HIPEC + Chemoradiation for Stomach Cancer

Recruiting at 2 trial locations

Overseen By Spiros Hiotis, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Icahn School of Medicine at Mount Sinai

Must not be taking: Carboplatin, Taxol, 5-FU, others

Disqualifiers: Metastatic disease, Early stage cancer, others

Stay on Your Current Meds You can continue your current medications while participating

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

29 Participants Needed

Trial Summary

What is the purpose of this trial?

Stomach cancer is the fifth most common digestive cancer and third main cause of death from cancer in the world. Modern management of Gastric cancer involves a multi-disciplinary approach involving surgical oncologists, medical oncologists, gastroenterologists and oncological radiologists. The most common clinical approach to Gastric adenocarcinoma is to begin with staging, which usually involves CT scan/ MRI combined with endoscopic US for more accurate T, N staging. Once the patient is deemed to have locally advanced gastric cancer (T3/T4,N0/+), a staging laparoscopy is recommended to rule out obvious or microscopic peritoneal metastatic disease. Additionally, neoadjuvant chemotherapy is initiated and followed by surgery +/- adjuvant radiation and chemotherapy.This protocol involves the addition of neoadjuvant HIPEC at the time of diagnostic laparoscopy as well as neoadjuvant radiation therapy for improved local and systemic control. The goal of this phase II clinical trial is to evaluate the efficacy of a multi-modality approach to treating patients with locally advanced Gastric cancer by incorporating diagnostic laparoscopy with HIPEC, neo-adjuvant chemo-radiotherapy, followed by surgical resection and adjuvant chemotherapy. The trial aims to assess this multi-modality approach in inducing pathological complete response; decreased rates of disease progression during neoadjuvant therapy; and increased overall, disease-free, and peritoneal disease-free survival.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor to get specific guidance based on your situation.

What evidence supports the effectiveness of the treatment HIPEC + Chemoradiation for Stomach Cancer?

Research on similar treatments, like paclitaxel and carboplatin combined with radiation for lung cancer, shows promising results with a 78% response rate and improved survival. This suggests potential effectiveness for stomach cancer as well. ^{1 2 3 4 5}

Is HIPEC with chemoradiation safe for humans?

HIPEC (Hyperthermic Intraperitoneal Chemotherapy) has been studied for safety in various cancers, including gastrointestinal and ovarian cancers. It can cause side effects mainly due to the chemotherapy drugs used, but studies have been conducted to manage these adverse effects and determine safe dosage levels. ^{6 7 8 9 10}

What makes the HIPEC + Chemoradiation treatment for stomach cancer unique?

The HIPEC + Chemoradiation treatment for stomach cancer is unique because it combines hyperthermic intraperitoneal chemotherapy (HIPEC), which involves delivering heated chemotherapy directly into the abdominal cavity, with advanced radiotherapy techniques like 3D conformal or intensity-modulated radiotherapy. This approach aims to target cancer cells more effectively by combining localized heat and chemotherapy with precise radiation, potentially offering benefits over standard treatments that do not use this combination. ^{1 2 4 11 12}

Research Team

Spiros Hiotis, MD, PhD

Principal Investigator

Icahn School of Medicine at Mount Sinai

Eligibility Criteria

This trial is for adults with advanced gastric cancer (T3/T4, N0/+), who haven't had previous cancer treatments and are planning surgery. They must be physically well enough to participate, not pregnant or nursing, without HIV/Hepatitis B/C, and have no history of severe allergies to the study drugs.

Inclusion Criteria

Ability to understand and the willingness to sign a written informed consent

I am able to get out of my bed or chair and move around.

My stomach cancer is at an advanced stage but hasn't spread to distant organs.

Exclusion Criteria

Subjects with a condition that may interfere with the subjects' ability to understand the requirements of the study

My gastric cancer is in the early stages (Stage 1 or 2, no spread to lymph nodes).

My cancer has spread beyond lymph nodes or the lining of my abdomen.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive neoadjuvant chemotherapy and radiation therapy, including HIPEC at the time of diagnostic laparoscopy

4 weeks

Surgical Resection

Participants undergo surgical resection to evaluate pathological response

1 week

Adjuvant Chemotherapy

Participants receive adjuvant chemotherapy post-surgery

8-12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 years

Treatment Details

Interventions

• 3D conformal or intensity modulated radiotherapy
• Carboplatin
• Dexamethasone
• Famotidine
• HIPEC
• Paclitaxel
• Palonosetron
• Surgical resection

Trial Overview The trial tests a combination treatment for stomach cancer: HIPEC during diagnostic laparoscopy, neoadjuvant chemo-radiotherapy before surgery, followed by more chemotherapy. It aims to see if this approach can improve survival rates and reduce disease progression.

Participant Groups

Group I: Patients With Local Regional Advanced Gastric Cancer Experimental Treatment 9 Interventions

Patients with local regional advanced gastric cancer after at least 4 weeks post diagnostic laparoscopy and HIPEC, will receive all of the treatments described in the study protocol.

3D conformal or intensity modulated radiotherapy is already approved in European Union, United States, Canada, Japan, China for the following indications:

Approved in European Union as 3D conformal radiotherapy for:

• Stomach cancer
• Esophageal cancer
• Rectal cancer
• Other solid tumors

Approved in United States as Intensity modulated radiotherapy for:

• Stomach cancer
• Esophageal cancer
• Rectal cancer
• Prostate cancer
• Head and neck cancers

Approved in Canada as External beam radiation therapy for:

• Stomach cancer
• Esophageal cancer
• Rectal cancer
• Prostate cancer
• Breast cancer

Approved in Japan as 3D conformal radiotherapy for:

• Stomach cancer
• Esophageal cancer
• Rectal cancer

Approved in China as Intensity modulated radiotherapy for:

• Stomach cancer
• Esophageal cancer
• Rectal cancer
• Lung cancer

Who Is Running the Clinical Trial?

Icahn School of Medicine at Mount Sinai

Lead Sponsor

Trials

933

Recruited

579,000+

Findings from Research

This randomized phase II trial is comparing the efficacy and toxicity of two chemoradiation regimens, OXCAP-RT and CarPac-RT, in patients with resectable oesophageal adenocarcinoma, with a primary focus on achieving a pathological complete response rate (pCR) after treatment.

The study involves 76 patients and aims to determine which regimen is more effective and safer, potentially leading to a future phase III trial against the current standard neo-adjuvant chemotherapy in the UK.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NEOSCOPE: a randomised Phase II study of induction chemotherapy followed by either oxaliplatin/capecitabine or paclitaxel/carboplatin based chemoradiation as pre-operative regimen for resectable oesophageal adenocarcinoma. Mukherjee, S., Hurt, CN., Gwynne, S., et al.[2023]

Induction chemotherapy with paclitaxel and carboplatin, followed by concurrent chemoradiation, showed a 55% response rate and a 1-year survival rate of 72% in patients with locally advanced non-small cell lung cancer, indicating promising efficacy.

The treatment regimen was well-tolerated, with mild myelotoxicity as the primary side effect from induction therapy and limited nonhematologic toxicity during concurrent therapy, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent chemoradiation using paclitaxel and carboplatin in locally advanced non-small cell lung cancer. Langer, CJ.[2015]

Combination therapy using paclitaxel with carboplatin and radiation shows promise as a safer and more effective treatment for non-small cell lung cancer compared to the standard regimen of etoposide and cisplatin.

The use of paclitaxel, a novel taxane drug, in conjunction with radiation therapy may enhance local control of the cancer and improve overall response rates, suggesting a potential advancement in treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent paclitaxel, carboplatin, and radiation therapy for locally advanced non-small cell lung cancer. Choy, H., Akerley, W., DeVore, RF.[2015]

Paclitaxel has demonstrated strong antitumor activity in various cancers, including ovarian, breast, and lung carcinoma, especially when combined with platinum compounds like cisplatin and carboplatin.

Recent large randomized trials in Europe have explored the effectiveness of paclitaxel in combination with platinum for treating non-small cell lung cancer, showing promising results and leading to ongoing studies on its use in preoperative settings and with radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

European perspectives on paclitaxel/platinum-based therapy for advanced non-small cell lung cancer. Novello, S., Le Chevalier, T.[2019]

In a study of 27 patients with inoperable stage IIA/IIIB non-small cell lung cancer, a combination of low-dose paclitaxel and carboplatin before radiotherapy resulted in a high overall response rate of 78%, with 19% achieving a complete response.

The treatment regimen was well-tolerated, with significant toxicities primarily being leuko/neutropenia, but no toxic deaths were reported, suggesting that this approach is both effective and safe enough to warrant further investigation in larger trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel (Taxol) and carboplatin followed by concomitant paclitaxel, cisplatin and radiotherapy for inoperable stage III NSCLC. Isokangas, OP., Joensuu, H., Halme, M., et al.[2019]

Hyperthermic intraperitoneal chemotherapy (HIPEC) for gastrointestinal cancers can lead to a range of significant side effects, including digestive fistulas, neutropenia, and renal impairment, as identified in a review of 79 articles.

Effective management strategies for these adverse events include forming a multidisciplinary team, considering alternative chemotherapy drugs, and utilizing careful preoperative assessments, which can help minimize the frequency and severity of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Side-effects of hyperthermic intraperitoneal chemotherapy in patients with gastrointestinal cancers. Hu, J., Wang, Z., Wang, X., et al.[2023]

In a multicenter phase-I study involving 30 patients with initially unresectable ovarian cancer, the recommended dose of cisplatin for hyperthermic intraperitoneal chemotherapy (HIPEC) after neoadjuvant chemotherapy was determined to be 70 mg/m², as higher doses led to significant dose-limiting toxicities (DLTs).

The study found that at the highest dose of 80 mg/m², there were serious adverse events including renal failure and hemorrhage, highlighting the importance of careful dose selection to minimize toxicity while maximizing treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results of a multicenter phase I dose-finding trial of hyperthermic intraperitoneal cisplatin after neoadjuvant chemotherapy and complete cytoreductive surgery and followed by maintenance bevacizumab in initially unresectable ovarian cancer. Gouy, S., Ferron, G., Glehen, O., et al.[2022]

The study involving 37 patients with gastric cancer demonstrated that combining cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) is feasible, particularly using 460 mg/m2 of oxaliplatin and a maximum tolerated dose of 50 mg/m2 of normothermic docetaxel.

While serious adverse events occurred in 17 out of 25 patients, the treatment showed manageable safety, with a reoperation rate of 16% and a treatment-related mortality rate of 8%, indicating that this approach can be considered for patients with limited peritoneal dissemination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of PERItoneal disease in Stomach Cancer with cytOreductive surgery and hyperthermic intraPEritoneal chemotherapy: PERISCOPE I initial results. van der Kaaij, RT., Wassenaar, ECE., Koemans, WJ., et al.[2021]

In a study involving 13 women with epithelial ovarian cancer, hyperthermic intraperitoneal chemotherapy (HIPEC) using cisplatin and paclitaxel resulted in high drug concentrations in the peritoneal tissue while maintaining low levels in the bloodstream, indicating a favorable pharmacokinetic profile.

The treatment was associated with some surgical complications, with four patients experiencing grade 3-4 complications, but overall, HIPEC was deemed feasible and showed potential for effective localized treatment after cytoreductive surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of concomitant cisplatin and paclitaxel administered by hyperthermic intraperitoneal chemotherapy to patients with peritoneal carcinomatosis from epithelial ovarian cancer. Ansaloni, L., Coccolini, F., Morosi, L., et al.[2018]

In a phase I trial involving 27 patients with gastric cancer, laparoscopic hyperthermic intraperitoneal perfusion (HIPEC) using mitomycin, cisplatin, and paclitaxel was found to be safe, with no dose-limiting toxicities and manageable treatment-related side effects.

The treatment showed promising overall survival rates, with 73.9% of patients alive at one year and 58.1% at two years, suggesting that HIPEC could be a viable option for patients with stage IV gastric cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Trial of Hyperthermic Intraperitoneal Chemoperfusion (HIPEC) with Cisplatin, Mitomycin, and Paclitaxel in Patients with Gastric Adenocarcinoma and Associated Carcinomatosis or Positive Cytology. Blum Murphy, M., Ikoma, N., Wang, X., et al.[2023]

In a phase II study of 43 patients with locally advanced non-small-cell lung cancer (NSCLC), carboplatin and paclitaxel treatment resulted in a 45% overall response rate, with 38% achieving partial responses and 7% complete responses, indicating its efficacy as an induction therapy.

The treatment was well-tolerated, with only 9% experiencing severe hematologic toxicity and a median survival of 15 months, suggesting that carboplatin/paclitaxel could be a viable alternative to cisplatin-based regimens in neoadjuvant settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Induction chemotherapy with carboplatin/paclitaxel followed by surgery or standard radiotherapy and concurrent daily low-dose cisplatin for locally advanced non-small cell lung cancer (NSCLC). De Candis, D., Stani, SC., Bidoli, P., et al.[2015]

In a phase II study involving 23 previously untreated patients with stages IIIA or IIIB non-small cell lung cancer, the combination of paclitaxel, carboplatin, and concurrent radiation achieved a high overall response rate of 82%.

The treatment was associated with manageable toxicity, primarily esophagitis, affecting 45% of patients, but most recovered quickly, indicating that this regimen is a promising option for locally advanced lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel plus carboplatin and concurrent radiation therapy for patients with locally advanced non-small cell lung cancer. Choy, H., Akerley, W., Safran, H., et al.[2015]

References

1. England pubmed.ncbi.nlm.nih.gov

NEOSCOPE: a randomised Phase II study of induction chemotherapy followed by either oxaliplatin/capecitabine or paclitaxel/carboplatin based chemoradiation as pre-operative regimen for resectable oesophageal adenocarcinoma. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Concurrent chemoradiation using paclitaxel and carboplatin in locally advanced non-small cell lung cancer. [2015]

3. United States pubmed.ncbi.nlm.nih.gov

Concurrent paclitaxel, carboplatin, and radiation therapy for locally advanced non-small cell lung cancer. [2015]

4. United States pubmed.ncbi.nlm.nih.gov

European perspectives on paclitaxel/platinum-based therapy for advanced non-small cell lung cancer. [2019]

5. Ireland pubmed.ncbi.nlm.nih.gov

Paclitaxel (Taxol) and carboplatin followed by concomitant paclitaxel, cisplatin and radiotherapy for inoperable stage III NSCLC. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

Side-effects of hyperthermic intraperitoneal chemotherapy in patients with gastrointestinal cancers. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Results of a multicenter phase I dose-finding trial of hyperthermic intraperitoneal cisplatin after neoadjuvant chemotherapy and complete cytoreductive surgery and followed by maintenance bevacizumab in initially unresectable ovarian cancer. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Treatment of PERItoneal disease in Stomach Cancer with cytOreductive surgery and hyperthermic intraPEritoneal chemotherapy: PERISCOPE I initial results. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of concomitant cisplatin and paclitaxel administered by hyperthermic intraperitoneal chemotherapy to patients with peritoneal carcinomatosis from epithelial ovarian cancer. [2018]

10. United States pubmed.ncbi.nlm.nih.gov

Phase I Trial of Hyperthermic Intraperitoneal Chemoperfusion (HIPEC) with Cisplatin, Mitomycin, and Paclitaxel in Patients with Gastric Adenocarcinoma and Associated Carcinomatosis or Positive Cytology. [2023]

11. United States pubmed.ncbi.nlm.nih.gov

Induction chemotherapy with carboplatin/paclitaxel followed by surgery or standard radiotherapy and concurrent daily low-dose cisplatin for locally advanced non-small cell lung cancer (NSCLC). [2015]

12. United States pubmed.ncbi.nlm.nih.gov

Paclitaxel plus carboplatin and concurrent radiation therapy for patients with locally advanced non-small cell lung cancer. [2015]