- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04361825
Durvalumab(MEDI4736) and AZD6738 Combination Therapy in Relapsed Small Cell Lung Cancer Subjects (SUKSES-N4)
Phase Ⅱ, Single-arm Study of Durvalumab(MEDI4736) and AZD6738 Combination Therapy in Relapsed Small Cell Lung Cancer Subjects [SUKSES-N4]
Study Overview
Detailed Description
Subjects will receive durvalumab and AZD6738 combination therapy. The arm is composed of 45 subjects.
Durvalumab 1500mg via IV administered for every 4weeks(fixed dosing for subjects > 30 kg body weight) in Day 1 of each cycle and AZD 6738 240mg bid per os administered in each cycle days 15 and 28. One cycle is consisted of 28 days.
Tumour evaluation using CT or MRI, RECIST 1.1, CEA, NSE and LDH will be conducted at screening (within 28days prior to first dose of Cycle1 Day1) and every 8weeks(±1week) for the first 56weeks relative to the start of combination therapy(Cycle1 Day1), and thereafter every 12weeks(±1week) until objective disease progression.
Study treatment will be continued until objective disease progression (unless other criteria for treatment discontinuation are met). Subjects may continue durvalumab and AZD6738 beyond progression(according to RECIST 1.1), at the discretion of the investigator if they are clinically benefiting from the treatment and they do not meet any other discontinuation criteria.
If a subjects discontinues study treatment prior to disease progression, they should continue to be assessed using RECIST 1.1 until disease progression and then followed up for survival.
Assessments for survival should be made every 3months following objective disease progression. The details of first and subsequent therapies for cancer, after discontinuation of durvalumab and AZD6738 treatment, will be collected.
The imaging modalities used for RECIST 1.1 assessment will be CT or MRI scans of chest, abdomen and pelvis. And CEA, NSE and LDH tests are also used for the evaluation. RECIST 1.1 scans will be analysed by the investigator on site.
Subjects may also be requested to provide tumour samples from the primary or metastatic tumours on progression to understand resistance mechanisms. Sample provision is optional and depend on the subject's will.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
-
Seoul, Korea, Republic of
- Samsung Medical Center
-
-
Gyeonggi-do
-
Seongnam-si, Gyeonggi-do, Korea, Republic of, 13620
- Seoul National University Bundang Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Provision of fully informed consent prior to any study specific procedures.
- Subjects must be ≥ 18years 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. The subjects must not exposed to the prior immunotherapy which could have been received separately, in combination, or in sequence with platinum-doublet chemotherapy.
- Refractory to first-line chemotherapy or relapse within 6months since the last dose of first-line chemotherapy
- If the subject correspond to sensitive relapse(relapse more than 6months since the last dose of first-line chemotherapy), (s)he should get second-line treatment prior to study entry.
- 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
- 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: negative urine or serum pregnancy test 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 Subjects and their partners, who are sexually active and of childbearing potential, must agree to the use of two highly effective forms of contraception in combination for acceptable methods, throughout the period of taking study treatment and for 6months after last dose of investigational product(s) to prevent pregnancy in a partner.
- Provision of 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.
Exclusion Criteria:
- Previous enrolment in the present study.
- More than two prior chemotherapy regimen for the treatment of small cell lung cancer(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 > 2years.
- Treatment with any investigational product during the last 14days before the enrollment (or a longer period depending on the defined characteristics of the agents used).
- Subjects receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) within 3weeks 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 4weeks prior to treatment.
- Rceiving, 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 2weeks, but 3weeks for St. John's Wort). Note these include common azole antifungals, macrolide antibiotics and other medications.
- Prior exposure to an ATR inhibitor.
- Refractory nausea and vomiting, chronic gastrointestinal diseases or previous significant bowel resection, with clinically significant sequelae that would preclude adequate absorption of AZD6738
Current or prior use of immunosuppressive medication within 14days 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 30days prior to the first dose of investigational product. Note: Subjects, if enrolled, should not receive live vaccine whilst receiving investigational product and up to 180days 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 5.0)
- Subjects with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician.
- Subjects with irreversible toxicity not reasonably expected tobe exacerabated by treatment with durvalumab may be included only after consultation with with the Study Physician.
- Intestinal obstruction or CTCAE 5.0 grade 3 or grade 4 upper GI bleeding within 4weeks 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(QTc) ≥ 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 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 of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab monotherapy.
- Any evidence of severe or uncontrolled intercurrent illness, including but limited to, ongoing or active infection, symptomatic conjestive 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 polymerage chain reaction is negative for HCV RNA.
- Known hypersensitivity to any of study drug 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 2weeks after treatment.
- Major surgical procedures ≤ 28days of beginning study treatment, or minor 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 study physician
- Subjects with cardiac disease controlled by diet alone
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Durvalumab(MEDI4736) and AZD6738 combination
|
Durvalumab 1500mg via IV administered for every 4weeks(fixed dosing for subjects > 30 kg body weight) in Day 1 of each cycle and AZD 6738 240mg bid per os administered in each cycle days 1 and 7.
One cycle is consisted of 28 days.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Efficacy of durvalumab and AZD6738 combination therapy in subjects with relapsed SCLC subjects as 2nd or 3rd line therapy: Objective response rate(ORR)
Time Frame: Up to 30 months
|
Objective response rate(ORR) by RECIST 1.1
|
Up to 30 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Duration of response
Time Frame: Up to 30 months
|
Duration of response (DOR) is the time from the date of the first dose of study treatment to the date of RECIST progression or death from any cause, whichever occurs first.
|
Up to 30 months
|
Disease control rate
Time Frame: 8 weaks
|
Disease control rate (DCR) is the number of patients having a CR or PR or stable disease via RECIST divided by the number of patients in the full analysis set.
|
8 weaks
|
Overall survival(OS)
Time Frame: Up to 30 months
|
Overall survival (OS) is the time from the date of the first dose of study treatment to the date of death from any cause.
|
Up to 30 months
|
progression-free survival(PFS)
Time Frame: Up to 30 months
|
Progression-free survival (PFS) is the time from the date of first dose of study treatment to the date of RECIST progression or death from any cause, whichever occurs first.
|
Up to 30 months
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Se-Hoon Lee, M.D,Ph.D., Samsung Medical Center
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2020-02-103
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Small Cell Lung Cancer
-
University of Wisconsin, MadisonNational Cancer Institute (NCI)CompletedStage IIIA Non-small Cell Lung Cancer | Stage IIIB Non-small Cell Lung Cancer | Extensive Stage Small Cell Lung Cancer | Recurrent Small Cell Lung Cancer | Recurrent Non-small Cell Lung Cancer | Stage IV Non-small Cell Lung Cancer | Healthy, no Evidence of Disease | Limited Stage Small Cell Lung... and other conditionsUnited States
-
AIO-Studien-gGmbHBristol-Myers Squibb; Eli Lilly and Company; Merck Sharp & Dohme LLC; Pfizer; Gilead... and other collaboratorsRecruitingSmall-cell Lung Cancer | Non-small Cell Lung Cancer Metastatic | Non-small Cell Lung Cancer Stage I | Metastatic Non-small Cell Lung Cancer (NSCLC) | Non Small Cell Lung Cancer Stage III | Non-small Cell Lung Cancer Stage IIGermany
-
WindMIL TherapeuticsBristol-Myers SquibbTerminatedNSCLC | Lung Cancer | Lung Cancer Metastatic | Lung Cancer, Non-small Cell | Non Small Cell Lung Cancer | Non-small Cell Lung Cancer | Non-small Cell Lung Cancer Metastatic | Non Small Cell Lung Cancer MetastaticUnited States
-
National Cancer Institute (NCI)CompletedStage IIIA Non-small Cell Lung Cancer | Stage IIIB Non-small Cell Lung Cancer | Extensive Stage Small Cell Lung Cancer | Recurrent Small Cell Lung Cancer | Recurrent Non-small Cell Lung Cancer | Stage IV Non-small Cell Lung CancerUnited States
-
University of California, San FranciscoAstraZenecaActive, not recruitingStage IIIA Non-Small Cell Lung Cancer | Stage I Non-Small Cell Lung Cancer | Stage IA Non-Small Cell Lung Cancer | Stage IB Non-Small Cell Lung Cancer | Stage II Non-Small Cell Lung Cancer | Stage IIA Non-Small Cell Lung Cancer | Stage IIB Non-Small Cell Lung CancerUnited States
-
Washington University School of MedicineMerck Sharp & Dohme LLCWithdrawnNSCLC | Non Small Cell Lung Cancer | Non-small Cell Lung Cancer | Small Cell Lung Extensive Stage
-
Wake Forest University Health SciencesNational Cancer Institute (NCI)CompletedTobacco Use Disorder | Stage IIIA Non-small Cell Lung Cancer | Stage IIIB Non-small Cell Lung Cancer | Recurrent Small Cell Lung Cancer | Limited Stage Small Cell Lung Cancer | Stage IA Non-small Cell Lung Cancer | Stage IB Non-small Cell Lung Cancer | Stage IIA Non-small Cell Lung Cancer | Stage IIB...United States
-
National Cancer Institute (NCI)TerminatedStage IIIA Non-small Cell Lung Cancer | Stage IA Non-small Cell Lung Cancer | Stage IB Non-small Cell Lung Cancer | Stage IIA Non-small Cell Lung Cancer | Stage IIB Non-small Cell Lung CancerUnited States
-
Peking Union Medical College HospitalRecruitingNon Small Cell Lung Cancer Stage III | Small-Cell Lung CancerChina
-
University of Maryland, BaltimoreUniversity of Maryland, College ParkTerminatedNon-Small Cell Lung Cancer, Small Cell Lung Cancer | Platinum Responsive MalignanciesUnited States
Clinical Trials on Durvalumab
-
AstraZenecaKappa SantéRecruiting
-
Yonsei UniversityRecruitingPotentially Resectable Stage II/IIIa NSCLCKorea, Republic of
-
MedImmune LLCCompletedStage III Non-small Cell Lung Cancer | UnresectableUnited States, Canada, Italy, Spain, France, Hong Kong, Portugal, Taiwan, Poland
-
Academic Thoracic Oncology Medical Investigators...AstraZenecaCompletedNon-Small Cell Lung Cancer NSCLCUnited States
-
Yonsei UniversityCompleted
-
NSABP Foundation IncCompletedRectal CancerUnited States
-
Yonsei UniversityNot yet recruitingNon Small Cell Lung CancerKorea, Republic of
-
Hark Kyun KimRecruiting
-
Oslo University HospitalAstraZenecaActive, not recruitingCancer | NSCLC | Non Small Cell Lung Cancer | NSCLC, Stage III | Non Small Cell Lung Cancer Stage IIINorway, Finland, Lithuania, Estonia
-
MedImmune LLCCompletedAdvanced Solid TumorsUnited States, France, Spain, Switzerland