What side effects are associated with this type of intervention?

Common side effects of treatments for solid tumors, particularly those involving DNA damage response inhibitors like AZD1390 combined with SBRT, include hematologic toxicities such as anemia, thrombocytopenia, and neutropenia. Non-hematologic side effects often include nausea, fatigue, and gastrointestinal disturbances. SBRT can cause localized side effects such as skin reactions, fatigue, and organ-specific effects like pneumonitis or gastrointestinal symptoms, depending on the treatment site.

What prior FDA approvals exist?

The FDA has approved several treatments for solid tumors that involve DNA damage response inhibitors and precise radiation therapies. For instance, PARP inhibitors like olaparib and rucaparib have been approved for certain types of ovarian and breast cancers, which work by exploiting the DNA repair weaknesses in cancer cells. Additionally, stereotactic body radiation therapy (SBRT) is a well-established treatment for various solid tumors, including lung, liver, and prostate cancers, due to its ability to deliver high doses of radiation with precision. Combining these approaches, such as using a DNA damage response inhibitor with SBRT, represents a promising strategy currently under investigation, as seen in the study of AZD1390 with SBRT for metastatic solid tumors.

What other types of research exist?

Promising alternatives to AZD1390 combined with SBRT for solid tumor patients include: 1) ATR inhibitor AZD6738, which has shown radiosensitization effects in multiple cancer cell lines. 2) ATM inhibitor AZD0156, which has demonstrated the ability to reverse chemoresistance in neuroblastoma and may enhance the effects of radiation therapy. 3) Combination therapies involving novel agents like PARP inhibitors (e.g., olaparib) with radiation, which have shown potential in enhancing the efficacy of radiation therapy in various solid tumors.

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ATM Kinase Inhibitor

AZD1390 + SBRT for Metastatic Cancer

Phase 1

Recruiting

Led By Daniel Higginson, MD

Research Sponsored by Memorial Sloan Kettering Cancer Center

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be older than 18 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 1 year

Awards & highlights

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Potential side effects are not detailed but may include typical reactions from radiotherapy like skin irritation or fatigue and any common drug-related effects such as nausea or allergic reactions. Specific side effects will depend on individual patient responses.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 1 year

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~1 year

This trial's timeline: 3 weeks for screening, Varies for treatment, and 1 year for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Assess participants for toxicities related to study treatment

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

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

Group VII: Arm A, Dose Level 2Experimental Treatment2 Interventions

Group VIII: Arm A, Dose Level 1Experimental Treatment2 Interventions

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Stereotactic Body Radiotherapy

2017

Completed Phase 2

~220

Do I qualify?Apply below to find out

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

DNA damage response inhibitors, such as AZD1390, disrupt the tumor cells' ability to repair DNA damage, making them more susceptible to treatments like radiation therapy. Stereotactic body radiation therapy (SBRT) delivers high doses of radiation precisely to the tumor, minimizing damage to surrounding healthy tissue. Combining these treatments can enhance the effectiveness of radiation therapy, leading to increased tumor cell death and potentially better outcomes for solid tumor patients, with fewer side effects.

Moving Synergistically Acting Drug Combinations to the Clinic by Comparing Sequential versus Simultaneous Drug Administrations.