DCC-3084 for Cancer

Not currently recruiting at 8 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new cancer drug, DCC-3084, to evaluate its effectiveness both alone and in combination with other treatments for advanced cancers. The trial begins by testing different doses and then expands to assess the treatment's efficacy. Individuals with solid tumors and specific gene mutations (such as BRAF), who have exhausted all standard treatments, may qualify. The trial requires participants to be able to take oral medication and have a life expectancy of more than six months. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

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.

Is there any evidence suggesting that DCC-3084 is likely to be safe for humans?

Research has shown that DCC-3084 is designed to block a specific process in cancer cells, potentially stopping tumor growth. Lab models have tested this treatment, showing promising results in shrinking tumors or halting their growth.

As the trial is in its early stages, the primary focus is on assessing the safety of DCC-3084 in humans. Researchers closely monitor how well participants tolerate the treatment and any side effects. At this stage, trials often test different doses to determine the safest and most effective amount for patients.

Although there is limited data from human studies, this phase of the trial is crucial to ensure the treatment's safety for broader use. If DCC-3084 receives approval for other uses in the future, it will have passed thorough safety evaluations. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

DCC-3084 is unique because it may offer a new mechanism of action for treating cancer, potentially targeting cancer cells in a way that existing therapies do not. While most standard treatments like chemotherapy and radiation target rapidly dividing cells broadly, DCC-3084 may have a more precise approach, which could lead to fewer side effects. Researchers are excited about this treatment because it could provide a more effective and safer option for patients, potentially improving outcomes and quality of life.

What evidence suggests that DCC-3084 could be an effective treatment for cancer?

Research has shown that DCC-3084 is a promising treatment for advanced cancers. The trial will evaluate DCC-3084 in two phases: the Escalation Phase (ModA Part 1) and the Expansion Phase (ModA Part 2). This treatment blocks certain proteins that help cancer cells grow, potentially slowing or stopping tumor growth. Studies have demonstrated that it can target different changes in cancer cells, leading to tumor shrinkage in early tests. Additionally, DCC-3084 can reach the brain, which is crucial for treating cancers that have spread there. These findings suggest that DCC-3084 could effectively treat various advanced cancers. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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, 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06287463

NCT06287463 | Study of DCC-3084 in Participants With ... 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.

2. deciphera.com deciphera.com/sites/default/files/publication-files/DCR2302068g%20AACR%202023%20DCC-3084%20RAF%20Dimer%20Inhibitor%20Poster_07Apr2023_66x42_FINAL%20%281%29.pdf

DCC-3084, a RAF dimer inhibitor, broadly inhibits BRAF ... This allows DCC-3084 to bind both monomers of a RAF dimer (left), enabling pathway inhibition in RAS-mutant cancers and limiting pERK activity.

3. aacrjournals.org aacrjournals.org/cancerres/article/84/6_Supplement/593/740530/Abstract-593-DCC-3084-a-brain-penetrant-RAF-dimer

Abstract 593: DCC-3084, a brain penetrant RAF dimer ... The switch-control inhibitor DCC-3084 broadly inhibits Class I, II and III BRAF mutations, BRAF fusions, and BRAF/CRAF heterodimers leading to tumor regression ...

4. researchgate.net researchgate.net/publication/369814233_Abstract_4045_DCC-3084_a_RAF_dimer_inhibitor_broadly_inhibits_BRAF_class_I_II_III_BRAF_fusions_and_RAS-driven_solid_tumors_leading_to_tumor_regression_in_preclinical_models

DCC-3084, a RAF dimer inhibitor, broadly inhibits BRAF ... LiPyDau demonstrated robust efficacy across all models including multidrug-resistant cancer, completely eradicating tumors in a genetically ...

5. synapse.patsnap.com synapse.patsnap.com/drug/12cfa20f1c254ee7b3471ed24e3ad053

DCC-3084 - Drug Targets, Indications, Patents Publication in Nature Medicine in January 2024 of the results of a ctDNA analysis from the INTRIGUE Phase 3 study demonstrating substantial clinical benefit ...

6. cancer.gov cancer.gov/publications/dictionaries/cancer-drug/def/raf-inhibitor-dcc-3084

Definition of RAF inhibitor DCC-3084 - NCI Drug Dictionary This prevents the activation of Raf-mediated signal transduction pathways, which may inhibit tumor cell growth. Raf protein kinases are critical enzymes in the ...

7. deciphera.com deciphera.com/sites/default/files/publication-files/R%26D%20Day%20Event%20Slide%20Deck_FINAL_0.pdf

One Mission, Inspired by Patients: Defeat Cancer.™ opportunity; submitting an IND for DCC-3084, presenting preclinical data for DCC-3084; nominating additional development candidates from our ...

8. aacrjournals.org aacrjournals.org/cancerres/article/83/7_Supplement/4045/724673/Abstract-4045-DCC-3084-a-RAF-dimer-inhibitor

DCC-3084, a RAF dimer inhibitor, broadly inhibits BRAF class ... DCC-3084, a RAF dimer inhibitor, broadly inhibits BRAF class I, II, III, BRAF fusions, and RAS-driven solid tumors leading to tumor regression ...