Intraperitoneal Paclitaxel for Appendiceal Cancer

Overseen By Beth Helmink, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Investigational agents

Disqualifiers: Active infection, Heart failure, others

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

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

Compensation: Varies

Number of Visits: Unknown

39 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the safest dose of paclitaxel, a chemotherapy drug, administered directly into the abdomen to treat metastatic appendiceal adenocarcinoma. This cancer originates in the appendix and spreads within the abdomen. Participants will assist researchers in identifying the highest dose that avoids severe side effects. The trial suits individuals diagnosed with this specific type of cancer that cannot be surgically removed and is confined to the abdominal area. As a Phase 1 trial, the research focuses on understanding the treatment's effects in people, providing participants the opportunity to contribute to groundbreaking research.

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. However, if you are on any investigational agents, you cannot participate in the trial.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that delivering paclitaxel directly into the abdominal area, known as intraperitoneal (IP) paclitaxel, is generally safe and effective. One study found that this method caused fewer side effects than administering the drug intravenously (IV), resulting in less discomfort and fewer negative reactions for patients.

Another study examined the safety and tolerability of IP paclitaxel, finding that patients managed the treatment well, with safety as a key focus. While specific side effects weren't detailed, the results suggest the treatment was manageable for participants.

Paclitaxel is also used in other cancer treatments, supporting its safety profile. However, since this trial is in its early stages, the main goal is to determine the best dose that avoids severe side effects. Safety remains a primary concern.

Overall, early findings suggest that IP paclitaxel is safe and well-tolerated, but this trial will provide more detailed safety information. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for appendiceal cancer, which often involve surgery and systemic chemotherapy, intraperitoneal paclitaxel offers a unique approach by delivering the drug directly into the abdominal cavity. This method allows higher concentrations of paclitaxel to directly target cancer cells in the abdomen with potentially fewer systemic side effects. Researchers are excited about this treatment because it could enhance the effectiveness of chemotherapy by maximizing drug exposure to tumors while minimizing harm to the rest of the body.

What evidence suggests that paclitaxel might be an effective treatment for appendiceal cancer?

Research has shown that delivering paclitaxel directly into the abdomen can help treat metastatic appendiceal adenocarcinoma, a type of cancer. In studies, patients who received chemotherapy with paclitaxel lived for a median of 8.8 months. In animal studies, mice treated with paclitaxel in the abdomen exhibited much smaller tumor growth compared to those given a placebo. These results suggest that paclitaxel, when administered this way, may help control tumor growth in this cancer. This trial will evaluate intraperitoneal paclitaxel as a promising treatment option for patients with this condition. ^{1 2 3 6 7}

Who Is on the Research Team?

Beth Helmink, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for individuals with metastatic appendiceal adenocarcinoma, which is a type of cancer that affects the appendix and has spread to other areas. The study aims to find participants who can receive paclitaxel directly into their abdominal cavity.

Inclusion Criteria

I can take care of myself but might not be able to do heavy physical work.

I had hepatitis C but am cured, or I'm being treated with no detectable virus.

I have another cancer type, but it won't affect this trial's treatment.

Exclusion Criteria

I have severe heart issues, including unstable chest pain or significant heart failure.

I've had surgery that makes it unsafe to have a diagnostic laparoscopy.

I do not have an active infection like pneumonia.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase I Treatment

Participants receive intraperitoneal paclitaxel to determine the maximum tolerated dose, administered every 14 days

Varies based on dose escalation

Bi-weekly visits for dose administration

Phase II Treatment

Participants receive paclitaxel at the recommended dose determined in Phase I

Until disease progression or unacceptable toxicity

Regular visits for treatment and monitoring

Follow-up

Participants are monitored for safety, effectiveness, and progression-free survival after treatment

Through study completion; an average of 1 year

What Are the Treatments Tested in This Trial?

Interventions

• Paclitaxel

Trial Overview The study is testing the administration of paclitaxel directly into the abdomen along with pre-medications like Diphenhydramine, Dexamethasone, and Famotidine. It's in phases I/II to determine the safest dose for patients.

How Is the Trial Designed?

Group I: Phase I/Phase II Experimental Treatment 4 Interventions

Participants will be assigned to a study phase (Phase I or Phase II) based on when participants join this study. Up to 4 groups of at least 3 participants will be enrolled in Phase I of the study, and up to 15 participants will be enrolled in Phase II. If you are enrolled in Phase I, the dose of paclitaxel you receive will depend on when the participants join this study. The first group of participants will receive the lowest dose level of paclitaxel. Each new group will receive a higher dose of paclitaxel than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of paclitaxel given intraperitoneally is found. Participants who are enrolled in Phase II, participants will receive paclitaxel at the recommended dose that was found in Phase I.

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+

Published Research Related to This Trial

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]

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 being tested in a Phase III trial for its effectiveness in treating ovarian cancer when administered directly into the abdominal cavity, showing promise as an intraperitoneal therapy.

Docetaxel, while needing further Phase II studies, has shown strong activity when given systemically, suggesting that intraperitoneal delivery could enhance its effectiveness against cancers that affect the peritoneal surface.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraperitoneal taxanes. Mohamed, F., Sugarbaker, PH.[2019]

Intraperitoneal (IP) administration of paclitaxel significantly reduced tumor growth in three patient-derived xenograft (PDX) models of appendiceal adenocarcinomas (AAs), with reductions of 81.9%, 98.3%, and 71.4% compared to control groups.

In contrast, intravenous (IV) administration of paclitaxel did not significantly reduce tumor growth in the same model, suggesting that IP delivery may be a more effective treatment strategy for AAs, which currently lack approved chemotherapeutic options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor activity of intraperitoneal paclitaxel in orthotopic patient-derived xenograft models of mucinous appendiceal adenocarcinoma. Ito, I., Yousef, AM., Dickson, PN., et al.[2023]

Intraperitoneal administration of paclitaxel shows prolonged retention in the peritoneal cavity and has demonstrated effectiveness in treating peritoneal metastases in ovarian cancer, malignant peritoneal mesothelioma, gastric cancer, and pancreatic cancer, based on existing literature.

While randomized controlled studies have shown positive results for ovarian cancer, the efficacy of intraperitoneal paclitaxel in preventing peritoneal metastases in other cancers remains inconclusive, indicating a need for further research and established treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraperitoneal paclitaxel: pharmacology, clinical results and future prospects. Sugarbaker, PH.[2021]

Intraperitoneal administration of paclitaxel significantly reduced tumor growth in three patient-derived xenograft models of appendiceal adenocarcinoma, suggesting it could be an effective treatment strategy for this rare cancer.

Compared to intravenous delivery, intraperitoneal paclitaxel showed greater efficacy and fewer systemic side effects, supporting its potential for clinical trials in patients with appendiceal adenocarcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraperitoneal Paclitaxel Is a Safe and Effective Therapeutic Strategy for Treating Mucinous Appendiceal Adenocarcinoma. Ito, I., Yousef, AMG., Chowdhury, S., et al.[2023]

Researchers developed three new cell lines resistant to intraperitoneal (i.p.) chemotherapy with paclitaxel from gastric cancer cells, which can help study the mechanisms behind this resistance.

They identified four up-regulated genes (KIF23, ERBB2IP, ATAD2, and PHF19) as potential predictive markers for paclitaxel resistance, which could aid in tailoring treatments for patients with peritoneal metastasis of gastric cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Establishment of new intraperitoneal paclitaxel-resistant gastric cancer cell lines and comprehensive gene expression analysis. Murakami, H., Ito, S., Tanaka, H., et al.[2022]

Intraperitoneal delivery of paclitaxel has been shown to be safe and provides a significant pharmacokinetic advantage for targeting ovarian cancer compared to systemic administration.

Further phase II and III trials are necessary to determine if this enhanced delivery method leads to better treatment outcomes for women with advanced ovarian cancer that has small-volume residual disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraperitoneal paclitaxel: a possible role in the management of ovarian cancer? Markman, M., Francis, P., Rowinsky, E., et al.[2015]

In a study of 107 patients with non-small cell lung cancer, the incidence of hypersensitivity reactions (HSRs) to paclitaxel was significantly higher in those using a short premedication regimen (45.2%) compared to a conventional regimen (32.3%), with severe reactions more common in the short regimen.

A modified premedication protocol showed promise in preventing HSRs, with no severe reactions reported among patients, although further case accumulation is necessary to confirm its effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preliminary experience with a modified premedication protocol that included intravenous diphenhydramine and calcium bromide for the prophylaxis of paclitaxel-related hypersensitivity reactions. Sasada, S., Hirashima, T., Nakamura, Y., et al.[2018]

The phase I trial of intraperitoneally administered paclitaxel (ip PTX) combined with systemic chemotherapy for colorectal cancer showed promising safety and efficacy, with a median survival time of 29.3 months, which is longer than previous studies.

In the interim analysis of the iPac-02 trial, ip PTX demonstrated a 25% response rate and a 50% improvement in the peritoneal cancer index, with no dose-limiting toxicities observed, indicating that this treatment approach is both safe and potentially effective for patients with unresectable peritoneal carcinomatosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraperitoneal paclitaxel combined with FOLFOX/CAPOX plus bevacizumab for colorectal cancer with peritoneal carcinomatosis (the iPac-02 trial): study protocol of a single arm, multicenter, phase 2 study. Murono, K., Yokoyama, Y., Nozawa, H., et al.[2023]

In a phase I study involving six colorectal cancer patients with peritoneal carcinomatosis, the combination of intraperitoneal paclitaxel (ip PTX) with either mFOLFOX6-bevacizumab or CapeOX-bevacizumab was found to be safe, with no dose-limiting toxicities observed.

While grade 3 adverse events like leukopenia and neutropenia occurred in some patients, there were no severe grade 4 adverse events or complications related to the peritoneal access port, suggesting that this treatment approach is manageable and does not significantly increase risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of intraperitoneal paclitaxel combined with conventional chemotherapy for colorectal cancer with peritoneal carcinomatosis: a phase I trial. Murono, K., Nagata, H., Ishimaru, K., et al.[2019]

Paclitaxel is a first-line chemotherapy for epithelial ovarian cancers, but it can cause serious hypersensitive reactions, leading some doctors to stop treatment.

The study suggests that after managing hypersensitivity with steroids and antihistamines, patients can safely resume paclitaxel therapy at a slower infusion rate without experiencing further reactions, indicating that reinduction therapy can be effective.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Reinduction of paclitaxel therapy after a successfully treated hypersensitivity reaction]. Lehoczky, O., Bagaméri, A., Pulay, T.[2015]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10592351/

Intraperitoneal paclitaxel is a safe and effective therapeutic ... Tumors grew in the peritoneum of control mice injected with IP saline, this growth was greatly impaired in mice treated with IP paclitaxel (Fig. 2B & C). Tumor ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10712908/

Taxane-Based Chemotherapy Is Effective in Metastatic ... In a cohort of 13 patients with metastatic appendiceal adenocarcinoma, treated with taxane chemotherapy the median overall survival was 8.8 months. Of 10 ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.TPS4215

A phase I/II study of intraperitoneal (IP) paclitaxel (PTX) in ... With 15 patients Based on historical data, we estimate that the proportion of patients who will demonstrate an objective response without going ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06207305

NCT06207305 | A Phase I/II Study of Intraperitoneal ... A Phase I/​II Study of Intraperitoneal Paclitaxel in Patients With Metastatic Appendiceal Adenocarcinoma · Study Overview · Contacts and Locations · Participation ...

5. medrxiv.org medrxiv.org/content/10.1101/2023.07.11.23292522v1.full.pdf

Taxane-based Chemotherapy is Effective in Metastatic ... The results of this study showing activity of taxane-based chemotherapy in appendiceal adenocarcinoma support further clinical investigation of.

6. academic.oup.com academic.oup.com/oncolo/article/28/12/e1303/7279402

Taxane-Based Chemotherapy Is Effective in Metastatic ... In a cohort of 13 patients with metastatic appendiceal adenocarcinoma, treated with taxane chemotherapy the median overall survival was 8.8 months.

7. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-00080

Intraperitoneal Paclitaxel for the Treatment of Patients with ... Giving paclitaxel intraperitoneally may be safe, tolerable and/or effective in treating patients with metastatic appendiceal adenocarcinoma.