Brain Metastases from Non-small Cell Lung CancerPhase 2NCT04889066
Durvalumab (MEDI4736) and Radiosurgery (fSRT Vs. PULSAR) for the Treatment of Non-Small Cell Lung Cancer Brain Metastases
A Phase 2 study testing Stereotactic Radiation Therapy and Durvalumab in people with Brain Metastases from Non-small Cell Lung Cancer, run by University of Texas Southwestern Medical Center.
Trial summary
This is a research study to find out if the new anti-cancer drug Durvalumab combined with radiation therapy to the brain will work in treating brain metastases from non-small cell lung cancer (NSCLC). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Brain Metastases from Non-small Cell Lung Cancer
- What is being tested?
- Stereotactic Radiation Therapy and Durvalumab
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 1 Oct 2024to Jan 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Biopsy-proven NSCLC primary with PD-L1 expression ≥ 1%
- At least one previously untreated, asymptomatic brain metastases (<=10 total) with at least one measurable (0.5 cm diameter or larger) as assessed by MRI
- No prior systemic treatment for metastatic NSCLC.
- age ≥ 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
- Life expectancy greater than six (6) months
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- Adequate normal organ and marrow function
- Body weight greater than 30 kg
- Ability to understand and willingness to sign written informed consent
Who cannot join
- Brain metastases that are symptomatic and/or with recent (<10 days) steroid use
- Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]).
- Subjects may not be receiving any other investigational agents for the treatment of the cancer under study.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent.
- Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
- Administration of one or more lines of systemic therapy for the diagnosis of metastatic non-small cell lung cancer
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- Prior receipt of systemic therapy for the management of high-risk early stage or locally advanced non-small cell lung cancer, prior to the development of metastatic disease, would not count towards the number of receipt of systemic therapy
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to durvalumab or other agents used in study
- Male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab monotherapy
- Participation in another clinical study with an investigational product during the last 1 month
- Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
- Receipt of the last dose of anticancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies) ≤ 7 days prior to the first dose of study drug If sufficient wash-out time has not occurred due to the schedule or PK properties of an agent, a longer wash-out period will be required, as agreed by AstraZeneca and the investigator
- Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, nausea, anorexia/weight loss, and the laboratory values defined in the inclusion criteria:
- Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician.
- Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the Study Physician.
- Any other concurrent immunotherapy, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
- Major surgical procedure (as defined by the Investigator) within 14 days prior to the first dose of immunotherapy.
- History of allogenic organ transplantation
- History of another primary malignancy except for:
- Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of immunotherapy and of low potential risk for recurrence
- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
- Adequately treated carcinoma in situ without evidence of disease
- History of leptomeningeal carcinomatosis
- History of active primary immunodeficiency
- Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C
- Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab
- Receipt of live attenuated vaccine within 30 days prior to the first dose of immunotherapy
- Receipt of any prohibited medication
About this study
Official title: A Phase II Clinical Trial of Durvalumab (MEDI4736) and Fractionated Stereotactic Radiotherapy (fSRT) Vs. Personalized Ultra-Fractionated Stereotactic Adaptive Radiotherapy (PULSAR) for the Treatment of Brain Metastases from Non-Small Cell Lung Cancer (NSCLC)
This is a research study to find out if the new anti-cancer drug Durvalumab combined with radiation therapy to the brain will work in treating brain metastases from non-small cell lung cancer (NSCLC). Focused, highly precise radiation therapy to the brain, known as stereotactic radiosurgery (SRS), is a standard of care treatment that is commonly used for patients with metastatic lung cancer to the brain. It is standardly used as an alternative to surgery to eradicate the targeted tumours in the brain and prevent them from growing and causing symptoms. This study will look at the combination of the novel immunotherapy Durvalumab with two different ways of delivering SRS: 1) with each radiation treatment given every other day for 3 treatments with the first dose of Durvalumab (fSRT), or 2) with each radiation treatment, referred to as a "pulse," given every 4 weeks with each dose of Durvalumab for 3 treatments (PULSAR).
- Being tested
- Stereotactic Radiation Therapy, Durvalumab
- Keywords
- Non-small cell lung cancer, Immunotherapy, Durvalumab, Radiotherapy, PULSAR, Stereotactic ablative radiotherapy
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Stereotactic Radiation TherapyRadiation
24-27 Gy in 3 fractions- one plan, given once every other day with first cycle of Durvalumab for comparator arm. 24-27 Gy in 3 "pulses"- each pulse of radiation re-planned, given once every 4 weeks with each Durvalumab for experimental arm.
DurvalumabDrug
Durvalumab (initially developed as MEDI4736) is a human monoclonal antibody of the immunoglobulin (Ig) G1 kappa subclass that inhibits binding of PD-L1 (B7-H1, CD274) to PD-1 (CD279) and CD80 (B7-1). MEDI4736 is composed of 2 identical heavy chains and 2 identical light chains, with an overall molecular weight of approximately 149 kDa. MEDI4736 contains a triple mutation in the constant domain of the Ig G1 heavy chain that reduces binding to complement protein C1q and the fragment crystallizable gamma receptors involved in triggering effector function.
| Study group | Role | What they receive |
|---|---|---|
| Durvalumab and standard fSRT | Active comparator | Fractionated stereotactic radiotherapy (fSRT) will be delivered to all previously untreated brain metastases noted at the time of treatment (up to 10 max). All brain metastases will be treated concurrently, 3 fractions total, delivered every other day (~2 times/week) with first cycle of Durvalumab. Receives: Radiation: Stereotactic Radiation Therapy; Drug: Durvalumab |
| Durvalumab and PULSAR | Experimental | Personalized ultra-fractionated stereotactic adaptive radiotherapy (PULSAR), will be delivered to all previously untreated brain metastases noted at the time of treatment (up to 10 max). All brain metastases will be treated concurrently, 3 "pulses" of radiation total, delivered one pulse monthly with each cycle of Durvalumab. Receives: Radiation: Stereotactic Radiation Therapy; Drug: Durvalumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Intercranial clinical benefit
Intracranial clinical benefit (Complete Response, Partial Response, or Stable Disease) assessed per the brain modified (bm) RECIST (response evaluation criteria in solid tumors) criteria
Measured: 6 months after initiation of treatment
Secondary outcomes (2)
Acute toxicity
All acute toxicities (CNS and non-CNS) will be evaluated using the NCI Common Terminology Criteria of Adverse Events (CTCAE) version 5.0, with results tabulated to examine frequency, severity, organs affected, and relationship to study treatment.
Measured: 6- and 12-months after initiation of treatment
Quality of life questionnaire
Functional Assessment of Cancer Therapy brain (FACT-Br) questionnaires. scoring range 0-200. Higher the score, the better the QOL
Measured: 6- and 12-months after initiation of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 May 2021
- Study start1 Oct 2024 (estimated)
- Primary completionJan 2025 (estimated)
- Study completionJan 2025 (estimated)
Why it stopped: Project Never Initiated since sponsor stopped support for the trial- no human subjects were enrolled and no data regarding humans was collected or studied
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Brain Metastases from Non-small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by University of Texas Southwestern Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Based on investigator's hypothesis of improved rate of intracranial clinical benefit at 6-months from historical control of 60% to 86% and 10% attrition rate, a sample size of 23 patients is needed per study arm (total N=46) using a two-sided exact binomial test with a two-sided α=0.1 and power=80%.
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Texas Southwestern Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Kiran Kumar, University of Texas Southwestern Medical Center
- Investigators
- Kiran Kumar, MD, Principal investigator, University of Texas Southwestern Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04889066
- Sponsor's protocol ID
- STU-2021-0466
- Status last verified
- Dec 2024
- First submitted
- 11 May 2021
- Last updated
- 20 Dec 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Clinical Trial of Durvalumab (MEDI4736) and Fractionated Stereotactic Radiotherapy (fSRT) Vs. Personalized Ultra-Fractionated Stereotactic Adaptive Radiotherapy (PULSAR) for the Treatment of Brain Metastases from Non-Small Cell Lung Cancer (NSCLC)
- ClinicalTrials.gov ID
- NCT04889066
- Acronym / sponsor ID
- STU-2021-0466
- Keywords
- Non-small cell lung cancer, Immunotherapy, Durvalumab, Radiotherapy, PULSAR, Stereotactic ablative radiotherapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Project Never Initiated since sponsor stopped support for the trial- no human subjects were enrolled and no data regarding humans was collected or studied
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of Texas Southwestern Medical CenterUniversity, hospital or other
- Study start
- 1 Oct 2024 (estimated)
- Primary completion
- Jan 2025 (estimated)
- Study completion
- Jan 2025 (estimated)
- First posted
- 17 May 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a research study to find out if the new anti-cancer drug Durvalumab combined with radiation therapy to the brain will work in treating brain metastases from non-small cell lung cancer (NSCLC). Focused, highly precise radiation therapy to the brain, known as stereotactic radiosurgery (SRS), is a standard of care treatment that is commonly used for patients with metastatic lung cancer to the brain. It is standardly used as an alternative to surgery to eradicate the targeted tumours in the brain and prevent them from growing and causing symptoms. This study will look at the combination of the novel immunotherapy Durvalumab with two different ways of delivering SRS: 1) with each radiation treatment given every other day for 3 treatments with the first dose of Durvalumab (fSRT), or 2) with each radiation treatment, referred to as a "pulse," given every 4 weeks with each dose of Durvalumab for 3 treatments (PULSAR).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Based on investigator's hypothesis of improved rate of intracranial clinical benefit at 6-months from historical control of 60% to 86% and 10% attrition rate, a sample size of 23 patients is needed per study arm (total N=46) using a two-sided exact binomial test with a two-sided α=0.1 and power=80%.
| Arm | Type | Receives |
|---|---|---|
| Durvalumab and standard fSRT | Active comparator | Radiation: Stereotactic Radiation Therapy, Drug: DurvalumabFractionated stereotactic radiotherapy (fSRT) will be delivered to all previously untreated brain metastases noted at the time of treatment (up to 10 max). All brain metastases will be treated concurrently, 3 fractions total, delivered every other day (~2 times/week) with first cycle of Durvalumab. |
| Durvalumab and PULSAR | Experimental | Radiation: Stereotactic Radiation Therapy, Drug: DurvalumabPersonalized ultra-fractionated stereotactic adaptive radiotherapy (PULSAR), will be delivered to all previously untreated brain metastases noted at the time of treatment (up to 10 max). All brain metastases will be treated concurrently, 3 "pulses" of radiation total, delivered one pulse monthly with each cycle of Durvalumab. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Biopsy-proven NSCLC primary with PD-L1 expression ≥ 1%
- At least one previously untreated, asymptomatic brain metastases (<=10 total) with at least one measurable (0.5 cm diameter or larger) as assessed by MRI
- No prior systemic treatment for metastatic NSCLC.
- age ≥ 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
Key exclusion criteria (28 listed)
- Brain metastases that are symptomatic and/or with recent (<10 days) steroid use
- Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]).
- Subjects may not be receiving any other investigational agents for the treatment of the cancer under study.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent.
- Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Stereotactic Radiation Therapy24-27 Gy in 3 fractions- one plan, given once every other day with first cycle of Durvalumab for comparator arm. 24-27 Gy in 3 "pulses"- each pulse of radiation re-planned, given once every 4 weeks with each Durvalumab for experimental arm. | Radiation | Durvalumab and PULSAR, Durvalumab and standard fSRT |
| DurvalumabDurvalumab (initially developed as MEDI4736) is a human monoclonal antibody of the immunoglobulin (Ig) G1 kappa subclass that inhibits binding of PD-L1 (B7-H1, CD274) to PD-1 (CD279) and CD80 (B7-1). MEDI4736 is composed of 2 identical heavy chains and 2 identical light chains, with an overall molecular weight of approximately 149 kDa. MEDI4736 contains a triple mutation in the constant domain of the Ig G1 heavy chain that reduces binding to complement protein C1q and the fragment crystallizable gamma receptors involved in triggering effector function. | Drug | Durvalumab and PULSAR, Durvalumab and standard fSRT |
Primary outcome
Intercranial clinical benefit
Time frame: 6 months after initiation of treatment
Intracranial clinical benefit (Complete Response, Partial Response, or Stable Disease) assessed per the brain modified (bm) RECIST (response evaluation criteria in solid tumors) criteria
2 secondary outcomes
Acute toxicity
Time frame: 6- and 12-months after initiation of treatment
Quality of life questionnaire
Time frame: 6- and 12-months after initiation of treatment
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Dec 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kiran Kumar, MD principal investigator
University of Texas Southwestern Medical Center
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Stereotactic Radiation Therapy and Durvalumab in people with Brain Metastases from Non-small Cell Lung Cancer, run by University of Texas Southwestern Medical Center.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 20 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Intercranial clinical benefit (time frame: 6 months after initiation of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Dec 2024.