PEEL-224 for Cancer

Recruiting in Palo Alto (17 mi)

+5 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Peel Therapeutics Inc

Must not be taking: CYP inhibitors, Corticosteroids

Disqualifiers: CNS tumors, Brain metastases, Cardiovascular, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial is testing PEEL-224, a new drug, in patients with advanced solid tumors. The drug aims to block an enzyme that cancer cells need to grow, potentially slowing down or stopping the cancer.

Will I have to stop taking my current medications?

The trial requires that you stop using certain medications, like strong CYP1A2 and CYP3A4 inhibitors or inducers, and systemic corticosteroids, at least 14 days before starting the study. It's best to discuss your current medications with the trial team to see if any need to be stopped.

What makes the drug PEEL-224 unique for cancer treatment?

PEEL-224 is unique because it may involve a novel mechanism of action or administration that is not detailed in the provided research, but it could be similar to other treatments like VP 16-213, which is a podophyllotoxin derivative known for its effectiveness in certain cancers and its schedule-dependent administration. This suggests that PEEL-224 might also have a unique approach in targeting cancer cells, potentially offering new benefits compared to existing treatments. ^{1 2 3 4 5}

Research Team

Eligibility Criteria

This trial is for adults with advanced solid tumors that have worsened after standard treatments, or when no standard care exists. Participants must be in good physical condition (ECOG 0 or 1), have measurable tumors, and proper organ function. They can't join if they've used certain drugs recently, have uncontrolled diseases, other cancers within the last 2 years, brain metastases unless treated and stable, are pregnant/breastfeeding, or plan to donate gametes.

Inclusion Criteria

My liver is working well.

I am fully active or can carry out light work.

My kidneys are working well.

Exclusion Criteria

I haven't taken strong drugs that affect liver enzymes in the last 14 days.

My brain or spinal cancer has been treated and hasn't worsened or bled in the last 14 days.

Currently enrolled in another therapeutic clinical study or a non-therapeutic clinical study that will conflict with scheduled visits required by this study

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

PEEL-224 is administered intravenously on Days 1, 8, and 15 of a 28-day cycle. Dose escalation will be guided by the mTPI-2 design until a recommended phase 2 dose is determined.

28 days per cycle, multiple cycles

Dose Confirmation

An additional arm of patients will be enrolled to confirm the recommended phase 2 dose.

28 days per cycle, multiple cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments every 8 weeks.

6 months

Treatment Details

Interventions

• PEEL-224 (Other)

Trial Overview The study tests PEEL-224's safety and effectiveness in treating advanced solid tumors. It's a first-in-human trial where doses will gradually increase to find the right balance between safety and response. The drug's behavior in the body (pharmacokinetics) and its impact on tumor size will also be assessed.

Participant Groups

Group I: PEEL-224 Dose Escalation Experimental Treatment 1 Intervention

PEEL-224 is administered intravenously (IV) on Days 1, 8, and 15 of a 28-day cycle. The study will begin at a low starting dose and will increase between cohorts according to mTPI-2 until a recommended phase 2 dose is determined. Approximately 10 dose levels are anticipated to be studied.

Group II: PEEL-224 Dose Confirmation Experimental Treatment 1 Intervention

An additional arm of patients will be enrolled after dose escalation is completed to confirm the recommended phase 2 dose.

Who Is Running the Clinical Trial?

Peel Therapeutics Inc

Lead Sponsor

Trials

3

Recruited

160+

Findings from Research

In a study involving 129 patients with locally advanced epithelial malignancies, high-dose cisplatin (100 mg/m2) combined with radiation showed promising median survival times, particularly for squamous cell carcinoma of the head and neck, which had a median survival of 36 months.

The treatment was administered every 3 weeks during radiation therapy, and while median survival times for ovarian and lung cancers were 19 and 14 months respectively, some cancers like cervical carcinoma and prostate adenocarcinoma have not yet reached median survival, indicating ongoing effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical experience with high-dose cisplatin and radiation for treatment of epithelial malignancies. Coughlin, CT.[2013]

In a phase I study involving 20 patients with high-risk squamous cell carcinoma of the head and neck, the maximum tolerated dose (MTD) of docetaxel combined with concurrent radiotherapy was determined to be 15 mg/m2, with oral stomatitis identified as the main dose-limiting toxicity.

The treatment was generally well tolerated, and while five patients experienced locoregional relapse after a median follow-up of 32 months, the results suggest that this combination therapy is safe enough to warrant further investigation in a phase II trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I adjuvant radiation with docetaxel in high-risk head and neck cancer. Clark, JI., Eisner, RM., Hofmeister, C., et al.[2021]

VP 16-213, a new drug derived from podophyllotoxin, shows significant effectiveness against small-cell bronchial carcinoma and may also be beneficial for other lung tumors, testicular teratomas, and certain leukemias, making it a promising treatment option.

The drug's mechanism of action is not fully understood, but it appears to cause the most damage to cancer cells during specific phases of the cell cycle, and prolonged administration may enhance its effectiveness compared to single doses, with no long-term toxicity reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Podophyllotoxin derivative VP 16-213. Arnold, AM.[2019]

The modified chimeric Pseudomonas exotoxin, PEdelta53L/TGF-alpha/KDEL, significantly increases the sensitivity of human tumors to radiation therapy by lowering the apoptotic threshold in tumor cells lacking functional p53, suggesting a new approach to overcome resistance to apoptosis.

Importantly, this treatment did not result in increased local or systemic toxicity, indicating a favorable safety profile while enhancing the effectiveness of radiation therapy in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modulation of apoptotic response of a radiation-resistant human carcinoma by Pseudomonas exotoxin-chimeric protein. Seetharam, S., Nodzenski, E., Beckett, MA., et al.[2023]

References

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

Clinical experience with high-dose cisplatin and radiation for treatment of epithelial malignancies. [2013]

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

Phase I adjuvant radiation with docetaxel in high-risk head and neck cancer. [2021]

3. Germany pubmed.ncbi.nlm.nih.gov

Podophyllotoxin derivative VP 16-213. [2019]

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

[Therapeutic experiences using the new podophyllotoxin derivative VP 16-213 in malignant human tumors]. [2013]

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

Modulation of apoptotic response of a radiation-resistant human carcinoma by Pseudomonas exotoxin-chimeric protein. [2023]