AZD6244 + Chemotherapy for Advanced Cancer

Not currently recruiting at 3 trial locations
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new cancer treatment by combining AZD6244, an oral medication, with standard chemotherapy. The study aims to determine if this combination is safe for individuals with advanced solid tumors and to identify the highest tolerable dose. Researchers will also examine how the body absorbs and processes the drugs. Individuals with advanced cancer who can swallow pills may be suitable candidates for this trial, particularly if other treatment options are unavailable. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it does exclude those who have taken a MEK inhibitor before, so you may need to discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that combining AZD6244 with various chemotherapy drugs is generally safe. In one study, patients taking AZD6244 with docetaxel experienced manageable side effects. Another study found that when AZD6244 was used with dacarbazine, common side effects included nausea and rash, but these were not severe for most participants.

Similarly, when AZD6244 was combined with erlotinib or temsirolimus, side effects were mostly mild to moderate. Common issues included diarrhea, rash, and fatigue. These side effects were manageable and did not prevent participants from continuing treatment.

Overall, the safety data suggest that while some side effects occur, the treatment combinations are generally well-tolerated. It is important to consult a healthcare provider about any concerns before joining a trial.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about AZD6244 because it targets a specific pathway in cancer cells called the MAPK/ERK pathway, which plays a key role in cell growth and survival. Unlike traditional chemotherapy drugs that target rapidly dividing cells more broadly, AZD6244 offers a more targeted approach by specifically inhibiting this pathway, potentially leading to fewer side effects. Moreover, when combined with other treatments like docetaxel, dacarbazine, erlotinib, or temsirolimus, AZD6244 could enhance their effectiveness by overcoming resistance mechanisms that cancer cells often develop. This targeted approach could mean better outcomes for patients with advanced cancer, offering a promising alternative to existing treatments.

What evidence suggests that this trial's treatments could be effective for advanced cancer?

This trial will evaluate the effectiveness of AZD6244 combined with different chemotherapy drugs for treating advanced cancers. Research has shown that combining AZD6244 with these drugs may improve outcomes. For instance, participants receiving AZD6244 with docetaxel may experience longer periods without cancer worsening, as one study found an increase from 2.8 months to 3.9 months compared to chemotherapy alone. Another arm of the trial will test AZD6244 with dacarbazine, where patients have experienced more stable disease conditions. Trials with AZD6244 and erlotinib have shown some improvement in controlling tumors for certain patients. Additionally, early research with AZD6244 and temsirolimus suggests it might be more effective against tumors, though more information is needed. Overall, AZD6244 shows promise when used with these chemotherapy drugs in the various treatment arms of this trial.12356

Who Is on the Research Team?

JI

Jeffrey Infante, MD

Principal Investigator

SCRI Development Innovations, LLC

PL

Patricia LoRusso, DO

Principal Investigator

Barbara Ann Karmanos Cancer Institute

RC

Roger Cohen, MD

Principal Investigator

Fox Chase Cancer Center

KK

Kevin Kim, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

My cancer can't be cured with surgery or radiation, and chemotherapy is the standard treatment for me.
I can carry out all my usual activities without help.
I can swallow capsules.

Exclusion Criteria

I have been treated with a MEK inhibitor before.
Participation in a clinical study during the last 30 days or have not recovered from side effects of an investigational study drug
My brain or spinal cord cancer has been treated, is stable for 1 month, and I'm not on steroids.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive AZD6244 in combination with standard doses of selected chemotherapies to assess safety, tolerability, and pharmacokinetics

28 days
Initial and periodic assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

  • AZD6244
Trial Overview 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.
How Is the Trial Designed?
4Treatment groups
Experimental Treatment
Group I: 4Experimental Treatment2 Interventions
Group II: 3Experimental Treatment2 Interventions
Group III: 2Experimental Treatment2 Interventions
Group IV: 1Experimental Treatment2 Interventions

Find a Clinic Near You

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials
4,491
Recruited
290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Published Research Related to This Trial

In a phase I trial involving 22 patients with hormone-resistant prostate cancer, the combination of docetaxel (DTX) and zoledronic acid (ZOL) administered bi-weekly showed promising anti-tumor activity, particularly with the sequence of DTX followed by ZOL.
Sequence A (DTX followed by ZOL) resulted in disease control in 6 out of 9 patients and a decrease in biological markers, while sequence B did not demonstrate any anti-tumor activity.
Metronomic administration of zoledronic acid and taxotere combination in castration resistant prostate cancer patients: phase I ZANTE trial.Facchini, G., Caraglia, M., Morabito, A., et al.[2020]
The combination of zoledronic acid (ZOL) and docetaxel significantly inhibited the growth of prostate cancer tumors in a bone environment, suggesting a potential new treatment strategy for hormone-refractory metastatic prostate cancer.
ZOL alone decreased the proliferation of prostate cancer cells in bone, while docetaxel did not show effectiveness in this environment, highlighting the importance of combining therapies to enhance treatment efficacy.
Administration of zoledronic acid enhances the effects of docetaxel on growth of prostate cancer in the bone environment.Brubaker, KD., Brown, LG., Vessella, RL., et al.[2018]
In a study of 114 patients with stage IV non-small cell lung cancer (NSCLC) and metastatic bone disease (MBD), only 37.7% received zoledronic acid (ZA) alongside their first chemotherapy treatment.
Patients who received ZA with chemotherapy (ZCt) had significantly better overall survival, with a median of 34 weeks compared to 19 weeks for those who received chemotherapy alone, suggesting that ZA may enhance treatment outcomes in this patient population.
Under usage of zoledronic acid in non-small cell lung cancer patients with metastatic bone disease--a short communication.Calderone, R., Nimako, K., Leary, A., et al.[2018]

Citations

1.pubmed.ncbi.nlm.nih.govpubmed.ncbi.nlm.nih.gov/28264648/
A phase I dose-escalation study of selumetinib in combination ...We assessed the safety, tolerability, and pharmacokinetics (PK) of selumetinib (AZD6244, ARRY-142886) in combination with docetaxel or dacarbazine in patients ...
Selumetinib in Combination With Dacarbazine in Patients ...In the selumetinib plus dacarbazine group, 82 patients (85%) experienced a PFS event, compared with 24 (75%) in the placebo plus dacarbazine ...
Articles Selumetinib plus dacarbazine versus placebo ...This study was designed to look for a signal of improved efficacy by comparing the combination of selumetinib and dacarbazine with dacarbazine alone.
A three-arm randomised phase II study of the MEK inhibitor ...3 Results ; Stable Disease (SD), 13 (50%), 30 (59%) ; Progressive Disease/Death (PD), 12 (46%), 12 (24%) ; Missing, 2 (4%) ; Objective Response Rate ...
A trial of selumetinib with dacarbazine for advanced ...Despite causing more side effects, the trial team concluded that having dacarbazine alongside selumetinib improved progression free survival for people ...
NCT00600496 | A Phase I, Open-Label, Multi-center Study ...This study is being conducted to determine if a combination of AZD6244 given orally twice a day with standard doses of selected chemotherapies will be safe ...
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