Dinaciclib for Advanced Melanoma

Recruiting at 220 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A4 inhibitors, inducers

Disqualifiers: Brain metastases, Ocular melanoma, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

Duration: 21 days per cycle, up to 3 years

72 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This phase II trial is studying the side effects and how well dinaciclib works in treating patients with stage IV melanoma. Dinaciclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Will I have to stop taking my current medications?

The trial requires that you do not take any other treatments like chemotherapy, hormonal therapy, or biologic therapy while participating. You also cannot take medications that affect the CYP3A4 enzyme, and you must avoid grapefruit and grapefruit juice.

How is the drug Dinaciclib unique in treating advanced melanoma?

Dinaciclib is unique because it is a cyclin-dependent kinase inhibitor, which works by blocking proteins that help cancer cells grow and divide. This mechanism is different from the commonly used BRAF and MEK inhibitors for melanoma, which target specific mutations in the cancer cells. ^{1 2 3 4 5}

Who Is on the Research Team?

Christopher D Lao

Principal Investigator

SWOG Cancer Research Network

Are You a Good Fit for This Trial?

This trial is for adults with stage IV melanoma who've had no more than one prior systemic treatment and have recovered from its side effects. They must not be pregnant or nursing, use effective contraception, and can't have brain metastases or ocular melanoma. Participants should not consume grapefruit, take certain other drugs, or have another cancer unless in remission for 5 years.

Inclusion Criteria

It has been over 28 days since my last chemotherapy.

I've had only one treatment for stage IV melanoma and any side effects are minimal.

I had surgery for my cancer and any side effects are mild.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive dinaciclib IV over 2 hours on day 1, with treatment repeating every 21 days in the absence of disease progression or unacceptable toxicity

21 days per cycle, up to 3 years

1 visit per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Every 6 months, up to 3 years

1 visit every 6 months (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Dinaciclib

Trial Overview The trial tests Dinaciclib's effectiveness and side effects on stage IV melanoma patients. Dinaciclib is thought to halt tumor growth by inhibiting enzymes necessary for cell proliferation. Patients' conditions are closely monitored to assess the drug's impact.

How Is the Trial Designed?

Group I: Arm I Experimental Treatment 1 Intervention

Patients receive dinaciclib IV over 2 hours on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

The combination of encorafenib (ENC) and binimetinib (BIN) was found to be cost-effective compared to cobimetinib (COB) and vemurafenib (VEM) only at a very high willingness-to-pay threshold of $573,000 per quality-adjusted life year (QALY).

The combination of dabrafenib (DAB) and trametinib (TRA) was determined to be the most optimal treatment option for BRAF-mutated advanced melanoma, dominating the COB + VEM combination in terms of cost-effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Economic Evaluation of Three BRAF + MEK Inhibitors for the Treatment of Advanced Unresectable Melanoma With BRAF Mutation From a US Payer Perspective. Halloush, S., Alkhatib, NS., Almutairi, AR., et al.[2023]

In a study of 78 BRAF inhibitor-naive patients with BRAF V600 mutation-positive metastatic melanoma treated with dabrafenib and trametinib, the median overall survival was over 2 years, with 72% of patients alive at 1 year and 47% at 3 years.

Approximately 20% of patients were progression-free at 3 years, with better outcomes associated with having fewer than three organ metastases and lower baseline lactate dehydrogenase levels, suggesting these factors may help predict durable responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overall Survival and Durable Responses in Patients With BRAF V600-Mutant Metastatic Melanoma Receiving Dabrafenib Combined With Trametinib. Long, GV., Weber, JS., Infante, JR., et al.[2022]

Targeted therapies for melanoma, such as BRAF inhibitors (vemurafenib and dabrafenib) and MEK inhibitors (trametinib), have significantly improved survival rates in patients with specific mutations, particularly BRAF mutations.

The combination of different kinase inhibitors is anticipated to further enhance overall survival and progression-free survival in patients with advanced melanoma, building on the success of existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted therapy in melanoma - the role of BRAF, RAS and KIT mutations. Goldinger, SM., Murer, C., Stieger, P., et al.[2022]

Dabrafenib and trametinib, both targeting the MAPK pathway, have shown significant efficacy in treating BRAF-mutant metastatic melanoma, with dabrafenib achieving a 59% objective response rate and improved progression-free survival compared to traditional chemotherapy.

The combination of dabrafenib and trametinib resulted in higher response rates and longer median progression-free survival than dabrafenib alone, while also presenting less cutaneous toxicity, making it a promising treatment option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dabrafenib and trametinib, alone and in combination for BRAF-mutant metastatic melanoma. Menzies, AM., Long, GV.[2022]

Citations

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

Economic Evaluation of Three BRAF + MEK Inhibitors for the Treatment of Advanced Unresectable Melanoma With BRAF Mutation From a US Payer Perspective. [2023]

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

Overall Survival and Durable Responses in Patients With BRAF V600-Mutant Metastatic Melanoma Receiving Dabrafenib Combined With Trametinib. [2022]

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

Dasatinib Resensitizes MAPK Inhibitor Efficacy in Standard-of-Care Relapsed Melanomas. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Targeted therapy in melanoma - the role of BRAF, RAS and KIT mutations. [2022]

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

Dabrafenib and trametinib, alone and in combination for BRAF-mutant metastatic melanoma. [2022]