PHST001 for Cancer

Recruiting at 9 trial locations

Overseen By Raphaël Rousseau, Chief Medical Officer, PhD, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Pheast Therapeutics

Must not be taking: Steroids, Anticancer agents

Disqualifiers: CNS metastases, Recent transplants, others

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

Compensation: Varies

Number of Visits: Unknown

155 Participants Needed

Trial Summary

What is the purpose of this trial?

PHST001-101 is a multicenter, open-label, Phase 1 study of PHST001 in patients with advanced solid tumors. The study design includes a Dose Escalation Phase and a Dose Expansion Phase, and will enroll patients with advanced relapsed and/or refractory solid tumors. The study's primary object is to evaluate the safety and tolerability of PHST001 and determine the RP2D (Recommended Phase 2 dose) of PHST001.

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, you must not have received any systemic anticancer therapy within 21 days before starting the trial treatment.

What safety data exists for PHST001 (imatinib) in humans?

Imatinib, also known as PHST001, has been used to treat conditions like chronic myeloid leukemia and gastrointestinal stromal tumors. It is generally well-tolerated, with most side effects being mild, such as muscle cramps and gastrointestinal symptoms. Severe side effects are rare, making it a relatively safe treatment option. ^{1 2 3 4 5}

How does the drug PHST001 differ from other cancer treatments?

PHST001, also known as amifostine, is unique because it protects normal tissues from the harmful effects of chemotherapy and radiation without reducing their effectiveness against cancer. This selective protection helps reduce side effects and allows for higher doses of cancer treatments, potentially improving outcomes. ^{6 7 8 9 10}

Eligibility Criteria

This trial is for adults with advanced solid tumors that have stopped responding to standard treatments. Participants must have adequate blood counts, liver and kidney function, and no other medical conditions that could interfere with the study.

Inclusion Criteria

My total bilirubin levels are within the normal range.

My liver function tests are within the required range.

My lipase and amylase levels are not more than twice the upper limit.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Seven dose levels will be tested to evaluate the safety and tolerability of PHST001 and determine the RP2D

21 days per dose level

Dose Expansion

Participants receive the RP2D of PHST001 to further evaluate safety and antitumor activity

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

90 days after the last dose

Treatment Details

Interventions

• PHST001

Trial Overview PHST001-101 is testing a new drug called PHST001 in two phases: first to find the safest dose (Dose Escalation Phase) and then to see how well it works at this dose in more people (Dose Expansion Phase).

Participant Groups

Group I: Dose Escalation Experimental Treatment 1 Intervention

Seven dose levels will be tested in dose escalation.

Who Is Running the Clinical Trial?

Pheast Therapeutics

Lead Sponsor

Trials

1

Recruited

160+

Findings from Research

In a study of 373 cancer patients under 65 years old who received COVID-19 vaccines, 76.1% experienced mild vaccine-related adverse events (VRAEs), with the most common being sore arm, fatigue, and headaches, indicating that the vaccines are generally well-tolerated in this population.

Only 2.1% of patients experienced grade 3 VRAEs, and there were no severe reactions (grade 4/5 or anaphylaxis), suggesting that COVID-19 vaccines have a favorable safety profile for patients undergoing cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

COVID-19 Vaccine Safety in Cancer Patients: A Single Centre Experience. So, ACP., McGrath, H., Ting, J., et al.[2021]

Imatinib mesylate has shown a high clinical response rate of 81.6% in patients with gastrointestinal stromal tumors (GIST), with 53.7% achieving a partial response and 27.9% having stable disease.

While most patients experienced only mild toxicities (grade 1 or 2), 21.1% had more severe side effects (grade 3 or higher), indicating that imatinib is relatively safe but can still cause significant adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The effect of imatinib for gastrointestinal tumor]. Mizunuma, N.[2015]

Imatinib, a tyrosine kinase inhibitor, has significantly improved the prognosis for patients with chronic myeloid leukaemia (CML) and gastrointestinal stromal tumours (GIST), showing high rates of cytogenetic and molecular responses across all phases of CML.

The drug is well tolerated, with only mild adverse effects such as joint pain and gastrointestinal symptoms, primarily occurring in the first two years of treatment, making it a safe and effective oral option for these cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A benefit-risk assessment of imatinib in chronic myeloid leukaemia and gastrointestinal stromal tumours. Wolf, D., Rumpold, H.[2021]

In a study of 250 patients with advanced renal cell carcinoma receiving first-line treatment with signal transduction inhibitors, 520 adverse drug reactions (ADRs) were documented, with 29% leading to treatment modifications.

The most common ADRs included mucositis/stomatitis, fatigue, diarrhea, and nausea, indicating that while the pattern of ADRs aligns with clinical trials, their frequency and impact in routine clinical practice may differ significantly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse reactions in mRCC patients documented in routine practice by German office-based oncologists and uro-oncologists. Marschner, N., Müller, L., Münch, A., et al.[2022]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

COVID-19 Vaccine Safety in Cancer Patients: A Single Centre Experience. [2021]

2. Japan pubmed.ncbi.nlm.nih.gov

[The effect of imatinib for gastrointestinal tumor]. [2015]

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

A benefit-risk assessment of imatinib in chronic myeloid leukaemia and gastrointestinal stromal tumours. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Safety of two-dose COVID-19 vaccination (BNT162b2 and CoronaVac) in adults with cancer: a territory-wide cohort study. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Adverse reactions in mRCC patients documented in routine practice by German office-based oncologists and uro-oncologists. [2022]

6. England pubmed.ncbi.nlm.nih.gov

The preclinical basis for broad-spectrum selective cytoprotection of normal tissues from cytotoxic therapies by amifostine (Ethyol). [2019]

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

Hypofractionated and accelerated radiotherapy with amifostine cytoprotection (HypoARC): a new concept in radiotherapy and encouraging results in breast cancer. [2022]

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

WR-1065, the active metabolite of amifostine (Ethyol), does not inhibit the cytotoxic effects of a broad range of standard anticancer drugs against human ovarian and breast cancer cells. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Repression of c-myc gene expression by the thiol and disulfide forms of the cytoprotector amifostine. [2019]

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

Amifostine reduces side effects and improves complete response rate during radiotherapy: results of a meta-analysis. [2018]