AzTrials
AzTrials

Non-small Cell Lung CancerPhase 1NCT03275597

Phase Ib Study of Stereotactic Body Radiotherapy (SBRT) in Oligometastatic Non-small Lung Cancer (NSCLC) With Dual Immune Checkpoint Inhibition

A Phase 1 study testing Durvalumab, Tremelimumab and Stereotactic Body Radiotherapy in people with Non-small Cell Lung Cancer and Non-small Cell Lung Cancer Stage IV, run by University of Wisconsin, Madison at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

This is a phase Ib study to evaluate safety and tolerability of dual checkpoint inhibition (DCI) of durvalumab (anti-PD-L1) and tremelimumab (anti-CTLA-4) with SBRT in the treatment of oligometastatic NSCLC. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Durvalumab, Tremelimumab and Stereotactic Body Radiotherapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
17 participants
Where
1 siteUnited States
Study dates
20 Feb 2018to 1 Jul 2020
Phase
Phase 1
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

  • Participants with histologically or cytologically confirmed stage IV NSCLC not amenable to curative surgery or radiation
  • Participants may have had prior chemotherapy or be chemotherapy naïve
  • Participants must have tumors that lack sensitizing EGFR mutation (e.g. exon 19 deletion or exon 21 L858R) or ALK rearrangement. If a participant has squamous histology, then EGFR and ALK testing is not required.
  • No prior treatment with cancer immunotherapy including, but not limited to, other anti-CTLA-4, anti-PD-1, anti-PD-L1, and anti-programmed cell death ligand 2 anti- (PD-L2) antibodies, excluding therapeutic anticancer vaccines.
  • Participants will have 6 or less extracranial sites, which can safely receive SBRT between 30 - 50 Gy in 5 fractions. A site may have multiple tumor lesions within it as long as the gross tumor volume (GTV) of the site is 8 cm or less and can be covered in an acceptable SBRT field determined by the PI. All gross disease must be amenable to treatment with SBRT, as allowable per normal tissue constraints. Participants will not have had any prior radiation therapy significantly overlapping a tumor site to be treated.
  • Participants must have evaluable disease, as defined by RECIST 1.1.
Show all 23Show fewer
  • World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at enrollment
  • Life expectancy of > 12 weeks
  • Participant is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
  • Participants with treated metastatic lesions to the brain may be enrolled after completing stereotactic radiosurgery (may enroll 14 days after treatment) or whole brain radiation (may enroll 14 days after treatment) and must be off corticosteroids for 14 days prior to start of SBRT.
  • Adequate normal organ and marrow function as defined below:
  • Hemoglobin ≥ 9.0 g/dL
  • Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L (> 1500 per mm^3)
  • Platelet count ≥ 100 x 10^9/L (>100,000 per mm^3)
  • Serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN). This will not apply for participants with confirmed Gilbert's syndrome, who will be allowed in consultation with their physician.
  • AST (SGOT)/ALT (SGPT) ≤ 2.5 x ULN unless liver metastases are present, in which case ALT and AST must be ≤ 5x ULN
  • Serum creatinine <1.5 x upper limit of normal (ULN) OR creatinine clearance (CrCl) ≥30 mL/min for participants with creatinine levels >1.5 × institutional ULN
  • Female participant of childbearing potential should have a negative urine or serum pregnancy prior to receiving the first study treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
  • Female participants of childbearing potential should be willing to use 1 method of highly effective birth control, 2 methods of effective birth control, be surgically sterile, or abstain from heterosexual activity for the course of the study through 180 days after the last dose of study medication. Participants of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
  • Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
  • Women < 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle- stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
  • Women ≥ 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced oophorectomy with last menses >1 year ago, had chemotherapy-induced menopause with > 1 year interval since last menses, or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
  • Participant must be willing and able to provide written informed consent for the trial.

Who cannot join

  • Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
  • Previous enrollment in the present study
  • Mixed small-cell lung cancer and sarcomatoid variant NSCLC histology
  • Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (eg, hormone replacement therapy) is acceptable.
  • Major surgical procedure (as defined by the Investigator) within 14 days prior to the start of study treatment.
  • Participants with untreated spinal cord compression. Participants with spinal cord compression may be enrolled if stable after completing surgery (may enroll 14 days after surgery) or radiation (may enroll 14 days after radiation) and must be off corticosteroids for at least 14 days prior to the start of SBRT.
Show all 37Show fewer
  • Participants with untreated brain metastasis. Participants with metastatic lesions to the brain may be enrolled after completing stereotactic radiosurgery or whole brain radiation (may enroll 14 days after radiation and must be off corticosteroids for at least 14 days prior to the start of SBRT.
  • Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab or an anti-CTLA4 inhibitor including tremelimumab
  • Participants with a known targetable EGFR mutation or ALK rearrangement
  • History of another primary malignancy except for:
  • Malignancy treated with curative intent and with no known active disease ≥2 years
  • Non-metastatic prostate adenocarcinoma, or treated superficial non-invasive bladder cancer
  • Adequately treated carcinoma in situ without evidence of disease (eg, cervical cancer in situ)
  • Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
  • Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) ≤ 14 days of registration
  • Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥470 ms. Abnormality must be confirmed on 3 ECGs.
  • Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab or tremelimumab
  • The following are exceptions to this criterion:
  • Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra-articular injection).
  • Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
  • Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication)
  • Active or known autoimmune disease that has required immunosuppressive systemic treatment in past 2 years (ie, with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed. The following are exceptions to this criterion:
  • Participants with vitiligo or alopecia,
  • Grave's disease,
  • Hypothyroidism (eg, following Hashimoto syndrome),
  • Psoriasis not requiring systemic treatment (within the past 2 years)
  • Participants with celiac disease controlled by diet alone
  • History of active primary immunodeficiency
  • History of allogeneic organ transplant
  • Active infection, including tuberculosis (clinical evaluation), hepatitis B, hepatitis C, or human immunodeficiency virus (HIV, positive HIV 1 or 2 antibodies). Active hepatitis B virus (HBV) is defined by a known positive HBV surface antigen (HBsAg) result. Participants with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody and absence of HBsAg) are eligible. Participants positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV ribonucleic acid (RNA).
  • History of leptomeningeal carcinomatosis
  • Receipt of live attenuated vaccination within 30 days prior to the first dose of IP. Note: Participants, if enrolled, should not receive live vaccine during the study and up to 30 days after the last dose of IP.
  • Any condition or uncontrolled intercurrent illness that, in the opinion of the Investigator, would interfere with the evaluation of IP or interpretation of patient safety or study results, including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs from durvalumab or tremelimumab, or compromise the ability of the patient to give written informed consent
  • Subjects with uncontrolled seizures.
  • Female participants who are pregnant or breast-feeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 180 days after the last dose of durvalumab and tremelimumab combination therapy or 90 days after the last dose of durvalumab monotherapy.
  • History of hypersensitivity to IP or comparator agents
  • History of medically diagnosed pneumonitis or interstitial lung disease

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Wisconsin Carbone Cancer Center

    Madison, Wisconsin, 53792

Other trials in United States

About this study

Official title: Comprehensive Stereotactic Body Radiotherapy (SBRT) to All Sites of Oligometastatic Non-small Cell Lung Cancer (NSCLC) Combined With Durvalumab (MEDI4736) and Tremelimumab Dual Immune Checkpoint Inhibition.

This is a phase Ib study to evaluate safety and tolerability of dual checkpoint inhibition (DCI) of durvalumab (anti-PD-L1) and tremelimumab (anti-CTLA-4) with SBRT in the treatment of oligometastatic NSCLC. This study will examine the sequential delivery of SBRT to all disease sites followed by combination of durvalumab and tremelimumab for patients for whom the goal is ablating all known sites of disease. The investigators anticipate that for many participants this will be the first line-therapy. Participants who have received prior-platinum-based chemotherapy and/or any line of prior chemotherapy are eligible. Prior immunotherapy treatment is not allowed.

Being tested
Durvalumab, Tremelimumab, Stereotactic Body 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.

  • DurvalumabDrug

    Also called 1428935-60-7, D10808

    Durvalumab is an FDA-approved immunotherapy for cancer. Durvalumab is a human monoclonal antibody (mAb) of the immunoglobulin G (IgG) 1 kappa subclass that inhibits binding of PD-L1 and is being developed by AstraZeneca/MedImmune for use in the treatment of cancer.

  • TremelimumabDrug

    Also called 745013-59-6, QEN1X95CIX

    Tremelimumab is a monoclonal antibody against CTLA-4. It is an IgG 2 kappa isotype mAb directed against the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) also known as CD152 (cluster of differentiation 152). This is an immunomodulatory therapy (IMT) that is being developed by AstraZeneca for use in the treatment of cancer.

  • Stereotactic Body RadiotherapyRadiation

    Also called SRBT, stereotactic ablative radiotherapy, SABR

    SBRT is a highly conformal approach to the delivery of radiation therapy, maximizing radiation dose to the tumor while minimizing dose to nearby normal tissues.

Study groups in NCT03275597
Study groupRoleWhat they receive
SBRT followed by Durvalumab+TremelimumabExperimentalTherapeutic Interventions Stereotactic Body Radiotherapy (SBRT) to all sites of disease between 30 and 50 Gy in five fractions administered over two weeks. Investigational Product(s), Dose, and Mode of Administration: to begin 7 days (+/- 3 days) after radiation Durvalumab 1500 mg via infusion Q4W (equivalent to 20 mg/kg Q4W) until disease progression in patients > 30 kg Tremelimumab 300 mg via infusion (equivalent to 4 mg/kg) in one dose in patients >30 kg Weight-based dosing should be utilized for patients ≤30 kg; durvalumab 20 mg/kg Q4W and tremelimumab 4 mg/kg
Receives: Drug: Durvalumab; Drug: Tremelimumab; Radiation: Stereotactic Body Radiotherapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Safety and tolerability of SBRT followed by combined durvalumab and tremelimumab, assessed by CTCAE v4.03

    Toxicities will be summarized by type and severity in tabular format. Toxicity rates (grade 2, grade 3, grade 4, grade ≥ 2, grade ≥ 3, etc.) will be calculated and reported along the corresponding 95% confidence intervals. The 95% confidence intervals will be constructed using the Wilson score method.

    Measured: Up to 3 years

Secondary outcomes (2)

  1. Progression Free Survival assessed with RECIST 1.1 tumor assessments

    Progression-free survival (PFS) will be defined as the difference (in months) between the date of study enrollment and the date of disease progression or death due to any cause. PFS will be analyzed using the Kaplan-Meier method, and the Brookmeyer-Crowley method will be used to construct the 95% confidence interval for the median PFS. PFS assessed with RECIST 1.1 tumor assessments. The effect of DCI with durvalumab and tremelimumab will be compared against historical controls for a 95% CI and p-value.

    Measured: Up to 4 years

  2. Overall Survival assessed with RECIST 1.1 tumor assessments

    Overall survival (OS) will be defined as the difference (in months) between the date of study enrollment to the date death due to any cause. OS will be analyzed using the Kaplan-Meier method, and the Brookmeyer-Crowley method will be used to construct the 95% confidence interval for the median OS. The effect of DCI with durvalumab tremelimumab will be compared against historical controls for a 95% CI and p-value.

    Measured: Up to 4 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Sep 2017
  2. Study start20 Feb 2018
  3. Primary completion1 Jul 2020
  4. Study completion1 Jul 2020

Why it stopped: slow accrual

Resources

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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
17 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03275597
Sponsor's protocol ID
UW17003
Other IDs
A533300, SMPH\HUMAN ONCOLOGY\HUMAN ONCO, NCI-2017-01952, Protocol Version 10/2//2020, 2017-0665
Status last verified
May 2023
First submitted
5 Sep 2017
Last updated
15 May 2023
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Durvalumab, Tremelimumab and Stereotactic Body Radiotherapy in people with Non-small Cell Lung Cancer and Non-small Cell Lung Cancer Stage IV, run by University of Wisconsin, Madison at 1 site in United States.

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 23 inclusion and 37 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: stopped early, as of the sponsor's last update on 15 May 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 stopped early (reason given: slow accrual). Results are not available in the source record.

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?

Safety and tolerability of SBRT followed by combined durvalumab and tremelimumab, assessed by CTCAE v4.03 (time frame: Up to 3 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03275597.

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 15 May 2023.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in