An Open-Label, Multi-Centre, Study to Assess the Safety of Fixed-Dose Durvalumab + Tremelimumab Combination Therapy or Durvalumab Monotherapy in Advanced Solid Malignancies.

Completed · Phase 3

Conditions studied: Advanced Solid Malignancies

In brief

To evaluate the safety, tolerability, and anti-tumor activity of the combination of durvalumab + tremelimumab or durvalumab alone in different solid tumors.

Key facts

Study ID

NCT03084471

Run by

AstraZeneca

People needed

867

Starts

2017-06-05

Expected to finish

2022-12-16

Last updated by the study team

2022-12-22

Who can join

Age: 18 and older, up to 130. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Must have a life expectancy of at least 12 weeks.
• Age ≥18 years at the time of screening. For patients aged <20 years and enrolled in Japan, a written informed consent should be obtained from the patient and his or her legally acceptable representative
• 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 (eg, Health Insurance Portability and Accountability Act in the US, European Union [EU] Data Privacy Directive in the EU) obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations. For patients aged <20 years and enrolling in Japan, a written informed consent should be obtained from the patient and his or her legally acceptable representative.
• Disease not amenable to curative surgery
• Eastern Cooperative Oncology Group (ECOG) performance status as defined in the specific module.
• Body weight >30 kg.
• No prior exposure to anti-PD-1 or anti-PD-L1, including on another AstraZeneca study. Exposure to other investigational agents may be permitted after discussion with the Sponsor.
• Adequate organ and marrow function as defined below
• Hemoglobin ≥9.0 g/dL
• Absolute neutrophil count ≥1.0 × 109 /L
• Platelet count ≥75 × 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 physician.
• ALT and AST ≤2.5 × ULN; for patients with hepatic metastases, ALT and AST ≤5 × ULN
• Measured creatinine clearance (CL) >40 mL/min or calculated creatinine clearance (CL) >40 mL/min as determined by Cockcroft-Gault (using actual body weight)
• Males:
• Creatinine CL = Weight (kg) × (140 - Age) (mL/min) 72 × serum creatinine (mg/dL)
• Females:
• Creatinine CL = Weight (kg) × (140 - Age) x 0.85 (mL/min) 72 × serum creatinine (mg/dL)
• Female patients of childbearing potential (ie, not surgically sterile or post menopausal) who are sexually active with a non sterilized male partner must use at least one highly effective method of contraception from the time of screening and must agree to continue using such precautions for 180 days after the last dose of durvalumab + tremelimumab combination therapy or 90 days after the last dose of durvalumab monotherapy (see Section 3.8 and specifically Table 1).
• Evidence of post-menopausal status or negative urinary or serum pregnancy test (per Section 4) for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
• Women <50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle- stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
• Women ≥50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses >1 year ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).
• Non sterilized male patients who are sexually active with a female partner of childbearing potential must use a male condom plus spermicide from screening through 180 days after receipt of the final dose of durvalumab + tremelimumab combination therapy or 90 days after receipt of the final dose of durvalumab monotherapy.

You may not qualify if…

• Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
• Previous IP assignment in the present study.
• Concurrent enrollment in another clinical study, or another sub-study of this protocol, 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 investigational product during the last 28 days or 5 half-lives, whichever is longer, prior to the first dose of study treatment.
• Any concurrent chemotherapy, investigational agent, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (eg, hormone replacement therapy) is acceptable.
• Local treatment of isolated lesions for palliative intent is acceptable (eg, local surgery or radiotherapy).
• Receipt of any investigational anticancer therapy within 28 days or 5 half-lives, whichever is longer, prior to the first dose of study treatment.
• Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug. Note: Local treatment of isolated lesions, excluding target lesions, for palliative intent 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 allogenic organ transplantation.
• Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, ILD, serious chronic GI 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 investigational product (durvalumab + tremelimumab) 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
• Has untreated central nervous system (CNS) metastases and/or carcinomatous meningitis identified either on baseline brain imaging (please refer to RECIST for details on the imaging modality) obtained during the screening period or identified prior to signing the ICF. Patients whose brain metastases have been treated may participate provided they show radiographic stability (defined as 2 brain images, both of which are obtained after treatment to the brain metastases. These imaging scans should both be obtained at least 4 weeks apart and show no evidence of intracranial progression). In addition, any neurologic symptoms that developed either as a result of the brain metastases or their treatment must have resolved or be stable either, without the use of steroids, or are stable on a steroid dose of ≤10 mg/day of prednisone or its equivalent and anti-convulsants for at least 14 days prior to the start of treatment. Brain metastases will not be recorded as RECIST Target Lesions at baseline.
• History of active primary immunodeficiency.
• Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis testing in line with local practice), hepatitis B (known positive hepatitis B virus [HBV] surface antigen (HBsAg) result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
• Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab or tremelimumab. The following are exceptions to this criterion:
• Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra articular injection)
• Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
• 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, uveitis, etc.]). The following are exceptions to this criterion:
• Patients with vitiligo or alopecia
• Patients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement

Where it is running

• Research Site — Washington D.C., District of Columbia, United States
• Research Site — Tinley Park, Illinois, United States
• Research Site — Omaha, Nebraska, United States
• Research Site — Hackensack, New Jersey, United States
• Research Site — East Setauket, New York, United States
• Research Site — Greenville, South Carolina, United States
• Research Site — Knoxville, Tennessee, United States
• Research Site — Blacksburg, Virginia, United States
• Research Site — Spokane, Washington, United States
• Research Site — Moncton, New Brunswick, Canada
• Research Site — Brampton, Ontario, Canada
• Research Site — Hamilton, Ontario, Canada
• Research Site — Kingston, Ontario, Canada
• Research Site — London, Ontario, Canada
• Research Site — Newmarket, Ontario, Canada
• Research Site — Toronto, Ontario, Canada
• Research Site — Toronto, Ontario, Canada
• Research Site — Greenfield Park, Quebec, Canada
• Research Site — Québec, Quebec, Canada
• Research Site — Besançon, France
• Research Site — Bordeaux, France
• Research Site — Bordeaux, France
• Research Site — Brest, France
• Research Site — Dijon, France
• Research Site — Santa Rosa, California, United States

Full record on ClinicalTrials.gov

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