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Radiation Therapy in Combination With Durvalumab for People With Pancreatic Cancer (DurvaRad)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03245541
Recruitment Status : Recruiting
First Posted : August 10, 2017
Last Update Posted : August 18, 2020
Sponsor:
Collaborators:
AstraZeneca
Cedars-Sinai Medical Center
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

Tracking Information
First Submitted Date  ICMJE August 7, 2017
First Posted Date  ICMJE August 10, 2017
Last Update Posted Date August 18, 2020
Actual Study Start Date  ICMJE August 14, 2020
Estimated Primary Completion Date September 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 14, 2020)
  • Number of participants with dose limiting toxicities in the first 10 weeks of treatment [ Time Frame: 10 weeks ]
  • Progression Free Survival [ Time Frame: 12 months ]
    Duration of time from diagnosis to time of progression
  • Proportion of participants who have resectable disease [ Time Frame: 24 weeks ]
    Based on overall downstaging of disease post-treatment
  • Progression Free Survival (Phase II) [ Time Frame: 6 months ]
    From study enrollment to time of progression
Original Primary Outcome Measures  ICMJE
 (submitted: August 7, 2017)
  • Number of participants with dose limiting toxicities in the first 10 weeks of treatment [ Time Frame: 10 weeks ]
  • Progression Free Survival [ Time Frame: 12 months ]
    Duration of time from diagnosis to time of progression
  • Proportion of participants who have resectable disease [ Time Frame: 24 weeks ]
    Based on overall downstaging of disease post-treatment
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 7, 2017)
  • Mean change in levels of inflammatory cytokines from baseline [ Time Frame: 10 weeks ]
    As measured from cytokine analysis from serum
  • Mean change in levels of immune cells from baseline [ Time Frame: 10 weeks ]
    As determined from flow cytometry from biopsies and blood
  • Mean change in protein levels from baseline [ Time Frame: 10 weeks ]
    As determined from quantitative immunohistochemistry on biopsy samples
  • Mean change in microbiome from baseline [ Time Frame: 10 weeks ]
    As determined from analysis of stool samples
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Radiation Therapy in Combination With Durvalumab for People With Pancreatic Cancer
Official Title  ICMJE A Phase I/II Study of Durvalumab (Medi 4736) and Stereotactic Ablative Body Radiotherapy in Locally Advanced Pancreatic Adenocarcinoma
Brief Summary The purpose of this study is to find out if combining durvalumab with standard stereotactic ablative radiotherapy (SABR) is an effective treatment for people with locally advanced or borderline resectable pancreatic cancer. The researchers will also look at the safety of the combination treatment and any side effects it causes.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Pancreatic Adenocarcinoma
Intervention  ICMJE
  • Drug: Durvalumab
    Durvalumab will be given 750 mg, intravenously (IV) over 60 minutes (+/- 5 minutes), Q14 days beginning D1. Durvalumab will continue as maintenance Q14 days up to 1 year or until progression, unacceptable toxicity or other reason. If a patient undergoes resection, they will resume Durvalumab once appropriately healed from surgery (approximately 4-8 weeks) at discretion of treating medical oncologist.
    Other Name: Medi 4736
  • Radiation: Stereotactic Ablative Body Radiotherapy (SABR)
    SABR delivered as 6.6 Gy/fraction x 5 QOD fractions will be administered weekdays and will begin D8.
Study Arms  ICMJE Experimental: Durvalumab + SABR
Durvalumab + Stereotactic Ablative Body Radiotherapy
Interventions:
  • Drug: Durvalumab
  • Radiation: Stereotactic Ablative Body Radiotherapy (SABR)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 14, 2020)
36
Original Estimated Enrollment  ICMJE
 (submitted: August 7, 2017)
30
Estimated Study Completion Date  ICMJE September 2022
Estimated Primary Completion Date September 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients with histopathological or cytological diagnosis of adenocarcinoma of the pancreas, or suspicious for malignancy per pathology, which is deemed BR or LAPC per NCCN guidelines or following evaluation by a Multidisciplinary group of physicians.
  • Patients must have received FOLFIRINOX for up to 6 months prior to enrollment with at least stable disease by restaging imaging.

Note: SOC treatment regimen derived from FOLFIRINOX dose modifications is acceptable.

To maximize potential efficacy no more than a 6-week treatment break is recommended between the completion of SOC chemotherapy (FOLFIRINOX) and initiation of study treatment (Durvalumab).

  • Age ≥ 18 years
  • Body weight >30kg
  • ECOG 0-2
  • Patients must have normal organ and marrow function as defined below:

    • Absolute Neutrophil Count (ANC) ≥1.0 K/mcL
    • Platelets ≥100 K/mcL
    • Hemoglobin ≥ 9 g/dL
    • Total bilirubin ≤ 1.5 X upper limit of normal (ULN)
    • AST(SGOT) and ALT(SGPT) ≤ 2.5 X ULN
    • Creatinine OR creatinine clearance ≤ 1.5 times the upper limit of normal OR > 40 mL/min for patients with creatinine levels above normal.

Note: Patients with biliary stent are eligible provided that all other inclusion criteria are met.

  • Negative pregnancy test in women of childbearing potential (WOCBP) within 30 days of Durvalumab administration or evidence of post-menopausal status. Women will be considered post-menopausal if they have been amenorrhoeic for 12 months without an alternative medical cause or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
  • Non-sterilized male subjects who are sexually active with a female partner of childbearing potential must be willing to use a highly effective method of contraception from Day 1 through 90 days after receipt of the final dose of investigational product(s). Not engaging in sexual activity for the total duration of the study and the drug washout period is an acceptable practice; however, occasional abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception. Male subjects must be willing to refrain from sperm donation throughout these periods.
  • Ability to understand and the willingness to sign an informed consent document.
  • Willingness and ability to comply with the protocol including study treatment, scheduled assessments and follow-up.

Exclusion Criteria:

  • History of another primary malignancy except for:

    °Malignancy treated with curative intent with no known active disease for 2 years before the first dose of study drug and low potential risk for recurrence.

  • Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
  • Patients who have had prior anti-cancer treatment or are currently receiving anti-cancer treatment for their disease other than chemotherapy as stipulated by protocol.
  • Women who are breastfeeding.
  • Any clinically significant, unresolved toxicity >CTCAE grade 2 from previous anti-cancer therapy with the exception of alopecia, vitiligo and laboratory values defined in the inclusion criteria.
  • Patients with Grade ≥ 2 neuropathy will be included at the investigator's discretion
  • Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included at the nvestigator's discretion
  • Patients who are currently receiving any other investigational agents for therapeutic treatment of their primary cancer.
  • Any previous treatment with a PD1 or PD-L1 inhibitor, including Durvalumab or other immunotherapy.
  • Known metastatic disease.
  • 12. Major surgical procedures based on clinical judgement of the investigator within 30 days prior to the first dose of study drug. Patients may undergo staging laparoscopy, PTC placement, ERCP, etc. at any time which should not interfere with study treatment.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to Durvalumab.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, interstitial lung disease, pneumonitis, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Patients who are receiving radiation treatment outside of the enrolling centers.
  • Patients with frank transmural macroscopic invasion of duodenum by tumor as determined by treating investigator.
  • Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis, Crohn's disease], diverticulitis with the exception of diverticulosis, celiac disease, irritable bowel syndrome, or other serious gastrointestinal chronic conditions associated with diarrhea); systemic lupus erythematosus; Wegener syndrome (granulomatosis with polyangiitis; Graves' disease; rheumatoid arthritis, hypophysitis, uveitis, etc) within the past 3 years prior to the start of treatment. The following are exceptions to this criterion: Patients with vitiligo or alopecia. Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement, or psoriasis not requiring systemic treatment
  • Current or prior use of immunosuppressive medication within 28 days before treatment, except with chemotherapy.
  • History of organ transplant that requires use of immunosuppressive agents.
  • History of active primary immunodeficiency.
  • Receipt of live attenuated vaccination within 30 days prior to receiving durvalumab.
  • Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results.
  • Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings and TB testing in line with local practices), active bleeding diatheses, hepatitis B (known positive HBV surface antigen result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies).
  • Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody and absence of HBsAg) are eligible.
  • Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
  • Patients with macroscopic invasion of the bowel or stomach submucosa by primary pancreatic tumor as determined by PI.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Richard Tuli, MD, PhD 848-225-6780 tulir@mskcc.org
Contact: Eileen O'Reilly, MD 646-888-4182
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03245541
Other Study ID Numbers  ICMJE 20-228
IIT2016-01-Tuli-DURVARAD ( Other Identifier: Memorial Sloan Kettering Cancer Center )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.
Responsible Party Memorial Sloan Kettering Cancer Center
Study Sponsor  ICMJE Memorial Sloan Kettering Cancer Center
Collaborators  ICMJE
  • AstraZeneca
  • Cedars-Sinai Medical Center
Investigators  ICMJE
Principal Investigator: Richard Tuli, MD, PhD Memorial Sloan Kettering Cancer Center
PRS Account Memorial Sloan Kettering Cancer Center
Verification Date August 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP