AZD6244 for Advanced Cancer

Not currently recruiting at 3 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: AstraZeneca

Must not be taking: Steroids, Anticonvulsants

Disqualifiers: Brain metastases, Severe disease, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 11.8 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called AZD6244, a potential cancer drug, for individuals with advanced cancer types that haven't responded to other treatments. The main goal is to determine the drug's safety and how the body processes it. Participants will receive varying doses to identify the most effective and safe amount. Suitable candidates have cancer that hasn't improved with standard therapies and are not currently undergoing treatments like chemotherapy. 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.

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. However, you cannot have had radiotherapy or chemotherapy within 21 days before joining the trial.

Is there any evidence suggesting that AZD6244 is likely to be safe for humans?

Research has shown that AZD6244, also known as selumetinib, has undergone safety testing in people. Earlier studies found that most patients tolerate it without major issues. However, like many medicines, it can cause some side effects. Common side effects include skin rash, diarrhea, and fatigue, similar to those of other drugs in its class. Serious side effects are rare but have been reported in a few cases. These results come from past research and are part of ongoing studies to assess the safety of AZD6244 for treating advanced cancer. Prospective trial participants should consult a healthcare provider to make an informed decision. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about AZD6244 for advanced cancer because it works by inhibiting a specific pathway known as MEK1/2, which plays a crucial role in cancer cell growth and survival. Unlike traditional chemotherapy that targets all rapidly dividing cells, AZD6244 specifically targets cancer cell signaling, potentially reducing side effects. This precision in targeting makes it a promising option that could offer more effective results with fewer side effects compared to current treatments like chemotherapy.

What evidence suggests that AZD6244 might be an effective treatment for advanced cancer?

Research has shown that AZD6244, also known as selumetinib, may help treat certain cancers. One study demonstrated that selumetinib, when combined with docetaxel, improved outcomes for patients with a specific type of lung cancer. Another study found that 72% of patients with a different condition responded well to the treatment, with many experiencing benefits for over six months. Selumetinib blocks proteins called MEK 1 and 2, which aid cancer cell growth. These findings suggest that AZD6244 could be effective for various advanced cancers by targeting the growth signals in cancer cells. Participants in this trial will receive different dosages of AZD6244 to evaluate its safety and effectiveness. ^{4 6 7 8 9}

Who Is on the Research Team?

Emerging Oncology Medical Science Director, MD

Principal Investigator

AstraZeneca

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors that haven't responded to standard treatments. Participants should be relatively active and mobile (WHO performance status 0-2), not pregnant, and must not have had recent chemotherapy or radiotherapy. Those with severe diseases or brain complications are excluded.

Inclusion Criteria

WHO performance status 0-2

evidence of post-menopausal status or negative pregnancy test

Your cancer has not responded to standard treatments.

Exclusion Criteria

You have taken part in another clinical trial with an experimental drug in the last 30 days.

You have received radiation or chemotherapy treatment within the last 21 days.

You have a severe and uncontrolled disease that affects your whole body.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single oral dose of AZD6244 followed by continuous dosing until disease progression or another protocol-defined discontinuation criterion is met

11.8 months

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 study is testing the safety and how the body processes a capsule form of AZD6244, a potential new cancer treatment. It's aimed at patients whose cancers have stopped responding to usual treatments.

How Is the Trial Designed?

Group I: Part B: Relative Bioavailability (Sequence 2) and Safety Assessment Phase Experimental Treatment 1 Intervention

Participants in relative bioavailability phase will receive a single oral dose of AZD6244 75 mg capsule on Day 1. Following a washout period of 7 days, participants will receive a single oral dose of AZD6244 100 mg free-base suspension (mix and drink) on Day 8 (Sequence 2). In the safety assessment phase, participants who will participate in the relative bioavailability phase will receive oral AZD6244 75 mg capsule bd dosing from Day 9 onwards until disease progression or another protocol-defined discontinuation criterion will be met, whichever will occur first.

Group II: Part B: Relative Bioavailability (Sequence 1) and Safety Assessment Phase Experimental Treatment 1 Intervention

Participants in relative bioavailability phase will receive a single oral dose of AZD6244 100 mg free-base suspension (mix and drink) on Day 1. Following a washout period of 7 days, participants will receive a single oral dose of AZD6244 75 mg capsule on Day 8 (Sequence 1). In the safety assessment phase, participants who will participate in the relative bioavailability phase will receive oral AZD6244 75 mg capsule bd dosing from Day 9 onwards until disease progression or another protocol-defined discontinuation criterion will be met, whichever will occur first.

Group III: Part A: Dose Escalation AZD6244 75 mg Experimental Treatment 1 Intervention

Participants will receive a single oral dose of AZD6244 75 mg capsule on Day 1 followed by continuous dosing from Day 2 onwards, until disease progression or another protocol-defined discontinuation criterion will be met, whichever will occur first.

Group IV: Part A: Dose Escalation AZD6244 50 mg Experimental Treatment 1 Intervention

Participants will receive a single oral dose of AZD6244 50 mg capsule on Day 1 followed by continuous dosing from Day 2 onwards, until disease progression or another protocol-defined discontinuation criterion will be met, whichever will occur first.

Group V: Part A: Dose Escalation AZD6244 25 mg Experimental Treatment 1 Intervention

Participants will receive a single oral dose of AZD6244 25 mg capsule on Day 1 followed by continuous twice daily (bd) dosing from Day 2 onwards, until disease progression or another protocol-defined discontinuation criterion will be met, whichever will occur first.

Group VI: Part A: Dose Escalation AZD6244 100 mg Experimental Treatment 1 Intervention

Participants will receive a single oral dose of AZD6244 100 mg capsule on Day 1 followed by continuous dosing from Day 2 onwards, until disease progression or another protocol-defined discontinuation criterion will be met, whichever will occur first.

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

AZD2171, a potent inhibitor of vascular endothelial growth factor receptors, can be safely combined with standard chemotherapy (carboplatin and paclitaxel) in patients with advanced non-small-cell lung cancer, showing no dose-limiting toxicities at doses of 30 mg or 45 mg per day.

The combination treatment resulted in a 45% response rate, with tumor shrinkage observed in nearly all patients, indicating promising antitumor activity despite some manageable side effects like fatigue and diarrhea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I and pharmacokinetic study of daily oral AZD2171, an inhibitor of vascular endothelial growth factor tyrosine kinases, in combination with carboplatin and paclitaxel in patients with advanced non-small-cell lung cancer: the National Cancer Institute of Canada clinical trials group. Laurie, SA., Gauthier, I., Arnold, A., et al.[2015]

ZD6474 effectively targets two important pathways in tumor growth, inhibiting both tumor angiogenesis and cell proliferation, which suggests a dual mechanism of action in fighting cancer.

Phase I trials indicate that ZD6474 is generally well tolerated and suitable for once-daily oral dosing, with ongoing Phase II studies comparing its efficacy against standard treatments in non-small-cell lung cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ZD6474--clinical experience to date. Heymach, JV.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4775365/

A Phase 2 Trial of AZD6244 (Selumetinib, ARRY-142886), an ... After AZD6244 discontinuation, 3 additional deaths occurred due to disease progression. The response rate (CR + PR) was 5.6% with a mean duration of response of ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5834012/

SELECT-2: a phase II, double-blind, randomized, placebo ... Results of a Phase II trial demonstrated that selumetinib in combination with docetaxel (SEL + DOC) improved clinical outcomes for patients with KRAS-mutant ( ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2018.36.15_suppl.10503

SPRINT: Phase II study of the MEK 1/2 inhibitor selumetinib ... Conclusions: The response rate from this study (72%) confirms our previously observed response rate (71%). Most responses were sustained ≥6 ...

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa1605943

Activity of Selumetinib in Neurofibromatosis Type 1– ... Selumetinib (AZD6244 or ARRY-142886) is an oral selective inhibitor of MEK 1 and 2 that has shown activity against several advanced adult ...

5. jto.org jto.org/article/S1556-0864(15)31811-6/fulltext

A Phase II, Open-Label, Randomized Study to Assess ... Median progression-free survival was not statistically significantly different between the AZD6244 and pemetrexed groups (67 versus 90 days, respectively; ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5613062/

A phase I dose-escalation study of Selumetinib in combination ... Selumetinib (AZD6244, ARRY-142886) is an oral, potent and highly selective, allosteric inhibitor of MEK1/2, a component of the RAS/RAF/MEK/ERK pathway which is ...

7. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT01809210

NCT01809210 | Assess Safety & Efficacy of Selumetinib ... Assess Safety & Efficacy of Selumetinib When Given in Combination With Standard First Line Treatment for Advanced Non-small Cell Lung Cancer (SELECT-3).

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2020/213756Orig1s000MultidisciplineR.pdf

213756Orig1s000 - accessdata.fda.gov The primary safety risks of selumetinib are consistent with the profiles of other approved MEK inhibitors. Adverse Drug Reactions (ADRs) in ...

9. thelancet.com thelancet.com/journals/lancet/article/PIIS0140-6736(25)00986-9/fulltext?rss=yes

Efficacy and safety of selumetinib in adults with ... Data from the primary analysis of KOMET indicate that selumetinib treatment achieved a significant objective response rate versus placebo by ...