Phase 2
Completed N=65
Immune Checkpoint Inhibition (Tremelimumab and/or MEDI4736) in Combination With Radiation Therapy in Patients With Unresectable Pancreatic Cancer
Source: ClinicalTrials.gov NCT02311361 ↗Enrolled (actual)
65
Serious AEs
48.4%
Results posted
Jul 2020
Primary outcomePrimary: Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug — 0; 0; 0; 1 Adverse events
Summary
Background:
- Stereotactic body radiation therapy (SBRT) is used to treat cancer. It is a way of giving very focused beams of radiation to tumors. Researchers think that the drugs being used in this study might work better when combined with SBRT in people with pancreatic cancer.
Objective:
- To study the safety and effectiveness of Durvalumab (MEDI4736) and/or tremelimumab with SBRT.
Eligibility:
- People 18 and older who have pancreatic cancer that has not responded or to chemotherapy. They must be candidates for radiation but not resection.
Design:
* Participants will be screened with medical history and physical exam. They will have blood tests. Their tumor will be measured using computerized tomography (CT) or magnetic resonance imaging (MRI).
* Participants will have their tumor biopsied with a needle. They will have also have a biopsy after cycle 1.
* Participants will get 1 or 2 drugs in combination with the SBRT.
* For MEDI4736, the duration of each cycle will be 28-days. Participants will get the drug through an intravenous (IV) infusion twice in each cycle (Days 1 and 15).
* For tremelimumab, the duration of the first 6 cycles will each last 28 days. Then the duration of the last 3 cycles will change to 12 weeks. Participants will get the drug through an IV once in each cycle.
* All participants will have SBRT. Some will get 1 dose of radiation and some will get 5. CT scans will map their tumor.
* Participants will have medical history, physical exam, and blood tests in each cycle. They will have a CT scan or MRI every 8 weeks. Cycles will continue for up to 12 months.
* Participants will be contacted yearly for follow-up.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug |
0; 0; 0; 1; 1; 0 | — |
| SECONDARY Plasma Pharmacokinetic (PK) |
— | — |
| SECONDARY Percentage of Participants With 6-month Overall Survival |
26; 58; 12; 40 | — |
| SECONDARY Overall Survival |
3.3; 9.0; 2.1; 4.2 | — |
| SECONDARY Tumor Response Assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as Measured by Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) |
0; 0; 0; 0; 1; 0 | — |
| SECONDARY Progression Free Survival (PFS) |
1.7; 2.5; 0.9; 2.3 | — |
| SECONDARY Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0) |
14; 10; 19; 20 | — |
Eligibility Criteria
- INCLUSION CRITERIA:
- Patients must have histopathological confirmation of pancreatic adenocarcinoma prior to entering this study by the Laboratory of Pathology of the National Cancer Institute (NCI) to entering this study by the Laboratory of Pathology of the NCI prior to entering this study
- Patients must have disease that is not amenable to potentially curative resection. Primary in-situ (or locally-recurrent) tumor must be present and, in the opinion of radiation oncology, be amenable to radiation therapy as planned in the protocol. Each case will be discussed at GI tumor board with multidisciplinary team.
- Patients must have at least 1 measurable metastatic lesion by Response Evaluation in Solid Tumors (RECIST) 1.1 criteria.
- There is no limit to the number of prior chemotherapy regimens received. Patients must have received at least one line of prior systemic chemotherapy for advanced unresectable and/or metastatic disease.
- Age greater than or equal to 18 years
- Life expectancy of greater than 3 months.
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- Patients must have normal organ and marrow function as defined below:
- absolute neutrophil count - > 1,000/mcL
- Platelets - greater than or equal to 100,000/mcL
- total bilirubin - Bili should be less than or equal to 2 x upper limit of normal (ULN) (patients with Gilbert's Syndrome must have a total bilirubin less than 3.0 mg/dL)
- serum albumin - greater than or equal 2.5 g/dL
Patients are eligible with alanine aminotransferase (ALT) or aspartate aminotransaminase (AST) up to 3 x ULN. (up to 5 x ULN if liver metastases present)
--Creatinine - 45 mL/min/1.73 m(2), for patients with creatinine levels above institutional normal
- Patients must have recovered from any acute toxicity related to prior therapy, including surgery. Toxicity should be less than or equal to grade 1 or returned to baseline.
- Patient must be able to understand and willing to sign a written informed consent document.
EXCLUSION CRITERIA
- Malignant ascites that is clinically detectable by physical examination or is symptomatic. Evidence of radiographic ascites that is not clinically significant will not be an exclusion criterion.
- Any prior Grade greater than or equal to 3 imAE while receiving immunotherapy, including anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4) treatment, or any unresolved imAE > Grade 1. Note: Active or history of vitiligo will not be a basis for exclusion.
- Patients must not have had standard of care chemotherapy, radiotherapy, or major surgery within the last 2 weeks prior to entering the study. Note: Local surgeries for isolated lesions for palliative intent are acceptable. For recent experimental therapies a 28 day period of time must have elapsed before commencing protocol treatment.
- Patients with known brain metastases will be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
- Uncontrolled intercurrent illness, including, but not limited to, ongoing or active infection, current pneumonitis, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring adverse events from Durvalumab (MEDI4736) or tremelimumab, or compromise the ability of the subject to give written informed consent.
- Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease, diverticulitis with the exception of diverticulosis, celiac disease, irritable bowel disease; Wegner syndrome; Hashimoto syndrome; Graves disease; rheumatoid arthritis, hypophysitis, uveitis, etc.) within the past 3 years prior to the start of treatment. The following are exceptions
Data sourced from ClinicalTrials.gov (NCT02311361). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.