HIPEC + Chemoradiation for Stomach Cancer

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for stomach cancer that has spread locally but not to distant parts of the body. Researchers aim to determine if heated chemotherapy during surgery (HIPEC), combined with radiation and other cancer-fighting drugs, can improve survival and reduce cancer progression. It targets individuals diagnosed with locally advanced stomach cancer who plan to undergo surgery. Participants should not have received previous cancer treatments or have known spread of cancer to distant sites. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

A previous study found that HIPEC, a treatment using heated chemotherapy in the abdomen, was safe for patients with stomach cancer. Research showed it was feasible and had a lower risk of post-surgery complications.

Regarding radiation therapy, research indicates that intensity-modulated radiation therapy (IMRT) is linked to fewer severe side effects. Most side effects, such as nausea or fatigue, typically resolve a few weeks after treatment ends.

Studies have shown that the combination of carboplatin and paclitaxel is generally well-tolerated. However, common side effects can include hair loss, nausea, and a decrease in blood cells, which may increase the risk of infection.

Overall, these treatments have been tested in various settings and are generally considered safe with manageable side effects. Participants should discuss any concerns with their healthcare provider to understand the potential risks and benefits. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the HIPEC + Chemoradiation treatment for stomach cancer because it combines several advanced therapies to potentially improve outcomes. Unlike traditional treatments that often rely solely on chemotherapy or radiation, this approach uses hyperthermic intraperitoneal chemotherapy (HIPEC) to deliver heated chemotherapy directly to the abdomen, targeting cancer cells more effectively. Additionally, the use of 3D conformal or intensity-modulated radiotherapy allows for precise targeting of tumors while sparing healthy tissue. This combination aims to enhance treatment efficacy and minimize side effects, offering new hope for patients with locally advanced gastric cancer.

What evidence suggests that this trial's treatments could be effective for stomach cancer?

Research has shown that Hyperthermic Intraperitoneal Chemotherapy (HIPEC), which participants in this trial will receive, may help treat stomach cancer. Studies have found that HIPEC can reduce the risk of cancer recurrence and extend patient survival. In this trial, participants will also receive 3D conformal and intensity-modulated radiotherapy (IMRT), which effectively targets stomach cancer cells while sparing healthy tissue. Evidence indicates that IMRT is well-tolerated and performs as well as other radiotherapy types. Additionally, the combination of carboplatin and paclitaxel, administered to participants, has demonstrated good results and is considered effective for stomach cancer. These treatments aim to extend patient survival and improve disease management. ^{6 7 8 9 10}

Who Is on the Research Team?

Spiros Hiotis, MD, PhD

Principal Investigator

Icahn School of Medicine at Mount Sinai

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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]

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]

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]

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]

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]

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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4438524/

Double-arc volumetric modulated therapy improves dose ... The MU for IMRT and RA were 694.25 ± 3.91 and 399.00 ± 6.81, respectively. Thus, RA significantly reduced the radiation dose received by 42.5 % compared with ...

2. journals.plos.org journals.plos.org/plosone/article?id=10.1371/journal.pone.0082642

Clinical Outcomes for Gastric Cancer following Adjuvant ... This study demonstrates that adjuvant chemoradiation for gastric cancer with IMRT to 50.4 Gy was well-tolerated and compared similarly in toxicity with 3DCRT ...

3. bcbsri.com bcbsri.com/providers/sites/providers/files/policies/2024/07/2023%20DRAFT%20UPDATE%20Intensity-Modulated%20Radiotherapy.Effective.10.1.24.pdf

Intensity-modulated radiotherapy (IMRT) has been proposed as ... Intensity-modulated radiotherapy may be considered medically necessary when dosimetric planning with standard 3-dimensional conformal radiotherapy (3D-CRT) ...

4. cambridge.org cambridge.org/core/journals/journal-of-radiotherapy-in-practice/article/comparing-treatment-plans-for-stomach-cancer-threedimensional-conformal-radiotherapy-3dcrt-physical-wedgebased-conformal-rt-wbcrt-and-intensitymodulated-radiotherapy-imrt/661BDB47283936ED5185E6371E4375F7

Comparing treatment plans for stomach cancer The aim of this study was to find the optimal radiotherapy (RT) method using three-dimensional (3D) conformal RT (CRT), physical wedge-based CRT (WB-CRT) and ...

5. southcarolinablues.com southcarolinablues.com/web/public/brands/medicalpolicy/external-policies/intensity-modulated-radiotherapy-abdomen-pelvis-and-chest

Intensity-Modulated Radiotherapy: Abdomen, Pelvis and Chest Relevant outcomes are overall survival (OS), disease-specific survival, recurrence, quality of life, and treatment-related morbidity. IMRT has been compared ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6532249/

Efficacy and safety of intensity-modulated radiation therapy ... Adjuvant therapy, such as radiotherapy, significantly increased the survival of patients with gastric cancer and reduced the risk of recurrence ...

7. cancer.org cancer.org/cancer/types/stomach-cancer/treating/radiation-therapy.html

Stomach Cancer Radiation & Possible Side Effects Side effects from radiation therapy for stomach cancer can include: These usually go away within a few weeks after the treatment is finished.

8. acsjournals.onlinelibrary.wiley.com acsjournals.onlinelibrary.wiley.com/doi/full/10.1002/cncr.25246

Comparison of intensity‐modulated radiotherapy and 3 ... The outcomes for gastric cancer continue to be poor, and the toxicity from treatment with chemotherapy and 3D CRT is high. There is a need to ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S0360301621028467

Radiation Therapy Techniques and Treatment-Related ... IMRT resulted in fewer grade ≥3 AEs during treatment and significantly lower rates of grade ≥2 diarrhea and hematologic AEs during follow-up.

10. bcbsm.com bcbsm.com/amslibs/content/dam/public/mpr/mprsearch/pdf/2047279.pdf

INTENSITY-MODULATED RADIATION THERAPY (IMRT) Boda-Heggemann et al (2009) evaluated the efficacy and safety of 2 different adjuvant chemoradiotherapy regimens using 3D-CRT or IMRT in 2 consecutive cohorts ...