AZD1390 + SBRT for Metastatic Cancer

Recruiting at4 trial locations

Overseen by Daniel Higginson, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Waitlist Available

Sponsor: Memorial Sloan Kettering Cancer Center

No Placebo Group

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.

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. ^{1 2 3 4 5}

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. ^{2 6 7 8 9}

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. ^{1 3 6 9 10}

Research Team

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.

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.

Treatment Details

Interventions

• AZD1390 (ATM Kinase Inhibitor)
• Stereotactic Body Radiotherapy (Radiation)

Trial Overview The 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

Group I: Arm B, Dose Level 4 Experimental Treatment 2 Interventions

Participants have peripheral metastasis with bowel and lung in SBRT treatment planning target

Group II: Arm B, Dose Level 3 Experimental Treatment 2 Interventions

Participants have peripheral metastasis with bowel and lung in SBRT treatment planning target

Group III: Arm B, Dose Level 2 Experimental Treatment 2 Interventions

Participants have peripheral metastasis with bowel and lung in SBRT treatment planning target

Group IV: Arm B, Dose Level 1 Experimental Treatment 2 Interventions

Participants have peripheral metastasis with bowel and lung in SBRT treatment planning target

Group V: Arm A, Dose Level 4 Experimental Treatment 2 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 3 Experimental Treatment 2 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 2 Experimental Treatment 2 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 1 Experimental Treatment 2 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).

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Lisa M. DeAngelis

Memorial Sloan Kettering Cancer Center

Chief Medical Officer since 2021

MD from Columbia University

Selwyn M. Vickers

Memorial Sloan Kettering Cancer Center

Chief Executive Officer since 2022

MD from Johns Hopkins University

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) 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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

This multicenter randomized phase III trial aims to determine if combining Stereotactic Body Radiation Therapy (SBRT) with standard systemic treatment improves progression-free survival in patients with solid tumors and up to 3 bone-only metastases, with a total of 196 patients expected to be enrolled over 4 years.

The primary goal is to assess progression-free survival at 1 year, while secondary outcomes will evaluate local control, cancer-specific survival, quality of life, and pain management, highlighting the potential for SBRT to enhance patient outcomes by controlling bone metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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). Thureau, S., Marchesi, V., Vieillard, MH., et al.[2021]

In a study of 46 patients treated with spine stereotactic body radiation therapy (SBRT), no cases of myelopathy were reported, suggesting that current guidelines may overestimate the risk of this complication, even when exceeding recommended dose limits.

The most common side effects observed were pain and nausea, with specific dose thresholds identified: a maximum dose to the spinal cord of 38.5 Gy and to the thecal sac of 67.7 Gy, indicating that higher doses may be tolerated without severe toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dosimetric analysis of varying cord planning organ at risk volume in spine stereotactic body radiation therapy. Owen, D., Mayo, CS., Song, L., et al.[2020]

High-dose stereotactic body radiation therapy (SBRT) demonstrated a 100% local control rate at one year and 96% at two years for patients with one to three lung metastases, indicating its efficacy in managing these tumors.

The treatment was well-tolerated, with only 8% of patients experiencing grade 3 toxicity and no grade 4 toxicity reported, suggesting a favorable safety profile for high-dose SBRT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multi-institutional phase I/II trial of stereotactic body radiation therapy for lung metastases. Rusthoven, KE., Kavanagh, BD., Burri, SH., et al.[2022]

Stereotactic body radiotherapy (SBRT) for localized renal cell carcinoma (RCC) was well-tolerated in 19 patients aged 59-89, with no dose-limiting toxicities observed at doses up to 48Gy in 4 fractions.

Among the patients treated, 3 showed a partial response and 12 had stable disease, indicating that SBRT can be an effective treatment option for patients who are poor surgical candidates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I dose-escalation study of stereotactic body radiotherapy (SBRT) for poor surgical candidates with localized renal cell carcinoma. Ponsky, L., Lo, SS., Zhang, Y., et al.[2022]

Stereotactic ablative radiotherapy (SABR) demonstrated a high local control rate of 91.2% for skeletal metastases in a study of 22 patients, with a median follow-up of 15.6 months, indicating its effectiveness in managing oligometastatic and oligoprogressive diseases.

The treatment resulted in significant pain control for two-thirds of symptomatic patients, with limited toxicities reported, including only two vertebral fractures and one case of grade 3 esophagitis, suggesting that SABR is a safe option for patients with skeletal metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Utilization of stereotactic ablative radiotherapy in oligometastatic & oligoprogressive skeletal metastases: Results and pattern of failure. Kam, TY., Chan, OSH., Hung, AWM., et al.[2019]

In a study of 84 patients with spinal metastases treated with stereotactic body radiotherapy (SBRT), targeting only the lesion (LO) showed similar tumor control and pain reduction compared to targeting the full vertebral body (FVB), indicating that LO may be a sufficient treatment approach.

There were no significant differences in the rates of compression fractures between the LO and FVB groups, suggesting that both treatment strategies are equally safe in terms of fracture risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Clinical Outcomes Stratified by Target Delineation for Patients Undergoing Stereotactic Body Radiotherapy for Spinal Metastases. Attiah, M., Sandler, K., Medina, R., et al.[2020]

Stereotactic body radiotherapy (SBRT) is increasingly used to treat spinal bone metastases, which are common in cancer patients, and can provide long-lasting relief and potential curative outcomes in select cases.

In particular, SBRT may be beneficial for oligometastatic patients or those with a longer life expectancy, shifting the focus from purely palliative care to a more therapeutic approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spinal metastases: Is stereotactic body radiation therapy supported by evidences? De Bari, B., Alongi, F., Mortellaro, G., et al.[2022]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Efficacy and safety of SBRT for spine metastases: A systematic review and meta-analysis for preparation of an ESTRO practice guideline. [2023]

2. China pubmed.ncbi.nlm.nih.gov

Stereotactic body radiotherapy as a primary treatment for spinal metastasis: a single institution experience. [2021]

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

Mature Local Control and Reirradiation Rates Comparing Spine Stereotactic Body Radiation Therapy With Conventional Palliative External Beam Radiation Therapy. [2022]

4. England pubmed.ncbi.nlm.nih.gov

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]

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

Dosimetric analysis of varying cord planning organ at risk volume in spine stereotactic body radiation therapy. [2020]

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

Multi-institutional phase I/II trial of stereotactic body radiation therapy for lung metastases. [2022]

7. Ireland pubmed.ncbi.nlm.nih.gov

Phase I dose-escalation study of stereotactic body radiotherapy (SBRT) for poor surgical candidates with localized renal cell carcinoma. [2022]

8. Australia pubmed.ncbi.nlm.nih.gov

Utilization of stereotactic ablative radiotherapy in oligometastatic & oligoprogressive skeletal metastases: Results and pattern of failure. [2019]

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

Comparison of Clinical Outcomes Stratified by Target Delineation for Patients Undergoing Stereotactic Body Radiotherapy for Spinal Metastases. [2020]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Spinal metastases: Is stereotactic body radiation therapy supported by evidences? [2022]