Small Cell Lung Carcinoma, Carcinoma, Squamous Cell of Head and Neck, Stomach Neoplasms, Triple Negative Breast Neoplasms, Ovarian Neoplasms, Fallopian Tube Neoplasms, Peritoneal Neoplasms, Esophagogastric Junction Neoplasms, Carcinoma, Pancreatic Ductal, Esophageal Squamous Cell Carcinoma
Conditions
Keywords
durvalumab, tremelimumab, metastatic, solid tumors, immuno-oncology, first-line chemotherapy, esophageal, pancreatic
Brief summary
Durvalumab and Tremelimumab in combination with first-line chemotherapy in the following indications: Ovarian/peritoneal/fallopian tube cancer, SCCHN, TNBC, SCLC and gastric/GEJ cancer, PDAC, ESCC.
Detailed description
7 cohorts of first-line chemotherapy regimens combined with durvalumab + tremelimumab. This study will evaluate the safety and tolerability of durvalumab (MEDI4736) + tremelimumab in combination with first line chemotherapy regimens in patients with locally advanced or metastatic solid tumors: ovarian/peritoneal/fallopian tube cancer, squamous cell carcinoma of the head and neck (SCCHN), triple negative breast cancer (TNBC), small cell lung carcinoma (SCLC), and gastric/gastro-esophageal junction (GEJ) cancer, pancreatic ductal adenocarcinoma (PDAC) and esophageal squamous cell carcinoma (ESCC).
Interventions
IV infusion
IV infusion
IV infusion
DRUGnab-paclitaxel (paclitaxel-albumin) + carboplatin
IV infusion
DRUGoxaliplatin + 5-fluorouracil (5FU) + leucovorin (calcium folinate/folinic acid)
IV infusion and bolus administration
BIOLOGICALdurvalumab
IV infusion
BIOLOGICALtremelimumab
IV infusion
DRUGnab-paclitaxel (paclitaxel-albumin) + gemcitabine
IV infusion
IV infusion
Sponsors
AstraZeneca
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
1. ≥18 years 2. Written informed consent 3. Patients with histologically or cytologically documented chemotherapy-naïve locally advanced unresectable or metastatic ovarian/peritoneal/fallopian tube cancer, SCCHN, TNBC, SCLC, gastric cancer/GEJ, PDAC and ESCC. 4. ECOG performance status of 0 or 1 5. Patients must be considered suitable candidates for, and able to receive, first line chemotherapy for metastatic disease 6. At least 1 lesion, not previously irradiated, that can be accurately measured at baseline 7. No prior exposure to immune-mediated therapy 8. Adequate organ and marrow function as defined below
Exclusion criteria
1. Receipt of any investigational anticancer therapy within 28 days or 5 halflives, whichever is longer, prior to the first dose of study treatment 2. Brain metastases or spinal cord compression unless asymptomatic or treated and stable off steroids and anti-convulsants for at least 1 month prior to study treatment 3. Any unresolved Grade ≥2 toxicity from previous anticancer therapy 4. Active or prior documented autoimmune or inflammatory disorders 5. Uncontrolled intercurrent illness, including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs from study drugs, or compromise the ability of the patient to give written informed consent 6. Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥470 ms 20. Active tuberculosis 7. Active infection including tuberculosis, hepatitis B, hepatitis C, or human immunodeficiency virus (HIV)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Laboratory findings (including: clinical chemistry, hematology, and urinalysis) | Throughout the study, approximately three years | To assess the safety and tolerability profile of first-line chemotherapy in combination with durvalumab + tremelimumab |
| Incidence of Adverse Events | Throughout the study, approximately three years | To assess incidence of Adverse Events for the safety and tolerability profile of first-line chemotherapy in combination with durvalumab and tremelimumab |
| Tumor assessment based on RECIST 1.1 (for cohort 6 only) | Throughout the study, approximately three years (for cohort 6 only) | To estimate the objective response rate (ORR) of durvalumab + tremelimumab + chemotherapy (for cohort 6 only) |
Countries
Japan, South Korea
Outcome results
None listed