Neoplasms

All Conditions

Digestive System Diseases

Gland and Hormone Related Diseases

Respiratory Tract (Lung and Bronchial) Diseases

Rare Diseases

Carcinoma

Pancreatic Neoplasms

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Colorectal Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Endocrine Gland Neoplasms

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Turcot Syndrome

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Durvalumab

Immunoglobulins

Immunoglobulin G

Immunoglobulins, Intravenous

Antibodies, Monoclonal

Antineoplastic Agents, Immunological

Immunologic Factors

Patients receive danvatirsen IV over 1 hour on days 7, 5 and 3 prior to cycle 1, then on days 1, 8, 15 and 22. Patients also receive durvalumab IV over 1 hour on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Danvatirsen

David S Hong

This phase II trial studies how well danvatirsen and durvalumab work in treating patients with pancreatic cancer, non-small cell lung cancer and mismatch repair deficient colorectal cancer that has spread to other places in the body and does not respond to treatment. Danvatirsen may be used to block the production of proteins needed for tumor cell growth. Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving danvatirsen and durvalumab may work better at treating pancreatic cancer, non-small cell lung cancer and mismatch repair deficient colorectal cancer.

PRIMARY OBJECTIVES:

I. Evaluate disease control rate (DCR) at 4 months. II. Evaluate tumor-based biomarkers in paired pre and post treatment biopsies (10 in each arm, 30 total) that may correlate with treatment or prospectively identify patients likely to respond to treatment with danvatirsen (AZD9150) in combination with durvalumab (MEDI4736) (may include PD-L1 expression, phosphorylated or total STAT3 expression, tumor genetics, characterization of immune infiltrates, or other stratification markers).

III. Explore the relationship between PD-L1 protein levels in the membrane of circulating tumor cells obtained by peripheral blood draws prior to, during, and after treatment with clinical endpoints including treatment efficacy and toxicity.

SECONDARY OBJECTIVES:

I. Evaluate the frequency of dose limiting toxicities. II. Evaluate frequency of objective response (as defined as partial response \[PR\] or complete response \[CR\] according to Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1 criteria).

III. Evaluate duration of response (DOR) measured from the time measurement criteria are first met for CR or PR, whichever is first recorded, until the first date that recurrent or progressive disease (PD) is objectively documented.

IV. Evaluate best overall response (including CR, PR, stable disease \[SD\], and PD, according to RECIST version 1.1 criteria).

V. Evaluate progression free survival (PFS) from allocation to the first documentation of PD as determined by the investigator or death from any cause, whichever occurs first.

EXPLORATORY OBJECTIVES:

I. Explore the relationship between radiologic metrics (radiomics) prior to, during, and after treatment with clinical endpoints including treatment efficacy and toxicity.

OUTLINE:

Patients receive danvatirsen intravenously (IV) over 1 hour on days 7, 5 and 3 prior to cycle 1, then on days 1, 8, 15 and 22. Patients also receive durvalumab IV over 1 hour on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, 1-3 months, then every 2 months thereafter.

Danvatirsen and Durvalumab in Treating Patients With Advanced and Refractory Pancreatic, Non-Small Cell Lung Cancer, and Mismatch Repair Deficient Colorectal Cancer

Phase II Clinical Trial Evaluating Intravenous AZD9150 (Antisense STAT3) With MEDI4736 (Anti-PD-L1) in Patients With Advanced Pancreatic, Non-Small Cell Lung Cancer, and Mismatch Repair Deficient Colorectal Cancer

Blood samples for routine coagulation assessments will be obtained at screening and once during week 4 of cycle 1.

Will be graded in accordance with National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v)4.03.

Vital signs will required at screening before dosing on Day -7 of the Lead-in; before dosing on Days 1, 8, 15, and 22 of each cycle; and at the EOT visit.

A complete physical examination is required at screening, before dosing on Day 7 of the Lead in, before dosing on Day 1 of each cycle, and at the EOT visit. A targeted physical examination as directed by disease, signs and symptoms is required before dosing on Day 15 of each cycle.

Will be defined as a compete response (CR), partial response (PR) or stable disease (SD), according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria.

Will be defined as a CR or PR according to RECIST version 1.1.

National Cancer Institute (NCI)

AstraZeneca

M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for refractory lung carcinoma