Thorsten Götze

Locations

1 EU/EEA country · 29 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 17 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications