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

NCT02983578 | Active Not Recruiting Phase 2 FDA Drug

• 2 other identifiers: 2016-0108NCI-2018-01296
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Advanced Colorectal Carcinoma; Advanced Lung Non-Small Cell Carcinoma; Lung Non-Small Cell Carcinoma; Mismatch Repair Deficiency; Refractory Colorectal Carcinoma; Refractory Lung Carcinoma; Refractory Pancreatic Carcinoma; Stage II Pancreatic Cancer AJCC v8; Stage III Colorectal Cancer AJCC v8; Stage III Lung Cancer AJCC v8; Stage III Pancreatic Cancer AJCC v8; Stage IIIA Colorectal Cancer AJCC v8; Stage IIIA Lung Cancer AJCC v8; Stage IIIB Colorectal Cancer AJCC v8; Stage IIIB Lung Cancer AJCC v8; Stage IIIC Colorectal Cancer AJCC v8; Stage IIIC Lung Cancer AJCC v8; Stage IV Colorectal Cancer AJCC v8; Stage IV Lung Cancer AJCC v8; Stage IV Pancreatic Cancer AJCC v8; Stage IVA Colorectal Cancer AJCC v8; Stage IVA Lung Cancer AJCC v8; Stage IVB Colorectal Cancer AJCC v8; Stage IVB Lung Cancer AJCC v8; Stage IVC Colorectal Cancer AJCC v8

Outcome Measures

Primary Outcomes (10)

• Incidence of adverse events (AEs), serious AEs

  Up to 4 years

• Physiological parameters (Laboratory evaluations)

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

  Up to 4 years

• Incidence of treatment-emergent AEs (TEAEs), SAEs and death(s)

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

  Up to 4 years

• PD-L1 expression

  Up to 4 years

• Phosphorylated or total STAT3 expression levels

  Up to 4 years

• Characterization of immune infiltrates

  Up to 4 years

• Quantification and characterization of CD8 staining pattern

  Up to 4 years

• PD-L1 protein levels in the membrane of circulating tumor cells

  Baseline up to 4 years

• Physiological parameters

  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.

  Up to 4 years

• Physical Examinations

  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.

  Up to 4 years

Secondary Outcomes (6)

• Disease control

  At 4 months

• Objective response

  Up to 4 years

• Duration of response according to RECIST version 1.1 criteria

  From the time measurement criteria are first met for CR or PR, assessed up to 4 years

• Best overall response (including CR, PR, SD, and progressive disease [PD], according to RECIST version 1.1 criteria)

  Up to 4 years

• Progression free survival

  From allocation assessed up to 4 years

Other Outcomes (1)

• Radiomic measurements

  Baseline up to 4 years

Study Arms (1)

Treatment (danvatirsen, durvalumab)

EXPERIMENTAL

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.

Drug: Danvatirsen; Biological: Durvalumab

Interventions

Danvatirsen DRUG

Given IV

Also known as: AZD9150, ISIS 481464, ISIS-STAT3rx

Treatment (danvatirsen, durvalumab)

Durvalumab BIOLOGICAL

Given IV

Also known as: Imfinzi, Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer, MEDI-4736, MEDI4736

Treatment (danvatirsen, durvalumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The patient/legal representative must be able to read and understand the informed consent form (ICF) and must have been willing to give written informed consent and any locally required authorization (e.g., Health Insurance Portability and Accountability Act in the United States of America \[USA\]; European Union Data Privacy Directive in the European Union \[EU\]) before any study-specific procedures, including screening evaluations, sampling, and analyses
• Has a histological confirmation of pancreatic cancer, mismatch deficient colorectal cancer, or non-small cell lung cancer (NSCLC) that is refractory to standard therapy or for which no standard of care regimen currently exists
• Has an Eastern Cooperative Oncology Group (ECOG) performance score (PS) score of 0 or 1
• Has measurable disease, defined as at least 1 lesion that can be accurately measured in at least 1 dimension (longest diameter to be recorded) with a minimum size of 10 mm by computerized tomography (CT) scan, except lymph nodes which must have minimum short axis size of 15 mm (CT scan slice thickness no greater than 5 mm in both cases). Indicator lesions must not have been previously treated with surgery, radiation therapy, or radiofrequency ablation unless there is documented progression after therapy
• Transfusions intended to elevate any parameters below solely for the intent of meeting study eligibility are not permitted
• Leukocytes \>= 3000 mcL
• Absolute neutrophil count \>= 1500 mcL
• Platelets \> = 100 000 mcL
• Hemoglobin \>= 9 g/dL
• Total bilirubin =\< 1.5 x upper limit of normal (ULN)
• Total bilirubin =\< 3 x ULN in patients with documented Gilbert's syndrome (unconjugated hyperbilirubinemia) or in the presence of liver metastases
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 2.5 x ULN if no demonstrable liver metastases or =\< 5 x ULN in the presence of liver metastases
• Creatinine within normal limits OR, for patients with levels above institutional normal: creatinine clearance measured by 24-hour urine collection \>= 60 mL/min, OR calculated corrected creatinine clearance \>= 60 mL/min/1.73 m\^2 using the Cockcroft-Gault formula (Cockcroft and Gault 1976) corrected for the body surface area
• Women of childbearing potential and men who are sexually active with a female partner of childbearing potential must be surgically sterilized, practicing abstinence, or agree to use 2 birth control methods before study entry, for the duration of study participation, and for 20 weeks after the final dose of study drug; cessation of birth control after this point should be discussed with a responsible physician. Women of childbearing potential are defined as those who are not surgically sterile (i.e., bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy) or postmenopausal (defined as 12 months with no menses without an alternative medical cause). Two methods of contraception which are considered accurate per protocol must be combined. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control
• Women of childbearing potential also may not be breast feeding and must have a negative serum or urine pregnancy test within 72 hours before the start of study treatment

You may not qualify if:

• Has a spinal cord compression unless asymptomatic, radiographically stable over the last 4 weeks, and not requiring steroids for at least 4 weeks before the start of study treatment
• Presently has a second malignancy other than squamous cell carcinoma of the head and neck (SCCHN), or history of treatment for invasive cancer other than SCCHN in the past 3 years. Exceptions are:
• Previously treated in-situ carcinoma (i.e., noninvasive)
• Cervical carcinoma stage 1B or less
• Noninvasive basal cell and squamous cell skin carcinoma
• Radically treated prostate cancer (prostatectomy or radiotherapy) with normal prostate-specific antigen, and not requiring ongoing antiandrogen hormonal therapy
• Patients must have completed previous cancer-related treatments before enrollment. Any concurrent chemotherapy, radiotherapy, immunotherapy, or biologic, or hormonal therapy for cancer excludes the patient (concurrent use of hormones for noncancer-related conditions \[e.g., insulin for diabetes or hormone replacement therapy\] is acceptable). The following intervals between end of the prior treatment and first dose of study drug must be observed:
• Port-a-cath placement: no waiting required
• Minor surgical procedures: \>= 7 postoperative days
• Major surgery: \>= 4 weeks
• Radiotherapy: \>= 4 weeks
• Chemotherapy: \>= 4 weeks
• Immunotherapy or investigational anticancer therapy with agents other than monoclonal antibodies (mAbs): \>= 4 weeks
• Immunotherapy or investigational anticancer therapy with mAbs: \>= 6 weeks
• Immunosuppressive medication: \>= 4 weeks with the exceptions of intranasal or inhaled corticosteroids or systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or equivalent

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator
• AstraZeneca: collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Tang C, Hartley GP, Couillault C, Yuan Y, Lin H, Nicholas C, Srinivasamani A, Dai J, Dumbrava EEI, Fu S, Karp DD, Naing A, Piha-Paul SA, Rodon Ahnert J, Pant S, Subbiah V, Yap TA, Tsimberidou AM, Guerrero P, Dhebat S, Proia T, Curran MA, Hong DS. Preclinical study and parallel phase II trial evaluating antisense STAT3 oligonucleotide and checkpoint blockade for advanced pancreatic, non-small cell lung cancer and mismatch repair-deficient colorectal cancer. BMJ Oncol. 2024 Jul 30;3(1):e000133. doi: 10.1136/bmjonc-2023-000133. eCollection 2024.

  PMID: 39886125 DERIVED

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Turcot syndrome; Colorectal Neoplasms; Lung Neoplasms; Pancreatic Neoplasms

Interventions

danvatirsen; durvalumab; Immunoglobulin G; Disulfides

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds; Organic Chemicals

Study Officials

• David S Hong

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2016
• First Posted: December 6, 2016
• Study Start: March 2, 2017
• Primary Completion: August 30, 2025
• Study Completion: August 30, 2025
• Last Updated: May 6, 2025

Record last verified: 2025-05

Locations

US (1)