Clinical Trials /

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

NCT02983578

Description:

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.

Related Conditions:
  • Colorectal Carcinoma
  • Non-Small Cell Lung Carcinoma
  • Pancreatic Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: AZD9150 With MEDI4736 in Patients With Advanced Pancreatic, Non-Small Lung and Colorectal Cancer
  • 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

Clinical Trial IDs

  • ORG STUDY ID: 2016-0108
  • NCT ID: NCT02983578

Conditions

  • Malignant Neoplasm of Digestive Organs Intestinal Tract Primary
  • Malignant Neoplasm of Respiratory and Intrathoracic Organ Carcinoma

Interventions

DrugSynonymsArms
AZD9150Advanced Non-Small Cell Lung Cancer Group
MEDI4736DurvalumabAdvanced Non-Small Cell Lung Cancer Group

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.

Detailed Description

      Study Drug Administration:

      Every study cycle will be 28 days.

      If you are found to be eligible to take part in this study, you will begin study treatment
      within 28 days after the screening tests are performed. You will receive AZD9150 by vein over
      1 hour 3 times before the first dose of MEDI4736 (7, 5, and 3 days beforehand), and then on
      Days 1, 8, 15, and 22 of every cycle.

      You will receive MEDI4736 by vein over about 1 hour on Day 1 of every cycle, about 30 minutes
      after the AZD9150 infusion.

      Length of Treatment:

      You may continue receiving the study drugs for as long as the doctor thinks is in your best
      interest. You will no longer be able to receive the study drugs if the disease gets worse, if
      intolerable side effects occur, or if you are unable to follow study directions.

      Study Visits:

      On Day 1 of Cycle 1 and beyond:

        -  You will have a physical exam.

        -  Blood (about 4 teaspoons) and urine will be collected for routine tests.

        -  Blood (about 2 teaspoons) will be drawn to check your thyroid function.

        -  If you can become pregnant, blood (about 1 teaspoon) or urine will be collected for a
           pregnancy test.

      On Days 8 and 22 of Cycles 1 and beyond:

        -  You will have a physical exam.

        -  Blood (about 4 teaspoons) will be drawn for routine tests (Cycle 1 only).

      On Day 15 of Cycles 1 and beyond:

        -  You will have a physical exam.

        -  Blood (about 4 teaspoons) will be drawn for routine tests.

        -  Urine will be collected for routine tests (Cycle 1 only).

      On Day 22 of Cycles 1 and beyond:

        -  Blood (about 2½ tablespoons) will be drawn for biomarker testing.

        -  You will have a core tumor biopsy for biomarker testing.

      Every 2 months, you will have a PET/CT scan or MRI to check the status of the disease.

      End-of-Treatment Visit:

      About 30 days after your last dose of the study drugs:

        -  You will have a physical exam.

        -  Blood (about 4 tablespoons) and urine will be collected for routine tests.

        -  Blood (about 2 teaspoons) will be drawn to check your thyroid function.

        -  Blood (about 2½ tablespoons) will be drawn for biomarker testing.

        -  You will have a PET/CT scan or MRI to check the status of the disease.

        -  If you can become pregnant, urine will be collected for a pregnancy test.

      Follow-Up:

      About 1-3 months after your last dose of the study drugs, you will have a PET/CT scan or MRI
      to check the status of the disease.

      If you cannot come to MD Anderson for your follow-up visits, you may be called every 12 weeks
      and asked about how you are doing. These calls will last about 10 minutes each.

      Your participation on the study will be over at the end of the follow-up period.

      Treatment Beyond Progression:

      If the disease appears to be getting worse or the tumors appear to be getting larger, you may
      still be able to receive the study drugs if you and your doctor decide it is in your best
      interest. The study doctor will discuss this option with you. If you choose to receive the
      study drugs after the disease gets worse, you will sign an additional informed consent form.
    

Trial Arms

NameTypeDescriptionInterventions
Advanced Non-Small Cell Lung Cancer GroupExperimentalPhase 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.
  • AZD9150
  • MEDI4736
Mismatch Repair-Deficient Colorectal Cancer GroupExperimentalPhase 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.
  • AZD9150
  • MEDI4736
Pancreatic Cancer GroupExperimentalPhase 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.
  • AZD9150
  • MEDI4736

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Disease Control Rate
Time Frame:4 months
Safety Issue:
Description:Disease control defined as a Complete Response, Partial Response or Stable Disease, according to RECIST version 1.1 criteria.

Secondary Outcome Measures

Measure:Objective Response
Time Frame:2 months
Safety Issue:
Description:Objective response defined as Partial Response or Complete Response according to RECIST 1.1 criteria.
Measure:Duration of Response
Time Frame:4 months
Safety Issue:
Description: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).

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:M.D. Anderson Cancer Center

Trial Keywords

  • Pancreatic cancer
  • Mismatch deficient colorectal cancer
  • Non-small cell lung cancer
  • NSCLC
  • AZD9150
  • MEDI4736
  • Durvalumab

Last Updated

September 8, 2017