Durvalumab and Tremelimumab in Combination With First-Line Chemotherapy in Advanced Solid Tumors
- Conditions
- Carcinoma, Squamous Cell of Head and NeckStomach NeoplasmsOvarian NeoplasmsCarcinoma, Pancreatic DuctalEsophageal Squamous Cell CarcinomaTriple Negative Breast NeoplasmsFallopian Tube NeoplasmsPeritoneal NeoplasmsEsophagogastric Junction NeoplasmsSmall Cell Lung Carcinoma
- Interventions
- Biological: durvalumabBiological: tremelimumab
- Registration Number
- NCT02658214
- Lead Sponsor
- AstraZeneca
- 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).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 32
- ≥18 years
- Written informed consent
- 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.
- ECOG performance status of 0 or 1
- Patients must be considered suitable candidates for, and able to receive, first line chemotherapy for metastatic disease
- At least 1 lesion, not previously irradiated, that can be accurately measured at baseline
- No prior exposure to immune-mediated therapy
- Adequate organ and marrow function as defined below
- Receipt of any investigational anticancer therapy within 28 days or 5 halflives, whichever is longer, prior to the first dose of study treatment
- 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
- Any unresolved Grade ≥2 toxicity from previous anticancer therapy
- Active or prior documented autoimmune or inflammatory disorders
- 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
- Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥470 ms 20. Active tuberculosis
- Active infection including tuberculosis, hepatitis B, hepatitis C, or human immunodeficiency virus (HIV)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort 5 oxaliplatin + 5-fluorouracil (5FU) + leucovorin (calcium folinate/folinic acid) Gastric/gastro-esophageal junction (GEJ) Cohort 2 carboplatin + etoposide Small-cell lung cancer (SCLC) Cohort 6 nab-paclitaxel (paclitaxel-albumin) + gemcitabine Pancreatic ductal adenocarcinoma (PDAC) Cohort 1 tremelimumab ovarian/peritoneal/fallopian tube cancer and squamous cell carcinoma of the head and neck (SCCHN) Cohort 3 tremelimumab Triple-negative breast cancer (TNBC) Cohort 4 durvalumab Triple-negative breast cancer (TNBC) Cohort 2 durvalumab Small-cell lung cancer (SCLC) Cohort 2 tremelimumab Small-cell lung cancer (SCLC) Cohort 5 tremelimumab Gastric/gastro-esophageal junction (GEJ) Cohort 6 tremelimumab Pancreatic ductal adenocarcinoma (PDAC) Cohort 7 tremelimumab Esophageal squamous cell carcinoma (ESCC) Cohort 7 cisplatin + 5-fluorouracil (5FU) Esophageal squamous cell carcinoma (ESCC) Cohort 1 paclitaxel + carboplatin ovarian/peritoneal/fallopian tube cancer and squamous cell carcinoma of the head and neck (SCCHN) Cohort 4 nab-paclitaxel (paclitaxel-albumin) + carboplatin Triple-negative breast cancer (TNBC) Cohort 4 tremelimumab Triple-negative breast cancer (TNBC) Cohort 5 durvalumab Gastric/gastro-esophageal junction (GEJ) Cohort 6 durvalumab Pancreatic ductal adenocarcinoma (PDAC) Cohort 7 durvalumab Esophageal squamous cell carcinoma (ESCC) Cohort 1 durvalumab ovarian/peritoneal/fallopian tube cancer and squamous cell carcinoma of the head and neck (SCCHN) Cohort 3 gemcitabine + carboplatin Triple-negative breast cancer (TNBC) Cohort 3 durvalumab Triple-negative breast cancer (TNBC)
- Primary Outcome Measures
Name Time Method 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
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
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)
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
Research Site
🇰🇷Seoul, Korea, Republic of