Perioperative Paclitaxel for Stomach Cancer

Overseen By Iqra Rehman, RN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must be taking: Cytotoxic chemotherapy

Disqualifiers: Solid organ metastases, Infections, Pregnancy, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

30 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that targeted therapy and immunotherapy may be continued, so it's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Paclitaxel for stomach cancer?

Research shows that Paclitaxel, when given directly into the abdomen (intraperitoneal), can be effective in treating advanced stomach cancer, especially when cancer has spread to the lining of the abdomen. It has been used successfully in combination with other drugs to manage cancer after surgery. ^{1 2 3 4 5}

Is paclitaxel generally safe for humans?

Paclitaxel has been studied in many patients and is generally safe, but it can cause side effects like low white blood cell counts (neutropenia), allergic reactions, nerve damage, joint and muscle pain, mouth sores, nausea, and hair loss. These side effects vary in severity and can be managed with premedication and careful monitoring. ^{6 7 8 9 10}

How is the drug Paclitaxel unique in treating stomach cancer?

Paclitaxel is unique for stomach cancer treatment because it can be administered directly into the abdominal cavity (intraperitoneal), allowing it to target cancer cells in the peritoneal area more effectively than standard intravenous methods. This approach helps maintain high drug concentrations at the site of cancer, potentially improving outcomes for patients with peritoneal metastasis. ^{1 3 5 11 12}

What is the purpose of this trial?

To learn about the effects of paclitaxel and gastrectomy (surgery to remove all or part of the stomach) on improving outcomes in patients with gastric cancer.

Research Team

Brian Badgwell, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for adults with gastric adenocarcinoma and either positive peritoneal cytology or carcinomatosis. Participants must have completed preoperative chemotherapy, have adequate organ function, and not be pregnant or breastfeeding. They should also agree to use effective contraception. Excluded are those with severe heart conditions, life-threatening reactions to certain chemotherapies, infections that could interfere with the study, other distant metastases outside the peritoneum, or previous surgeries preventing safe treatment.

Inclusion Criteria

I can communicate in English or another language.

My cancer is confirmed to be adenocarcinoma in the stomach or where the stomach meets the esophagus.

I can take care of myself but may not be able to do active work.

Exclusion Criteria

I've had surgery that makes it unsafe to remove my tumor or place a port in my belly.

I do not have infections like pneumonia that would stop me from following the treatment plan.

I am a man who can father children and agree to use birth control.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive paclitaxel every 2 weeks for 6 weeks, followed by a potential gastrectomy, and may receive additional paclitaxel every 2 weeks for another 6 weeks

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Paclitaxel

Trial Overview The trial studies the effects of paclitaxel (a chemotherapy drug) combined with gastrectomy (surgical removal of all or part of the stomach) on patients with gastric cancer. It aims to understand how this combination can improve patient outcomes.

Participant Groups

Group I: Paclitaxel Experimental Treatment 4 Interventions

Participant will receive paclitaxel every 2 weeks for 6 weeks, and then participants may have a gastrectomy based on what the doctor thinks is in your best interest. You may then receive additional paclitaxel every 2 weeks for 6 weeks.

Paclitaxel is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Taxol for:

• Ovarian cancer
• Breast cancer
• Non-small cell lung cancer
• Kaposi's sarcoma

Approved in European Union as Taxol for:

• Ovarian cancer
• Breast cancer
• Non-small cell lung cancer
• Kaposi's sarcoma

Approved in Canada as Paclitaxel for:

• Ovarian cancer
• Breast cancer
• Non-small cell lung cancer
• Kaposi's sarcoma

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Findings from Research

In a phase II trial involving 37 patients with serosa-positive gastric cancer, the perioperative chemotherapy regimen, which included intraperitoneal paclitaxel followed by intravenous paclitaxel and S-1, achieved a treatment completion rate of 67.6%, significantly exceeding the predefined threshold of 50%.

The chemotherapy regimen demonstrated a high response rate of 71.4% in patients with target lesions, and the overall survival rates at 3 and 5 years were promising at 78.0% and 74.9%, respectively, indicating both efficacy and safety of the treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II trial of perioperative chemotherapy involving a single intraperitoneal administration of paclitaxel followed by sequential S-1 plus intravenous paclitaxel for serosa-positive gastric cancer. Peng, YF., Imano, M., Itoh, T., et al.[2015]

In a study of 17 patients with advanced gastric cancer who received intraperitoneal paclitaxel (PTX) after surgery, the five-year overall survival rate was 88.2%, indicating a strong potential for this treatment in high-risk patients.

The low recurrence rates (11.7% in the liver and 5.9% in the peritoneum) suggest that intraperitoneal PTX, combined with oral S-1, is an effective adjuvant therapy for preventing peritoneal recurrence in patients with serosal exposure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraperitoneal Paclitaxel is useful as adjuvant chemotherapy for advanced gastric cancer with serosal exposure. Kitayama, J., Ishigami, H., Yamaguchi, H., et al.[2022]

A phase II randomized trial involving 86 patients with advanced gastric cancer found that intraperitoneal (IP) administration of paclitaxel did not significantly improve 2-year survival rates compared to intravenous (IV) administration, with rates of 64.1% for IP and 72.3% for IV (p=0.5731).

The study indicated that IP paclitaxel was particularly ineffective in patients with residual disease, suggesting that this method may not be a superior option for treating peritoneal metastasis after surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized phase II multicenter trial to explore efficacy of weekly intraperitoneal in comparison with intravenous paclitaxel administered immediately after gastrectomy to the patients with high risk of peritoneal recurrence: final results of the INPACT trial. Takahashi, N., Kanda, M., Yoshikawa, T., et al.[2022]

In a phase 2 trial involving 90 participants with untreated advanced gastric cancer, both intravenous and intraperitoneal paclitaxel combined with mFOLFOX6 significantly improved progression-free survival compared to mFOLFOX6 alone, with median survival times of 6.52 and 5.83 months versus 4.55 months, respectively.

The addition of paclitaxel resulted in manageable adverse events, with neutropenia being the most common severe side effect, but no treatment-related deaths were reported, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2 randomized controlled trial of intravenous or intraperitoneal paclitaxel plus mFOLFOX6 vs. mFOLFOX6 as first-line treatment of advanced gastric cancer. Zhao, S., Su, L., Chen, Y., et al.[2022]

A 68-year-old man with advanced gastric cancer and peritoneal dissemination was successfully treated with a combination of paclitaxel (PTX) and ramucirumab (RAM) after other treatments failed, demonstrating the efficacy of this regimen as a second-line chemotherapy.

Despite experiencing some adverse effects like proteinuria, lower limb edema, and neutropenia, the patient was able to continue treatment and survived without disease progression for 18 months, highlighting the potential safety and effectiveness of PTX plus RAM in advanced gastric cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A Case of Advanced Gastric Cancer with Peritoneal Dissemination after Gastrectomy Successfully Treated with Paclitaxel plus Ramucirumab]. Miyamoto, K., Tadano, Y., Itoh, R.[2023]

Taxol, when administered intravenously, has a well-established safety profile based on data from 655 patients, with myelosuppression, particularly neutropenia, identified as the main dose-limiting toxicity, which was less severe with a 3-hour infusion schedule.

Severe hypersensitivity reactions were effectively managed with a premedication regimen, and while mild to moderate peripheral neuropathy was observed, it rarely led to treatment discontinuation, indicating a generally manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overview of Taxol safety. Onetto, N., Canetta, R., Winograd, B., et al.[2015]

In a preliminary study involving 15 gastric cancer patients with peritoneal metastasis, a single intraperitoneal dose of paclitaxel combined with intravenous paclitaxel and S-1 was found to be well-tolerated, with mild toxic effects reported.

The treatment showed promising efficacy, with a one-year overall survival rate of 66.7%, indicating that this combination therapy could be a feasible option for managing advanced gastric cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A preliminary study of single intraperitoneal administration of paclitaxel followed by sequential systemic chemotherapy with S-1 plus paclitaxel for advanced gastric cancer with peritoneal metastasis. Imano, M., Peng, YF., Itoh, T., et al.[2015]

In a study of 6 patients with gastric cancer, intraperitoneal administration of paclitaxel (TXL) showed that a dosage of 80-90 mg/m2 resulted in significant toxicity, including grade 4 leukopenia in one patient.

Lower dosages of TXL (60 mg/m2) administered intraperitoneally resulted in only mild toxicities, suggesting that lower doses may be safer and warrant further investigation in a larger phase I/II study for patients with malignant peritoneal effusion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Safety of intraperitoneal chemotherapy with paclitaxel in gastric cancer patients with peritoneal dissemination]. Fujitani, K., Hirao, M., Tsujinaka, T.[2015]

Paclitaxel (TAXOL) therapy presents unique challenges and side effects that require careful management by healthcare professionals, particularly nurses, to ensure patient safety and treatment success.

The review emphasizes the importance of a collaborative nursing plan that identifies specific toxicities associated with paclitaxel and outlines interventions to mitigate these side effects during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nursing considerations in paclitaxel (Taxol) administration. Lubejko, BG., Sartorius, SE.[2015]

Paclitaxel is an effective treatment for treatment-refractory ovarian cancer, working by stabilizing microtubules to induce cytotoxicity, despite facing challenges like severe hypersensitivity reactions and formulation issues.

The drug is associated with significant side effects, including myelosuppression, mucositis, and neurotoxicity, which are dose-dependent, highlighting the need for careful management in clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel (taxol). Kohler, DR., Goldspiel, BR.[2019]

A study involving 100 patients with advanced gastric cancer showed that a combination of S-1 and both intravenous and intraperitoneal paclitaxel chemotherapy resulted in a median survival time of 23.6 months and an 80% one-year survival rate.

The treatment was well tolerated, suggesting that combining systemic chemotherapy with repeated intraperitoneal administration of paclitaxel could be an effective strategy for managing peritoneal metastasis in gastric cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

S-1 plus intravenous and intraperitoneal Paclitaxel for gastric cancer with peritoneal metastasis. Kitayama, J., Ishigami, H., Yamaguchi, H., et al.[2022]

Intraperitoneal (IP) chemotherapy using taxanes like paclitaxel and docetaxel shows promising results for treating peritoneal carcinomatosis (PC) of gastric cancer, with high drug concentrations maintained for 48-72 hours directly targeting metastatic nodules.

Phase II studies indicate that patients receiving IP chemotherapy have a median survival time of 14.4-24.6 months and a 1-year overall survival rate of 67%-78%, but further randomized controlled trials are necessary to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Breakthrough therapy for peritoneal carcinomatosis of gastric cancer: Intraperitoneal chemotherapy with taxanes. Yamaguchi, H., Kitayama, J., Ishigami, H., et al.[2020]

References

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

A phase II trial of perioperative chemotherapy involving a single intraperitoneal administration of paclitaxel followed by sequential S-1 plus intravenous paclitaxel for serosa-positive gastric cancer. [2015]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Intraperitoneal Paclitaxel is useful as adjuvant chemotherapy for advanced gastric cancer with serosal exposure. [2022]

3. Japan pubmed.ncbi.nlm.nih.gov

A randomized phase II multicenter trial to explore efficacy of weekly intraperitoneal in comparison with intravenous paclitaxel administered immediately after gastrectomy to the patients with high risk of peritoneal recurrence: final results of the INPACT trial. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Phase 2 randomized controlled trial of intravenous or intraperitoneal paclitaxel plus mFOLFOX6 vs. mFOLFOX6 as first-line treatment of advanced gastric cancer. [2022]

5. Japan pubmed.ncbi.nlm.nih.gov

[A Case of Advanced Gastric Cancer with Peritoneal Dissemination after Gastrectomy Successfully Treated with Paclitaxel plus Ramucirumab]. [2023]

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

Overview of Taxol safety. [2015]

7. Greece pubmed.ncbi.nlm.nih.gov

A preliminary study of single intraperitoneal administration of paclitaxel followed by sequential systemic chemotherapy with S-1 plus paclitaxel for advanced gastric cancer with peritoneal metastasis. [2015]

8. Japan pubmed.ncbi.nlm.nih.gov

[Safety of intraperitoneal chemotherapy with paclitaxel in gastric cancer patients with peritoneal dissemination]. [2015]

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

Nursing considerations in paclitaxel (Taxol) administration. [2015]

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

Paclitaxel (taxol). [2019]

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

S-1 plus intravenous and intraperitoneal Paclitaxel for gastric cancer with peritoneal metastasis. [2022]

12. China pubmed.ncbi.nlm.nih.gov

Breakthrough therapy for peritoneal carcinomatosis of gastric cancer: Intraperitoneal chemotherapy with taxanes. [2020]