CBL0137 for Cancer

Recruiting in Palo Alto (17 mi)

+32 other locations

Overseen by David S Ziegler

Age: < 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

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

Trial Summary

What is the purpose of this trial?

This trial tests CBL0137, a drug that blocks signals inside cancer cells, in patients whose solid tumors, including CNS tumors or lymphoma, have returned or not responded to treatment. By interfering with the cells' internal communication, the drug aims to stop their growth and cause them to die. CBL0137, also known as Curaxin, has shown antitumor activity in multiple cancers, including glioblastoma, renal cell carcinoma, melanoma, neuroblastoma, and small cell lung cancer.

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.

What makes the drug CBL0137 unique for cancer treatment?

CBL0137 is unique because it targets the FACT complex, a protein complex involved in DNA transcription, replication, and repair, which is not a common target for existing cancer treatments. This novel mechanism of action may offer a new approach to treating cancers that are resistant to other therapies. ^{1 2 3 4 5}

Research Team

David S Ziegler

Principal Investigator

Pediatric Early Phase Clinical Trial Network

Eligibility Criteria

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

Trial Timeline

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

Treatment Details

Interventions

• CBL0137 (Curaxin)

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.

Participant Groups

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 also undergo bone marrow aspirate and/or biopsy at baseline, ECHO prior to cycle 1, and as clinically indicated undergo collection of blood samples throughout the trial.

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

UCSF Medical Center-Mission Bay San Francisco, CA

UT Southwestern/Simmons Cancer Center-Dallas Dallas, TX

Oregon Health and Science University Portland, OR

Children's Healthcare of Atlanta - Egleston Atlanta, GA

More Trial Locations

Who Is Running the Clinical Trial?

Children's Oncology Group

Lead Sponsor

Trials

467

Patients Recruited

241,000+

Incuron LLC

Collaborator

Trials

1

Patients Recruited

100+

National Cancer Institute (NCI)

Collaborator

Trials

14080

Patients Recruited

41,180,000+

Findings from Research

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]

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]

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]

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]

References

1. United States 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. [2018]

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

Exploiting the TRIP-Br family of cell cycle regulatory proteins as chemotherapeutic drug targets in human cancer. [2020]

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

A stapled peptide mimetic of the CtIP tetramerization motif interferes with double-strand break repair and replication fork protection. [2022]

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

Inhibition effect of a custom peptide on lung tumors. [2023]

5. United States 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. [2019]