Olaparib and Durvalumab With Carboplatin, Etoposide, and/or Radiation Therapy for the Treatment of Extensive-Stage Small Cell Lung Cancer, PRIO Trial

NCT04728230 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 2020-0612NCI-2020-06178
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 1

Brief 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. 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.

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

Outcome Measures

Primary Outcomes (1)

• 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.

  From start of olaparib, at the end of cycle 6 (each cycle is 28 days)

Secondary Outcomes (4)

• Progression-free survival (PFS)

  Time from starting chemo-immunotherapy until disease progression or death from any cause, assessed up to 1 year

• Overall survival (OS)

  Time from starting chemo-immunotherapy until death from any cause, assessed up to 1 year

• Overall response rate (ORR)

  Up to 1 year

• Intra- and extra-thoracic recurrence rates

  Up to 1 year

Study Arms (1)

Treatment (chemo-immunotherapy, radiation therapy)

EXPERIMENTAL

See detailed description.

Drug: Carboplatin; Biological: Durvalumab; Drug: Etoposide; Drug: Olaparib; Radiation: Radiation Therapy

Interventions

Durvalumab BIOLOGICAL

Given IV

Also known as: Imfinzi, Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer, MEDI-4736, MEDI4736

Treatment (chemo-immunotherapy, radiation therapy)

Etoposide DRUG

Given IV

Also known as: Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar, Vepesid, VP 16, VP 16-213, VP-16, VP-16-213, VP16

Treatment (chemo-immunotherapy, radiation therapy)

Olaparib DRUG

Given PO

Also known as: AZD 2281, AZD-2281, AZD2281, KU-0059436, Lynparza, PARP Inhibitor AZD2281

Treatment (chemo-immunotherapy, radiation therapy)

Carboplatin DRUG

Given IV

Also known as: Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carboplatinum, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo

Treatment (chemo-immunotherapy, radiation therapy)

Radiation Therapy RADIATION

Undergo consolidative thoracic radiation therapy

Also known as: Cancer Radiotherapy, ENERGY_TYPE, Irradiate, Irradiated, Irradiation, Radiation, Radiation Therapy, NOS, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation

Treatment (chemo-immunotherapy, radiation therapy)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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)

You may not qualify if:

• 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:
• 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 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

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator
• AstraZeneca: collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• M D Anderson Cancer Center

MeSH Terms

Conditions

Lung Neoplasms

Interventions

Carboplatin; durvalumab; Immunoglobulin G; Disulfides; Etoposide; olaparib; Radiotherapy; Radiation

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Therapeutics; Physical Phenomena

Study Officials

• Marcelo V Negrao

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 31, 2020
• First Posted: January 28, 2021
• Study Start: January 5, 2021
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: December 18, 2025

Record last verified: 2025-12

Locations

US (1)