54 Participants Needed

AZD1390 + SBRT for Metastatic Cancer

Recruiting at 4 trial locations
DH
DG
Overseen ByDavid Guttmann, MD
Age: 18+
Sex: Any
Trial Phase: Phase 1
Sponsor: Memorial Sloan Kettering Cancer Center
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called AZD1390 combined with a precise form of radiation therapy to treat people with cancer that has spread to other parts of the body. The goal is to see if this combination is safe and effective. AZD1390 helps make cancer cells more vulnerable to radiation, potentially improving treatment outcomes.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you must stop all current medications. However, you cannot take strong inhibitors or inducers of CYP3A4 within 2 weeks before starting AZD1390, and you should avoid certain medications like prazosin, cimetidine, simvastatin, dofetilide, metformin, dabigatran, digoxin, and fexofenadine while on the study.

Will I have to stop taking my current medications?

The trial does not specify if you must stop all current medications, but you should avoid certain drugs like strong inhibitors or inducers of CYP3A4 and sensitive substrates of BCRP, OATP1B1, MATE1, MATE2K, and P-gp. It's best to discuss your current medications with the study team to see if any adjustments are needed.

What data supports the idea that AZD1390 + SBRT for Metastatic Cancer is an effective treatment?

The available research shows that Stereotactic Body Radiation Therapy (SBRT) is effective in treating spinal metastases, which are cancerous growths that spread to the spine. One study found that SBRT improved pain relief for patients with spinal metastases compared to traditional radiation therapy. Another study suggests that using SBRT along with standard treatments for certain cancers with bone metastases could lead to longer periods without the cancer getting worse. This indicates that SBRT, when combined with other treatments, can be a promising option for managing metastatic cancer.12345

What data supports the effectiveness of the treatment AZD1390 + SBRT for Metastatic Cancer?

Research shows that Stereotactic Body Radiation Therapy (SBRT) is effective in managing spinal metastases, improving pain response and local control compared to conventional radiation therapy. This suggests that SBRT, as part of the treatment, may help control cancer spread and improve patient outcomes.12345

What safety data is available for AZD1390 + SBRT treatment?

The provided research articles focus on the safety and efficacy of stereotactic body radiotherapy (SBRT) and stereotactic ablative radiotherapy (SABR) for various types of metastases, including spinal, lung, renal cell carcinoma, and skeletal metastases. These studies generally evaluate the tolerability and toxicities associated with SBRT/SABR, indicating that safety data exists for the radiotherapy component of the treatment. However, specific safety data for the combination of AZD1390 with SBRT is not directly addressed in these articles.26789

Is the combination of AZD1390 and SBRT generally safe for humans?

The safety of stereotactic body radiotherapy (SBRT), which is part of the treatment, has been evaluated in various studies for different conditions like spinal and lung metastases, and it is generally considered tolerable. However, specific safety data for the combination of AZD1390 with SBRT is not provided in the available research.26789

Is the treatment AZD1390 and SBRT a promising treatment for metastatic cancer?

Yes, AZD1390 combined with SBRT is a promising treatment for metastatic cancer. SBRT is effective in controlling pain and targeting cancer in specific areas like the spine and lungs. It offers long-lasting relief and can sometimes aim for a cure, especially in patients with fewer cancer spread areas.136910

How does the treatment AZD1390 + SBRT for metastatic cancer differ from other treatments?

The combination of AZD1390, a novel drug, with Stereotactic Body Radiotherapy (SBRT) is unique because it targets cancer cells more precisely and effectively, potentially offering better pain control and tumor management compared to conventional radiation therapies. SBRT is already known for its precision in treating spinal metastases, and combining it with AZD1390 may enhance its effectiveness.136910

Research Team

DH

Daniel Higginson, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

Adults with confirmed metastatic solid tumor cancer, suitable for SBRT treatment to two disease sites, and meeting specific health criteria (e.g., adequate blood counts, liver function). Must not be pregnant or breastfeeding and willing to use contraception. Excludes those with severe medical conditions, brain metastases treatments ongoing, recent heart issues, certain lung diseases, high risk of heart rhythm problems.

Inclusion Criteria

My cancer has spread, as shown by scans. A biopsy to confirm this was preferred but not mandatory.
Willing and able to provide written informed consent
I am eligible for a specific radiation therapy targeting 2 cancer sites.
See 5 more

Exclusion Criteria

I haven't taken strong CYP3A4 inhibitors or inducers in the last 2 weeks.
I have had lung inflammation or damage that needed steroids.
I have had serious lung infections.
See 12 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive AZD1390 in combination with stereotactic body radiation therapy (SBRT) to assess safety and tolerability

1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Treatment Details

Interventions

  • AZD1390
  • Stereotactic Body Radiotherapy
Trial OverviewThe trial is testing the safety of a new drug called AZD1390 when given alongside Stereotactic Body Radiotherapy (SBRT) in adults with various types of advanced cancers that have spread to other parts of the body.
Participant Groups
8Treatment groups
Experimental Treatment
Group I: Arm B, Dose Level 4Experimental Treatment2 Interventions
Participants have peripheral metastasis with bowel and lung in SBRT treatment planning target
Group II: Arm B, Dose Level 3Experimental Treatment2 Interventions
Participants have peripheral metastasis with bowel and lung in SBRT treatment planning target
Group III: Arm B, Dose Level 2Experimental Treatment2 Interventions
Participants have peripheral metastasis with bowel and lung in SBRT treatment planning target
Group IV: Arm B, Dose Level 1Experimental Treatment2 Interventions
Participants have peripheral metastasis with bowel and lung in SBRT treatment planning target
Group V: Arm A, Dose Level 4Experimental Treatment2 Interventions
Participants have peripheral metastases only, without bowel and lung in SBRT treatment planning target. Once 2 dosing cohorts of safety data are available from concomitant dosing of AZD1390 with SBRT in Arm A, and provided that Arm A is advancing to Cohort 3, Arm B (with bowel and lung in SBRT treatment planning target \[PTV\]) may be triggered at the initial dose level).
Group VI: Arm A, Dose Level 3Experimental Treatment2 Interventions
Participants have peripheral metastases only, without bowel and lung in SBRT treatment planning target. Once 2 dosing cohorts of safety data are available from concomitant dosing of AZD1390 with SBRT in Arm A, and provided that Arm A is advancing to Cohort 3, Arm B (with bowel and lung in SBRT treatment planning target \[PTV\]) may be triggered at the initial dose level).
Group VII: Arm A, Dose Level 2Experimental Treatment2 Interventions
Participants have peripheral metastases only, without bowel and lung in SBRT treatment planning target. Once 2 dosing cohorts of safety data are available from concomitant dosing of AZD1390 with SBRT in Arm A, and provided that Arm A is advancing to Cohort 3, Arm B (with bowel and lung in SBRT treatment planning target \[PTV\]) may be triggered at the initial dose level).
Group VIII: Arm A, Dose Level 1Experimental Treatment2 Interventions
Participants have peripheral metastases only, without bowel and lung in SBRT treatment planning target. Once 2 dosing cohorts of safety data are available from concomitant dosing of AZD1390 with SBRT in Arm A, and provided that Arm A is advancing to Cohort 3, Arm B (with bowel and lung in SBRT treatment planning target \[PTV\]) may be triggered at the initial dose level).

Find a Clinic Near You

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials
1,998
Recruited
602,000+

AstraZeneca

Industry 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

Stereotactic body radiotherapy (SBRT) for spinal metastases demonstrated high efficacy, achieving an overall pain response rate of 83% and a 1-year local control rate of 94% across 69 studies involving 5736 patients.
SBRT was found to be safe, with a low vertebral fracture rate of 9% and no reported cases of radiation-induced myelopathy, indicating it provides effective pain and disease control with minimal risks.
Efficacy and safety of SBRT for spine metastases: A systematic review and meta-analysis for preparation of an ESTRO practice guideline.Guninski, RS., Cuccia, F., Alongi, F., et al.[2023]
Stereotactic body radiotherapy (SBRT) demonstrated high local control rates for spinal metastasis, with 83% at 1 year and 71% at 2 years, and a median overall survival of 30.6 months among 26 patients with 32 lesions.
The treatment was found to be safe, with only 16% of patients experiencing acute pain flare, which was manageable, and no cases of radiation-induced myelopathy reported.
Stereotactic body radiotherapy as a primary treatment for spinal metastasis: a single institution experience.Yeung, WME.[2021]
Stereotactic body radiation therapy (SBRT) significantly reduces the risk of local failure and the need for reirradiation in patients with spinal metastases compared to conventional external beam radiation therapy (cEBRT), with local failure rates at 24 months being 14.8% for SBRT versus 35.6% for cEBRT (P < .001).
While SBRT has a lower reirradiation rate (2.2% at 1 year) compared to cEBRT (15.8% at 1 year), it is associated with a higher incidence of grade 3 vertebral compression fractures, indicating a need for careful monitoring of this adverse effect.
Mature Local Control and Reirradiation Rates Comparing Spine Stereotactic Body Radiation Therapy With Conventional Palliative External Beam Radiation Therapy.Zeng, KL., Myrehaug, S., Soliman, H., et al.[2022]

References

Efficacy and safety of SBRT for spine metastases: A systematic review and meta-analysis for preparation of an ESTRO practice guideline. [2023]
Stereotactic body radiotherapy as a primary treatment for spinal metastasis: a single institution experience. [2021]
Mature Local Control and Reirradiation Rates Comparing Spine Stereotactic Body Radiation Therapy With Conventional Palliative External Beam Radiation Therapy. [2022]
Efficacy of extracranial stereotactic body radiation therapy (SBRT) added to standard treatment in patients with solid tumors (breast, prostate and non-small cell lung cancer) with up to 3 bone-only metastases: study protocol for a randomised phase III trial (STEREO-OS). [2021]
Dosimetric analysis of varying cord planning organ at risk volume in spine stereotactic body radiation therapy. [2020]
Multi-institutional phase I/II trial of stereotactic body radiation therapy for lung metastases. [2022]
Phase I dose-escalation study of stereotactic body radiotherapy (SBRT) for poor surgical candidates with localized renal cell carcinoma. [2022]
Utilization of stereotactic ablative radiotherapy in oligometastatic & oligoprogressive skeletal metastases: Results and pattern of failure. [2019]
Comparison of Clinical Outcomes Stratified by Target Delineation for Patients Undergoing Stereotactic Body Radiotherapy for Spinal Metastases. [2020]
Spinal metastases: Is stereotactic body radiation therapy supported by evidences? [2022]