Houston, Texas 77030


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.


Study summary:

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.


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


NCT ID:

NCT02983578


Primary Contact:

Principal Investigator
David S. Hong, MD
M.D. Anderson Cancer Center

David S. Hong, MD
Phone: 713-563-1930
Email: CR_Study_Registration@mdanderson.org


Backup Contact:

N/A


Location Contact:

Houston, Texas 77030
United States

Clinical Research Operations
Email: CR_Study_Registration@mdanderson.org

Site Status: Recruiting


Data Source: ClinicalTrials.gov

Date Processed: January 21, 2020

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