DCC-3084 for Cancer

Recruiting at 7 trial locations

Overseen By Clinical Team

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Deciphera Pharmaceuticals LLC

Must not be taking: BRAF dimer inhibitors

Disqualifiers: Pregnancy, Cardiac issues, Recent surgery, others

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

Compensation: Varies

Number of Visits: 1

140 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a multicenter, Phase 1/2 clinical trial to evaluate DCC-3084 alone or in combination with other cancer therapies in participants with advanced cancers. Module A will enroll participants with advanced/metastatic solid tumors. Additional modules exploring other cancers may be added to the master protocol at a later date. Each module will be conducted in 2 parts: Part 1 (Dose Escalation) and Part 2 (Dose Expansion).

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but it mentions that you should not have received any medications or therapies that are prohibited with DCC-3084 within 14 days before starting the trial. It's best to discuss your current medications with the trial team to see if they are allowed.

What makes the drug DCC-3084 unique for cancer treatment?

DCC-3084 is unique because it targets the DCC gene, which is a tumor-suppressor gene often altered in cancers like colorectal cancer. This drug may work by restoring the function of this gene, potentially preventing cancer cells from growing and spreading. ^{1 2 3 4 5}

Eligibility Criteria

This trial is for adults with advanced cancers, including lung cancer, melanoma, and pancreatic cancer that are linked to specific genetic changes in the MAPK pathway. Participants should have a type of tumor or condition like RASopathy or Neurofibromatosis.

Inclusion Criteria

My cancer has a BRAF gene mutation.

I can take medicine by mouth.

I can provide a new biopsy and, if possible, an older sample of my cancer.

Exclusion Criteria

I haven't had any cancer other than my current type in the last 2 years.

Known allergy or hypersensitivity to any component of the study drug

I haven't taken any medications or therapies that conflict with DCC-3084 in the last 14 days.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive DCC-3084 in ModA Part 1 to determine the maximum tolerated dose

4 weeks

Cycle 1 (28 days)

Dose Expansion

Participants receive DCC-3084 in ModA Part 2 to further evaluate safety and efficacy

Estimated up to 24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Estimated up to 36 months

Treatment Details

Interventions

• DCC-3084

Trial Overview The study is testing DCC-3084, either alone or with other treatments. It's divided into two parts: first finding the right dose (Dose Escalation), then giving it to more people at this dose (Dose Expansion) to see how well it works and its safety.

Participant Groups

Group I: DCC-3084 Module A Expansion Phase (ModA Part 2) Experimental Treatment 1 Intervention

Participants will receive DCC-3084 in ModA Part 2, Expansion Phase.

Group II: DCC-3084 Module A Escalation Phase (ModA Part 1) Experimental Treatment 1 Intervention

Participants will receive DCC-3084 in ModA Part 1, Escalation Phase.

Who Is Running the Clinical Trial?

Deciphera Pharmaceuticals LLC

Lead Sponsor

Trials

17

Recruited

1,900+

Deciphera Pharmaceuticals, LLC

Lead Sponsor

Trials

19

Recruited

2,100+

Findings from Research

In a study of 30 colorectal cancer patients, DCC gene mRNA expression was significantly lower in cancerous tissues compared to adjacent non-cancerous tissues, indicating its potential role as a tumor-suppressor gene.

All colorectal cancer specimens with liver metastasis showed decreased DCC mRNA expression, suggesting that the loss of DCC function may contribute to the spread of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Decreased expression of DCC mRNA in human colorectal cancers. Itoh, F., Hinoda, Y., Ohe, M., et al.[2019]

The DCC gene, identified as a potential tumor suppressor, is significantly downregulated or absent in 88% of colorectal carcinoma cases, indicating its crucial role in this type of cancer.

The study also found reduced or absent expression of the DCC gene in some leukemias, suggesting it may have a role in the development of blood cancers as well.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[DCC gene and leukemia]. Miyake, K., Inokuchi, K.[2011]

The DCC gene was successfully transfected into the ovarian cancer cell line SKOV-3, leading to a significant reduction in cell proliferation and a lower half maximal inhibitory concentration (IC50) compared to control cells.

Expression of the DCC gene resulted in G1 phase cell cycle arrest and induced apoptosis in SKOV-3 cells, while in vivo studies showed that mice with SKOV-3/DCC cells had smaller tumor volumes and no tumorigenicity, suggesting a strong tumor-suppressive effect of the DCC gene.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of deleted in colorectal carcinoma gene on proliferation of ovarian cancer cell line SKOV-3 in vivo and in vitro. Cai, Y., Hu, CJ., Wang, J., et al.[2019]

The DCC gene, which is a candidate tumor-suppressor gene, spans approximately 1.4 Mb and consists of 29 exons, providing a detailed structure for future studies on its role in cancer.

Analysis of colorectal tumors revealed that many had lost the DCC gene region, and specific mutations were identified in some tumors, indicating potential links between DCC alterations and tumorigenesis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The DCC gene: structural analysis and mutations in colorectal carcinomas. Cho, KR., Oliner, JD., Simons, JW., et al.[2007]

In a study of 36 patients with gastric cancer, aberrant methylation of the DCC gene was found in 44% of primary gastric carcinomas, indicating a potential role in the early stages of gastric cancer development.

The presence of DCC methylation was significantly associated with the TNM stage of the cancer, suggesting that it may be a useful biomarker for assessing the progression of gastric carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Methylation of the DCC gene is lost in advanced gastric cancer. Hibi, K., Sakata, M., Sakuraba, K., et al.[2010]

References

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

Decreased expression of DCC mRNA in human colorectal cancers. [2019]

2. Japan pubmed.ncbi.nlm.nih.gov

[DCC gene and leukemia]. [2011]

3. China pubmed.ncbi.nlm.nih.gov

Influence of deleted in colorectal carcinoma gene on proliferation of ovarian cancer cell line SKOV-3 in vivo and in vitro. [2019]

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

The DCC gene: structural analysis and mutations in colorectal carcinomas. [2007]

5. Greece pubmed.ncbi.nlm.nih.gov

Methylation of the DCC gene is lost in advanced gastric cancer. [2010]