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SCLC, RecurrentPhase 2SUKSES-N5NCT04525391

AZD2811 and Durvalumab (MEDI4736) Combination Therapy in Relapsed Small Cell Lung Cancer

A Phase 2 study testing Durvalumab+AZD2811 to SCLC patients in people with SCLC, Recurrent, run by Se-Hoon Lee at 1 site in South Korea.

Terminated

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

Official record
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Trial summary

Samsung Medical Centre, Seoul, Korea. Additional 0~5 Korea Lung Cancer Consortium (KLCC) centres in Korea Up to 40 subjects will be enrolled in two-stages (first stage: 19 evaluable subjects and second stage: 17 evaluable subjects and additional 4 subjects considering the drop out rate) If the study is conducted as… Read more about this study

Who is it for?
Ages 19 years and older
Conditions the study is for
SCLC, Recurrent
What is being tested?
Durvalumab+AZD2811 to SCLC patients
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
4 participants
Where
1 siteSouth Korea
Study dates
18 Sep 2020to 14 Jan 2022
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 19 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Provision of fully informed consent prior to any study specific procedures.
  • Subjects must be ≥ 18 years of age.
  • Body weight > 30kg
  • Small cell lung cancer that has progressed during or after first-line therapy.
  • The 1st line regimen must have contained platinum based regimen and must have documented radiological and/or clinical progression on treatment.
  • Refractory to first-line chemotherapy or relapse within 6 months since the last dose of first-line chemotherapy
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  • If the subject has sensitive relapse (relapse more than 6 months since the last dose of first-line chemotherapy), (s)he should receive second-line treatment prior to study entry.
  • Histologically confirmed SCLC with documented c-MYC expression (≥ c-MYC IHC 1+)
  • Subjects are willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations.
  • ECOG performance status 0-1
  • Subjects must have a life expectancy ≥ 3months from proposed first dose date.
  • Subjects must have normal organ and bone marrow function measured within 28 days prior to administration of study treatment as defined below:
  • Haemoglobin ≥ 9.0g/dL)
  • White blood cells (WBC) ≥ 3 x 109/L
  • Platelet count ≥ 100 x 109/L
  • Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
  • Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) (Serum Glutamic Oxaloacetic Transaminase (SGOT)) / Alanine aminotransferase (ALT) (Serum Glutamic Pyruvate Transaminase (SGPT)) ≤ 2.5 x institutional upper limit of normal unless liver metastases are present in which case they must be ≤ 5x ULN
  • Subjects must have serum creatinine (CR) ≤1.5 times the normal upper limit of the study institution or creatinine clearance estimated using the Cockcroft-Gault equation of ≥ 45 mL/min: Estimated creatinine clearance = (140-age [years]) x weight (kg) (x F)a serum creatinine (mg/dL) x 72 a where F=0.85 for females and F=1 for males.
  • At least one measurable lesion that can be accurately assessed at baseline by imaging or physical examination at baseline and is suitable for repeated assessment.
  • Postmenopausal or evidence of non-childbearing status for women of childbearing Potential or a negative urine or serum pregnancy test at screening and confirmed prior to treatment on Day 1 of every cycle
  • Postmenopausal is defined as:
  • Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments
  • Luteinizing hormone(LH) and Follicle stimulating hormone(FSH) levels in the post menopausal range for women under 50
  • Radiation-induced oophorectomy with last menses >1 year ago
  • Chemotherapy-induced menopause with >1 year interval since last menses
  • Surgical sterilisation(bilateral oophorectomy or hysterectomy)
  • Male and women of childbearing portential , who are sexually active and of childbearing potential, must agree to the use of two highly effective forms of contraception in combination, throughout the period of taking study treatment and for 6 months after last dose of investigational product(s) to prevent pregnancy in a partner.
  • Provision of tumor sample (from either archival and/or fresh biopsy)
  • Optional: Provision of separate informed consent for genetic research. If a subject declines to participate in the genetic research, there will be no penalty or loss of benefit to the subject. The subject will not be excluded from other aspects of the study described in this Clinical Study Protocol, so long as they consent to the main informed consent.

Who cannot join

  • Previous enrolment in the present study or 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
  • More than two prior chemotherapy regimens for the treatment of small cell lung cancer refractory to first-line chemotherapy or relapse within 6 months.
  • (However, immunotherapy is not counted the prior chemotherapy regimen.)
  • Subjects with second primary cancer, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for > 2 years. Or patients with a history of leptomeningeal carcinomatosis.
  • Treatment with any investigational product during the last 14 days before the first dose on study.
  • Subjects receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) within 3 weeks from the last dose prior to study treatment (or a longer period depending on the defined characteristics of the agents used). The subject can receive a stable dose of bisphosphonates or denosumab for bone metastases, before and during the study as long as these were started at least 4 weeks prior to treatment.
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  • Receiving, or having received, concomitant medications, herbal supplements and/or foods that significantly modulate cytochrome P450 3A4(CYP3A4) or P-glycoprotein(P-gp) activity (washout periods of 2 weeks, but 3 weeks for St. John's Wort). Note these include common azole antifungals, macrolide antibiotics and other medications.
  • Prior exposure to an AURKB inhibitor or PD-1 or PD-L1 or CTLA-4 inhibitor.
  • Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. 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 10mg/day of prednisone or its equivalent
  • Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication)
  • Receipt of live attenuated vaccine within 30 days prior to the first dose of investigational product. Note: Subjects, if enrolled, should not receive live vaccine whilst receiving investigational product and up to 180 days after the last dose of investigational product.
  • Any unresolved toxicity NCI CTCAE grade≥2 from previous anticancer therapy with the exception of alopecia, vitilgo, and the laboratory values defined in the inclusion criteria (CTCAE version 5.0)
  • Subjects with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Investigator.
  • Subjects with irreversible toxicity not reasonably expected to be exacerabated by treatment with durvalumab may be included only after consultation with with the Investigator.
  • Intestinal obstruction or CTCAE grade 3 or grade 4 upper GI bleeding within 4 weeks before the enrollment.
  • Haematuria: +++ on microscopy or dipstick
  • INR ≥ 1.5 or other evidence of impaired hepatic synthesis function
  • Subject has any of the following cardiac criteria:
  • Mean QT interval corrected for heart rate(QTcF) ≥ 470ms calculated from 3 electrocardiograms (ECGs) using Fridericia's correction.
  • Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG eg, complete left bundle branch block, third degree heart block, second degree heart block, first degree heart block.
  • Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40years of age or any concomitant medication known to prolong the QT interval.
  • Uncontrolled hypertension-blood pressure (BP) ≥ 150/95mmHg despite medical therapy.
  • Unstable atrial fibrillation or unstable cardiac arrhythmia with a ventricular rate > 100bpm on an ECG at rest.
  • Symptomatic heart failure - New York Heart Association Grade II to Grade IV.
  • Prior or current cardiomyopathy.
  • Severe valvular heart disease.
  • Uncontrolled angina (Canadian Cardiovascular Society Grade II to Grade IV despite medical therapy) or acute coronary syndrome within 6months prior to screening.
  • Subjects at risk of brain perfusion problems (e.g., carotid stenosis hypotension, including a fall in blood pressure of > 20mm Hg)
  • Female subjects who are pregnant or breast-feeding or child-bearing or male or female subjects of reproductive potential who are not willing to employ effective birth control from screening to 6 months after the last dose of durvalumab or AZD2811.
  • Any evidence of severe or uncontrolled intercurrent illness, including but 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 would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the subject to give written informed consent.
  • History of allogenic organ transplantation.
  • 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, or human immunodeficiency virus (positive HIV 1/2 antibodies). Subjects with a past or resolved HBV infection (defined as the antibody[anti-HBc] and absence of HBsAg) are eligible. Subjects positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
  • Known hypersensitivity to any of the study drugs or any of the study drug excipients.
  • Known central nervous system (CNS) disease other than neurologically stable, treated brain metastases - defined as metastasis having no evidence of progression or haemorrhage for at least 2 weeks after treatment.
  • Major surgical procedures ≤ 28 days of beginning study treatment, or minor (outpatient) surgical procedures ≤ 7days
  • History of active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease, diverticulitis [with the exception of diverticulosis], systemic lupus erythematosis, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]).
  • The following are exceptions to this criterion:
  • Subjects with vitiligo or alopecia
  • Subjects with hypothyroidism(e.g., following Hashimoto syndrome) stable on hormone replacement
  • Any chronic skin condition that dose not require systemic therapy
  • Subjects without active disease in the last 5 years may be included but only after consultation with the Investigator.
  • Subjects with cardiac disease controlled by diet alone

Trial locations and contacts

1 site in 1 country.

South Korea1 site

  • Samsung Medical Center

    Seoul, Gangnam-gu

Other trials in South Korea

About this study

Official title: Phase II, Single-arm Study of AZD2811 and Durvalumab (MEDI4736) Combination Therapy in Relapsed Small Cell Lung Cancer Subjects [SUKSES-N5]

Samsung Medical Centre, Seoul, Korea. Additional 0~5 Korea Lung Cancer Consortium (KLCC) centres in Korea Up to 40 subjects will be enrolled in two-stages (first stage: 19 evaluable subjects and second stage: 17 evaluable subjects and additional 4 subjects considering the drop out rate) If the study is conducted as de-escalated dosage (Durvalumab 1120mg) after the safety run-in, number of the patients will be counted from the second safety-run in phase.

Read the detailed description

This study is a single arm, open-label, multi-centre phase II study of AZD2811NP and durvalumab combination therapy in subjects with relapsed small cell lung cancer (SCLC) as a second or third line treatment.

Subjects will receive AZD2811 and durvalumab combination therapy. The arm is composed of up to approximately 36 evaluable subjects.

After the initiation of the study, a safety run-in period will be conducted with 6 patients to confirm the safety profile.

Thus a safety run-in will be undertaken in the first 6 patients with 1500mg of Durvalumab q 3weeks with 500mg of AZD2811. During the safety follow-up, if 2 or more DLT is observed, another safety run-in with new 6 patients will be initiated with 1120mg of Durvalumab q 3weeks with 500mg of AZD2811.

In case of a positive risk benefit profile the recruitment will continue.

Subjects will receive AZD2811 500mg and durvalumab 1500mg via IV administered on Day 1 for every 3weeks (fixed dosing for subjects > 30 kg body weight). One cycle consists of 3 weeks. The sequence of the infusion is Durvalumab administered over 1 hour, followed by AZD2811 administered over 2 hours. The optimal proposed time between infusions is 15 min to 30 min. The compatibility of drug products in infusion line has not been tested. Therefore, the infusion line must be flushed with saline after the administration of one drug product and before the start of the second drug product.

Conditions
SCLC, Recurrent
Being tested
Durvalumab+AZD2811 to SCLC patients
Medical subject headings
Recurrence

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Durvalumab+AZD2811 to SCLC patientsDrug

    AZD2811 must NOT be infused through a 0.2-µm or 0.22-µm filter and therefore durvalumab and AZD2811 MUST be infused through different infusion lines. In order not to exceed the endotoxin limit, durvalumab and AZD2811 mustbe administered consecutively. Durvalumab is administered first over 1 hour, followed by AZD2811 administered over 2 hours. AZD2811 should be administered at 30 minutes after the end of the durvalumab infusion, as long as there are no acute infusion reactions to durvalumab.

Study groups in NCT04525391
Study groupRoleWhat they receive
Durvalumab+AZD2811 to SCLC patientsExperimentalDosage and Schedule: AZD2811 500mg and durvalumab 1500mg via IV administered on Day 1 for every 3weeks (fixed dosing for subjects > 30 kg body weight for durvalumab). One cycle is consisted of 3 weeks. The drug products must be dosed consecutively using different infusion lines. The sequence of infusions is as follows: durvalumab is administered first over 1 hour, followed by AZD2811 administered over 2 hours. A waiting time interval of at least 30 minutes between the end of durvalumab infusion and start of AZD2811 infusion should be adhered to.
Receives: Drug: Durvalumab+AZD2811 to SCLC patients

What is being measured

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

  1. Disease control rate is defined as the proportion of patients with best response of CR, PR, or who have SD for at least 12 weeks

    To investigate the efficacy of AZD2811 and durvalumab combination therapy in subjects with relapsed SCLC subjects with c-MYC expression ≥ 1+ as 2nd or 3rd line therapy

    Measured: 12 weeks

Secondary outcomes (4)

  1. Duration of response (SD, PR, CR) calculated by Kaplan-Meier method

    To assess secondary measures of clinical efficacy

    Measured: 12 weeks

  2. Overall survival(OS) calculated by Kaplan-Meier method

    To assess secondary measures of clinical efficacy

    Measured: 12 weeks

  3. Progression-free survival(PFS) calculated by Kaplan-Meier method

    To assess secondary measures of clinical efficacy

    Measured: 12 weeks

  4. Time to first relapse (resistant relapse or sensitive relapse)

    Planned subgroup analyses

    Measured: 12 weeks

Timeline

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

  1. First posted25 Aug 2020
  2. Study start18 Sep 2020
  3. Primary completion14 Jan 2022
  4. Study completion14 Jan 2022

Why it stopped: Recommended completion of the study due to SUSAR occurring in other clinical trials conducted with the same drug.

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
4 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04525391
Sponsor's protocol ID
SUKSES-N5
Acronym
SUKSES-N5
Status last verified
Feb 2022
First submitted
14 Aug 2020
Last updated
25 Feb 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Durvalumab+AZD2811 to SCLC patients in people with SCLC, Recurrent, run by Se-Hoon Lee at 1 site in South Korea.

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 30 inclusion and 44 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 25 Feb 2022. 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 South Korea. 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 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 stopped early (reason given: Recommended completion of the study due to SUSAR occurring in other clinical trials conducted with the same drug.). 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?

Disease control rate is defined as the proportion of patients with best response of CR, PR, or who have SD for at least 12 weeks (time frame: 12 weeks). 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 NCT04525391.

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 25 Feb 2022.

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