DCR-STAT3 for Cancer

Recruiting in Palo Alto (17 mi)

+1 other location

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Dicerna Pharmaceuticals, Inc., a Novo Nordisk company

Must not be taking: Chemotherapy, Immunotherapy, Radiotherapy, others

Disqualifiers: HIV, HBV, HCV, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called DCR-STAT3 in adults with hard-to-treat solid tumors. The drug aims to block a protein that helps cancer grow, potentially shrinking the tumors or stopping their growth. Another compound, OPB-31121, is also being studied for its effects on the same protein.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that you cannot have other chemotherapy, immunotherapy, or radiotherapy within 28 days of starting the trial. Hormonal therapy is allowed.

What data supports the effectiveness of the drug DCR-STAT3 for cancer?

Research suggests that targeting STAT3, a protein involved in cancer growth and resistance to treatment, can help overcome resistance to standard cancer therapies. Inhibiting STAT3 has shown promise in reducing cancer cell survival and growth, indicating potential benefits for cancer treatment. ^{1 2 3 4 5}

What makes the drug DCR-STAT3 unique for cancer treatment?

DCR-STAT3 is unique because it targets the STAT3 pathway, which is crucial in creating an immunosuppressive environment that helps tumors grow and resist treatment. By inhibiting STAT3, this drug aims to enhance the body's immune response against cancer, potentially overcoming resistance to standard therapies. ^{1 6 7 8 9}

Research Team

John Hanrahan, MD MPH

Principal Investigator

Dicerna Phamaceuticals, a Novo Nordisk Company

Eligibility Criteria

Adults over 18 with advanced solid tumors or non-Hodgkin's lymphoma that can't be surgically removed and haven't responded to standard treatments. Participants must not be pregnant, agree to contraception, have a life expectancy of at least 3 months, and an ECOG status of 0-2 (able to perform daily activities). They cannot join if they've had certain recent treatments or are HIV/HBV/HCV positive.

Inclusion Criteria

My cancer is advanced and hasn't responded to standard treatments.

My condition worsened after treatment that usually works.

I cannot tolerate the standard treatment for my condition.

Exclusion Criteria

Known hypersensitivity to any of the components of DCR-STAT3

I haven't fully recovered from side effects of previous cancer treatment.

I have tested positive for HIV, HBV, or HCV but meet specific conditions if treated for HCV.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive DCR-STAT3 as a monotherapy in a dose-ranging study to evaluate safety, tolerability, and pharmacokinetics

8 weeks

Visits on Day 1 and Day 29 of each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• DCR-STAT3 (RNAi Therapeutics)

Trial Overview The trial is testing DCR-STAT3, a new drug for people with solid tumors that no longer respond to usual treatment. It's given in increasing doses to check its safety and how the body processes it. The study will gradually enroll more patients as it confirms lower doses are safe.

Participant Groups

Group I: DCR-STAT3 Experimental Treatment 1 Intervention

DCR-STAT3

Who Is Running the Clinical Trial?

Dicerna Pharmaceuticals, Inc., a Novo Nordisk company

Lead Sponsor

Trials

19

Recruited

580+

Findings from Research

STAT3 is a key player in many cancers, promoting tumor growth and survival, and its activation can be triggered by various signaling pathways, making it a critical target for cancer therapies.

Resistance to standard cancer treatments is often linked to persistent STAT3 activation, suggesting that combining these treatments with STAT3 inhibitors could improve patient outcomes, especially for cancer stem cells that are resistant to chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of STAT3 signaling in mediating tumor resistance to cancer therapy. Tan, FH., Putoczki, TL., Stylli, SS., et al.[2019]

Chemoradiotherapy (CRT) is a common treatment for many cancers, but some tumors show resistance, leading to ineffective treatment and unnecessary side effects for patients.

Recent evidence suggests that the STAT3 protein is a key player in mediating resistance to CRT, and targeting STAT3 could be a promising strategy to enhance the effectiveness of cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

STAT3: A Novel Molecular Mediator of Resistance to Chemoradiotherapy. Spitzner, M., Ebner, R., Wolff, HA., et al.[2021]

In a study of 154 patients with oesophageal adenocarcinoma (OAC) and squamous cell carcinoma (SCC), high levels of activated STAT3 (pSTAT3) were linked to worse survival outcomes in SCC, while higher pSTAT3 levels in OAC were associated with better survival, indicating a complex role of STAT3 in different cancer types.

Treatment with the STAT3 inhibitor STATTIC in cancer cell lines led to reduced survival, proliferation, and migration, along with increased apoptosis, suggesting that targeting STAT3 could be a promising therapeutic strategy for both OAC and SCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

pSTAT3 Levels Have Divergent Expression Patterns and Associations with Survival in Squamous Cell Carcinoma and Adenocarcinoma of the Oesophagus. O' Sullivan, KE., Michielsen, AJ., O' Regan, E., et al.[2018]

Constitutive activation of STAT3 is commonly found in many human tumors, including various hematological malignancies and solid tumors, and it plays a critical role in promoting cancer by inhibiting cell death and encouraging tumor growth and spread.

Targeting and suppressing STAT3 activation can induce apoptosis in cancer cells, and various strategies, such as tyrosine kinase inhibitors and RNA interference, are being explored to develop effective cancer therapies that target this pathway.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting the STAT3 signaling pathway in cancer: role of synthetic and natural inhibitors. Siveen, KS., Sikka, S., Surana, R., et al.[2022]

References

1. United Arab Emirates pubmed.ncbi.nlm.nih.gov

The role of STAT3 signaling in mediating tumor resistance to cancer therapy. [2019]

2. Switzerland pubmed.ncbi.nlm.nih.gov

STAT3: A Novel Molecular Mediator of Resistance to Chemoradiotherapy. [2021]

3. Switzerland pubmed.ncbi.nlm.nih.gov

pSTAT3 Levels Have Divergent Expression Patterns and Associations with Survival in Squamous Cell Carcinoma and Adenocarcinoma of the Oesophagus. [2018]

4. China pubmed.ncbi.nlm.nih.gov

[Molecular mechanisms involved in regulation of proliferation and apoptosis by STAT3 antisense oligonucleotide and chemotherapy in laryngeal cancer cells]. [2013]

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

Safety, tolerability, pharmacokinetics and preliminary antitumour activity of an antisense oligonucleotide targeting STAT3 (danvatirsen) as monotherapy and in combination with durvalumab in Japanese patients with advanced solid malignancies: a phase 1 study. [2022]

6. Germany pubmed.ncbi.nlm.nih.gov

STAT3: a target to enhance antitumor immune response. [2021]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Targeting the STAT3 signaling pathway in cancer: role of synthetic and natural inhibitors. [2022]

8. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Signal Transducer and Activator of Transcription Protein 3 (STAT3): An Update on its Direct Inhibitors as Promising Anticancer Agents. [2020]

9. France pubmed.ncbi.nlm.nih.gov

Targeting the STAT3 oncogenic pathway: Cancer immunotherapy and drug repurposing. [2023]