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Trial record 1 of 1 for:    NCT03057106
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Durvalumab and Tremelimumab ± Platinum-Based Chemotherapy in Patients With Metastatic Squamous or Non-Squamous NSCLC

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ClinicalTrials.gov Identifier: NCT03057106
Recruitment Status : Recruiting
First Posted : February 17, 2017
Last Update Posted : July 12, 2018
Sponsor:
Collaborators:
AstraZeneca
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
National Health and Medical Research Council, Australia
Information provided by (Responsible Party):
Canadian Cancer Trials Group

Brief 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.


Condition or disease Intervention/treatment Phase
Lung Cancer Metastatic Drug: Durvalumab Drug: Tremelimumab Drug: Platinum-Based Drug Phase 2

Detailed 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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 300 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : February 15, 2017
Estimated Primary Completion Date : August 2019
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Durvalumab

Arm Intervention/treatment
Active Comparator: Durvalumab and Tremelimumab
Durvalumab q4 weeks until PD + Tremelimumab q 4 wk x 4 doses
Drug: Durvalumab
MEDI4736

Drug: Tremelimumab
Tremelimumab

Active Comparator: Platinum based chemotherapy + Durvalumab + Tremelimumab

4 cycles platinum plus gem or pem + Durva + Treme (q 3 wk x 4 cycles)

Followed by:

Squamous Cell: Maintenance Durva q 4 wk until PD Non-Squamous Cell: Pemetrexed + Durva q 4 wk until PD

Drug: Durvalumab
MEDI4736

Drug: Tremelimumab
Tremelimumab

Drug: Platinum-Based Drug
Pemetrexed, cisplatin, carboplatin or gemcitibine




Primary Outcome Measures :
  1. Overall Survival [ Time Frame: 33 months ]
    time from randomization to the date of death


Secondary Outcome Measures :
  1. Progression-free Survival using RECIST 1.1 [ Time Frame: 33 months ]
    time from randomization to the date of the first documented disease progression

  2. Objective Response Rate using RECIST 1.1 and iRECIST [ Time Frame: 33 months ]
    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.

  3. Number and Severity of Adverse Events [ Time Frame: 33 months ]
    using the NCI Common Terminology Criteria for Adverse Events Version 4.0. A Fisher's exact test will be used to compare adverse events between the study new treatment and the standard control arms if required.

  4. Cost Effectiveness of Durvalumab and Tremelimumab concurrently with combination chemotherapy [ Time Frame: 33 months ]
    The mean overall cost per patient for each of the two study treatment arms will be calculated to determine the addition cost per life-year gained.

  5. Correlate the expression of correlative markers with outcomes and response [ Time Frame: 33 months ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 be high risk, defined as the presence of one or more of the following unfavourable prognostic factors:

    • Stage IVB disease
    • Stage IVA disease with at least one of the following:
    • Elevated LDH,

      • Weight loss ≥ 5% over 3 months before randomization,
      • Poorly differentiated histology.
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03057106


Contacts
Contact: Francisco Vera-Badillo 613-533-6430 paco@ctg.queensu.ca

  Show 46 Study Locations
Sponsors and Collaborators
Canadian Cancer Trials Group
AstraZeneca
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
National Health and Medical Research Council, Australia
Investigators
Study Chair: Natasha Leighl Princess Margaret Hospital, Toronto, ON Canada

Responsible Party: Canadian Cancer Trials Group
ClinicalTrials.gov Identifier: NCT03057106     History of Changes
Other Study ID Numbers: BR34
First Posted: February 17, 2017    Key Record Dates
Last Update Posted: July 12, 2018
Last Verified: February 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Antibodies, Monoclonal
Tremelimumab
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents