Phase II Study of Durvalumab (MEDI4736) (Anti-PD-L1) and Trametinib (MEKi) in MSS Metastatic Colon Cancer

M.D. Anderson Cancer Center1 site in 1 country29 target enrollmentMarch 21, 2018

ConditionsMalignant Neoplasms of Digestive Organs Colorectal Cancer Colon Cancer

InterventionsDurvalumab Trametinib

DrugsDurvalumab Trametinib

Overview

Phase: Phase 2
Intervention: Durvalumab
Conditions: Malignant Neoplasms of Digestive Organs
Sponsor: M.D. Anderson Cancer Center
Enrollment: 29
Locations: 1
Primary Endpoint: Immune-related Best Overall Response Rate.
Status: Completed
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The goal of this clinical research study is to learn if durvalumab and trametinib can help to control microsatellite stable (MSS) colorectal cancer. The safety of these drugs will also be studied.

This is an investigational study. Durvalumab is FDA approved and commercially available for the treatment of previously treated advanced bladder cancer. Trametinib is FDA approved in combination with another drug called dabrafenib for the treatment of unresectable or metastatic melanoma with BRAF V600E or BRAF V600K.

It is investigational to use durvalumab and trametinib to treat MSS colorectal cancer.

Up to 56 participants will be enrolled in this study. All will take part at MD Anderson.

Detailed Description

Study Drug Administration: Each cycle is 28 days. Participant will take trametinib tablets by mouth every day with at least 8 ounces of water. Each dose should be taken at about the same time each day, 1 hour before or 2 hours after a meal. Participant should not crush, cut, or chew the tablets. If participant misses a dose of trametinib, participant may take the tablets as soon as participant remembers but only if participant's next scheduled dose is at least 12 hours later. If participant's next scheduled dose is less than 12 hours, participant should wait and take participant's next dose as scheduled. Participant will take trametinib alone for the first 7 days of the study and then participant will begin receiving it in combination with durvalumab. Every 4 weeks, participant will receive durvalumab by vein over about 60 minutes. Length of Treatment: Participant will be able to receive the study drugs for as long as the doctor thinks it is in participant's best interest. Participant no longer will take the study drugs if intolerable side effects occur or if the study doctor decides that the drugs are no longer working. It is expected that participation in this study may last about 12 months. Participation in this study will be over after follow-up. Study Visits: On Day 1 of Weeks 0, 2, 4, 6, 12, and then every 4 weeks after that (Weeks 16, 20, 24, and so on): * Participant will have a physical exam. * Blood (about 6 tablespoons) will be drawn for routine tests, immune system testing, and biomarker testing. * If participant had a biopsy at screening, participant will have another biopsy during Week 4 to check the status of the disease and for biomarker testing. Depending on when participant joins the study, this biopsy may be optional. On Day 1 of Week 8: * Participant will have a physical exam. * Blood (about 6 tablespoons) will be drawn for routine tests, immune system testing, and biomarker testing. * Participant will have a CT scan. On Day 1 of Week 16 and then every 8 weeks after that (Weeks 24, 32, 40, and so on), participant will have a CT scan. End-of-Treatment: About 28 days after participant's last dose of study drugs, participant will have a physical exam. Follow-Up: After participant's end-of-treatment visit, participant will be called by the study staff every 3 months for up to 18 months to ask how participant is doing. Each call should last about 5-10 minutes.

Registry

clinicaltrials.gov

Start Date

March 21, 2018

End Date

May 5, 2022

Last Updated

2 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

M.D. Anderson Cancer Center

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Patients must have histologically or cytologically confirmed metastatic colorectal cancer.
•Patients must have measurable disease per RECIST v1.1 criteria.
•Patients must have had at least prior treatment with a fluoropyrimidine and either oxaliplatin or irinotecan.
•Age \>/=18 years. Because no dosing or adverse event data are currently available on the use of this combination in patients \<18 years of age, children are excluded from this study.
•Body weight \> 30kg.
•Life expectancy of greater than 6 months.
•ECOG performance status 0-1 (Karnofsky \>/=70%).
•Patients must have normal organ and marrow function as defined below: - Leukocytes \>/=3,000/mcL, Absolute neutrophil count \>/=1,500/mcL, Hemoglobin \>/=9.0g/dL, Platelets \>/=75,000/mcL, Total bilirubin \< 1.5 X institutional normal limits (subjects with known Gilbert syndrome are eligible with total bilirubin \< 3.0 mg/dL), AST(SGOT)/ALT(SGPT) \</=2.5 X institutional ULN (\</= 5 if liver metastases present), Creatinine within normal institutional limits OR, Creatinine clearance \> 40mL/min by Cockcroft-Gault or 24h urine collection.
•Known MSS status by either IHC or PCR. Known or evaluable BRAF and KRAS status.
•Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal subjects. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply: -- Women \<50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).

Exclusion Criteria

•Patients who have had chemotherapy within 2 weeks prior to first dose of study drug.
•Any unresolved toxicity NCI CTCAE Grade \>/=2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria: -- Subjects with Grade \>/=2 neuropathy will be evaluated on a case-by-case basis after consultation with the Principal investigator.-- Subjects with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the Principal investigator.
•Patients may not be receiving any other investigational agents.
•Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of study medication. Note: Local surgery of isolated lesions for palliative intent is acceptable.
•Patients with known brain metastases or leptomeningeal carcinomatosis will be excluded from this clinical trial. Patients with suspected brain metastases at screening should have an MRI (preferred) or CT each preferably with IV contrast of the brain prior to study entry.
•Mean QT interval corrected for heart rate (QTc) \>/= 470 ms calculated from 3 electrocardiograms (ECGs) using Fridericia's Correction.
•History of pneumonitis or interstitial lung disease (ILD).
•History of allogenic organ transplantation.
•Subjects with active, known, or suspected autoimmune disease including patients with a history of inflammatory bowel disease (ulcerative colitis or Crohn's disease); patients with a history of symptomatic disease (e.g., rheumatoid arthritis, systemic sclerosis \[scleroderma\], systemic lupus erythematosus, autoimmune vasculitis (e.g., Wegener's granulomatosis), and central nervous system or motor neuropathy considered of autoimmune origin (e.g., Guillain-Barre Syndrome, myasthenia gravis, multiple sclerosis). Subjects with vitiligo, type I diabetes mellitus, Grave's disease, Hashimoto thyroiditis, psoriasis, and other mild autoimmune disease not requiring systemic treatment are permitted to enroll at the discretion of the investigator.
•Subjects with a condition requiring systemic treatment with either corticosteroids (\>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.

Arms & Interventions

Durvalumab + Trametinib

Participants take Trametinib tablets by mouth every day. Trametinib taken alone for the first 7 days of the study then participants begin receiving it in combination with Durvalumab. Participants receive Durvalumab by vein every 4 weeks. Each cycle is 28 days.

Intervention: Durvalumab