CBL0137 for Cancer

Recruiting at 36 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Children's Oncology Group

Must not be taking: Corticosteroids, Anti-cancer agents, CYP3A4 drugs, others

Disqualifiers: Pregnancy, Peripheral vascular disease, others

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

Compensation: Varies

Number of Visits: 5

Duration: Up to 12 months

63 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new drug called CBL0137 (also known as Curaxin 137) to determine the optimal dose and understand its effects on solid tumors, including brain tumors and lymphoma that have returned or are difficult to treat. The drug aims to disrupt signals in cancer cells, potentially stopping their growth and causing them to die. This trial may suit patients whose cancer has relapsed or does not respond to treatment, particularly those with solid tumors or lymphoma, including brain cancers, with no other effective treatment options available. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering patients the opportunity to be among the first to receive this new drug.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before starting CBL0137. You must avoid drugs that affect specific liver enzymes (CYP3A4, CYP2B6, CYP1A2) and those with a risk of heart rhythm issues (Torsades de Pointes) for at least 7 days before and during the trial. If you're on corticosteroids, you need to be on a stable or decreasing dose for at least 7 days before joining the trial.

Is there any evidence suggesting that CBL0137 is likely to be safe for humans?

Research has shown that CBL0137 may help combat various cancers, including brain cancer (glioblastoma), skin cancer (melanoma), and lung cancer. Earlier studies suggest it can kill cancer cells and slow their growth. Researchers have tested CBL0137 to determine the right dose and identify side effects. These studies ensure that any serious side effects are detected and managed. However, since testing continues, some side effects might not be fully known yet. Prospective participants should discuss potential risks and benefits with the trial team before deciding to join. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

CBL0137 is unique because it targets cancer cells differently from traditional treatments. Most standard cancer treatments, like chemotherapy, attack rapidly dividing cells indiscriminately, but CBL0137 works by interfering with the structure of chromatin within cancer cells, preventing them from multiplying. Researchers are excited about CBL0137 because it has the potential to be effective against a wide range of cancers with fewer side effects, offering hope for patients who may not respond well to existing therapies. Additionally, its unique delivery method via a 30-minute IV infusion could make it a more convenient option for patients.

What evidence suggests that CBL0137 might be an effective treatment for cancer?

Research has shown that CBL0137, the investigational treatment in this trial, may help combat various cancers, including glioblastoma, melanoma, and lymphoma. Studies have found that CBL0137 interferes with signals inside cancer cells, leading to increased cell death and reduced growth. This is particularly effective in cancers with a specific protein complex called FACT, which CBL0137 targets. Additionally, it enhances the effectiveness of other treatments, such as rituximab, by promoting natural cell death processes like apoptosis (programmed cell death) and autophagy (self-digestion by the cell). These findings suggest that CBL0137 could be valuable, especially for cancers resistant to other therapies. ^{1 2 3 4 6}

Who Is on the Research Team?

David S Ziegler

Principal Investigator

Pediatric Early Phase Clinical Trial Network

Are You a Good Fit for This Trial?

This trial is for young people aged 1-21 (up to 30 for certain bone cancers) with solid tumors or lymphoma that have returned or are treatment-resistant. They must have a history of cancer confirmed by tests, meet specific health criteria like kidney function and heart health, and not be pregnant. Treatments must be finished within set time frames before joining.

Inclusion Criteria

My cancer has returned or worsened after radiation therapy.

I am between 12 and 30 years old and have relapsed or refractory osteosarcoma.

My osteosarcoma has come back or didn't respond to treatment.

Exclusion Criteria

You are currently taking other medications for cancer, except for leukemia patients taking hydroxyurea.

You have had an organ transplant in the past.

Patients who may not be able to comply with the safety monitoring requirements of the study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive CBL0137 intravenously over 30 minutes on days 1 and 8, repeating every 21 days for up to 17 cycles

Up to 12 months

2 visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 60 months

Follow-up visits at 3, 6, 9, 12, 18, 24, 36, 48, and 60 months

What Are the Treatments Tested in This Trial?

Interventions

• CBL0137

Trial Overview The trial is testing CBL0137's optimal dose and its effects on patients with relapsed/refractory solid tumors including brain/CNS tumors or lymphoma. It aims to block cell signals involved in cancer cell growth and survival, potentially leading to the death of cancer cells.

How Is the Trial Designed?

Group I: Treatment (CBL0137) Experimental Treatment 5 Interventions

Patients receive CBL0137 IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for up to 17 cycles in the absence of disease progression or unacceptable toxicity. Patients with pseudoprogression may remain on treatment, as per the treating physician. Patients also undergo ECHO collection of blood samples throughout the trial. Patients may also undergo bone marrow aspirate and/or biopsy as clinically indicated.

Who Is Running the Clinical Trial?

Children's Oncology Group

Lead Sponsor

Trials

467

Recruited

241,000+

Incuron LLC

Collaborator

Trials

1

Recruited

100+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

The study identified that the pro-survival protein Bcl-2 is upregulated in lung cancer cells resistant to paclitaxel, contributing to chemotherapy resistance.

A peptide derived from the Nur77 nuclear receptor can convert Bcl-2 from promoting cell survival to inducing cell death, effectively triggering apoptosis in paclitaxel-resistant lung cancer cells and significantly inhibiting tumor growth in a zebrafish model.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Induction of apoptosis and suppression of tumor growth by Nur77-derived Bcl-2 converting peptide in chemoresistant lung cancer cells. Pearce, MC., Gamble, JT., Kopparapu, PR., et al.[2019]

Human NOXA protein binds more strongly to the Bfl-1 antiapoptotic protein than to Mcl-1, suggesting that targeting Bfl-1 could be a promising strategy for overcoming cancer cell resistance to treatments.

The study introduces novel covalent BH3-based agents designed to specifically target Bfl-1, which could lead to new therapeutic options for cancers that rely on this protein for survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

hBfl-1/hNOXA Interaction Studies Provide New Insights on the Role of Bfl-1 in Cancer Cell Resistance and for the Design of Novel Anticancer Agents. Barile, E., Marconi, GD., De, SK., et al.[2018]

TRIP-Br decoy peptides have shown strong anti-proliferative effects in various cancer cell lines, including nasopharyngeal, cervical, and melanoma cancers, both in vitro and in vivo, indicating their potential as a new cancer treatment.

Topical application of TRIP-Br decoy peptides significantly suppressed tumor growth in chick embryo models, suggesting that targeting the TRIP-Br integrator function could be a novel approach for treating cutaneous and intracavitary lesions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exploiting the TRIP-Br family of cell cycle regulatory proteins as chemotherapeutic drug targets in human cancer. Zang, ZJ., Sim, KG., Cheong, JK., et al.[2020]

CB1a, an engineered version of the antimicrobial peptide Cecropin B, effectively kills lung cancer cells without harming normal lung cells in vitro, and it also prevents cancer cells from forming tumor-like structures.

In mouse models, CB1a significantly inhibits tumor growth compared to docetaxel, showing higher selectivity for cancer cells and lower toxicity to healthy cells, suggesting it could be a safer alternative for lung cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibition effect of a custom peptide on lung tumors. Huang, CY., Huang, HY., Forrest, MD., et al.[2023]

A new peptide mimetic (SP18-28) that inhibits the activity of the CtIP protein has been developed, which disrupts DNA double-strand break repair and leads to increased DNA damage in cancer cells.

This peptide shows promise in selectively reducing the viability of BRCA1-mutated cancer cell lines, suggesting it could be a potential targeted therapy for certain types of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A stapled peptide mimetic of the CtIP tetramerization motif interferes with double-strand break repair and replication fork protection. Kuster, A., Mozaffari, NL., Wilkinson, OJ., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6292929/

Curaxin CBL0137 Exerts Anticancer Activity via Diverse ... CBL0137 exhibits an antitumor activity in multiple cancers, including glioblastoma, renal cell carcinoma, melanoma, neuroblastoma, and small cell lung cancer ( ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4294371/

Curaxin CBL0137 eradicates drug resistant cancer stem ... Taken together, these data suggested that CBL0137 may be effective against PDA. In the studies presented here, the levels of the indirect ...

3. cancer.gov cancer.gov/publications/dictionaries/cancer-drug/def/fact-complex-targeting-curaxin-cbl0137

Definition of FACT complex-targeting curaxin CBL0137 This causes an increase in tumor cell apoptosis and a decrease in tumor cell proliferation, in FACT-positive cancers. In addition, this agent is able to ...

4. biosignaling.biomedcentral.com biosignaling.biomedcentral.com/articles/10.1186/s12964-022-01031-x

The FACT-targeted drug CBL0137 enhances the effects of ... The FACT-targeted drug CBL0137 enhances the effects of rituximab to inhibit B-cell non-Hodgkin's lymphoma tumor growth by promoting apoptosis and autophagy.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04870944

CBL0137 for the Treatment of Relapsed or Refractory Solid ... This phase I/II trial evaluates the best dose, side effects and possible benefit of CBL0137 in treating patients with solid tumors, including central ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S0753332223003177

CBL0137 activates ROS/BAX signaling to promote ... Results of in vivo experiments revealed that CBL0137 also had anti-tumor effects on ovarian cancer cells in vivo. Our study outcomes reveal the mechanisms and ...