PM14 for Advanced Cancer

Recruiting at 8 trial locations

Overseen By Cristian Fernández, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: PharmaMar

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

Disqualifiers: Uncontrolled hypertension, Active infection, HIV, others

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

Compensation: Varies

Number of Visits: 4

150 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a new drug called PM14 for patients with advanced cancers that are hard to treat. The goal is to find the safest and most effective dose by adjusting the amount given to avoid severe side effects.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking all current medications, but there are specific 'washout' periods (time without taking certain medications) for chemotherapy, monoclonal antibody therapies, and some hormonal therapies. If you have hormone-sensitive breast cancer, you must stop all hormonal therapies at least one week before starting the trial, except for certain medications. If you have castrate-resistant prostate cancer, you may continue hormone therapy during the trial.

Is PM14 generally safe for humans?

The treatment, also known as pembrolizumab, has been associated with skin-related side effects in some patients with lung cancer, but these effects might indicate the treatment is working. It's important for medical staff to monitor these side effects closely. ^{1 2 3 4 5}

Eligibility Criteria

This trial is for adults over 18 with advanced solid tumors where no cure exists. It's specifically for those with certain gastrointestinal cancers, sarcomas, or tumors linked to BRCA mutations, among others. Participants should be in relatively good health (ECOG ≤1) and have had a limited number of prior chemotherapy treatments.

Inclusion Criteria

I am fully active and can carry on all my pre-disease activities without restriction.

My cancer can be measured by standard health scans.

Confirmed progressive disease after last therapy at study entry

Exclusion Criteria

I haven't taken specified medications in the last 6 months.

I am taking medication that could affect my heart rhythm.

I am currently being treated for an infection.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Patients receive PM14 at increasing dose levels to determine the maximum tolerated dose (MTD) and recommended dose (RD).

3 weeks per cycle

Visits on Day 1 and Day 8 of each cycle

Expansion

Patients are treated at the recommended dose to assess safety and antitumor activity.

Up to 9 cycles

Visits every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 72 months

Treatment Details

Interventions

• PM14

Trial Overview The trial is testing PM14, an investigational drug for patients with advanced solid tumors. The study aims to find new treatment options that are not yet available and may work differently from existing therapies without having completely overlapping side effects.

Participant Groups

Group I: PM14 Experimental Treatment 1 Intervention

Patients will receive PM14 as an i.v. infusion in a total volume of 100 mL of 0.9% sodium chloride at the first three dose escalation levels. Thereafter, the volume of infusion can be increased to 250 mL.

Who Is Running the Clinical Trial?

PharmaMar

Lead Sponsor

Trials

93

Recruited

11,800+

José María Fernández de Sousa-Faro

PharmaMar

Chief Executive Officer since 1986

PhD in Biochemistry, Complutense University of Madrid

Carmen Cuevas Marchante

PharmaMar

Chief Medical Officer since 2002

MD, University of Navarra

Findings from Research

In a study of 32 patients with non-small cell lung cancer treated with pembrolizumab, 31% experienced skin immune-related adverse effects (irAEs), indicating that these side effects are relatively common in this treatment group.

Patients who developed skin irAEs had a significantly longer progression-free survival (390 days) compared to those without skin irAEs (128.5 days), suggesting that the presence of these skin reactions may be a positive indicator of treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association between immune-related dermatologic adverse events and efficacy of pembrolizumab in non-small cell lung cancer patients. Fukuoka, T., Yamamoto, Y., Utsunomiya, J., et al.[2022]

A comprehensive review of 41 randomized controlled trials involving 23,121 patients found that treatments combining chemotherapy with immune checkpoint inhibitors (ICIs) significantly increased the risk of treatment-related adverse events compared to ICI-only regimens.

Among the various ICI treatments, the combination of PD-L1 and CTLA-4 with chemotherapy had the highest risk of immune-related adverse events, with severe cases like myocarditis and pneumonitis showing notably high fatality rates, indicating the need for careful monitoring and management in patients receiving these therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity spectrum of immunotherapy in advanced lung cancer: A safety analysis from clinical trials and a pharmacovigilance system. Yan, YD., Zhao, Y., Zhang, C., et al.[2022]

In a retrospective study of 123 patients receiving FOLFOX 4 chemotherapy for advanced colorectal cancer, significant adverse reactions were reported, including hemotoxicity (52.8%), chronic sensory neuropathy (16.2%), and allergic reactions (15.4%).

Common side effects during initial treatment included appetite loss (60.1%), vomiting (19.5%), and acute sensory neuropathy (33.3%), highlighting the need for improved patient education and pharmaceutical care to manage these reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Drug information brochure for patients undergoing FOLFOX 4 chemotherapy based on survey of adverse reactions]. Imada, H., Kawakami, K., Hiraoka, T., et al.[2013]

The updated ASCO guidelines provide essential recommendations for managing immune-related adverse events in adult cancer patients undergoing treatment with immune checkpoint inhibitors, ensuring better patient safety and care.

These guidelines reflect the latest evidence and expert consensus, helping healthcare providers effectively address and mitigate potential side effects associated with immune checkpoint therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical guideline highlights for the hospitalist: Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy. Chitnis, SD., Mortazavi, A.[2023]

The paper emphasizes the importance of developing robust serious adverse event (SAE) reporting procedures in non-pharmaceutical palliative care trials, as patients often face high risks of hospitalization or death due to their underlying conditions rather than the trial interventions.

Recommendations for improving SAE management include allowing sufficient planning time, defining what constitutes a serious adverse event for the specific study population, and refining reporting procedures throughout the trial to enhance patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

What should we report? Lessons learnt from the development and implementation of serious adverse event reporting procedures in non-pharmacological trials in palliative care. Dunleavy, L., Collingridge Moore, D., Korfage, I., et al.[2021]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Association between immune-related dermatologic adverse events and efficacy of pembrolizumab in non-small cell lung cancer patients. [2022]

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

Toxicity spectrum of immunotherapy in advanced lung cancer: A safety analysis from clinical trials and a pharmacovigilance system. [2022]

3. Japan pubmed.ncbi.nlm.nih.gov

[Drug information brochure for patients undergoing FOLFOX 4 chemotherapy based on survey of adverse reactions]. [2013]

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

Clinical guideline highlights for the hospitalist: Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy. [2023]

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

What should we report? Lessons learnt from the development and implementation of serious adverse event reporting procedures in non-pharmacological trials in palliative care. [2021]