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AZD9150 With MEDI4736 in Patients With Advanced Pancreatic, Non-Small Lung and Colorectal Cancer

This study is currently recruiting participants.
Verified September 2017 by M.D. Anderson Cancer Center
Sponsor:
ClinicalTrials.gov Identifier:
NCT02983578
First Posted: December 6, 2016
Last Update Posted: September 11, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
  Purpose

The goal of this clinical research study is to learn if AZD9150 given in combination with MEDI4736 (durvalumab) can help to control advanced pancreatic, lung, or colorectal cancer.

This is an investigational study. AZD9150 and MEDI4736 are not FDA approved or commercially available. They are currently being used for research purposes only. The study doctor can explain how the study drugs are designed to work.

Up to 75 participants will take part in this study. All will be enrolled at MD Anderson.


Condition Intervention Phase
Malignant Neoplasm of Digestive Organs Intestinal Tract Primary Malignant Neoplasm of Respiratory and Intrathoracic Organ Carcinoma Drug: AZD9150 Drug: MEDI4736 Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Disease Control Rate [ Time Frame: 4 months ]
    Disease control defined as a Complete Response, Partial Response or Stable Disease, according to RECIST version 1.1 criteria.

  • Evaluation of Tumor-Based Biomarkers in Paired Pre and Post Treatment Biopsies [ Time Frame: Baseline up to 30 days after last study drug dose ]
  • PD-L1 Protein Levels in the Membrane of Circulating Tumor Cells [ Time Frame: Baseline up to 30 days after last study drug dose ]

Secondary Outcome Measures:
  • Objective Response [ Time Frame: 2 months ]
    Objective response defined as Partial Response or Complete Response according to RECIST 1.1 criteria.

  • Duration of Response [ Time Frame: 4 months ]
    Duration of response according to RECIST version 1.1 criteria (measured from the time measurement criteria are first met for Complete Response or Partial Response, whichever is first recorded, until the first date that recurrent or Progressive Disease is objectively documented (taking as reference for Progressive Disease the smallest measurements recorded on study).


Estimated Enrollment: 75
Actual Study Start Date: March 2, 2017
Estimated Study Completion Date: March 2021
Estimated Primary Completion Date: March 2021 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Advanced Non-Small Cell Lung Cancer Group

Phase 1: Participants receive AZD9150 3 times over a week during the initial lead in phase.

After interim evaluation, participants then receive AZD9150 every week and MED4736 every 4 weeks.

Participants receive treatment until progression or unacceptable toxicity.

Drug: AZD9150
During the 7-day Lead-in period, AZD9150 3mg/kg IBW administered by vein as a loading dose on Days -7, -5, and -3. Starting with Cycle 1, AZD9150 administered every week on Days 1, 8, 15, and 22 of each 28 day treatment cycle.
Drug: MEDI4736
MEDI4736 administered at 20 mg/kg by vein on Day 1 of each 28 day treatment cycle, starting with Cycle 1.
Other Name: Durvalumab
Experimental: Mismatch Repair-Deficient Colorectal Cancer Group

Phase 1: Participants receive AZD9150 3 times over a week, then AZD9150 every week and MED4736 every 4 weeks.

Participants receive treatment until progression or unacceptable toxicity.

Drug: AZD9150
During the 7-day Lead-in period, AZD9150 3mg/kg IBW administered by vein as a loading dose on Days -7, -5, and -3. Starting with Cycle 1, AZD9150 administered every week on Days 1, 8, 15, and 22 of each 28 day treatment cycle.
Drug: MEDI4736
MEDI4736 administered at 20 mg/kg by vein on Day 1 of each 28 day treatment cycle, starting with Cycle 1.
Other Name: Durvalumab
Experimental: Pancreatic Cancer Group

Phase 1: Participants receive AZD9150 3 times over a week during the initial lead in phase.

After interim evaluation, participants then receive AZD9150 every week and MED4736 every 4 weeks.

Participants receive treatment until progression or unacceptable toxicity.

Drug: AZD9150
During the 7-day Lead-in period, AZD9150 3mg/kg IBW administered by vein as a loading dose on Days -7, -5, and -3. Starting with Cycle 1, AZD9150 administered every week on Days 1, 8, 15, and 22 of each 28 day treatment cycle.
Drug: MEDI4736
MEDI4736 administered at 20 mg/kg by vein on Day 1 of each 28 day treatment cycle, starting with Cycle 1.
Other Name: Durvalumab

  Show Detailed Description

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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 authorisation (eg, Health Insurance Portability and Accountability Act in the USA; European Union Data Privacy Directive in the EU) before any study-specific procedures, including screening evaluations, sampling, and analyses.
  2. Has a histological confirmation of pancreatic cancer, mismatch deficient colorectal cancer, or NSCLC that is refractory to standard therapy or for which no standard of care regimen currently exists.
  3. Male and female patients must be at least 18 years of age.
  4. Has an Eastern Cooperative Oncology Group (ECOG) PS score of 0 or 1.
  5. 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 computerised 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.
  6. Has adequate organ and marrow function as defined below. 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 ULN; total bilirubin </=3×ULN in patients with documented Gilbert's Syndrome (unconjugated hyperbilirubinaemia) or in the presence of liver metastases - ALT and AST </=2.5×ULN if no demonstrable liver metastases or </=5×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.
  7. Women of childbearing potential and men who are sexually active with a female partner of childbearing potential must be surgically sterilised, 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 (ie, 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.
  8. 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.
  9. The patient/legal representative must be willing to provide written consent for collection of formalin fixed paraffin-embedded blocks or slides from archival diagnostic histology samples, where available.

Exclusion Criteria:

  1. 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.
  2. Presently has a second malignancy other than SCCHN, or history of treatment for invasive cancer other than SCCHN in the past 3 years. Exceptions are: Previously treated in-situ carcinoma (ie, 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
  3. 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 [eg, 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 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 10mg/day of prednisone or equivalent.
  4. Is still experiencing toxicity related to prior treatment and assessed as CTCAE grade >1. Exceptions are alopecia and/or anorexia. The eligibility of patients who are still experiencing irreversible toxicity that is not reasonably expected to be exacerbated by the study drugs in this study (eg, hearing loss) must be reviewed and approved by both the Principal Investigator and Medical Monitor.
  5. Has experienced immune-related AEs (irAEs) while receiving prior immunotherapy (including anti-CTLA4 treatment) and assessed as CTCAE grade >/= 3
  6. Has active or prior documented autoimmune disease within the past 2 years with the exceptions of vitiligo, Grave's disease, and/or psoriasis not requiring systemic treatment
  7. Has active or prior documented inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis)
  8. Has a history of primary immunodeficiency
  9. Has undergone an organ transplant that requires use of immunosuppressive treatment
  10. Has a history of interstitial lung disease or pneumonitis from any cause
  11. Has a history of allergic reactions attributed to the study treatments (AZD9150 or MEDI4736), their compounds, or agents of similar chemical or biologic composition (eg, antibody therapeutics)
  12. Suffers from a comorbidity that in the opinion of the Investigator renders the patient unsuitable for participation in the study. Such comorbidity may include, but is not limited to, uncontrolled intercurrent illness such as active infection, severe active peptic ulcer disease or gastritis, myocardial infarction within 6 months before entry, congestive heart failure, symptomatic congestive heart failure, active cardiomyopathy, unstable angina pectoris, cardiac arrhythmia, uncontrolled hypertension, or psychiatric illness/social situations that would limit compliance with study requirements.
  13. As judged by the Investigator, has any evidence of severe or uncontrolled systemic diseases such as active bleeding diatheses, is positive for human immunodeficiency virus (HIV), or has active hepatitis B virus (HBV) and/or hepatitis C virus (HCV)
  14. Has a known history of tuberculosis
  15. Has a condition that, in the opinion of the Investigator, would interfere with the evaluation of the study drugs or the interpretation of patient safety or study results
  16. Has received a live attenuated vaccine within 28 days before the first dose of study drug
  17. Judgment by the Investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions, and requirements
  18. Patients with clinically active brain metastases (known or suspected) are excluded unless the brain metastases have been previously treated and are considered stable. Stable brain metastases are defined as no change on CT scan or magnetic resonance imaging (MRI) scan for a minimum of 2 months AND no change in steroid dose for a minimum of 4 weeks, unless change due to intercurrent infection or other acute event.
  19. Female subjects who are pregnant, breast-feeding or male or female patients of reproductive potential who are not employing an effective method of birth control
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02983578


Contacts
Contact: David S. Hong, MD 713-563-1930 CR_Study_Registration@mdanderson.org

Locations
United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Clinical Research Operations       CR_Study_Registration@mdanderson.org   
Sponsors and Collaborators
M.D. Anderson Cancer Center
AstraZeneca
Investigators
Principal Investigator: David S. Hong, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT02983578     History of Changes
Other Study ID Numbers: 2016-0108
First Submitted: December 1, 2016
First Posted: December 6, 2016
Last Update Posted: September 11, 2017
Last Verified: September 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by M.D. Anderson Cancer Center:
Pancreatic cancer
Mismatch deficient colorectal cancer
Non-small cell lung cancer
NSCLC
AZD9150
MEDI4736
Durvalumab

Additional relevant MeSH terms:
Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs