What side effects are associated with this type of intervention?

Common treatments for melanoma, particularly those involving MEK inhibitors like AZD6244, include drugs such as cobimetinib. The most frequent side effects of these treatments are diarrhea, rash, fatigue, edema, nausea, and vomiting. Additionally, other adverse events may include ocular toxicities, such as keratitis and uveitis, and cutaneous side effects like alopecia and vitiligo. These side effects can vary in severity and may impact the patient's quality of life.

What prior FDA approvals exist?

The FDA has approved several treatments for melanoma, including MEK inhibitors similar to AZD6244. Trametinib, a MEK inhibitor, is approved for use in combination with dabrafenib, a BRAF inhibitor, for the treatment of patients with BRAF V600E or V600K mutation-positive unresectable or metastatic melanoma. Additionally, checkpoint inhibitors such as pembrolizumab and nivolumab, either alone or in combination with ipilimumab, have been approved for advanced melanoma. These treatments have shown efficacy in improving progression-free survival and overall survival in patients with metastatic melanoma.

What other types of research exist?

Promising novel alternatives to AZD6244 for melanoma patients include: 1) Dabrafenib-Trametinib combination, particularly for patients with BRAF-V600 mutations, which has shown efficacy and safety in systematic reviews and meta-analyses. 2) Anti-PD-1/PD-L1 therapies such as pembrolizumab and nivolumab, which have demonstrated significant benefits in advanced melanoma. 3) Combination therapies involving BRAF inhibitors (e.g., vemurafenib) and MEK inhibitors (e.g., cobimetinib) for targeted treatment. 4) Emerging therapies like talimogene laherparepvec (T-VEC) combined with pembrolizumab, which are being evaluated in advanced clinical trials.

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MEK Inhibitor

AZD6244 + Chemotherapy for Advanced Cancer

Phase 1

Waitlist Available

Led By Jeffrey Infante, MD

Research Sponsored by AstraZeneca

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patients will have measurable and/or non-measurable disease, lacking curative options for whom the selected chemotherapy agents represent the standard of care

WHO performance status 0-1

Must not have

Prior treatment with a MEK inhibitor

Timeline

Screening 3 weeks

Treatment Varies

Follow Up cycle 1 day 3 and cycle 2 day 1

Awards & highlights

No Placebo-Only Group

Summary

This study is evaluating whether a combination of AZD6244 given orally twice a day with standard doses of selected chemotherapies will be safe and tolerable for cancer patients with advanced solid tumors. The highest tolerated dose of AZD6244 in combination with selected chemotherapies will be evaluated

Who is the study for?

This trial is for cancer patients with advanced solid tumors who have a good performance status, measurable disease, and no curative options left. They must be able to swallow pills and not have used MEK inhibitors before or been in another study within the last month.

What is being tested?

The trial tests AZD6244 taken orally twice daily alongside standard chemotherapy drugs like Temsirolimus, Dacarbazine, Erlotinib, and Docetaxel. It aims to find the highest dose of AZD6244 that's safe when combined with these chemotherapies.

What are the potential side effects?

Potential side effects may include typical reactions from chemotherapy such as nausea, fatigue, hair loss, increased risk of infection due to low blood cell counts; specific side effects related to AZD6244 are being studied.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My cancer can't be cured with surgery or radiation, and chemotherapy is the standard treatment for me.

Select...

I can carry out all my usual activities without help.

Select...

I can swallow capsules.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I have been treated with a MEK inhibitor before.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ cycle 1 day 3 and cycle 2 day 1

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~cycle 1 day 3 and cycle 2 day 1

This trial's timeline: 3 weeks for screening, Varies for treatment, and cycle 1 day 3 and cycle 2 day 1 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Safety and tolerability of twice daily oral doses of AZD6244 when administered in combination with standard doses of selected chemotherapies.

Secondary study objectives

Define highest tolerated dose of AZD6244 when in combination with selected chemotherapies.

Pharmacotherapy

Tumor response.

Side effects data

From 2020 Phase 2 trial • 334 Patients • NCT01248247

50%

Rash Acneiform

36%

Diarrhea

32%

Nausea

32%

Dry skin

27%

Anorexia

23%

Increased blood bilirubin

23%

Vomiting

23%

Increased AST

14%

Oral mucositis

14%

Weight loss

14%

Other skin and subcutaneous tissue disorders, specify

14%

Rash Maculopapular

14%

Epistaxis

Fatigue

Hyperglycemia

Increased alkaline phosphatase

Dry mouth

Lung infection

Pruritus

Hyponatremia

Dyspnea

Palmar-plantar erythrodysesthesia syndrome

Multi-organ failure

Hypoalbuminemia

Dysgeusia

100%

80%

60%

40%

20%

Study treatment Arm

Arm 1 - Erlotinib

Arm 3 - AZD6244 + MK-2206

Arm 4 - Sorafenib

Arm 2 - Erlotinib + MK-2206

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

4Treatment groups

Experimental Treatment

Group I: 4Experimental Treatment2 Interventions

AZD6244 + Temsirolimus

Group II: 3Experimental Treatment2 Interventions

AZD6244 + Erlotinib

Group III: 2Experimental Treatment2 Interventions

AZD6244 + Dacarbazine

Group IV: 1Experimental Treatment2 Interventions

AZD6244 + docetaxel

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Temsirolimus

2008

Completed Phase 2

~1940

AZD6244

2011

Completed Phase 2

~2220

Dacarbazine

2005

Completed Phase 3

~5350

Erlotinib

2011

Completed Phase 4

~2290

Docetaxel

1995

Completed Phase 4

~6550

0 / 4Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Melanoma treatments often target specific molecular pathways involved in cancer cell growth and survival. MEK inhibitors, such as AZD6244, block the MEK enzyme in the MAPK/ERK pathway, which is frequently overactive in melanoma cells, particularly those with BRAF mutations. This inhibition prevents cell proliferation and induces apoptosis. BRAF inhibitors target the BRAF V600E mutation directly, further disrupting the same pathway. Immunotherapies, including PD-1 inhibitors, enhance the immune system's ability to recognize and destroy cancer cells. These treatments are crucial for melanoma patients as they offer targeted approaches that can lead to more effective and personalized cancer care, potentially improving outcomes and reducing side effects compared to traditional chemotherapies.