An Open Label, Multicenter Phase 2 Study of Durvalumab (MEDI4736) + Olaparib as Maintenance Therapy in Chinese

NCT05245994 | Unknown Phase 2

• 1 other identifier: ESR-20-20659
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study was to evaluate the efficacy and safety of combining durvalumab with EP followed by durvalumab + olaparib maintenance therapy as first-line treatment in patients with extensive-disease small-cell lung cancer (SCLC).

Conditions

Lung Cancer; Small Cell Lung Cancer; Durvalumab

Keywords

ES-SCLC; Durvalumab; Olaparib

Outcome Measures

Primary Outcomes (1)

• APF12-Alive and Progression Free

  A proportion of patients alive and progression free at 12 months from the first date of first-line treatment

  1 year

Secondary Outcomes (4)

• PFS0-Progression Free Survival 0

  2 years

• PFS-Progression Free Survival

  2 years

• OS-Overall Survival

  2 years

• ORR-Objective Response Rate

  2 years

Other Outcomes (1)

• AE-Adverse Events

  2 years

Study Arms (1)

Durvalumab, etoposide, and cisplatin/carboplatin followed by durvalumab and olaparib

EXPERIMENTAL

Drug: Durvalumab, etoposide, and cisplatin/carboplatin followed by durvalumab and olaparib

Interventions

Durvalumab, etoposide, and cisplatin/carboplatin followed by durvalumab and olaparib DRUG

Durvalumab 1500 mg intravenous infusion, started to be used simultaneously with chemotherapy at week 0 and continued after chemotherapy. Starting from week 0, the dose of etoposide + carboplatin or cisplatin in the study will not exceed the dose for specific indications in the product instructions (etoposide \[80 to 100mg/m2\] via intravenous infusion and carboplatin \[ The area under the curve (AUC) is 5-6\] by intravenous infusion or cisplatin \[75-80 mg/m2\] by intravenous infusion), using up to 4 cycles. The choice of platinum drugs is at the discretion of the investigator. The initial dose of olaparib is 300mg twice daily. Olaparib tablets should be taken at the same time each day, approximately 12 hours apart with one glass of water. The tablets should be swallowed whole and not chewed, crushed, dissolved or divided. Olaparib tablets can be taken with or without food.

Durvalumab, etoposide, and cisplatin/carboplatin followed by durvalumab and olaparib

Eligibility Criteria

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

You may qualify if:

• Male or female ≥18 years at the time of screening.
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
• Written informed consent and any locally required authorization obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations.
• Histologically or cytologically documented extensive disease (American Joint Committee on Cancer Stage (7th edition) IV SCLC \[T any, N any, M1 a/b\]), or 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.
• Brain metastases; must be asymptomatic or treated and stable off steroids and anti-convulsants for at least 1 month prior to study treatment. Patients with suspected brain metastases at screening should have a CT/MRI of the brain prior to study entry.
• Provision of an archived tumor tissue block (or at least 15 newly cut unstained slides) where such samples exist.
• Patients must be considered suitable to receive a platinum based chemotherapy regimen as 1st line treatment for the ED-SCLC. Chemotherapy must contain either cisplatin or carboplatin in combination with etoposide.
• Life expectancy ≥16 weeks at Day 1.
• World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2 at enrollment. PS2 patients are permitted to receive first-line treatment, and PS score should be reassessed after first-line treatment. Then patients who are assessed as PS2 at the completion of chemotherapy+durvalumab will be excluded.
• Body weight \>30 kg.
• At least 1 lesion, not previously irradiated, that can be accurately measured at baseline as ≥10 mm in the longest diameter (except lymph nodes which must have a short axis ≥15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) and that is suitable for accurate repeated measurements as per RECIST 1.1 guidelines.
• No prior exposure to immune-mediated therapy including, but not limited to, other PARP inhibitor, anti-PD-1, anti-PD-L1, and anti-programmed cell death ligand 2 (anti-PD-L2) antibodies, excluding therapeutic anticancer vaccines.
• Adequate organ and marrow function which is measured within 28 days prior to administration of study treatment as defined below:
• Hemoglobin ≥ 10.0 g/dL with no blood transfusion in the past 28 days Absolute neutrophil count ≥1.5 × 109/L (use of granulocyte colony-stimulating factor is not permitted at screening).
• Platelet count ≥100 × 109/L. Serum bilirubin ≤1.5 × the upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert's syndrome, who will be allowed in consultation with their physicians.

You may not qualify if:

• Previous IP assignment in the present study.
• Concurrent enrollment in another clinical study, unless it is an observational (non interventional) clinical study or during the follow up period of an interventional study.
• Participation in another clinical study with an IP during the last 4 weeks.
• Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication.
• Medical contraindication to etoposide platinum (carboplatin or cisplatin) based chemotherapy.
• Any history of radiotherapy to the chest prior to systemic therapy or planned consolidation chest radiation therapy. Radiation therapy outside of the chest for palliative care (ie, bone metastasis) is allowed but must be completed before first dose of the study medication.
• 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 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable.
• History of allogeneic organ transplantation.
• Has a paraneoplastic syndrome (PNS) of autoimmune nature, requiring systemic treatment (systemic steroids or immunosuppressive agents) or has a clinical symptomatology suggesting worsening of PNS.
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[eg, colitis or Crohn's disease\], diverticulitis with the exception of diverticulosis, systemic lupus erythematosus, sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, and uveitis, etc\]). The following are exceptions to this criterion:
• Patients with vitiligo or alopecia Patients with hypothyroidism (eg, following Hashimoto syndrome) and stable on hormone replacement Any chronic skin condition that does not require systemic therapy Patients without active disease in the last 5 years may be included but only after consultation with the investigator Patients with celiac disease controlled by diet alone
• Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, interstitial lung disease, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, 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 patient to give written informed consent.
• History of another primary malignancy except for Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of IP and of low potential risk for recurrence Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease Adequately treated carcinoma in situ without evidence of disease
• History of leptomeningeal carcinomatosis.

Sponsors & Collaborators

• Li Zhang, MD: lead

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

RECRUITING

MeSH Terms

Conditions

Lung Neoplasms; Small Cell Lung Carcinoma

Interventions

durvalumab; Etoposide; Cisplatin; olaparib

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms

Intervention Hierarchy (Ancestors)

Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Central Study Contacts

LI ZHANG

CONTACT

020-87343533; zhangli@sysucc.org.cn

YAN HUANG

CONTACT

020-87342331; huangyan@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 23, 2022
• First Posted: February 18, 2022
• Study Start: August 21, 2021
• Primary Completion: May 1, 2023
• Study Completion: November 1, 2023
• Last Updated: February 18, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)