Dinaciclib for Advanced Melanoma

Not currently recruiting at 224 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of the drug dinaciclib for patients with advanced melanoma, a type of skin cancer. Dinaciclib may help by inhibiting the growth of cancer cells. Researchers seek to understand its side effects and effectiveness in individuals with stage IV melanoma, particularly if the cancer originates from the skin or mucous membranes. Those diagnosed with stage IV melanoma, without brain metastasis, might be suitable candidates. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that dinaciclib is likely to be safe for humans?

Research has shown that dinaciclib has undergone safety testing in several studies. One study found that when patients with various advanced solid tumors received dinaciclib, it was generally safe and well-tolerated. Patients received the treatment once a week for three weeks, and most managed it well.

Another study indicated that dinaciclib can help kill cancer cells, showing promise for treating melanoma. However, earlier trials in melanoma stopped due to insufficient patient enrollment, not safety concerns.

Overall, while early evidence suggests safety, this trial is part of ongoing research to better understand dinaciclib's side effects and effectiveness in treating stage IV melanoma. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Dinaciclib is unique because it targets specific proteins called cyclin-dependent kinases (CDKs), which play a crucial role in cell division and are often overactive in melanoma cells. Unlike traditional treatments like checkpoint inhibitors or targeted therapies that focus on different pathways, dinaciclib aims directly at halting the cancer cell cycle, potentially leading to more effective tumor control. Researchers are excited about this treatment as it offers a novel mechanism of action that could work even in cases where other treatments have failed, providing hope for patients with advanced melanoma.

What evidence suggests that dinaciclib might be an effective treatment for advanced melanoma?

Research has shown that dinaciclib, which participants in this trial will receive, might help treat advanced melanoma by blocking enzymes that enable cancer cell growth. Studies have found that it can cause melanoma cells to die, especially when specific proteins are active. In earlier trials, about 20% of patients with advanced melanoma did not experience cancer progression for three years after treatment with dinaciclib. This suggests that the treatment might slow or halt cancer growth in some patients. Overall, early results are promising, particularly for those with less severe disease. ^{2 3 5 6 7}

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.

No concurrent grapefruit or grapefruit juice

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

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

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]

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]

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]

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]

Citations

1. acsjournals.onlinelibrary.wiley.com acsjournals.onlinelibrary.wiley.com/doi/full/10.1002/cncr.35587

Southwest Oncology Group S0826: A phase 2 trial of SCH ... Dinaciclib (SCH 727965) is a CDK2 inhibitor with additional activity against CDK1, CDK5, and CDK9, which has demonstrated activity in xenograft ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7007861/

Rational combination therapy for melanoma with dinaciclib ... We demonstrated that dinaciclib has potent anti-melanoma effects by inducing BAK-dependent apoptosis through MCL1 reduction. Contrary to dinaciclib, the ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT01026324

Dinaciclib in Treating Patients With Stage III-IV Melanoma This is a phase I/II trial is studying the side effects and best dose of dinaciclib and to see how well it works in treating patients with advanced melanoma ...

4. withpower.com withpower.com/trial/dinaciclib-for-advanced-melanoma-7c005

Dinaciclib for Advanced Melanoma · Info for Participants Approximately 20% of patients were progression-free at 3 years, with better outcomes associated with having fewer than three organ metastases and lower baseline ...

5. journals.plos.org journals.plos.org/plosone/article?id=10.1371/journal.pone.0059588

The Anti-Melanoma Activity of Dinaciclib, a Cyclin-Dependent ... These data show that dinaciclib induces apoptosis in a large panel of melanoma cell lines through a mechanism requiring p53 expression.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5672931/

Phase 1 safety, pharmacokinetic and pharmacodynamic study ... This Phase 1 study evaluated the safety, tolerability and pharmacokinetics of various dosing schedules of dinaciclib in advanced solid tumour patients and ...

7. translational-medicine.biomedcentral.com translational-medicine.biomedcentral.com/articles/10.1186/1479-5876-11-259

A first-in-human, phase 1, dose-escalation study of dinaciclib ... Dinaciclib administered every week for 3 weeks (on days 1, 8, and 15 of a 28-day cycle) was generally safe and well tolerated.