A Phase I Study Assessing the Safety and Tolerability of Ascending Doses of AZD1390 in Combination With Stereotactic Body Radiation Therapy (SBRT) in Patients With Metastatic Solid Tumor Malignancies
Overview
- Phase
- Phase 1
- Intervention
- AZD1390
- Conditions
- Solid Tumor
- Sponsor
- Memorial Sloan Kettering Cancer Center
- Enrollment
- 54
- Locations
- 5
- Primary Endpoint
- Assess participants for toxicities related to study treatment
- Status
- Active, not recruiting
- Last Updated
- 11 months ago
Overview
Brief Summary
The purpose of this study is to find out whether AZD1390 combined with stereotactic body radiation therapy/SBRT is a safe treatment for people with metastatic solid tumor cancer
Investigators
Eligibility Criteria
Inclusion Criteria
- •Willing and able to provide written informed consent
- •Aged at least 18 years.
- •Karnofsky Performance Score (KPS) of ≥
- •Histologically confirmed diagnosis of cancer with clear evidence of metastasis on imaging. Confirmation of metastasis by biopsy is preferred but not required.
- •Candidates for SBRT delivered as 6Gy x 5 daily fractions to 2 sites of disease. The radiation plan should meet departmental guidelines. Patients can have more than 2 sites of disease. If patient requires RT to other sites of disease this can be done after completion of DLT period.
- •Adequate organ system functions, as outlined below:
- •Absolute neutrophil count (ANC) ≥1.0 x 109/L
- •Platelets ≥75 x 109/L
- •Hemoglobin ≥8 g/dL
- •Total bilirubin ≤1.5 times the ULN
Exclusion Criteria
- •Prior radiotherapy to the same region within the last 3 months.
- •Ongoing treatment for brain metastases. Patients with brain metastases may participate in this trial however, treatment for brain metastases will have to be completed prior to study enrollment. Treatments can begin or resume two weeks after completing protocol therapy.
- •History of epilectic disorder.
- •For Arm B patients with cancers involving the spinal cord, the length of the spinal cord lesion requiring palliative treatment is greater than 10 cm.
- •Past medical history of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease.
- •Evidence of established ILD on screening CT scan.
- •Evidence of severe pulmonary infections, as judged by the investigator, based on clinical findings and investigations.
- •Concurrent severe and/or uncontrolled medical condition (e.g., severe COPD).
- •Cardiac dysfunction defined as: Myocardial infarction within six months of study entry, NYHA Class II/III/IV heart failure, unstable angina or unstable cardiac arrhythmias.
- •Any of the following cardiac criteria:
Arms & Interventions
Arm A, Dose Level 1
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).
Intervention: AZD1390
Arm A, Dose Level 1
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).
Intervention: Stereotactic Body Radiotherapy
Arm A, Dose Level 2
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).
Intervention: AZD1390
Arm A, Dose Level 2
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).
Intervention: Stereotactic Body Radiotherapy
Arm A, Dose Level 3
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).
Intervention: AZD1390
Arm A, Dose Level 3
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).
Intervention: Stereotactic Body Radiotherapy
Arm A, Dose Level 4
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).
Intervention: AZD1390
Arm A, Dose Level 4
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).
Intervention: Stereotactic Body Radiotherapy
Arm B, Dose Level 1
Participants have peripheral metastasis with bowel and lung in SBRT treatment planning target
Intervention: AZD1390
Arm B, Dose Level 1
Participants have peripheral metastasis with bowel and lung in SBRT treatment planning target
Intervention: Stereotactic Body Radiotherapy
Arm B, Dose Level 2
Participants have peripheral metastasis with bowel and lung in SBRT treatment planning target
Intervention: AZD1390
Arm B, Dose Level 2
Participants have peripheral metastasis with bowel and lung in SBRT treatment planning target
Intervention: Stereotactic Body Radiotherapy
Arm B, Dose Level 3
Participants have peripheral metastasis with bowel and lung in SBRT treatment planning target
Intervention: AZD1390
Arm B, Dose Level 3
Participants have peripheral metastasis with bowel and lung in SBRT treatment planning target
Intervention: Stereotactic Body Radiotherapy
Arm B, Dose Level 4
Participants have peripheral metastasis with bowel and lung in SBRT treatment planning target
Intervention: AZD1390
Arm B, Dose Level 4
Participants have peripheral metastasis with bowel and lung in SBRT treatment planning target
Intervention: Stereotactic Body Radiotherapy
Outcomes
Primary Outcomes
Assess participants for toxicities related to study treatment
Time Frame: 1 year
The primary objective is to assess the safety and tolerability of concurrent AZD1390 with SBRT for patients with solid tumor metastases with solid tumor metastases. Participant toxicities will be assessed using the CTCAE v5.0