AZD6244 for Advanced Cancer

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

58 Participants Needed

Trial Summary

What is the purpose of this trial?

The primary purpose of the study is to assess the safety, tolerability and pharmacokinetics of a capsule of AZD6244 in participants with advanced solid malignancies.

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.

What safety data exists for AZD6244 in humans?

AZD6244, also known as Selumetinib, has been studied for safety in patients with advanced non-small cell lung cancer and multiple myeloma. These studies suggest that AZD6244 is generally safe for human use, but like all medications, it may have side effects, which should be discussed with a healthcare provider. ^{1 2 3 4 5}

How is the drug AZD6244 unique for treating advanced cancer?

AZD6244 is unique because it is an oral drug that specifically inhibits MEK1/2, a key enzyme in a pathway that helps cancer cells grow and survive. This targeted approach is different from traditional chemotherapy, which often affects both cancerous and healthy cells. ^{1 2 3 4 6}

Research Team

Emerging Oncology Medical Science Director, MD

Principal Investigator

AstraZeneca

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

A phase II, open-label, randomized study to assess the efficacy and safety of AZD6244 (ARRY-142886) versus pemetrexed in patients with non-small cell lung cancer who have failed one or two prior chemotherapeutic regimens. [2015]

2. United States pubmed.ncbi.nlm.nih.gov

A Phase II Trial of AZD6244 (Selumetinib, ARRY-142886), an Oral MEK1/2 Inhibitor, in Relapsed/Refractory Multiple Myeloma. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

The mitogen-activated protein/extracellular signal-regulated kinase kinase 1/2 inhibitor AZD6244 (ARRY-142886) enhances the radiation responsiveness of lung and colorectal tumor xenografts. [2021]

4. United States 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. [2015]

5. England pubmed.ncbi.nlm.nih.gov

Antitumor activity of selective MEK1/2 inhibitor AZD6244 in combination with PI3K/mTOR inhibitor BEZ235 in gefitinib-resistant NSCLC xenograft models. [2021]

6. England pubmed.ncbi.nlm.nih.gov

ZD6474--clinical experience to date. [2023]