A Phase 1 interventional study of Doxorubicin and Cisplatin in Gastric Adenocarcinoma and Gastric Cancer, sponsored by Michael Bau Mortensen. Completed at 2 sites in 2 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2022-10-06.
Sponsored by Michael Bau Mortensen · Phase 1, Interventional, and Other
In this study patients will be offered intraperitoneal atomized chemotherapy as a supplement to the standard treatment of high-risk gastric cancer (laparoscopic removal of the stomach). Two commercially available oncologic drugs will be used (doxorubicin and cisplatin).
Gastric adenocarcinoma (GAC) is considered the fifth most common cancer in the word and the third leading cause of cancer death globally. The majority of GAC patients presents with advanced stages of disease leading to a dismal prognosis even after treatments with curative intent.
Irrespective of these tumors' origin, the peritoneum is one of the most frequent sites of metastases and recurrences that generally determines the subsequent prognosis. Additionally, it is observed that none of the currently available perioperative chemotherapy regimens have been able to reduce the risk for peritoneal deposits. Peritoneal metastases (PMs) are formed during processes that entraps the malignant cells and this restrictive milieu is thought to hinder the penetrance of drugs delivered systemically and provides grounds for the early administration of intraperitoneal treatments. The presence of malignant intraperitoneal cells that is not cleared by chemotherapy before surgery, and/or seeding of malignant cells during surgery, are probably the major reasons for the development of PM and thus the poor prognosis after seemingly micro-radical surgery.
Since only a fraction of the systemically administered chemotherapy reaches the peritoneum, the effect of intraperitoneal chemotherapy has been eagerly studied. A recent systematic review and meta-analysis identified three trials evaluating the effect of intraperitoneal chemotherapy and/or extensive peritoneal lavage in gastric cancer patients who underwent subsequent surgery. Two and five-year overall survival increased significantly in patients who had intraperitoneal chemotherapy (RR=1.62 and 3.10) and survival further increased by the addition of extensive lavage (RR= 2.33 and 6.19).
The intraperitoneal delivery and subsequent uptake of chemotherapy is improved by a new aerosol technique. Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) has shown promising results in patients with PM from colorectal, ovarian and gastric cancer (see below), and PIPAC is feasible, safe and well tolerated by the majority of patients. Our own database assessed the outcome of PIPAC, with low-dose cisplatin and doxorubicin, in GAC patients with chemotherapy-resistant PM. Objective tumor response was documented in 40% of the patients after PIPAC, including complete histological regression in some, whereas an additional 20% had no further tumor progression (manuscript in preparation). These observations in GAC patients deliver further evidence suggesting that PIPAC can induce regression of resistant PMs in several cancer types and might meet the clinical need for new and better therapies for fatal cancer disease states. Our results also provide evidence that low-dose PIPAC therapy might be effective in treating patients with recurrent, chemo-resistant gastric PMs, including the aggressive signet-ring histology.
The imminent question is whether PIPAC delivered immediately after a laparoscopic gastrectomy for GAC, in patients being exposed to a significant risk of early recurrent disease, can be safely carried out? If so, for the first time, a corresponding therapeutic concept can be offered to similar GAC patients in addition to surgery with curative intent. This could potentially increase progression free and eventually overall survival.
Twenty patients will be enrolled from two Danish and Swedish hospitals according to the inclusion and exclusion criteria and included in the data analysis if laparoscopic removal of the stomach and subsequent immediate PIPAC has been performed.
Exclusion Criteria:
The study population of high-risk gastric cancer patients will be offered one session of PIPAC immediately after laparoscopic removal of the stomach.
Drug: Doxorubicin · Drug: Cisplatin
Conventional PIPAC with doxorubicin (2.1 mg/m2 body surface in 50ml saline) is performed through the CE-certified nebulizer by certified PIPAC surgeons directly after the completion of the laparoscopic gastric resection and reconstruction using the remaining relevant ports. Chemotherapy is installed at a rate of 0.5-0.8 ml/s with a maximum pressure of 300 pressure per square inch and 30 minutes of simple diffusion.
Conventional PIPAC with cisplatin (10.5 mg/m2 body surface in 150ml saline) is performed through the CE-certified nebulizer by certified PIPAC surgeons directly after the completion of the laparoscopic gastric resection and reconstruction using the remaining relevant ports. Chemotherapy is installed at a rate of 0.5-0.8 ml/s with a maximum pressure of 300 pressure per square inch and 30 minutes of simple diffusion.
Medical adverse events
According to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.
Time frame: 30 days
Surgical complications
According to the Dindo-Clavien classification
Time frame: 30 days
Length of stay
The amount of time the patient is hospitalized
Time frame: 30 days
Positive peritoneal lavage
The rate of positive peritoneal lavage before and after surgery
Time frame: 30 days
Adjuvant chemotherapy
The number of patients that receive adjuvant systemic chemotherapy
Time frame: 30 days
Plan to share: No
This study is completed, as verified in Oct 2022. You cannot join it, but the record below documents what was studied.
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Michael Bau Mortensen