Durvalumab and Tremelimumab ± Platinum-Based Chemotherapy in Patients With Metastatic Squamous or Non-Squamous NSCLC

Lung Cancer Metastatic Clinical Trial

Official title:

A Randomized Trial of Durvalumab and Tremelimumab ± Platinum-Based Chemotherapy in Patients With Metastatic (Stage IV) Squamous or Non-Squamous Non-Small Cell Lung Cancer (NSCLC)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03057106
• Other study ID #: BR34
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: March 28, 2017
• Est. completion date: December 31, 2024

Study information

• Verified date: April 2024
• Source: Canadian Cancer Trials Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Durvalumab is a new type of drug for many kinds of cancer. It is considered "immunotherapy" and not "chemotherapy". Laboratory tests show that it works by allowing the immune system to detect cancer and reactivate the immune response. This may help to slow down the growth of cancer or may cause cancer cells to die. Durvalumab has been shown to shrink tumours in animals and has been studied in more than 5000 people and seems promising. Tremelimumab is a new type of drug for various types of cancers. It works in a similar way to durvalumab and may improve the effect of durvalumab. Tremelimumab may also help slow the growth of the cancer cells or may cause cancer cells to die. It has been shown to shrink tumours in animals and has been studied in over 1200 people and seems promising.

Description:

Combinations of durvalumab and tremelimumab have also been studied. While the combination has been studied in over 200 people, it is not clear if it can offer better results when it is combined with chemotherapy. Recently, immunotherapies that target the PD-1/PD-L1 axis have shown promise in treating patients with non-small cell lung cancer.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 301
• Est. completion date: December 31, 2024
• Est. primary completion date: February 24, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients must have histologically and/or cytologically confirmed diagnosis of squamous or non-squamous, non-small cell carcinoma of the lung. Patients with poorly differentiated tumours will only be eligible if NSCLC is confirmed by immunohistochemistry markers (TTF1/P63 or P40/CK5). Patients with known sensitizing EGFR mutations or known ALK-fusion are not eligible.
• Patients must have stage IV disease according to the 8th TNM version staging.
• Patients must have an adequate histopathology specimen and must consent to release this specimen for protocol required testing. This is a mandatory component of the study.
• Patient must consent to provision of samples of blood in order that the specific correlative marker assays proscribed may be conducted.
• All patients must have measurable disease as defined by RECIST 1.1 All radiology studies must be performed within 28 days prior to randomization (within 35 days if negative).

The criteria for defining measurable disease are as follows:

• CT scan (with slice thickness of 5 mm) = 10 mm --> longest diameter
• Physical exam (using calipers) = 10 mm
• Lymph nodes by CT scan = 15 mm --> measured in short axis Measurable lesions must be outside a previous radiotherapy field if they are the sole site of disease, unless disease progression has been documented.
• Patients must be 18 years of age or older.
• ECOG performance status of 0 or 1.
• Absolute neutrophils = 1.5 x 10^9/L
• Platelets = 100 x 10^9/L
• Hemoglobin = 90 g/L
• Bilirubin = 1.5 x UNL (upper limit of normal)
• AST and ALT = 2.5 x UNL (if liver metastases are present, =5 x UNL) Creatinine < 1.25 UNL or Creatinine clearance = 45 mL/min
• Cytotoxic Chemotherapy: Patients may not have received prior cytotoxic chemotherapy for advanced/metastatic disease.
• Adjuvant Chemotherapy: Patients may have had prior adjuvant therapy for completely resected disease, providing it has been completed at least 12 months prior to randomization.
• Patients treated with concurrent chemotherapy/radiation regimens for unresectable locally advanced Stage III disease will be eligible providing it has been completed at least 12 months prior to randomization.
• Other Systemic Therapy: Patients may not have received prior EGFR or alk inhibitors. Patients may not have received prior treatment with immune-based therapy, including durvalumab and tremelimumab vaccines or oncolytic viral therapy. Patients must have recovered from any reversible treatment related toxicities prior to randomization.
• Prior external beam radiation is permitted provided a minimum of 14 days (2 weeks) have elapsed between the last dose of radiation and date of randomization. Concurrent radiotherapy is not permitted. Patients must have recovered from any acute toxic effects from radiation prior to randomization.
• Patients must have recovered from any acute toxic effects from radiation prior to randomization.
• Surgery: Previous surgery is permitted provided that wound healing has occurred and at least 14 days have elapsed (major surgery) prior to randomization.
• Patient must be able (i.e. sufficiently fluent) and willing to complete the quality of life and health economics questionnaires.
• Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements.
• Patients must be accessible for treatment and follow-up. All randomized patients must be followed and treated at participating centres.
• In accordance with CCTG policy, protocol treatment is to begin within 2 working days of patient randomization.
• Female patients of childbearing potential who are sexually active with a non-sterilized male partner must use at least one highly effective method of contraception while on study and for 6 months after the last dose of durvalumab and tremelimumab or for 3 months after the last dose of durvalumab alone

Exclusion Criteria:

• Patients with a history of other malignancies, 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 = 3 years. Patients with a history of other malignancies detected at an early stage and whom the investigator believes have been curatively treated and are at low risk of recurrence MAY be eligible. Contact CCTG to discuss eligibility prior to enrolling.
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease (e.g. colitis or Crohn's disease), diverticulitis with the exception of diverticulosis, celiac disease or other serious gastrointestinal chronic conditions associated with diarrhea), systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome (granulomatosis with polyangiitis), rheumatoid arthritis, hypophysitis, uveitis, etc., within the past 3 years prior to the start of

treatment. The following are exceptions to this criterion:

• Patients with alopecia.
• Patients with Grave's disease, vitiligo or psoriasis not requiring systemic treatment (within the last 2 years).
• Patients with hypothyroidism (e.g. following Hashimoto syndrome) stable on hormone replacement.
• History of primary immunodeficiency, history of allogenic organ transplant that requires therapeutic immunosuppression and the use of immunosuppressive agents within 28 days of randomization* or a prior history of severe (grade 3 or 4) immune mediated toxicity from other immune therapy or grade = 3 infusion reaction.
• Live attenuated vaccination administered within 30 days prior to randomization
• History of hypersensitivity to durvalumab or tremelimumab or any excipient. Patients who have received other treatment or other antibodies must not have had intolerable toxicity or required steroids to manage toxicity.
• Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) = 470 msec in screening ECG measured using standard institutional method or history of familial long QT syndrome.
• Patients who have untreated and/or uncontrolled cardiovascular conditions and/or have symptomatic cardiac dysfunction (unstable angina, congestive heart failure, myocardial infarction within the previous year or cardiac ventricular arrhythmias requiring medication, history of 2nd or 3rd degree atrioventricular conduction defects). Patients with a significant cardiac history, even if now controlled, should have a LVEF = 45%. (Note: patients with uncomplicated controlled hypertension do not require LVEF measurement in the absence of other significant cardiac history)
• Concurrent treatment with other investigational drugs or anti-cancer therapy
• Patients with untreated brain or meningeal metastases are not eligible. Patients with treated CNS disease who have radiologic AND clinical evidence of stable brain metastases, with no evidence of cavitation or hemorrhage in the brain lesion, are eligible providing that they are asymptomatic and do not require corticosteroids (must have discontinued steroids at least 1 week prior to randomization).
• Pregnant or Lactating Women: Women of childbearing potential must have a pregnancy test (urine or serum) proven negative within 14 days prior to randomization. If urine test is positive, pregnancy testing may then include an ultrasound to rule-out pregnancy if a false-positive is suspected. For example, when beta-human chorionic gonadotropin is high and partner is vasectomized, it may be associated with tumour production of hCG, as seen with some cancers. Patient will be considered eligible if an ultrasound is negative for pregnancy. Men and women of child-bearing potential must agree to use adequate contraception.
• Patients with serious illnesses or medical conditions which would not permit the patient to be managed according to the protocol (including corticosteroid administration), or would put the patient at risk. This includes but is not limited

to:

• Contraindications to the use of pemetrexed, gemcitabine, cisplatin and/or carboplatin (consult product monograph);
• History of significant neurologic or psychiatric disorder which would impair the ability to obtain consent or limit compliance with study requirements;
• Active infection requiring systemic therapy; (including any patient known to have active hepatitis B, hepatitis C or human immunodeficiency virus (HIV) or tuberculosis);
• Active peptic ulcer disease or gastritis;
• Known pneumonitis or pulmonary fibrosis with clinically significant impairment of pulmonary function.

Related Conditions & MeSH terms

• Lung Cancer Metastatic
• Lung Neoplasms

Intervention

Drug:
• Durvalumab
MEDI4736
• Tremelimumab
Tremelimumab
• Platinum-Based Drug
Pemetrexed, cisplatin, carboplatin or gemcitibine

Locations

Country	Name	City	State
Australia	Ballarat Health Services	Ballarat	Victoria
Australia	Princess Alexandra Hospital	Brisbane	Queensland
Australia	Campbelltown Hospital	Campbelltown	New South Wales
Australia	The Prince Charles Hospital	Chermside	Queensland
Australia	Coffs Habour Health Campus - NCCI	Coffs Harbour	New South Wales
Australia	Concord Repatriation General Hospital	Concord	New South Wales
Australia	Royal Hobart Hospital	Hobart	Tasmania
Australia	Nepean Hospital	Kingswood	New South Wales
Australia	St. George Hospital, Cancer Care Centre	Kogarah	New South Wales
Australia	The Tweed Hospital	Lismore	New South Wales
Australia	Liverpool Cancer Therapy Centre, Liverpool Hospital	Liverpool	New South Wales
Australia	Prince of Wales Hospital	Randwick	New South Wales
Australia	Epworth HealthCare - Richmond	Richmond	Victoria
Australia	Mater Research Institute South Brisbane	South Brisbane	Queensland
Australia	Gold Coast University Hospital	Southport	Queensland
Australia	Saint John of God Hospital Subiaco	Subiaco	Western Australia
Australia	Toowoomba Hospital	Toowoomba	Queensland
Australia	St. Vincent's Hospital	Victoria Park
Australia	Border Medical Oncology	Wodonga	Victoria
Canada	Cambridge Memorial Hospital	Cambridge	Ontario
Canada	PEI Cancer Treatment Centre	Charlottetown	Prince Edward Island
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	Horizon Health Network	Fredericton	New Brunswick
Canada	Juravinski Cancer Centre at Hamilton Health Sciences	Hamilton	Ontario
Canada	Kingston Health Sciences Centre	Kingston	Ontario
Canada	Grand River Regional Cancer Centre	Kitchener	Ontario
Canada	Hopital de la Cite-de-la-Sante	Laval	Quebec
Canada	The Moncton Hospital	Moncton	New Brunswick
Canada	The Vitalite Health Network - Dr. Leon Richard	Moncton	New Brunswick
Canada	CHUM-Centre Hospitalier de l'Universite de Montreal	Montreal	Quebec
Canada	The Jewish General Hospital	Montreal	Quebec
Canada	Stronach Regional Health Centre at Southlake	Newmarket	Ontario
Canada	Ottawa Hospital Research Institute	Ottawa	Ontario
Canada	CHU de Quebec-Hopital l'Enfant-Jesus (HEJ)	Quebec City	Quebec
Canada	University Institute of Cardiology and	Quebec City	Quebec
Canada	Allan Blair Cancer Centre	Regina	Saskatchewan
Canada	Regional Health Authority B, Zone 2	Saint John	New Brunswick
Canada	Saskatoon Cancer Centre	Saskatoon	Saskatchewan
Canada	Algoma District Cancer Program	Sault Ste. Marie	Ontario
Canada	Centre hospitalier universitaire de Sherbrooke	Sherbrooke	Quebec
Canada	Niagara Health System	St. Catharines	Ontario
Canada	Health Sciences North	Sudbury	Ontario
Canada	BCCA - Fraser Valley Cancer Centre	Surrey	British Columbia
Canada	Humber River Regional Hospital	Toronto	Ontario
Canada	Michael Garron Hospital	Toronto	Ontario
Canada	North York General Hospital	Toronto	Ontario
Canada	University Health Network	Toronto	Ontario
Canada	BCCA - Vancouver Cancer Centre	Vancouver	British Columbia
Canada	Windsor Regional Cancer Centre	Windsor	Ontario

Sponsors (4)

Lead Sponsor	Collaborator
Canadian Cancer Trials Group	AstraZeneca, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, National Health and Medical Research Council, Australia

Countries where clinical trial is conducted

Australia,  Canada, 

References & Publications (1)

Leighl NB, Laurie SA, Goss GD, Hughes BGM, Stockler M, Tsao MS, Hwang DM, Joubert P, Kulkarni S, Blais N, Joy AA, Mates M, Rana P, Yadav SK, Underhill C, Lee C, Bradbury PA, Hiltz A, Dancey J, Ding K, Vera-Badillo F; Canadian Cancer Trials Group Lung Dise — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival	time from randomization to the date of death	33 months
Secondary	Progression-free Survival Using RECIST 1.1	time from randomization to the date of the first documented disease progression. Progression was defined as: at least a 20% increase in the sum of diameters of measured lesions taking as references the smallest sum of diameters recorded on study (including baseline) AND an absolute increase of =5 mm, or appearance of new lesions.	33 months
Secondary	Objective Response Rate Using RECIST 1.1 and iRECIST	proportion of patients with a documented complete response, partial response (CR + PR) based on iRECIST criteria. The primary estimate of ORR will be based on all patients randomized, and compared using Cochran- Mantel-Haeszel test stratified by stratification factors at randomization between the study new treatment and the standard control arms.	33 months