- About Pancreatic Cancer
- Get Support
Caregivers
- Get Involved
- Events
- More
2014-07
2019-02-18
2019-02-18
64
NCT02151448
University of Pittsburgh
University of Pittsburgh
INTERVENTIONAL
αDC1 Vaccine + Chemokine Modulatory Regimen (CKM) as Adjuvant Treatment of Peritoneal Surface Malignancies
This trial is to determine the safest dose of a triple combination (chemokine modulatory regimen or CKM) of celecoxib, interferon alfa (IFN), and rintatolimod that can be given with a DC vaccine as treatment of peritoneal surface malignancies after standard of care surgery. The first phase of this study will determine the safest dose of IFN that can be given in combination with celecoxib and rintatolimod along with a DC vaccine. The doses of celecoxib (400 mg) and rintatolimod (200 mg) will be consistent while the dose of IFN will be increased (5, 10, or 20 MU/m2) as participants are enrolled to the trial. The high dose of IFN in combination with celecoxib and rintatolimod will be used for the next phase of the clinical trial. After surgery, participants will receive 2 cycles of the investigational treatment. The second phase of this study will test if the investigational treatment has any effects on peritoneal surface malignancies. The doses of the combination determined in the first phase will be used in this phase of the clinical trial. After surgery, participants will receive 2 cycles of the investigational treatment, followed by standard chemotherapy as determined by their oncologist, and then 2 more cycles of the investigational treatment.
This trial will evaluate the safety and effectiveness of autologous alpha-type-1 polarized dendritic cell (alpha-DC1) vaccines (patients' autologous alpha-DC1s loaded with autologous tumor material), combined with a systemic chemokine modulation regimen [CKM; intravenous rintatolimod (TLR3 ligand, a derivative of Poly-I:C) + intravenous interferon-alfa + oral celecoxib] as adjuvant therapy, after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), in patients with peritoneal surface malignancies (PSM), including but not limited to malignant peritoneal mesothelioma and peritoneal carcinomatosis (PC) of appendiceal and colorectal origin. All patients judged to have peritoneal surface malignancy and considered able to be cytoreduced to Peritoneal Cancer Index (PCI) Completeness of Cytoreduction (CC) score of 1 or less will undergo CRS + HIPEC. Postoperative immunotherapy will start at least 4 weeks after CRS + HIPEC. Immunotherapy regimen will include four cycles of intranodal (3M cells) and intradermal (3M cells) αDC1 vaccines. Each booster αDC1 vaccine dose (treatment cycles 2-4) will be followed by 4-days of systemic CKM, starting the day after vaccination (IFNα [dose-escalation: 5-20 MU/m2], intravenous [IV], once a day for 4 days; rintatolimod [short-half-life TLR3 ligand] 200 mg intravenous [IV], on Wednesday and Friday only of the CKM regimen; and celecoxib 200 mg, orally, twice a day for 4 days). In order to avoid overlap between experimental immunotherapy and potential adjuvant chemotherapy (which can be clinically indicated as a part of standard care in the subset of patients), the experimental treatments will be interrupted after cycles 1 and 2, to allow adjuvant chemotherapy that is done for each patient's clinical care, and is not a part of this research study. Whenever clinically indicated as a part of standard care, adjuvant chemotherapy may start at least 5 days after completion of the 2nd cycle of immunotherapy (first booster vaccine plus the first CKM). The 3rd cycle of immunotherapy may start at least 5 days after the completion of chemotherapy.
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
| Study Registration Dates | Results Reporting Dates | Study Record Updates |
|---|---|---|
2014-05-28 | 2020-01-16 | 2020-07-06 |
2014-05-28 | 2020-01-16 | 2020-07-20 |
2014-05-30 | 2020-01-28 | 2020-07 |
This section provides details of the study plan, including how the study is designed and what the study is measuring.
Primary Purpose:
Treatment
Allocation:
Na
Interventional Model:
Single Group
Masking:
None
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
|---|---|
| EXPERIMENTAL: vaccine + chemokine modulatory regimen Week 1 (at recovery from surgery; ≥ 6 weeks post-surgery)-Priming Vaccine dose; no chemokine modulation; 1 day: αDC1 vaccine; Oral celecoxib, 200 mg, before & after treatment on day of vaccination; Weeks 2-3 -Rest; Week 4 (target) - Booster C1; Mon: αDC1 | BIOLOGICAL: DC vaccine
DRUG: Celecoxib
DRUG: Interferon Alfa-2b
BIOLOGICAL: rintatolimod
|
| Primary Outcome Measures | Measure Description | Time Frame |
|---|---|---|
| Recommended Phase 2 Dose (RP2D) (Phase 1) | Number of patients treated at each of the three possible dose levels of Interferon α (5 MU/m^2, 10 MU/m^2 or 20 MU/m^2) during the Phase 1 portion of the study. | Up to 24 weeks |
| Adverse Events Possibly, Probably or Definitely Related to Study Treatment | Number of participants with adverse events (by Grade) that were possibly, probably or definitely related to the combined study immunotherapy regimen (αDC1 vaccines + CKM) per CTCAE v 4.0 (Common Terminology Criteria for Adverse Events). | Up to 24 weeks |
| Secondary Outcome Measures | Measure Description | Time Frame |
|---|---|---|
| Time to Progression (TTP) | The length of time from the start of treatment until disease progression, per RECIST 1.1 considering only patients whose deaths were from cancer. Disease progression per RECIST 1.1 Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression). | Up to18 months |
| Overall Survival (OS) | The length of time from the start of treatment that diagnosed patients are still alive. | Up to 5 years |
| Progression-free Survival (PFS) | The length of time during and after the treatment that patients remain alive with disease that does not progress. Per RECIST 1.1, Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression). | Up to 5 years |
| CXCL10 (Interferon Gamma-induced Protein 10) Levels | Chemokine CXCL10 (Interferon gamma-induced protein 10) concentration levels measures in peripheral blood as a biomarker of anti-tumor activity. Increased levels can be predictive of good prognosis. | Prior to vaccine administration (Week 1), prior to vaccine booster (Week 4) and after vaccine booster (Week 8) |
| CXCL11 (C-X-C Motif Chemokine 11) Levels | CXCL11 (C-X-C motif chemokine 11) protein concentration levels measures in peripheral blood. Increased levels can be predictive of good prognosis. | Prior to vaccine administration (Week 1), prior to vaccine booster (Week 4) and after vaccine booster (Week 8) |
| Interleukin 10 (IL-10) Levels | Interleukin 10 (IL-10) (human cytokine synthesis inhibitory factor (CSIF)) concentration levels measures in peripheral blood. Increased levels of IL-10 is associated with advanced disease and poor prognosis. | Prior to vaccine administration (Week 1), prior to vaccine booster (Week 4) and after vaccine booster (Week 8) |
| Interleukin 6 (IL-6) Cytokine Levels | Interleukin 6 (IL-6) concentration levels measures in peripheral blood. Increased levels of IL-6 is associated with associated with advanced disease and poor prognosis. | Prior to vaccine administration (Week 1), prior to vaccine booster (Week 4) and after vaccine booster (Week 8) |
| Interleukin-8 (IL-8) Cytokine Levels | Interleukin-8 (IL-8) cytokine concentration levels measures in peripheral blood. Increased levels of IL-8 is associated with associated with advanced disease and poor prognosis. | Prior to vaccine administration (Week 1), prior to vaccine booster (Week 4) and after vaccine booster (Week 8) |
| Stromal Derived Factor 1 Alpha (SDF-1A/CXCL-12) Chemokine Levels | Levels of stromal derived factor 1 alpha (SDF-1A/CXCL-12) chemokine in peripheral blood. Higher levels of SDF-1A/CXCL-12 is associated with good prognosis. | Prior to vaccine administration (Week 1), prior to vaccine booster (Week 4) and after vaccine booster (Week 8) |
| Tumor Necrosis Factor (TFNα) Cytokine Levels | Tumor necrosis factor (TFNα) cytokine concentration levels measures in peripheral blood. Higher TFNα levels is associated with good prognosis. | Prior to vaccine administration (Week 1), prior to vaccine booster (Week 4) and after vaccine booster (Week 8) |
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.
Ages Eligible for Study:
ALL
Sexes Eligible for Study:
18 Years
Accepts Healthy Volunteers:
This is where you will find people and organizations involved with this study.
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
No publications available
