J12138, A Phase II trial to improve outcomes in patients with resected pancreatic adenocarcinoma at high risk for recurrence using epigenetic therapy
Johns Hopkins Kimmel Cancer Center in Baltimore
To improve progression free survival in high risk patients with resected pancreatic adenocarcinoma who have node positive disease, margin positive disease, and/or elevation in CA 19-9 treated with CC-486 as compared to observation after completion of adjuvant therapy.
Inclusion: 1.Understand and voluntarily sign an informed consent form. 2.Age greater than or equal to 18 years at the time of signing the informed consent form. 3.Able to adhere to the study visit schedule and other protocol requirements. 4.Subjects must have a histologically confirmed pancreatic adenocarcinoma that has had an R0 (negative margins) or R1 (microscopically positive margins) resection. 5.Subjects must have finished adjuvant therapy, which can include chemotherapy and/or chemoradiation therapy or have been determined to be unable to take adjuvant therapy. Although patients will be expected to complete chemoradiation or chemotherapy per physician recommendations, patients who are unable to complete chemotherapy Â± radiation therapy secondary to dose limiting toxicities will be eligible provided they meet study criteria. 6.Subjects must be able to undergo randomization within 3 months of finishing adjuvant therapy or the decision that they are unable to take adjuvant therapy. 7.All previous cancer therapy including radiation, chemotherapy, and surgery, must have been discontinued at least 4 weeks prior to treatment in this study 8.Subjects must either have a CA 19-9 value greater than the institutional ULN on two separate checks at least 2 weeks apart OR have had an R1 resection margin OR N1 nodal disease regardless of CA 19-9 level 9.Subjects must be free of visible disease on imaging (CT, PETCT or MRI) evaluating chest, abdomen, and pelvis within 28 days of enrollment on the study. 10.Life expectancy of greater than 12 weeks 11.ECOG performance status of less than or equal to 1 at study entry 12.Subjects must have normal organ and marrow function. 13.Free of prior malignancies for greater than or equal to 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma in situ of the cervix or breast. 14.Women of childbearing potential should be advised to avoid becoming pregnant and men should be advised to not father a child while receiving treatment with CC-486 or nab-paclitaxel. All men and women of childbearing potential must use effective methods of birth control throughout the study and for three months after completing treatment. 15.Women of childbearing potential must have a negative serum or urine Î²-hCG pregnancy test at screening. 16.Subjects must have less than Grade 2 pre-existing peripheral neuropathy (per CTCAE) Exclusion criteria Subjects who meet any of the following exclusion criteria are not eligible for the study: 1.Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form. 2.Pregnant or breastfeeding women. 3.Use of any other chemotherapy, radiotherapy, or experimental drug or therapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to enrollment on study or those who have not recovered from adverse events greater than or equal to grade 1 due to agents administered more than 4 weeks earlier except for stable grade 2 neuropathy. 4.Subjects may not receive any other concomitant investigational agents. 5.Known or suspected hypersensitivity to 5-azacitidine or mannitol 6.Known positive for HIV or infectious hepatitis, type B or C. HIV patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. 7.Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. 8.Any known gastrointestinal disorders which would preclude oral administration of 5-azacitidine.
This trial is for patients with resected pancreatic adenocarcinoma who have concluded adjuvant therapy or were deemed unable to receive adjuvant therapy with an elevated CA 19-9 or node positive or margin positive disease. CA 19-9 elevation is defined as two levels greater than the institutional upper limit of normal (ULN) taken at least 2 weeks apart. These levels should be measured after adjuvant therapy has concluded or upon the decision that adjuvant therapy will not be offered. Patients will be randomized to one of two arms. Randomization must occur within 3 months of finishing adjuvant therapy or from the decision that adjuvant therapy will not be offered. Group A, the treatment arm, will be started on CC-486. Group B, the control arm, will receive no additional therapy. CA 19-9 will be followed monthly and CT scans every 2 months in both arms. When patients have visible disease recurrence on imaging, CC-486 will be stopped and both groups will start first-line chemotherapy. Assuming the maximum accrual with a goal of 3 subjects accrued per month, we estimate enrollment duration of 24 months with an additional 6 months for follow-up, and an additional 6 months for data analysis and manuscript preparation. Maximum 80 patients, with 40 patients in each of the two arms.
07/01/2016 05:03 AM