Paclitaxel TPM for Cancer

Overseen By Carlos H.F. Chan, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Carlos Chan

Must not be taking: ART agents

Disqualifiers: Mucinous ascites, Extra-peritoneal metastases, others

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

Compensation: Varies

Number of Visits: 2

30 Participants Needed

Trial Summary

What is the purpose of this trial?

A first-in-human, unblinded, phase I trial of Paclitaxel-loaded tumor penetrating microparticles (TPM) in peritoneal carcinomatosis patients who are not eligible for standard-of-care therapeutic interventions.

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

The trial protocol does not specify if you need to stop taking your current medications. However, if you are using other investigational agents or have received chemotherapy or radiotherapy within 3 weeks prior to enrollment, you may not be eligible.

What data supports the effectiveness of the drug Paclitaxel TPM for cancer treatment?

Research shows that Paclitaxel-loaded tumor-penetrating microparticles (TPM) are more effective and less toxic than traditional formulations, providing greater tumor targeting and longer survival in preclinical models of ovarian and other cancers. TPM also requires less frequent dosing, making it a promising option for intraperitoneal chemotherapy. ^{1 2 3 4 5}

Is Paclitaxel TPM generally safe for humans?

Paclitaxel, including its form as submicron particle paclitaxel (SPP), has been studied for safety in various clinical trials. It has shown negligible toxicity when administered locally to tumors, and common side effects like hypersensitivity reactions and neutropenia (low white blood cell count) have been managed with premedication. Intraperitoneal administration has been well tolerated, with abdominal pain being the dose-limiting side effect at higher doses. ^{4 6 7 8 9}

How is the drug Paclitaxel TPM unique compared to other cancer treatments?

Paclitaxel TPM uses tumor-penetrating microparticles to deliver the drug directly to tumors, allowing for higher concentrations of the drug at the tumor site with reduced systemic toxicity. This method enhances the drug's effectiveness and minimizes side effects compared to traditional formulations. ^{4 10 11 12 13}

Research Team

Carlos Chan, MD, PhD

Principal Investigator

University of Iowa

Eligibility Criteria

This trial is for adults aged 18-75 with peritoneal carcinomatosis from specific cancers, who can't have standard treatments. They must understand the study and agree to participate, have measurable disease, be medically fit for surgery, and use effective contraception. Exclusions include inaccessible abdominal cavity due to prior surgery, uncontrolled illnesses, pregnancy or breastfeeding women, certain infections like HIV/Hepatitis B/C on treatment.

Inclusion Criteria

You are currently using birth control pills, implants, injections, or have an intrauterine device (IUD) for contraception.

AST (SGOT) < 3 x institutional upper limit of normal

I am fit for surgery and can handle general anesthesia.

Exclusion Criteria

I am allergic to paclitaxel, PLG, mannitol, or polysorbate 80.

I am currently receiving treatment for another cancer.

Pregnancy, nursing, or plans to become pregnant for the duration of study participation including 10 months beyond the last dose of TPM

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Laparoscopy and Initial Treatment

Participants undergo laparoscopy for pressure measurement, tumor biopsy, and catheter placement, followed by initial intraperitoneal TPM treatment during hospital stay

1 week

1 visit (in-person)

Dose Escalation and Second Treatment

Participants receive a second dose of TPM in clinic if no disease progression or significant adverse events are observed

6-8 weeks

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including pharmacokinetics and immune response assessments

12 weeks

Treatment Details

Interventions

• Paclitaxel-loaded tumor penetrating microparticles

Trial Overview The trial tests a new therapy using Paclitaxel-loaded microparticles designed to penetrate tumors in patients with peritoneal carcinomatosis. It's an early-phase study (phase I) focusing on people who don't qualify for existing treatment options.

Participant Groups

Group I: Intraperitoneal paclitaxel-loaded tumor penetrating microparticles (TPM) Experimental Treatment 1 Intervention

Paclitaxel-loaded tumor penetrating microparticles (TPM), dose escalation starting at 50 mg/m\^2 instilled in the peritoneal cavity at study start and again 6-8 weeks after the first TPM treatment.

Who Is Running the Clinical Trial?

Carlos Chan

Lead Sponsor

Trials

1

Recruited

30+

Institute of Quantitative Systems Pharmacology (IQSP)

Collaborator

Trials

1

Recruited

30+

Findings from Research

Tumor-penetrating microparticles (TPM) have been developed to improve the efficacy and reduce the toxicity of intraperitoneal chemotherapy, showing better results in preclinical studies against various types of metastatic tumors compared to traditional intravenous treatments.

TPM allows for less frequent dosing while providing sustained antitumor activity, making it a promising candidate for clinical development in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Versatility of Particulate Carriers: Development of Pharmacodynamically Optimized Drug-Loaded Microparticles for Treatment of Peritoneal Cancer. Au, JL., Lu, Z., Wientjes, MG.[2018]

Paclitaxel-loaded PLGA microparticles were developed for targeted delivery in tumor treatment, showing a biphasic release pattern with 28% of the drug released over one month, indicating effective sustained release.

The microparticles demonstrated a dose-dependent antitumor effect on human uterine cancer cells, with an IC(50) value comparable to that of the commercial drug Taxol, suggesting their potential as a powerful treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel-loaded microparticles for intratumoral administration via the TMT technique: preparation, characterization, and preliminary antitumoral evaluation. Hamoudeh, M., Diab, R., Fessi, H., et al.[2019]

Drug-loaded polymeric tumor-penetrating microparticles (TPM) significantly enhance the delivery of paclitaxel to various types of pancreatic tumors, achieving up to 55-fold higher drug levels in tumors compared to traditional methods.

TPM not only improves the efficacy of treatment, leading to longer survival and higher cure rates, but also demonstrates that a single dose of TPM is as effective as multiple doses of standard paclitaxel, making it a promising alternative for treating bulky tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activity of drug-loaded tumor-penetrating microparticles in peritoneal pancreatic tumors. Lu, Z., Tsai, M., Wang, J., et al.[2019]

Local administration of submicron particle paclitaxel (SPP) allows for sustained release of the drug directly into solid tumors, leading to effective tumor cell death through both apoptosis and necroptosis, which enhances treatment outcomes for various carcinomas.

This method of delivery not only minimizes systemic toxicity but also potentially improves the effectiveness of other therapies, such as chemotherapy and immunotherapy, making it a promising complementary treatment for metastatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Local administration of submicron particle paclitaxel to solid carcinomas induces direct cytotoxicity and immune-mediated tumoricidal effects without local or systemic toxicity: preclinical and clinical studies. Verco, S., Maulhardt, H., Baltezor, M., et al.[2022]

Paclitaxel-loaded microparticles (TPM) designed for intraperitoneal chemotherapy significantly improve drug targeting and penetration in ovarian tumors, achieving 16 times higher and more sustained drug concentrations compared to traditional formulations.

TPM not only enhance therapeutic efficacy, leading to longer survival and higher cure rates, but also reduce treatment-related toxicity and improve patient compliance with less frequent dosing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor-penetrating microparticles for intraperitoneal therapy of ovarian cancer. Lu, Z., Tsai, M., Lu, D., et al.[2021]

Paclitaxel (TAXOL) is an effective chemotherapy drug that works by disrupting microtubule function, showing significant activity against advanced ovarian, breast, and non-small cell lung cancers, among others.

With proper premedication, the incidence of hypersensitivity reactions to paclitaxel has been reduced to 3%, although neutropenia remains a major dose-limiting side effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Paclitaxel (Taxol)]. Hájek, R.[2015]

Intraperitoneal administration of paclitaxel in 14 patients with gastric cancer showed a significant pharmacokinetic advantage, with exposure in the peritoneal cavity being 550-2,000 times higher than in the bloodstream.

The treatment was generally well tolerated, with abdominal pain as the main dose-limiting toxicity at the highest dose of 180 mg/body, alongside some cases of neutropenia, finger numbness, and hair loss.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pharmacologic study of intraperitoneal paclitaxel in gastric cancer patients with peritoneal dissemination]. Fushida, S., Furui, N., Kinami, S., et al.[2015]

Paclitaxel, an antineoplastic agent, was found to have a unique mechanism of action by stabilizing microtubules, leading to its effectiveness against various cancers, including ovarian and breast cancer, after initial skepticism due to formulation issues.

Severe hypersensitivity reactions were managed with a premedication regimen, and while neutropenia was a dose-limiting toxicity, it was less severe with a 3-hour infusion schedule, highlighting the importance of administration methods in optimizing safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A preliminary risk-benefit assessment of paclitaxel. Bitton, RJ., Figg, WD., Reed, E.[2018]

The maximum tolerated dose (MTD) of intraperitoneally infused paclitaxel (PTX) for patients with advanced gastric cancer and peritoneal metastasis was determined to be 90 mg/m², while the recommended dose (RD) was set at 80 mg/m², with grade 3 leukocytopenia identified as the dose-limiting toxicity.

PTX concentrations in the ascites were found to be approximately 1000 times higher than in serum for 48 hours post-infusion, indicating effective localized delivery of the drug to the tumor site.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraperitoneal infusion of paclitaxel with S-1 for peritoneal metastasis of advanced gastric cancer: phase I study. Kurita, N., Shimada, M., Iwata, T., et al.[2019]

A new nanoformulation of paclitaxel (PTX) shows exceptional solubility (up to 45 g/L) and a high drug loading capacity of 50% wt, which could enhance its effectiveness as an anticancer treatment.

In preclinical studies, this nanoformulation demonstrated improved safety profiles and higher maximum tolerated doses compared to existing formulations, leading to better therapeutic outcomes in aggressive breast cancer models.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A high capacity polymeric micelle of paclitaxel: Implication of high dose drug therapy to safety and in vivo anti-cancer activity. He, Z., Wan, X., Schulz, A., et al.[2022]

The study developed biodegradable polymer particles that can encapsulate both a dye and the cancer drug paclitaxel, showing that these particles are taken up more effectively by breast cancer cells when heated above a specific temperature.

Paclitaxel-loaded particles were found to be less toxic below the thermal transition temperature but exhibited increased cytotoxicity above this temperature, suggesting that temperature can be used to enhance the effectiveness of cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhanced uptake of nanoparticle drug carriers via a thermoresponsive shell enhances cytotoxicity in a cancer cell line. [2020]

Oral administration of SMA-PTX micelles significantly increased the maximum tolerated dose of paclitaxel from 30 mg/kg to 60 mg/kg, indicating improved safety and bioavailability compared to the standard formulation.

In a murine colon cancer model, SMA-PTX micelles reduced tumor weight by 54% and 69% at doses of 30 mg/kg and 60 mg/kg, respectively, while the standard formulation showed no significant effect, demonstrating enhanced efficacy in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Styrene maleic acid-encapsulated paclitaxel micelles: antitumor activity and toxicity studies following oral administration in a murine orthotopic colon cancer model. Parayath, NN., Nehoff, H., Norton, SE., et al.[2022]

The new PTX-RUB formulation significantly enhances the solubility and permeability of paclitaxel, allowing it to remain soluble in gastric and intestinal fluids for extended periods, which could improve oral bioavailability.

Despite being a new formulation, PTX-RUB nanoparticles maintain similar cytotoxic effects against cancer cells as traditional Taxol, indicating that they could be an effective alternative for cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytotoxic and antiangiogenic paclitaxel solubilized and permeation-enhanced by natural product nanoparticles. Liu, Z., Zhang, F., Koh, GY., et al.[2021]

References

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

Versatility of Particulate Carriers: Development of Pharmacodynamically Optimized Drug-Loaded Microparticles for Treatment of Peritoneal Cancer. [2018]

2. England pubmed.ncbi.nlm.nih.gov

Paclitaxel-loaded microparticles for intratumoral administration via the TMT technique: preparation, characterization, and preliminary antitumoral evaluation. [2019]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Activity of drug-loaded tumor-penetrating microparticles in peritoneal pancreatic tumors. [2019]

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

Local administration of submicron particle paclitaxel to solid carcinomas induces direct cytotoxicity and immune-mediated tumoricidal effects without local or systemic toxicity: preclinical and clinical studies. [2022]

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

Tumor-penetrating microparticles for intraperitoneal therapy of ovarian cancer. [2021]

6. Czech Republic pubmed.ncbi.nlm.nih.gov

[Paclitaxel (Taxol)]. [2015]

7. Japan pubmed.ncbi.nlm.nih.gov

[Pharmacologic study of intraperitoneal paclitaxel in gastric cancer patients with peritoneal dissemination]. [2015]

8. New Zealand pubmed.ncbi.nlm.nih.gov

A preliminary risk-benefit assessment of paclitaxel. [2018]

9. Japan pubmed.ncbi.nlm.nih.gov

Intraperitoneal infusion of paclitaxel with S-1 for peritoneal metastasis of advanced gastric cancer: phase I study. [2019]

10. Netherlands pubmed.ncbi.nlm.nih.gov

A high capacity polymeric micelle of paclitaxel: Implication of high dose drug therapy to safety and in vivo anti-cancer activity. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Enhanced uptake of nanoparticle drug carriers via a thermoresponsive shell enhances cytotoxicity in a cancer cell line. [2020]

12. New Zealand pubmed.ncbi.nlm.nih.gov

Styrene maleic acid-encapsulated paclitaxel micelles: antitumor activity and toxicity studies following oral administration in a murine orthotopic colon cancer model. [2022]

13. England pubmed.ncbi.nlm.nih.gov

Cytotoxic and antiangiogenic paclitaxel solubilized and permeation-enhanced by natural product nanoparticles. [2021]