AZD6244 + Chemotherapy for Advanced Cancer

Recruiting at 3 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: AstraZeneca

Must not be taking: Steroids

Disqualifiers: Brain metastases, Spinal cord compression, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 28 days

140 Participants Needed

Trial Summary

What is the purpose of this trial?

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

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.

How is the drug AZD6244 unique compared to other treatments for advanced cancer?

AZD6244 is unique because it is a targeted therapy that specifically inhibits a protein involved in cancer cell growth, which may offer a different approach compared to traditional chemotherapy that affects both cancerous and healthy cells. ^{1 2 3 4 5}

Research Team

Jeffrey Infante, MD

Principal Investigator

SCRI Development Innovations, LLC

Patricia LoRusso, DO

Principal Investigator

Barbara Ann Karmanos Cancer Institute

Roger Cohen, MD

Principal Investigator

Fox Chase Cancer Center

Kevin Kim, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

Group I: 4 Experimental Treatment 2 Interventions

AZD6244 + Temsirolimus

Group II: 3 Experimental Treatment 2 Interventions

AZD6244 + Erlotinib

Group III: 2 Experimental Treatment 2 Interventions

AZD6244 + Dacarbazine

Group IV: 1 Experimental Treatment 2 Interventions

AZD6244 + docetaxel

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

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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 study determined that zoledronic acid (ZA) can be safely combined with conventional chemotherapy in patients with metastatic osteosarcoma, with a maximum tolerated dose (MTD) established at 2.3 mg/m² (max 4 mg).

Out of 24 patients treated, five experienced dose-limiting toxicities, but there were no significant concerns regarding renal toxicity or osteonecrosis of the jaw, indicating a favorable safety profile for ZA in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility and dose discovery analysis of zoledronic acid with concurrent chemotherapy in the treatment of newly diagnosed metastatic osteosarcoma: a report from the Children's Oncology Group. Goldsby, RE., Fan, TM., Villaluna, D., et al.[2021]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Under usage of zoledronic acid in non-small cell lung cancer patients with metastatic bone disease--a short communication. [2018]

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

Metronomic administration of zoledronic acid and taxotere combination in castration resistant prostate cancer patients: phase I ZANTE trial. [2020]

3. England pubmed.ncbi.nlm.nih.gov

Feasibility and dose discovery analysis of zoledronic acid with concurrent chemotherapy in the treatment of newly diagnosed metastatic osteosarcoma: a report from the Children's Oncology Group. [2021]

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

A phase II trial of estramustine and etoposide in hormone refractory prostate cancer: A Southwest Oncology Group trial (SWOG 9407). [2019]

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

Administration of zoledronic acid enhances the effects of docetaxel on growth of prostate cancer in the bone environment. [2018]