Pidnarulex for Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

Disqualifiers: Pregnancy, Lactation, Cirrhosis, others

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

Compensation: Varies

Number of Visits: 4

Duration: Up to 3 years

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called pidnarulex to determine its safety and effectiveness for individuals with solid tumors that have metastasized. The primary goal is to identify the optimal dose and understand any side effects. Pidnarulex blocks a protein essential for cancer cell growth and repair. This trial may suit those whose cancer has progressed after at least one other treatment and who have measurable and biopsy-accessible tumors. Participants will receive the treatment through an IV and undergo regular scans and tests. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you cannot participate if you are taking strong CYP3A4 inhibitors or inducers, as they may interact with the study drug. It's best to discuss your current medications with the trial team to determine eligibility.

Is there any evidence suggesting that pidnarulex is likely to be safe for humans?

Studies have shown that pidnarulex, also known as CX-5461, is generally safe at certain doses. In one study, researchers found it was well-tolerated by patients with solid tumors, although not everyone experienced a strong benefit. Safety data from this study suggest that pidnarulex can be used without causing severe side effects at the tested doses.

However, another study found that pidnarulex can cause changes in DNA, which might lead to unwanted effects. The exact risk of this occurring in humans is still under investigation.

Overall, while pidnarulex shows promise, its safety is still under careful evaluation, especially since this trial is in its early stages. Although some data are reassuring, more research is needed to fully understand its safety in humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Pidnarulex is unique because it targets a specific mechanism in cancer cells, offering a new way to attack tumors. Unlike many standard treatments that focus on killing rapidly dividing cells, Pidnarulex works by interfering with the DNA repair process in cancer cells, which could lead to more effective tumor control. Researchers are excited about Pidnarulex because it offers a targeted approach that might minimize damage to healthy cells and potentially reduce side effects compared to traditional chemotherapies.

What evidence suggests that pidnarulex might be an effective treatment for metastatic cancer?

Studies have shown that pidnarulex, also known as CX-5461, can be effective against certain types of cancer. Research indicates it works well in cancers with specific gene defects, such as BRCA1/2 or PALB2. These genes help repair DNA, and pidnarulex blocks the enzymes cancer cells need to grow and repair their DNA. In some hard-to-treat breast cancers, it has also reduced tumor growth. Early research suggests it might cause significant changes in cancer cells, potentially stopping their growth. Participants in this trial will receive pidnarulex as part of their treatment regimen. ^{5 6 7 8 9}

Who Is on the Research Team?

A P Chen

Principal Investigator

National Cancer Institute LAO

Are You a Good Fit for This Trial?

This trial is for adults with solid tumors that have spread and worsened after at least one prior treatment. They must have a tumor measurable by medical imaging, be able to undergo a biopsy, and be in decent physical shape (able to perform light activities). Blood counts and liver function need to meet specific levels.

Inclusion Criteria

My total bilirubin levels are within the normal range.

I have Gilbert's syndrome with a bilirubin level up to 3 mg/dl.

My cancer has spread and worsened after at least one treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Patients receive pidnarulex IV over 60 minutes on days 1 and 8 of each 28-day cycle. Patients also undergo CT or MRI, biopsy, and collection of blood samples throughout the trial.

Up to 3 years

2 visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Pidnarulex

Trial Overview The trial is testing the safety, side effects, and best dose of Pidnarulex (CX-5461), an oral drug designed to block enzymes involved in cell division and DNA repair. This could potentially kill cancer cells. The study includes tests like echocardiography, MRI, CT scans, biopsies, and biospecimen collection.

How Is the Trial Designed?

Group I: Treatment (pidnarulex) Experimental Treatment 6 Interventions

Patients receive pidnarulex IV over 60 minutes on days 1 and 8 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI, biopsy, and collection of blood samples throughout the trial. Patients may undergo ECHO at screening and then as clinically indicated.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study of 176 patients with idiopathic pulmonary fibrosis treated with either pirfenidone or nintedanib, adverse drug reactions (ADRs) were reported in 78.3% of those on pirfenidone and 70.5% on nintedanib, indicating a high incidence of side effects for both medications.

The incidence of serious ADRs was about 33 per 100 person-years for both drugs, while non-serious ADRs were more frequent, with 102 per 100 person-years for pirfenidone and 130 per 100 person-years for nintedanib, highlighting the need for careful monitoring of patients on these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world safety profiles of pirfenidone and nintedanib in idiopathic pulmonary fibrosis patients. Fournier, D., Jouneau, S., Bouzillé, G., et al.[2022]

Panobinostat, a histone deacetylase inhibitor, shows significant synergy with gemcitabine and paclitaxel, and particularly strong synergistic effects when combined with doxorubicin and carboplatin in treating metastatic ovarian cancer cell lines.

The study utilized in vitro assays on three ovarian cancer cell lines (SK-OV3, CaOV-3, and ES-2) to identify effective drug combinations, suggesting that these combinations could enhance treatment efficacy and warrant further clinical investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The histone deacetylase inhibitor panobinostat demonstrates marked synergy with conventional chemotherapeutic agents in human ovarian cancer cell lines. Budman, DR., Tai, J., Calabro, A., et al.[2021]

CX-5461, a chemotherapeutic agent, is being fast-tracked for clinical studies targeting cancers with BRCA1, BRCA2, and PALB2 mutations, showing promise for synthetic lethality in BRCA-deficient cells.

However, the drug also causes significant nonselective mutagenesis in various cell lines, raising safety concerns as the levels of mutations exceed those caused by known environmental carcinogens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The chemotherapeutic drug CX-5461 is a potent mutagen in cultured human cells. Koh, GCC., Boushaki, S., Zhao, SJ., et al.[2023]

MetaADEDB 2.0 is an updated online database that now includes 744,709 drug-adverse drug event (ADE) associations, representing a 40% increase from its previous version, making it a more comprehensive resource for researchers.

The new version features a user-friendly web interface, enhancing accessibility for drug safety assessments and studies in drug discovery and development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MetaADEDB 2.0: a comprehensive database on adverse drug events. Yu, Z., Wu, Z., Li, W., et al.[2021]

A mathematical framework using virtual clinical trial simulations was developed to evaluate the effectiveness of combinatorial treatments for overcoming platinum resistance in high-grade serous ovarian cancer.

The study found that drugs designed to resensitize chemoresistant cells were more effective than those that simply trigger cell death or enhance platinum availability, highlighting the importance of targeting specific resistance mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Virtual clinical trials identify effective combination therapies in ovarian cancer. Kozłowska, E., Vallius, T., Hynninen, J., et al.[2021]

The Adverse Drug Reaction Classification System-Target Profile (ADReCS-Target) is a new database that compiles extensive information on adverse drug reactions (ADRs), including 66,573 relationships between drugs, proteins, genes, and genetic variations, which can aid in understanding drug safety.

A case study using ADReCS-Target identified key genes (HLA, C1QA, and APOA1) associated with drug-induced rashes, suggesting these could be potential targets for monitoring and preventing such adverse reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ADReCS-Target: target profiles for aiding drug safety research and application. Huang, LH., He, QS., Liu, K., et al.[2019]

In a study of 138 patients with relapsing epithelial ovarian cancer, paclitaxel treatment resulted in a 28% overall response rate, with 14% achieving a complete response, indicating its potential efficacy as a second-line treatment.

The treatment was well-tolerated with no serious toxicity reported, and patients with platinum-sensitive tumors and good performance status had significantly better survival outcomes, highlighting the importance of patient selection for optimal results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term results from a phase II study of single agent paclitaxel (Taxol) in previously platinum treated patients with advanced ovarian cancer: the Nordic experience. Tropé, C., Hogberg, T., Kaern, J., et al.[2020]

Paclitaxel has shown significant efficacy in treating various cancers, with response rates of 24%-30% in platinum refractory ovarian cancer and up to 62% in untreated advanced breast cancer, indicating its potential as a key chemotherapy agent.

The drug's unique mechanism of action, along with its ability to be combined with other therapies, suggests it can be effectively used in early-stage disease and has demonstrated superiority over standard treatments in ovarian and lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel (Taxol®): A new natural product with major anticancer activity. De Furia, MD.[2012]

A meta-analysis of 53 Phase II/III/IV trials involving nearly 20,000 patients revealed that molecular target anticancer drugs significantly increase the risk of serious adverse events (SAEs) by 57% and fatal adverse events (FAEs) by 51% compared to placebo.

The overall incidence rates for SAEs and FAEs were found to be 26.9% and 2.3%, respectively, highlighting the need for careful monitoring and preventive measures for patients receiving these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of serious adverse event and fatal adverse event with molecular target anticancer drugs in cancer patients: A meta-analysis. Wang, Z., Yang, X., Wang, J., et al.[2020]

The novel paclitaxel-aminoguanidine conjugate significantly improves water solubility compared to paclitaxel alone, enhancing its potential effectiveness against metastatic breast cancer.

This conjugate not only releases both paclitaxel and aminoguanidine within cancer cells but also demonstrates stronger cytotoxicity, increased apoptosis, and superior anti-metastatic effects compared to either drug used separately.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis and Biological Evaluation of Paclitaxel-aminoguanidine Conjugates for Suppressing Breast Cancer. Dai, Y., Zhang, Y., Zhang, L., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07147231

Study Details | NCT07147231 | Testing the Effectiveness of ... This phase I/II trial studies the side effects and best dose of pidnarulex when given together with cemiplimab and to see how well it works ...

2. senhwabio.com senhwabio.com/en/news/20240909

Senhwa Biosciences Presents Clinical Data The abstract highlights Pidnarulex's demonstrated efficacy in treating various solid tumors harbouring BRCA1/2 or PALB2 gene defects.

3. dfhcc.harvard.edu dfhcc.harvard.edu/fileadmin/media/ETCTN/02_Developing_an_ETCTN_Study/PTMA_Requests/Pidnarulex_NSC_845292_PTMA.pdf

FOR CONDUCTING CLINICAL TRIALS USING ... Pidnarulex was also shown to reduce tumor growth in taxane resistant triple-negative breast cancer (TNBC) patient derived xenograft (PDX) tumor models, with ...

4. nature.com nature.com/articles/s41588-023-01602-9

The chemotherapeutic drug CX-5461 is a potent mutagen ... Even with a single, ultrashort (2 h) and low (0.1 μM) dose, CX-5461 yielded ~1.5 times the number of mutations of BaP and ~2.6 times over ...

5. withpower.com withpower.com/trial/phase-1-metastatic-malignant-solid-neoplasm-11-2024-d84ed

Pidnarulex for Cancer · Recruiting Participants for Phase ... Pidnarulex, also known as CX-5461, has been shown to cause significant genetic changes in human cells, which could be harmful. This suggests potential safety ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT07137416

Study Details | NCT07137416 | Testing the Safety of the ... This phase I trial tests the safety, side effects, and best dose of Pidnarulex in combination with trastuzumab deruxtecan in treating ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12007140/

The G-quadruplex ligand CX-5461 - PubMed Central - NIH Although the response rate in this clinical trial was not exceptionally high, it indicated that CX-5461 is safe at doses associated with ...

8. senhwabio.com senhwabio.com/en/news/20240712

Senhwa Biosciences Clinical Data Abstract Senhwa Biosciences' new drug Pidnarulex (CX-5461) has demonstrated efficacy in treating various solid tumors with BRCA2 or PALB2 gene defects.

9. prnewswire.com prnewswire.com/news-releases/senhwa-biosciences-presents-clinical-data-abstract-on-pidnarulex-at-2024-esmo-congress-302241441.html

Senhwa Biosciences Presents Clinical Data Abstract on ... The abstract highlights Pidnarulex's demonstrated efficacy in treating various solid tumors harbouring BRCA1/2 or PALB2 gene defects.