Extensive Stage Lung Small Cell CarcinomaPhase 1/2NCT04728230
Olaparib and Durvalumab With Carboplatin, Etoposide, and/or Radiation Therapy for the Treatment of Extensive-Stage Small Cell Lung Cancer, PRIO Trial
A Phase 1/2 study testing Carboplatin, Durvalumab and Etoposide in people with Extensive Stage Lung Small Cell Carcinoma and Stage IV Lung Cancer AJCC v8, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
This phase I/II trials investigates the side effects of olaparib and durvalumab and how well it works in combination with carboplatin, etoposide, and/or radiation therapy in treating patients with extensive stage-small cell lung cancer (ES-SCLC) who have not received treatment for their disease. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Extensive Stage Lung Small Cell Carcinoma, Stage IV Lung Cancer AJCC v8, Stage IVA Lung Cancer AJCC v8
- What is being tested?
- Carboplatin, Durvalumab and Etoposide
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 63 participants
- Where
- 1 siteUnited States
- Study dates
- 5 Jan 2021to 31 Dec 2027
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
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
- Provision of signed and dated written informed consent form prior to any mandatory study specific procedures, sampling, and analyses. For inclusion in i) the optional exploratory genetic research and ii) the optional biomarker research, patients must fulfill the following criteria:
- Provision of informed consent for genetic research prior to collection of sample;
- Provision of informed consent for biomarker research prior to collection of sample;
- If a patient declines to participate in the optional exploratory genetic research or the optional biomarker research, there will be no penalty or loss of benefit to the patient. The patient will not be excluded from other aspects of the study
- At least one lesion (measurable and/or non-measurable) that can be accurately assessed at baseline by computed tomography (CT) and is suitable for repeated assessment
- Patients with previously treated brain metastases that are asymptomatic for at least 14 days and only require prednisone equivalent of 10 mg daily or less prior to study treatment
Show all 25Show fewer
- Histological or cytological documented ES-SCLC: American Joint Committee on Cancer (AJCC) stage IV SCLC (T any, N any, M1 a/b), including patients with T3-4 due to multiple lung nodules that are too extensive or have tumor/nodal volume that is too large to be encompassed in a tolerable radiation plan
- No prior systemic therapy for ES-SCLC, including, but not limited to, chemotherapy, PARP inhibitor, and PD-1/PD-L1 checkpoint inhibitors. Palliative radiation is allowed if completed a minimum of three days prior to beginning of study treatment
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 at enrollment
- Body weight > 30 kg
- Hemoglobin >=10.0 g/dL with no blood transfusion in the past 28 days (measured within 28 days prior to administration of study treatment)
- Absolute neutrophil count >= 1.5 x 10^9 /L (measured within 28 days prior to administration of study treatment)
- Platelet count >= 100 x 10^9/L (measured within 28 days prior to administration of study treatment)
- Serum bilirubin =<1.5 x institutional upper limit of normal (ULN) (measured within 28 days prior to administration of study treatment)
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x institutional ULN, unless liver metastases are present in which case they must be =< 5 x ULN (measured within 28 days prior to administration of study treatment)
- Calculated estimated creatinine clearance >= 51 mL/min using the Cockcroft- Gault equation or based on a 24-hour urine test (measured within 28 days prior to administration of study treatment)
- Evidence of post-menopausal status or evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test within 28 days of study treatment and confirmed prior to treatment on day 1. Postmenopausal status 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 sterilization (bilateral oophorectomy or hysterectomy)
- Women of childbearing potential and their partners, who are sexually active, must agree to the use of TWO highly effective forms of contraception in combination. This should be started from the signing of the informed consent and continue throughout the period of taking study treatment and for at least 3 months after last dose of study drug(s)
- Male patients must use a condom during treatment and for 3 months after the last dose of study treatment when having sexual intercourse with a pregnant woman or with a woman of childbearing potential. Female partners of male patients should also use a highly effective form of contraception if they are of childbearing potential. Male patients should not donate sperm throughout the period of taking study treatment and for 3 months following the last dose of study treatment
- Subject 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
Who cannot join
- Histology other than SCLC
- Prior systemic therapy for ES-SCLC (e.g. chemotherapy, PARP inhibitor, other DNA damage response [DDR] inhibitors, PD-1/PD-L1 inhibitors)
- Patients with untreated brain metastases
- Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days
- Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of study treatment and patients must have recovered from any effects of any major surgery. Note: Local surgery of isolated lesions for palliative intent is acceptable
- Other malignancy unless curatively treated with no evidence of disease for >= 3 years except:
Show all 28Show fewer
- Adequately treated non-melanoma skin cancer.
- Curatively treated in situ cancer of the cervix; ductal carcinoma in situ (DCIS); stage 1, grade 1 endometrial carcinoma; and in situ bladder cancer
- Any concurrent anticancer therapy
- Resting electrocardiogram (ECG) indicating uncontrolled, potentially reversible cardiac conditions, as judged by the investigator (e.g. unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, QT corrected by Fridericia [QTcF] prolongation > 500 ms, electrolyte disturbances, etc.), or patients with congenital long QT syndrome
- Current or prior use of immunosuppressive medication within 14 days prior to cycle 1 (C1) of study treatment, with the exceptions of intranasal and inhaled corticosteroids, or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone or an equivalent corticosteroid
- Active or prior documented autoimmune disease within the past 2 years. NOTE: vitiligo, alopecia, chronic skin condition that does not require systemic therapy, psoriasis not requiring systemic treatment (within the past 2 years), and hypothyroidism (if stable on hormonal therapy) are not exclusion criteria
- Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis) or pneumonitis
- Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV)
- Previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT)
- Patients considered high medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on high resolution computed tomography (HRCT) scan or any psychiatric disorder that prohibits obtaining informed consent
- Patients with myelodysplastic syndrome (MDS) / acute myeloid leukemia (AML) or with features suggestive of MDS/AML
- Whole blood transfusions in the last 120 days prior to entry to the study (packed red blood cells and platelet transfusions are acceptable outside of 28 days prior to treatment)
- Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication
- Concomitant use of known strong CYP3A inhibitors (e.g. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (e.g. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting study treatment is 2 weeks
- Concomitant use of known strong (e.g. phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate CYP3A inducers (e.g. bosentan, efavirenz, modafinil). The required washout period prior to starting study treatment is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents
- Participation in another clinical study with an investigational product (IP) administered in the last 6 months
- Involvement in the planning and/or conduct of the study
- Previous enrollment in the present study
- Receipt of live attenuated vaccination within 30 days prior to study entry
- Female subjects who are pregnant, breast-feeding or male or female patients of reproductive potential who are not employing two highly effective methods of birth control
- Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results
- Known allergy or hypersensitivity to durvalumab, olaparib or any excipients
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I/II Trial of PARP Inhibition, Radiation, and Immunotherapy in Patients With Extensive-Stage Small Cell Lung Cancer (ES-SCLC) - PRIO Trial
This phase I/II trials investigates the side effects of olaparib and durvalumab and how well it works in combination with carboplatin, etoposide, and/or radiation therapy in treating patients with extensive stage-small cell lung cancer (ES-SCLC) who have not received treatment for their disease. PARPs are proteins that help repair DNA mutations. PARP inhibitors, such as olaparib, can keep PARP from working, so tumor cells can't repair themselves, and they may stop growing. Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as carboplatin and etoposide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy sources to kill tumor cells and shrink tumors. Giving olaparib and durvalumab together with carboplatin, etoposide, and/or radiation therapy may help treat patients with ES-SCLC.
Read the detailed description
PRIMARY OBJECTIVE:
- To assess the toxicity and feasibility of sequential treatment with olaparib, thoracic radiotherapy (TRT)/durvalumab, and olaparib/durvalumab for consolidation and maintenance therapy in patients status post (s/p) chemoimmunotherapy for ES-SCLC.
SECONDARY OBJECTIVE:
- To assess the efficacy of sequential treatment with olaparib, TRT/durvalumab, and olaparib/durvalumab for consolidation and maintenance therapy in patients s/p chemoimmunotherapy for ES-SCLC.
EXPLORATORY OBJECTIVES:
- Perform a comparative analysis of patient clinical outcome according to tumor biomarkers in circulating tumor cell (CTC), blood samples and tumor tissue, such as SLFN11 expression H- scores and stratifying tumors as SLFN11 positive or negative on the basis of H-score >= 1.
II. Perform a comparative analysis of patient clinical outcome according to immune biomarkers in blood and tumor tissue, such as PD-L1 immunohistochemistry (IHC) 22C3 pharmDx assay and stratifying tumors as PD-L1 positive or negative on the basis of PD-L1 combined positive score >= 1% in patients treated with anti- PD-L1 therapy.
III. Perform whole exome sequencing (WES) and methylation profiling on tumor samples and from circulating-free deoxyribonucleic acid (cfDNA) to evaluate whether tumor mutational burden (TMB) or specific genomic alterations are associated with improved progression free survival (PFS) with the trial regimen.
IV. Gene and protein expression of tumor tissue through ribonucleic acid (RNA) sequencing and Reverse Phase Protein Array (RPPA).
- Quantify pre-treatment, pre- and post-olaparib, post-TRT, and at progression levels for blood-based biomarkers, such as cytokines associated with immune activation (e.g., STING pathway cytokines, CXCL10 and CCL5) to establish correlations with PFS and overall survival (OS).
VI. Using longitudinal blood samples (e.g. pre-treatment, pre- and post-olaparib, post-TRT, and at progression), assess CTC number, CTC (single-cell) biomarker expression (such as SLFN11 and PD-L1 expression), and immune profile of PBMCs.
VIa. Correlate baseline expression or changes with PFS and OS. VII. Assess pre- and post-olaparib, and at progression tumor tissue for immune markers, such as CD8+ T cells, through multiplex IHC.
VIII. Assessment of single-cell biomarker expression on CTCs and tumor tissue (such as SLFN11 and PD-L1 expression) and immune profile of peripheral blood mononuclear cells (PBMCs).
VIIIa. Correlate pre-treatment expression or changes with PFS and/or OS. IX. Generation of CTC-derived and/or biopsy-derived xenograft models from individual patients
OUTLINE:
CHEMO-IMMUNOTHERAPY: Patients receive durvalumab intravenously (IV) over 60 minutes on day 1, carboplatin IV over 60 minutes on day 1, etoposide IV over 60 minutes on days 1-3. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients with response or stable disease (SD) after cycle 4 and are candidates for TRT proceed to Induction. Patients that are not candidates for TRT proceed to Single-Agent Maintenance.
INDUCTION (WEEKS 13-14): Patients receive olaparib orally (PO) twice daily (BID) on days 1-11 in the absence of disease progression or unacceptable toxicity.
IMMUNORADIATION (WEEKS 15-18): Patients receive durvalumab IV over 60 minutes on day 1. Patients also undergo consolidative TRT daily on days 1-5 and 8-12 in the absence of disease progression or unacceptable toxicity.
MAINTENANCE (WEEKS 19 AND BEYOND): Patients without progressive disease receive durvalumab IV over 60 minutes on day 1, and olaparib PO BID. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
SINGLE-AGENT MAINTENANCE: Patients receive durvalumab IV over 60 minutes on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed for 30 days, then every 3 months.
- Conditions
- Extensive Stage Lung Small Cell Carcinoma, Stage IV Lung Cancer AJCC v8, Stage IVA Lung Cancer AJCC v8, Stage IVB Lung Cancer AJCC v8
- Being tested
- Carboplatin, Durvalumab, Etoposide, Olaparib, Radiation Therapy
- Medical subject headings
- Lung Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CarboplatinDrug
Also called Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino
Given IV
DurvalumabBiological
Also called Imfinzi, Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer, MEDI-4736, MEDI4736
Given IV
EtoposideDrug
Also called Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar
Given IV
OlaparibDrug
Also called AZD 2281, AZD-2281, AZD2281, KU-0059436
Given PO
Radiation TherapyRadiation
Also called Cancer Radiotherapy, ENERGY_TYPE, Irradiate, Irradiated
Undergo consolidative thoracic radiation therapy
| Study group | Role | What they receive |
|---|---|---|
| Treatment (chemo-immunotherapy, radiation therapy) | Experimental | See detailed description. Receives: Drug: Carboplatin; Biological: Durvalumab; Drug: Etoposide; Drug: Olaparib; Radiation: Radiation Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of dose limiting toxicity
Will be assessed per Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0. Toxicity data by type and severity will be summarized in frequency tables.
Measured: From start of olaparib, at the end of cycle 6 (each cycle is 28 days)
Secondary outcomes (4)
Progression-free survival (PFS)
Assessed per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. PFS will be compared to the pre-specified parameter obtained from historical data of comparable patients with extensive-stage small cell lung cancer (ES-SCLC) treated with frontline etoposide plus either cisplatin or carboplatin (EP) chemotherapy followed by thoracic radiation. Will be estimated using the Kaplan-Meier method. Comparison of time-to-event endpoints by important subgroups will be made using the log-rank test. Cox regression model will be applied to evaluate the effect of potential covariates on PFS.
Measured: Time from starting chemo-immunotherapy until disease progression or death from any cause, assessed up to 1 year
Overall survival (OS)
Will be estimated using the Kaplan-Meier method. Comparison of time-to-event endpoints by important subgroups will be made using the log-rank test. Cox regression model will be applied to evaluate the effect of potential covariates on OS.
Measured: Time from starting chemo-immunotherapy until death from any cause, assessed up to 1 year
Overall response rate (ORR)
The patient's best overall response assignment will depend on the findings of both target and non-target disease and will also take into consideration the appearance of new lesions.
Measured: Up to 1 year
Intra- and extra-thoracic recurrence rates
Measured: Up to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jan 2021
- Study start5 Jan 2021
- Primary completion31 Dec 2027 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Extensive Stage Lung Small Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 63 participants (estimated)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI), AstraZeneca
- Responsible party
- Sponsor
- Investigators
- Marcelo V Negrao, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04728230
- Sponsor's protocol ID
- 2020-0612
- Other IDs
- NCI-2020-06178, 2020-0612
- Status last verified
- Jun 2026
- First submitted
- 31 Aug 2020
- Last updated
- 11 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Trial of PARP Inhibition, Radiation, and Immunotherapy in Patients With Extensive-Stage Small Cell Lung Cancer (ES-SCLC) - PRIO Trial
- ClinicalTrials.gov ID
- NCT04728230
- Acronym / sponsor ID
- 2020-0612
- Conditions
- Extensive Stage Lung Small Cell Carcinoma, Stage IV Lung Cancer AJCC v8, Stage IVA Lung Cancer AJCC v8, Stage IVB Lung Cancer AJCC v8
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 63 participants (estimated)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI), AstraZeneca
- Study start
- 5 Jan 2021 (actual)
- Primary completion
- 31 Dec 2027 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 28 Jan 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 phase I/II trials investigates the side effects of olaparib and durvalumab and how well it works in combination with carboplatin, etoposide, and/or radiation therapy in treating patients with extensive stage-small cell lung cancer (ES-SCLC) who have not received treatment for their disease. PARPs are proteins that help repair DNA mutations. PARP inhibitors, such as olaparib, can keep PARP from working, so tumor cells can't repair themselves, and they may stop growing. Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as carboplatin and etoposide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy sources to kill tumor cells and shrink tumors. Giving olaparib and durvalumab together with carboplatin, etoposide, and/or radiation therapy may help treat patients with ES-SCLC.
Detailed description
PRIMARY OBJECTIVE:
- To assess the toxicity and feasibility of sequential treatment with olaparib, thoracic radiotherapy (TRT)/durvalumab, and olaparib/durvalumab for consolidation and maintenance therapy in patients status post (s/p) chemoimmunotherapy for ES-SCLC.
SECONDARY OBJECTIVE:
- To assess the efficacy of sequential treatment with olaparib, TRT/durvalumab, and olaparib/durvalumab for consolidation and maintenance therapy in patients s/p chemoimmunotherapy for ES-SCLC.
EXPLORATORY OBJECTIVES:
- Perform a comparative analysis of patient clinical outcome according to tumor biomarkers in circulating tumor cell (CTC), blood samples and tumor tissue, such as SLFN11 expression H- scores and stratifying tumors as SLFN11 positive or negative on the basis of H-score >= 1.
II. Perform a comparative analysis of patient clinical outcome according to immune biomarkers in blood and tumor tissue, such as PD-L1 immunohistochemistry (IHC) 22C3 pharmDx assay and stratifying tumors as PD-L1 positive or negative on the basis of PD-L1 combined positive score >= 1% in patients treated with anti- PD-L1 therapy.
III. Perform whole exome sequencing (WES) and methylation profiling on tumor samples and from circulating-free deoxyribonucleic acid (cfDNA) to evaluate whether tumor mutational burden (TMB) or specific genomic alterations are associated with improved progression free survival (PFS) with the trial regimen.
IV. Gene and protein expression of tumor tissue through ribonucleic acid (RNA) sequencing and Reverse Phase Protein Array (RPPA).
- Quantify pre-treatment, pre- and post-olaparib, post-TRT, and at progression levels for blood-based biomarkers, such as cytokines associated with immune activation (e.g., STING pathway cytokines, CXCL10 and CCL5) to establish correlations with PFS and overall survival (OS).
VI. Using longitudinal blood samples (e.g. pre-treatment, pre- and post-olaparib, post-TRT, and at progression), assess CTC number, CTC (single-cell) biomarker expression (such as SLFN11 and PD-L1 expression), and immune profile of PBMCs.
VIa. Correlate baseline expression or changes with PFS and OS. VII. Assess pre- and post-olaparib, and at progression tumor tissue for immune markers, such as CD8+ T cells, through multiplex IHC.
VIII. Assessment of single-cell biomarker expression on CTCs and tumor tissue (such as SLFN11 and PD-L1 expression) and immune profile of peripheral blood mononuclear cells (PBMCs).
VIIIa. Correlate pre-treatment expression or changes with PFS and/or OS. IX. Generation of CTC-derived and/or biopsy-derived xenograft models from individual patients
OUTLINE:
CHEMO-IMMUNOTHERAPY: Patients receive durvalumab intravenously (IV) over 60 minutes on day 1, carboplatin IV over 60 minutes on day 1, etoposide IV over 60 minutes on days 1-3. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients with response or stable disease (SD) after cycle 4 and are candidates for TRT proceed to Induction. Patients that are not candidates for TRT proceed to Single-Agent Maintenance.
INDUCTION (WEEKS 13-14): Patients receive olaparib orally (PO) twice daily (BID) on days 1-11 in the absence of disease progression or unacceptable toxicity.
IMMUNORADIATION (WEEKS 15-18): Patients receive durvalumab IV over 60 minutes on day 1. Patients also undergo consolidative TRT daily on days 1-5 and 8-12 in the absence of disease progression or unacceptable toxicity.
MAINTENANCE (WEEKS 19 AND BEYOND): Patients without progressive disease receive durvalumab IV over 60 minutes on day 1, and olaparib PO BID. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
SINGLE-AGENT MAINTENANCE: Patients receive durvalumab IV over 60 minutes on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed for 30 days, then every 3 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (chemo-immunotherapy, radiation therapy) | Experimental | Drug: Carboplatin, Biological: Durvalumab, Drug: Etoposide, Drug: Olaparib, Radiation: Radiation TherapySee detailed description. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- Provision of signed and dated written informed consent form prior to any mandatory study specific procedures, sampling, and analyses. For inclusion in i) the optional exploratory genetic research and ii) the optional biomarker research, patients must fulfill the following criteria:
- At least one lesion (measurable and/or non-measurable) that can be accurately assessed at baseline by computed tomography (CT) and is suitable for repeated assessment
- Patients with previously treated brain metastases that are asymptomatic for at least 14 days and only require prednisone equivalent of 10 mg daily or less prior to study treatment
- Histological or cytological documented ES-SCLC: American Joint Committee on Cancer (AJCC) stage IV SCLC (T any, N any, M1 a/b), including patients with T3-4 due to multiple lung nodules that are too extensive or have tumor/nodal volume that is too large to be encompassed in a tolerable radiation plan
- No prior systemic therapy for ES-SCLC, including, but not limited to, chemotherapy, PARP inhibitor, and PD-1/PD-L1 checkpoint inhibitors. Palliative radiation is allowed if completed a minimum of three days prior to beginning of study treatment
Key exclusion criteria (28 listed)
- Histology other than SCLC
- Prior systemic therapy for ES-SCLC (e.g. chemotherapy, PARP inhibitor, other DNA damage response [DDR] inhibitors, PD-1/PD-L1 inhibitors)
- Patients with untreated brain metastases
- Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days
- Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of study treatment and patients must have recovered from any effects of any major surgery. Note: Local surgery of isolated lesions for palliative intent is acceptable
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 |
|---|---|---|
| CarboplatinAlso: Blastocarb, Carboplat, Carboplatin Hexal, CarboplatinoGiven IV | Drug | Treatment (chemo-immunotherapy, radiation therapy) |
| DurvalumabAlso: Imfinzi, Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer, MEDI-4736, MEDI4736Given IV | Biological | Treatment (chemo-immunotherapy, radiation therapy) |
| EtoposideAlso: Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, ToposarGiven IV | Drug | Treatment (chemo-immunotherapy, radiation therapy) |
| OlaparibAlso: AZD 2281, AZD-2281, AZD2281, KU-0059436Given PO | Drug | Treatment (chemo-immunotherapy, radiation therapy) |
| Radiation TherapyAlso: Cancer Radiotherapy, ENERGY_TYPE, Irradiate, IrradiatedUndergo consolidative thoracic radiation therapy | Radiation | Treatment (chemo-immunotherapy, radiation therapy) |
Primary outcome
Incidence of dose limiting toxicity
Time frame: From start of olaparib, at the end of cycle 6 (each cycle is 28 days)
Will be assessed per Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0. Toxicity data by type and severity will be summarized in frequency tables.
4 secondary outcomes
Progression-free survival (PFS)
Time frame: Time from starting chemo-immunotherapy until disease progression or death from any cause, assessed up to 1 year
Overall survival (OS)
Time frame: Time from starting chemo-immunotherapy until death from any cause, assessed up to 1 year
Overall response rate (ORR)
Time frame: Up to 1 year
Intra- and extra-thoracic recurrence rates
Time frame: Up to 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jun 2026.
- M D Anderson Cancer CenterLink provided by the sponsor.
Related trials for Extensive Stage Lung Small Cell Carcinoma
Active, not recruitingPhase 3
Study Comparing Tarlatamab and Durvalumab Versus Durvalumab Alone in First-Line Extensive-Stage Small-Cell Lung Cancer (ES-SCLC) Following Platinum, Etoposide and Durvalumab
Extensive-Stage Small-Cell Lung Cancer, Small-Cell Lung Cancer
RecruitingPhase 2
A Study of Lurbinectedin in Combination With Durvalumab for the Treatment of Participants With ES-SCLC
Extensive-stage Small-cell Lung Cancer
Active, not recruitingPhase 2
Safety, Preliminary Effectiveness of BNT327, an Investigational Therapy for Patients With Small-cell Lung Cancer in Combination With Chemotherapy
Extensive-stage Small-cell Lung Cancer, Small-cell Lung Cancer
RecruitingPhase 2
MOnaliZumab in Combination With durvAlumab (MEDI4736) for tRreatmenT of Small Cell Lung Cancer
Small Cell Lung Cancer, SCLC
Not yet recruitingPhase 2
Low-Dose Radiotherapy Plus Adebrelimab and Chemotherapy for Extensive-Stage Small Cell Lung Cancer
Small Cell Lung Cancer (SCLC), SCLC, Extensive Stage
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.
Marcelo V Negrao principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Carboplatin, Durvalumab and Etoposide in people with Extensive Stage Lung Small Cell Carcinoma and Stage IV Lung Cancer AJCC v8, run by M.D. Anderson Cancer Center 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 25 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: under way, not looking for participants, as of the sponsor's last update on 11 Jun 2026. 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 combined 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.
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?
This study is still under way. Results are not available in the source record yet.
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?
Incidence of dose limiting toxicity (time frame: From start of olaparib, at the end of cycle 6 (each cycle is 28 days)). 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 11 Jun 2026.