Chemotherapy (FID-007) for Cancer

Recruiting at 1 trial location

Overseen By Lorraine Martinez, RN

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Southern California

Must not be taking: Paclitaxel, Nab-paclitaxel, Warfarin, others

Disqualifiers: Hypersensitivity to paclitaxel, Heart failure, Active infection, others

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

Compensation: Varies

Number of Visits: 3

Duration: 28 days per cycle

36 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase I trial studies the side effects and best dose of PEOX-based polymer encapsulated paclitaxel FID-007 (FID-007) in treating participants with malignant neoplasms that have spread to other places in the body and do not respond to treatment. FID-007 is a packaged form of the chemotherapy drug paclitaxel, and uses a polyethylozaxoline (PEOX) polymer which may allow the drug to reach deeper into tumors and less into normal cells by being smaller.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you must have finished any previous chemotherapy, radiotherapy, or targeted therapy at least 4 weeks before starting the trial.

What data supports the effectiveness of the drug FID-007 for cancer treatment?

Research shows that using nanoparticles to deliver paclitaxel, like in FID-007, can improve how the drug targets tumors and enhances its ability to stop tumor growth. Studies have found that these nanoparticles can lead to better drug distribution in tumors and reduce tumor size more effectively than traditional methods. ^{1 2 3 4 5}

Is the chemotherapy treatment FID-007 generally safe for humans?

The safety data for treatments similar to FID-007, like PNU166945, show that while some formulations have mild side effects, others have caused severe neurotoxicity in animal studies. A phase I study in humans showed mild blood-related side effects, but the study was stopped due to severe nerve damage observed in animals. ^{1 3 6 7 8}

What makes the drug FID-007 unique compared to other cancer treatments?

FID-007 is unique because it uses a PEOX-based polymer to encapsulate paclitaxel, forming nanoparticles that improve drug delivery to tumors. This method enhances the drug's stability and targeting ability, potentially leading to better treatment outcomes compared to traditional formulations. ^{1 2 3 5 9}

Research Team

Anthony El-Khoueiry, MD

Principal Investigator

University of Southern California

Eligibility Criteria

This trial is for adults with advanced solid tumors that have spread and don't respond to treatment. They must have acceptable blood counts, organ function, and a life expectancy of at least 3 months. Participants need measurable disease, no severe allergies to paclitaxel, no more than three prior chemotherapy treatments for advanced disease, and cannot be on certain anticoagulants or have serious heart conditions.

Inclusion Criteria

My kidney function is within the required range for the trial.

Hemoglobin ? 8 g/dL

I am a woman who can have children and my pregnancy test was negative.

Exclusion Criteria

I have brain metastasis but am stable after treatment and not on steroids.

I have had 3 or fewer chemotherapy treatments for my advanced disease.

I have never been treated with paclitaxel or nab-paclitaxel.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive FID-007 intravenously over 60 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

28 days per cycle

3 visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

Treatment Details

Interventions

• PEOX-based Polymer Encapsulated Paclitaxel FID-007

Trial Overview The study tests FID-007, a new form of the chemotherapy drug paclitaxel encapsulated in PEOX-based polymer which may target tumors more effectively while sparing normal cells. The trial aims to find the safest dose with the fewest side effects by gradually increasing doses among participants.

Participant Groups

Group I: Treatment (FID-007) Experimental Treatment 3 Interventions

Participants receive FID-007 IV over 60 minutes on days 1, 8 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

University of Southern California

Lead Sponsor

Trials

956

Recruited

1,609,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

The amphiphilic block copolymer PEO-PBO effectively forms nanoparticles for delivering the cancer drug paclitaxel, with a size of approximately 92.71 nm, which is suitable for targeting tumors due to the enhanced permeability and retention effect.

PEO-PBO nanoparticles demonstrated superior pharmacokinetics, biodistribution, and tumor inhibition compared to the commonly used PEG-PDLLA, along with better biocompatibility and stability, indicating its potential as a promising drug delivery system.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Delivery of paclitaxel using nanoparticles composed of poly(ethylene oxide)-b-poly(butylene oxide) (PEO-PBO). Wang, L., Yao, J., Zhang, X., et al.[2018]

Intraperitoneal (i.p.) administration of paclitaxel formulated as PTX-30W significantly reduced metastatic nodules and tumor volume in a gastric cancer model, leading to prolonged survival compared to conventional PTX dissolved in Cremophor EL.

PTX-30W showed higher drug accumulation in peritoneal tumors and preferentially targeted hypovascular areas, suggesting it may be a more effective treatment for peritoneal malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraperitoneal administration of paclitaxel solubilized with poly(2-methacryloxyethyl phosphorylcholine-co n-butyl methacrylate) for peritoneal dissemination of gastric cancer. Soma, D., Kitayama, J., Konno, T., et al.[2022]

Increasing the amount of D-a-tocopheryl polyethylene glycol 1000 succinate (TPGS) in paclitaxel (PTX) nanocrystals transformed their shape from rod-like to stable spherical micelles, enhancing their cytotoxicity and cellular uptake in drug-resistant cancer cells.

Despite a faster clearance rate compared to Taxol, PTX/TPGS micelles showed improved accumulation in drug-resistant tumors, likely due to TPGS's ability to inhibit P-glycoprotein, which is responsible for drug resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effect of Surfactant on Paclitaxel Nanocrystals: An In Vitro and In Vivo Study. Liu, H., Ma, Y., Liu, D., et al.[2019]

PTX-loaded PLGA nanoparticles (PTX-PLGA NPs) were developed as a drug carrier and showed enhanced antitumor effects against non-small-cell lung carcinoma (NSCLC) cells, particularly in promoting apoptosis and inhibiting cell migration and invasion.

While PTX-PLGA NPs initially had weaker effects than free PTX at shorter time points (12 and 24 hours), they demonstrated stronger inhibition of NSCLC cell activity at 48 and 72 hours, indicating their potential for sustained drug release and improved therapeutic efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study on the Mechanism of Action of Paclitaxel-Loaded Polylactic-co-glycolic Acid Nanoparticles in Non-Small-Cell Lung Carcinoma Cells. Zuo, Y., Shen, W., Wang, L., et al.[2023]

Paclitaxel-loaded nanoparticles significantly reduced tumor weight and ascites volume in ovarian carcinoma xenografts in F344 rats, demonstrating effective tumor inhibition with weights of 4.55 g compared to 10.13 g in controls.

The nanoparticles also showed enhanced delivery to pelvic lymph nodes, with concentrations significantly higher than free paclitaxel, indicating a safe and effective lymphatic targeting mechanism for treating ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The inhibitory effect of paclitaxel nanoparticles on ovarian cancer xenografts and lymphatic targeting]. Lu, HX., Xu, CJ., Li, B., et al.[2017]

The study found that PTX-loaded polymeric micelles (PM/PTX) are more stable and safer than the conventional formulation (CrEL/EtOH/PTX), showing no hemolytic activity and reduced toxicity in healthy mice, particularly avoiding peripheral neuropathy.

PM/PTX demonstrated significantly higher antitumor activity, with an inhibition ratio approximately 1.5 times greater than CrEL/EtOH/PTX, indicating its potential as a more effective treatment for breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Encapsulating paclitaxel in polymeric nanomicelles increases antitumor activity and prevents peripheral neuropathy. Oda, CMR., Silva, JO., Fernandes, RS., et al.[2021]

The synthesized PEO-b-PCL copolymers with paclitaxel (PTX) side groups showed limited drug release (5.0% at pH 7.4 and 6.7% at pH 5.0) over 72 hours, indicating a controlled release mechanism that may be beneficial for targeted therapy.

While the cytotoxicity of the PEO-b-P(CL-PTX) particles against cancer cells increased over time, it was still significantly lower than that of free PTX, suggesting that while the copolymer can solubilize PTX, its effectiveness in killing cancer cells may require further optimization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel self-associating poly(ethylene oxide)-b-poly(epsilon-caprolactone) based drug conjugates and nano-containers for paclitaxel delivery. Shahin, M., Lavasanifar, A.[2018]

The phase I study of PNU166945, a polymer-conjugated derivative of paclitaxel, involved 12 patients with refractory solid tumors and showed that it could be administered safely without dose-limiting toxicities up to 196 mg/m², with mild hematologic toxicity.

While one patient experienced a partial response and the pharmacokinetics of PNU166945 were linear, the study was halted due to severe neurotoxicity observed in rat studies, indicating potential safety concerns that differ from standard paclitaxel formulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I clinical and pharmacokinetic study of PNU166945, a novel water-soluble polymer-conjugated prodrug of paclitaxel. Meerum Terwogt, JM., ten Bokkel Huinink, WW., Schellens, JH., et al.[2019]

A new formulation using 3rd generation taxoids with doubly amphiphilic poly(2-oxazoline)s (POx) significantly improves the solubility of these drugs, which are typically very hydrophobic, allowing for effective parenteral administration.

The selected taxoid SB-T-1214 showed one to two orders of magnitude greater activity against multidrug-resistant breast cancer cells compared to paclitaxel, and it effectively inhibited tumor growth in resistant models, outperforming both commercial paclitaxel and its traditional formulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Poly(2-oxazoline) based micelles with high capacity for 3rd generation taxoids: preparation, in vitro and in vivo evaluation. He, Z., Schulz, A., Wan, X., et al.[2019]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Delivery of paclitaxel using nanoparticles composed of poly(ethylene oxide)-b-poly(butylene oxide) (PEO-PBO). [2018]

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

Intraperitoneal administration of paclitaxel solubilized with poly(2-methacryloxyethyl phosphorylcholine-co n-butyl methacrylate) for peritoneal dissemination of gastric cancer. [2022]

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

The Effect of Surfactant on Paclitaxel Nanocrystals: An In Vitro and In Vivo Study. [2019]

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

Study on the Mechanism of Action of Paclitaxel-Loaded Polylactic-co-glycolic Acid Nanoparticles in Non-Small-Cell Lung Carcinoma Cells. [2023]

5. China pubmed.ncbi.nlm.nih.gov

[The inhibitory effect of paclitaxel nanoparticles on ovarian cancer xenografts and lymphatic targeting]. [2017]

6. France pubmed.ncbi.nlm.nih.gov

Encapsulating paclitaxel in polymeric nanomicelles increases antitumor activity and prevents peripheral neuropathy. [2021]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Novel self-associating poly(ethylene oxide)-b-poly(epsilon-caprolactone) based drug conjugates and nano-containers for paclitaxel delivery. [2018]

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

Phase I clinical and pharmacokinetic study of PNU166945, a novel water-soluble polymer-conjugated prodrug of paclitaxel. [2019]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Poly(2-oxazoline) based micelles with high capacity for 3rd generation taxoids: preparation, in vitro and in vivo evaluation. [2019]