Dabrafenib + Trametinib Access for Cancer

Recruiting at 15 trial locations

Overseen By Novartis Pharmaceuticals

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Novartis Pharmaceuticals

Must be taking: Dabrafenib, Trametinib

Disqualifiers: Unresolved toxicities, Commercial availability, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 10 years

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial continues treatment for cancer patients who have used dabrafenib (a BRAF inhibitor) and/or trametinib in a previous study. The main goal is to provide ongoing access to these medications for patients who have benefited from them. Participants can receive dabrafenib alone, trametinib alone, or a combination of both. Suitable candidates for this trial are those currently on these treatments and advised by their doctor to continue them. As a Phase 4 trial, this study involves treatments already FDA-approved and proven effective, aiming to understand how they benefit more patients.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It seems focused on continuing treatment with dabrafenib and/or trametinib for those already on these medications.

What is the safety track record for dabrafenib and trametinib?

Research has shown that dabrafenib and trametinib, whether used alone or together, are generally safe. Dabrafenib has proven safe and effective over the long term, particularly for treating BRAF-mutant melanoma, a type of skin cancer. Patients often live longer without their cancer worsening.

Trametinib has also been studied for safety and effectiveness. While some side effects occur, they are usually manageable. Like dabrafenib, trametinib treats similar conditions.

When used together, dabrafenib and trametinib significantly decrease the risk of cancer returning or spreading. This combination also extends patient survival. Some reports mention skin-related side effects, such as basal cell carcinoma, but these are uncommon.

Overall, these treatments are considered safe, especially since the FDA has approved them for certain conditions, indicating they have undergone thorough testing to ensure safety. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about dabrafenib and trametinib because these treatments target specific mutations in cancer cells, offering a more personalized approach compared to traditional chemotherapy. Dabrafenib works by inhibiting the BRAF protein, which is often mutated in certain cancers, while trametinib targets the MEK protein in the same pathway. This combined action disrupts cancer cell growth more effectively. Unlike standard treatments that might not specifically target these pathways, this combination therapy aims to halt cancer progression by directly interfering with the molecular processes that fuel tumor growth.

What is the effectiveness track record for dabrafenib and trametinib in cancer treatment?

Research shows that using dabrafenib and trametinib together has successfully treated certain cancers. In this trial, participants may receive either the combination therapy of dabrafenib and trametinib or monotherapy with either drug. Studies have found that the combination helps patients with advanced melanoma live longer compared to using either drug alone. Specifically, one study found that 45% of patients who received the combination were still alive after three years. When dabrafenib was used alone, some patients showed a 69% overall response rate. Conversely, trametinib alone led to an average of 4.9 months before the cancer worsened in another study. This evidence suggests these treatments can be effective options for cancer patients. ^{1 4 6 7 8}

Who Is on the Research Team?

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Are You a Good Fit for This Trial?

This trial is for patients already taking dabrafenib and/or trametinib in a Novartis or former GSK study, who have met the main goals of that study and are seen by their doctor as benefiting from ongoing treatment. It's not open to those who've had to stop these drugs due to side effects or if the drugs are available commercially with reimbursement in their country.

Inclusion Criteria

In the opinion of the Investigator would benefit from continued treatment.

I am currently on dabrafenib/trametinib treatment in a Novartis or GSK study.

Exclusion Criteria

Patient has been previously permanently discontinued from study treatment in the parent protocol.

My treatment is approved and covered by insurance in my country.

I had side effects from dabrafenib/trametinib that stopped my treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive dabrafenib and/or trametinib as monotherapy or combination therapy

Up to 10 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Participants continue to receive treatment until it becomes commercially available or another access program is available

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Dabrafenib
• Trametinib

Trial Overview The trial provides continued access to dabrafenib and/or trametinib for patients with certain cancers like lung cancer, melanoma, solid tumors, rare cancers, or brain tumors. These medications were part of previous studies by Novartis/GSK where participants showed benefits.

How Is the Trial Designed?

Group I: trametinib monotherapy Experimental Treatment 1 Intervention

Patients in this study may receive: \- monotherapy of trametinib

Group II: dabrafenib monotherapy Experimental Treatment 1 Intervention

Patients in this study may receive: \- monotherapy of dabrafenib

Group III: Combination therapy (dabrafenib & trametinib) Experimental Treatment 2 Interventions

Patients in this study may receive: \- the combination of dabrafenib and trametinib

Dabrafenib is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Tafinlar for:

• Unresectable or metastatic melanoma with a BRAF V600 mutation
• Adjuvant treatment of melanoma with a BRAF V600 mutation

Approved in United States as Tafinlar for:

• Unresectable or metastatic melanoma with a BRAF V600E mutation
• Adjuvant treatment of melanoma with a BRAF V600E or V600K mutation
• Metastatic non-small cell lung cancer with a BRAF V600E mutation

Approved in Canada as Tafinlar for:

• Unresectable or metastatic melanoma with a BRAF V600 mutation
• Adjuvant treatment of melanoma with a BRAF V600 mutation

Approved in Japan as Tafinlar for:

• Unresectable or metastatic melanoma with a BRAF V600 mutation

Who Is Running the Clinical Trial?

Novartis Pharmaceuticals

Lead Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Published Research Related to This Trial

In a study of 66 patients with metastatic BRAF-mutated melanoma treated with dabrafenib and trametinib, 15 patients achieved a complete response (CR), indicating a significant survival benefit from this treatment.

The likelihood of achieving a complete response was higher in patients with smaller lesions (39.3% CR rate) compared to those with larger lesions (10.5% CR rate), suggesting that lesion size and the number of metastatic sites are important factors in treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BRAFi/MEKi in patients with metastatic melanoma: predictive factors of complete response. Ribero, S., Malavenda, O., Fava, P., et al.[2019]

The combination of dabrafenib and trametinib significantly improves progression-free survival and overall survival in patients with unresectable or metastatic melanoma with a BRAF (V600E/K) mutation, compared to monotherapy with dabrafenib or vemurafenib, based on results from two large phase III studies.

This combination therapy is well-tolerated, showing no increase in overall toxicity compared to monotherapy, and results in fewer skin-related adverse events, likely due to reduced activation of the MAPK pathway.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dabrafenib plus Trametinib: a Review in Advanced Melanoma with a BRAF (V600) Mutation. Dhillon, S.[2022]

In a compassionate-use setting involving 271 patients with BRAF V600-mutant unresectable or metastatic melanoma, the combination of dabrafenib and trametinib demonstrated a high overall response rate of 67.3% and a median overall survival of 20.0 months for BRAFi-naive patients.

The treatment was well tolerated with no new safety concerns, showing significant clinical activity even in patients with brain metastases, indicating its effectiveness across different treatment lines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dabrafenib plus trametinib is effective in the treatment of BRAF V600-mutated metastatic melanoma patients: analysis of patients from the dabrafenib plus trametinib Named Patient Program (DESCRIBE II). Atkinson, V., Sandhu, S., Hospers, G., et al.[2023]

A validated assay was developed to simultaneously measure the levels of dabrafenib and trametinib in human plasma, which is crucial for therapeutic drug monitoring in patients with BRAF V600 mutation positive melanoma.

The assay demonstrated high accuracy and precision, with results meeting US FDA and EMA guidelines, ensuring reliable monitoring of these medications in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Simultaneous quantification of dabrafenib and trametinib in human plasma using high-performance liquid chromatography-tandem mass spectrometry. Nijenhuis, CM., Haverkate, H., Rosing, H., et al.[2017]

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 dabrafenib and trametinib showed promising antitumor activity in Japanese patients with BRAF V600E/K mutant melanoma, with an overall response rate of 83% in both phase 1 and phase 2 of the study involving 12 patients.

The treatment was generally well-tolerated, with common adverse events including fever (75%) and increased liver enzymes (67%), indicating that while effective, monitoring for side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1/2 study assessing the safety and efficacy of dabrafenib and trametinib combination therapy in Japanese patients with BRAF V600 mutation-positive advanced cutaneous melanoma. Yamazaki, N., Tsutsumida, A., Takahashi, A., et al.[2018]

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 demonstrated significant clinical activity in patients with BRAF(V600E/K) mutation-positive metastatic melanoma, with a 59% overall response rate in the BRAF(V600E) group and a median overall survival of 13.1 months.

The treatment was generally well tolerated, with common side effects including arthralgia and hyperkeratosis, and baseline circulating cell-free DNA (cfDNA) levels were found to predict treatment response and progression-free survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial (BREAK-2) of the BRAF inhibitor dabrafenib (GSK2118436) in patients with metastatic melanoma. Ascierto, PA., Minor, D., Ribas, A., et al.[2022]

Dabrafenib is an effective treatment for unresectable or metastatic melanoma in patients with the BRAF V600E mutation, which is present in about 50% of malignant melanomas, and has received approval in the US and a positive opinion in the EU.

Ongoing studies are exploring dabrafenib's use both as a standalone treatment and in combination with trametinib, as well as its potential for treating other cancers like colorectal and non-small cell lung cancers, particularly in patients with BRAF V600E/K mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dabrafenib: first global approval. Ballantyne, AD., Garnock-Jones, KP.[2021]

The combination of dabrafenib and erlotinib significantly enhances the inhibition of cell proliferation, colony formation, and migration in BRAF-mutated anaplastic thyroid carcinoma (ATC) cells, compared to using either drug alone.

This combination treatment also effectively suppresses tumor growth and induces apoptosis in an in vivo xenograft model, suggesting it could be a promising strategy to overcome resistance to dabrafenib in patients with BRAF-mutated ATC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of dabrafenib and erlotinib combination treatment on anaplastic thyroid carcinoma. Choi, YS., Kwon, H., You, MH., et al.[2022]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/jco.2012.30.15_suppl.8510

Updated safety and efficacy results from a phase I/II study ... Demographic and efficacy data for the 77 melanoma pts with no prior BRAFi and safety data for all 125 Part 2 pts are reported. Results ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31166680/

Five-Year Outcomes with Dabrafenib plus Trametinib in ... The overall survival rates were 37% (95% CI, 33 to 42) at 4 years and 34% (95% CI, 30 to 38) at 5 years. In multivariate analysis, several ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa1904059

Five-Year Outcomes with Dabrafenib plus Trametinib in ... First-line treatment with dabrafenib plus trametinib led to long-term benefit in approximately one third of the patients who had unresectable or metastatic ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0169500224005725

Real-world efficacy of the dabrafenib-trametinib (D-T) ... The findings confirmed the significant efficacy of DT in combination with BRAF V600E-mutated metastatic NSCLC in pretreated and untreated patients.

5. annalsofoncology.org annalsofoncology.org/article/S0923-7534(19)50260-5/fulltext

Updated efficacy and safety data of dabrafenib (D) ... Among 16 pts, overall response rate (ORR) was 69%, and median duration of response (DOR), progression-free survival (PFS), and OS were not reached (NR) due to ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/28475671/

long-term survival and safety analysis of a phase 3 study These data demonstrate that durable (≥3 years) survival is achievable with dabrafenib plus trametinib in patients with BRAF V600-mutant metastatic melanoma.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT01072175

NCT01072175 | Investigate Safety, Pharmacokinetics and ... This was an open-label, dose escalation study to investigate the safety, pharmacokinetics, pharmacodynamics and clinical activity of GSK2118436 and GSK1120212 ...

8. ema.europa.eu ema.europa.eu/en/documents/rmp/tafinlar-epar-risk-management-plan_en.pdf

Dabrafenib EU Safety Risk Management Plan - EMA Based on 2006 to 2008 SEER cancer registry data among ... This study will facilitate data collection of the long-term outcomes of pediatric subjects who.