Malignant Neoplasm of Pancreas Metastatic to Peritoneal Surface, Malignant Peritoneal Mesothelioma, Peritoneal Carcinomatosis
Conditions
Brief summary
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.
Detailed description
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.
Interventions
BIOLOGICALDC vaccine
Administered on Monday of each cycle: 1 intranodal ultrasound-guided injection (target dose of 3 x 10e6 cells in 0.5 mL) + 1 intradermal injection (target dose of 3 x 10e6 cells in 0.5 mL)
DRUGCelecoxib
Administered at 200 mg, once a day orally, starting the day of the first DC vaccine through week 4/cycle 2. Participants will not take celecoxib while receiving standard of care chemotherapy as instructed by their local oncologist. Celecoxib will continue starting week 20/cycle 3 and continue until the Friday of the last day of the CKM administration, cycle 4. Administered at 400 mg, 200 mg twice a day orally, on days participants receive vaccine and CKM.
DRUGInterferon Alfa-2b
Intravenous infusion over 20 minutes: doses tested in Phase 1 portion (5, 10, or 20 MU/m2) will determine the Phase 2 dose. Administered on the Tuesday of each CKM cycle.
BIOLOGICALrintatolimod
Intravenous infusion of 200 mg on Wednesday and Friday only of the CKM regimen. The protocol allows for de-escalation to 100 mg if attributable adverse effects are observed.
Sponsors
National Cancer Institute (NCI)
David Bartlett
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with histologically confirmed peritoneal surface malignancies, including but not limited to malignant peritoneal mesothelioma and peritoneal carcinomatosis (PC) from presumed appendiceal and colorectal primary tumors. Most patients will have received extensive prior treatments, due to the recurrent nature of PC. Prior therapies involve previous CRS, local and systemic chemotherapies. None of these prior treatments disqualifies the patient from receiving the protocol-mandated experimental treatment. * Patients must be deemed able to undergo optimal cytoreductive surgery (CRS) defined as CC-score of 0 or 1 based on imaging. Cytoreduction is defined as the burden of residual disease nodules left at the end of surgery (CC-0: no visible disease; CC-1: residual tumor nodules ≤ 2.5 mm in size; CC-2: residual tumor nodules 2.5 mm - 2.5 cm in size; CC-3: residual tumor nodules \> 2.5 cm in size). * Patients may be enrolled in the study regardless of prior chemotherapy regimens * An ECOG performance status of 0, 1 or 2 * Age equal to 18 years or older * Patients must be able to understand and be willing to sign a written informed consent document * Able to swallow pills * Must have normal organ and marrow function as defined below: Platelet ≥ 75,000/µL Hemoglobin ≥ 9.0 g/dL Hematocrit ≥ 27.0% Absolute Neutrophil Count (ANC) ≥ 1500/µL WBC \>2000/mm3 Creatinine \< 1.5 x institutional upper limit of normal (ULN), OR Creatinine clearance ≥ 50 mL/min/1.73 m2 for patients with creatinine levels greater than 1.5 x ULN Total bilirubin ≤ 1.5 x ULN AST(SGOT) and ALT(SGPT) ≤ 2.5 X ULN * Must be eligible for pheresis within 8 weeks of surgery * Availability of sufficient number of tumor cells for cryopreservation and subsequent vaccine production * Must have had HIPEC during surgery * Must have a CC score of 0
Exclusion criteria
* Infection of tumor tissue with pathogens resistant to radiation and fungizone * Patients on systemic immunosuppressive agents, including steroids. Patients who are able to be removed from immunosuppressives at least 5 days prior to the first vaccine will be considered eligible. * Patients with active autoimmune disease or history of transplantation. Patients with indolent or chronic autoimmune disease not requiring steroid treatment are considered eligible. * Patients who are pregnant or nursing * Patients experiencing a cardiac events (acute coronary syndrome, myocardial infarction, or ischemia) within the 3 months prior to accrual * Patients with a New York Heart Association classification of III or IV * Prior allergic reaction or hypersensitivity to celecoxib or NSAIDs
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Recommended Phase 2 Dose (RP2D) (Phase 1) | Up to 24 weeks | 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. |
| Adverse Events Possibly, Probably or Definitely Related to Study Treatment | Up to 24 weeks | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) | Up to 5 years | 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). |
| CXCL10 (Interferon Gamma-induced Protein 10) Levels | Prior to vaccine administration (Week 1), prior to vaccine booster (Week 4) and after vaccine booster (Week 8) | 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. |
| CXCL11 (C-X-C Motif Chemokine 11) Levels | 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) protein concentration levels measures in peripheral blood. Increased levels can be predictive of good prognosis. |
| Interleukin 10 (IL-10) Levels | Prior to vaccine administration (Week 1), prior to vaccine booster (Week 4) and after vaccine booster (Week 8) | 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. |
| Time to Progression (TTP) | Up to18 months | 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). |
| Interleukin-8 (IL-8) Cytokine Levels | Prior to vaccine administration (Week 1), prior to vaccine booster (Week 4) and after vaccine booster (Week 8) | 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. |
| Stromal Derived Factor 1 Alpha (SDF-1A/CXCL-12) Chemokine Levels | Prior to vaccine administration (Week 1), prior to vaccine booster (Week 4) and after vaccine booster (Week 8) | 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. |
| Tumor Necrosis Factor (TFNα) Cytokine Levels | Prior to vaccine administration (Week 1), prior to vaccine booster (Week 4) and after vaccine booster (Week 8) | Tumor necrosis factor (TFNα) cytokine concentration levels measures in peripheral blood. Higher TFNα levels is associated with good prognosis. |
| Interleukin 6 (IL-6) Cytokine Levels | Prior to vaccine administration (Week 1), prior to vaccine booster (Week 4) and after vaccine booster (Week 8) | 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. |
| Overall Survival (OS) | Up to 5 years | The length of time from the start of treatment that diagnosed patients are still alive. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| α DC1 Vaccine + 1 Cycle of Chemokine Modulatory Regimen Phase 1:
α DC1 vaccine and
Chemokine Modulatory Regimen:
Celecoxib: Administered at 200 mg, once a day orally (T-TH) Rintatolimod: Intravenous infusion of 200 mg (Wed & and Fri, only) Interferon Alfa-2b: Intravenous infusion - 5 MU/m\^2 or 20 MU/m\^2 (T-Fri)
Phase 2:
α DC1 vaccine and
Chemokine Modulatory Regimen:
Celecoxib: Administered at 200 mg, once a day orally (T-TH) Rintatolimod: Intravenous infusion of 200 mg (Wed & and Fri, only) Interferon Alfa-2b: Intravenous infusion - 20 MU/m\^2 (T-Fri) | 64 |
| Total | 64 |
Baseline characteristics
| Characteristic | α DC1 Vaccine + 1 Cycle of Chemokine Modulatory Regimen |
|---|---|
| Age, Continuous | 53 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 63 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 61 Participants |
| Sex: Female, Male Female | 22 Participants |
| Sex: Female, Male Male | 42 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 23 / 64 |
| other Total, other adverse events | 46 / 64 |
| serious Total, serious adverse events | 17 / 64 |
Outcome results
Primary
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).
Time frame: Up to 24 weeks
Population: Patients treated with at least 1 course of α DC1 vaccine + 1 cycle of chemokine modulatory regimen who were evaluable for for completing surgery.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Adverse Events Possibly, Probably or Definitely Related to Study Treatment | Anemia : Grade 1-2 | 3 Participants |
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Adverse Events Possibly, Probably or Definitely Related to Study Treatment | Anemia : Grade 3-4 | 1 Participants |
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Adverse Events Possibly, Probably or Definitely Related to Study Treatment | Blurred vision : Grade 1-2 | 1 Participants |
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Adverse Events Possibly, Probably or Definitely Related to Study Treatment | Blurred vision : Grade 3-4 | 0 Participants |
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Adverse Events Possibly, Probably or Definitely Related to Study Treatment | Bruising : Grade 1-2 | 1 Participants |
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Adverse Events Possibly, Probably or Definitely Related to Study Treatment | Bruising : Grade 3-4 | 0 Participants |
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Adverse Events Possibly, Probably or Definitely Related to Study Treatment | Chills : Grade 1-2 | 34 Participants |
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Adverse Events Possibly, Probably or Definitely Related to Study Treatment | Chills : Grade 3-4 | 0 Participants |
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Adverse Events Possibly, Probably or Definitely Related to Study Treatment | Diarrhea : Grade 1-2 | 7 Participants |
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Adverse Events Possibly, Probably or Definitely Related to Study Treatment | Diarrhea : Grade 3-4 | 1 Participants |
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Adverse Events Possibly, Probably or Definitely Related to Study Treatment | Dizziness : Grade 1-2 | 1 Participants |
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Adverse Events Possibly, Probably or Definitely Related to Study Treatment | Dizziness : Grade 3-4 | 0 Participants |
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Adverse Events Possibly, Probably or Definitely Related to Study Treatment | Eye disorders - Other, specify : Grade 1-2 | 0 Participants |
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Adverse Events Possibly, Probably or Definitely Related to Study Treatment | Eye disorders - Other, specify : Grade 3-4 | 1 Participants |
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Adverse Events Possibly, Probably or Definitely Related to Study Treatment | Fatigue : Grade 1-2 | 15 Participants |
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Adverse Events Possibly, Probably or Definitely Related to Study Treatment | Fatigue : Grade 3-4 | 0 Participants |
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Adverse Events Possibly, Probably or Definitely Related to Study Treatment | Fever : Grade 1-2 | 7 Participants |
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Adverse Events Possibly, Probably or Definitely Related to Study Treatment | Fever : Grade 3-4 | 0 Participants |
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Adverse Events Possibly, Probably or Definitely Related to Study Treatment | Flu like symptoms : Grade 1-2 | 5 Participants |
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Adverse Events Possibly, Probably or Definitely Related to Study Treatment | Flu like symptoms : Grade 3-4 | 0 Participants |
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Adverse Events Possibly, Probably or Definitely Related to Study Treatment | Flushing : Grade 1-2 | 3 Participants |
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Adverse Events Possibly, Probably or Definitely Related to Study Treatment | Flushing : Grade 3-4 | 0 Participants |
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Adverse Events Possibly, Probably or Definitely Related to Study Treatment | General disorders and administration : Grade 1-2 | 7 Participants |
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Adverse Events Possibly, Probably or Definitely Related to Study Treatment | General disorders and administration: Grade 3-4 | 0 Participants |
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Adverse Events Possibly, Probably or Definitely Related to Study Treatment | Headache : Grade 1-2 | 10 Participants |
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Adverse Events Possibly, Probably or Definitely Related to Study Treatment | Headache : Grade 3-4 | 0 Participants |
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Adverse Events Possibly, Probably or Definitely Related to Study Treatment | Heart failure : Grade 1-2 | 0 Participants |
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Adverse Events Possibly, Probably or Definitely Related to Study Treatment | Heart failure : Grade 3-4 | 1 Participants |
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Adverse Events Possibly, Probably or Definitely Related to Study Treatment | Hypotension : Grade 1-2 | 1 Participants |
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Adverse Events Possibly, Probably or Definitely Related to Study Treatment | Hypotension : Grade 3-4 | 0 Participants |
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Adverse Events Possibly, Probably or Definitely Related to Study Treatment | Hypothyroidism : Grade 1-2 | 2 Participants |
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Adverse Events Possibly, Probably or Definitely Related to Study Treatment | Hypothyroidism : Grade 3-4 | 0 Participants |
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Adverse Events Possibly, Probably or Definitely Related to Study Treatment | Lymphocyte count decreased : Grade 1-2 | 4 Participants |
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Adverse Events Possibly, Probably or Definitely Related to Study Treatment | Lymphocyte count decreased : Grade 3-4 | 1 Participants |
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Adverse Events Possibly, Probably or Definitely Related to Study Treatment | Myalgia : Grade 1-2 | 3 Participants |
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Adverse Events Possibly, Probably or Definitely Related to Study Treatment | Myalgia : Grade 3-4 | 0 Participants |
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Adverse Events Possibly, Probably or Definitely Related to Study Treatment | Nausea : Grade 1-2 | 13 Participants |
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Adverse Events Possibly, Probably or Definitely Related to Study Treatment | Nausea : Grade 3-4 | 0 Participants |
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Adverse Events Possibly, Probably or Definitely Related to Study Treatment | Neutrophil count decreased : Grade 1-2 | 3 Participants |
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Adverse Events Possibly, Probably or Definitely Related to Study Treatment | Neutrophil count decreased : Grade 3-4 | 0 Participants |
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Adverse Events Possibly, Probably or Definitely Related to Study Treatment | Pain : Grade 1-2 | 6 Participants |
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Adverse Events Possibly, Probably or Definitely Related to Study Treatment | Pain : Grade 3-4 | 0 Participants |
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Adverse Events Possibly, Probably or Definitely Related to Study Treatment | Platelet count decreased : Grade 1-2 | 1 Participants |
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Adverse Events Possibly, Probably or Definitely Related to Study Treatment | Platelet count decreased : Grade 3-4 | 0 Participants |
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Adverse Events Possibly, Probably or Definitely Related to Study Treatment | Pleural effusion : Grade 1-2 | 1 Participants |
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Adverse Events Possibly, Probably or Definitely Related to Study Treatment | Pleural effusion : Grade 3-4 | 0 Participants |
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Adverse Events Possibly, Probably or Definitely Related to Study Treatment | Serum amylase increased : Grade 1-2 | 1 Participants |
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Adverse Events Possibly, Probably or Definitely Related to Study Treatment | Serum amylase increased : Grade 3-4 | 0 Participants |
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Adverse Events Possibly, Probably or Definitely Related to Study Treatment | Sinus bradycardia : Grade 1-2 | 2 Participants |
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Adverse Events Possibly, Probably or Definitely Related to Study Treatment | Sinus bradycardia : Grade 3-4 | 0 Participants |
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Adverse Events Possibly, Probably or Definitely Related to Study Treatment | Vomiting : Grade 1-2 | 7 Participants |
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Adverse Events Possibly, Probably or Definitely Related to Study Treatment | Vomiting : Grade 3-4 | 0 Participants |
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Adverse Events Possibly, Probably or Definitely Related to Study Treatment | Weight gain : Grade 1-2 | 1 Participants |
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Adverse Events Possibly, Probably or Definitely Related to Study Treatment | Weight gain : Grade 3-4 | 0 Participants |
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Adverse Events Possibly, Probably or Definitely Related to Study Treatment | White blood cell decreased : Grade 1-2 | 3 Participants |
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Adverse Events Possibly, Probably or Definitely Related to Study Treatment | White blood cell decreased : Grade 3-4 | 0 Participants |
Primary
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.
Time frame: Up to 24 weeks
Population: Only includes patients participating in the Phase 1 portion.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Recommended Phase 2 Dose (RP2D) (Phase 1) | 5 MU/M^2IFN alpha | 5 Participants |
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Recommended Phase 2 Dose (RP2D) (Phase 1) | 10 MU/M^2 IFN alpha | 0 Participants |
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Recommended Phase 2 Dose (RP2D) (Phase 1) | 20 MU/M^2IFN alpha (RP2D) | 4 Participants |
Secondary
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.
Time frame: Prior to vaccine administration (Week 1), prior to vaccine booster (Week 4) and after vaccine booster (Week 8)
Population: Patients treated with at least 1 course of α DC1 vaccine + 1 cycle of chemokine modulatory regimen who were evaluable for completing surgery and response to treatment, and with ≥80% of samples available with measurable cytokine profiles via peripheral blood assay.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | CXCL10 (Interferon Gamma-induced Protein 10) Levels | Prior to vaccine administration (Week 1) | 1221.5 pg/mL | Standard Deviation 135.4 |
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | CXCL10 (Interferon Gamma-induced Protein 10) Levels | Prior to vaccine booster (Week 4) | 16335.0 pg/mL | Standard Deviation 59.3 |
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | CXCL10 (Interferon Gamma-induced Protein 10) Levels | After vaccine booster (Week 8) | 137.6 pg/mL | Standard Deviation 17098.5 |
Secondary
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.
Time frame: Prior to vaccine administration (Week 1), prior to vaccine booster (Week 4) and after vaccine booster (Week 8)
Population: Patients treated with at least 1 course of α DC1 vaccine + 1 cycle of chemokine modulatory regimen who were evaluable for completing surgery and response to treatment, and with ≥80% of samples available with measurable cytokine profiles via peripheral blood assay.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | CXCL11 (C-X-C Motif Chemokine 11) Levels | Prior to vaccine administration (Week 1) | 359.4 pg/mL | Standard Deviation 340.2 |
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | CXCL11 (C-X-C Motif Chemokine 11) Levels | Prior to vaccine booster (Week 4) | 12893.2 pg/mL | Standard Deviation 190.3 |
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | CXCL11 (C-X-C Motif Chemokine 11) Levels | After vaccine booster (Week 8) | 208.9 pg/mL | Standard Deviation 5717.1 |
Secondary
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.
Time frame: Prior to vaccine administration (Week 1), prior to vaccine booster (Week 4) and after vaccine booster (Week 8)
Population: Patients treated with at least 1 course of α DC1 vaccine + 1 cycle of chemokine modulatory regimen who were evaluable for completing surgery and response to treatment, and with ≥80% of samples available with measurable cytokine profiles via peripheral blood assay.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Interleukin 10 (IL-10) Levels | Prior to vaccine administration (Week 1) | 1.2 pg/ml | Standard Deviation 2.4 |
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Interleukin 10 (IL-10) Levels | Prior to vaccine booster (Week 4) | 7.9 pg/ml | Standard Deviation 1.4 |
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Interleukin 10 (IL-10) Levels | After vaccine booster (Week 8) | 7.5 pg/ml | Standard Deviation 12.6 |
Secondary
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.
Time frame: Prior to vaccine administration (Week 1), prior to vaccine booster (Week 4) and after vaccine booster (Week 8)
Population: Patients treated with at least 1 course of α DC1 vaccine + 1 cycle of chemokine modulatory regimen who were evaluable for completing surgery and response to treatment, and with ≥80% of samples available with measurable cytokine profiles via peripheral blood assay.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Interleukin 6 (IL-6) Cytokine Levels | Prior to vaccine administration (Week 1) | 15.2 pg/mL | Standard Deviation 10.7 |
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Interleukin 6 (IL-6) Cytokine Levels | Prior to vaccine booster (Week 4) | 32.8 pg/mL | Standard Deviation 19 |
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Interleukin 6 (IL-6) Cytokine Levels | After vaccine booster (Week 8) | 11.1 pg/mL | Standard Deviation 32.7 |
Secondary
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.
Time frame: Prior to vaccine administration (Week 1), prior to vaccine booster (Week 4) and after vaccine booster (Week 8)
Population: Patients treated with at least 1 course of α DC1 vaccine + 1 cycle of chemokine modulatory regimen who were evaluable for completing surgery and response to treatment, and with ≥80% of samples available with measurable cytokine profiles via peripheral blood assay.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Interleukin-8 (IL-8) Cytokine Levels | Prior to vaccine administration (Week 1) | 9.5 pg/mL | Standard Deviation 15.7 |
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Interleukin-8 (IL-8) Cytokine Levels | Prior to vaccine booster (Week 4) | 16.9 pg/mL | Standard Deviation 5.4 |
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Interleukin-8 (IL-8) Cytokine Levels | After vaccine booster (Week 8) | 28.6 pg/mL | Standard Deviation 12.7 |
Secondary
Overall Survival (OS)
The length of time from the start of treatment that diagnosed patients are still alive.
Time frame: Up to 5 years
Population: Patients treated with at least 1 course of α DC1 vaccine + 1 cycle of chemokine modulatory regimen who were evaluable for completing surgery.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Overall Survival (OS) | 52 months |
Secondary
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).
Time frame: Up to 5 years
Population: Patients treated with at least 1 course of α DC1 vaccine + 1 cycle of chemokine modulatory regimen who were evaluable for completing surgery and response to treatment.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Progression-free Survival (PFS) | colon cancer | 19 months |
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Progression-free Survival (PFS) | appendiceal cancer | 16 months |
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Progression-free Survival (PFS) | Mesothelioma | NA months |
Secondary
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.
Time frame: Prior to vaccine administration (Week 1), prior to vaccine booster (Week 4) and after vaccine booster (Week 8)
Population: Patients treated with at least 1 course of α DC1 vaccine + 1 cycle of chemokine modulatory regimen who were evaluable for completing surgery and response to treatment, and with ≥80% of samples available with measurable cytokine profiles via peripheral blood assay.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Stromal Derived Factor 1 Alpha (SDF-1A/CXCL-12) Chemokine Levels | Prior to vaccine administration (Week 1) | 1267.3 pg/mL | Standard Deviation 5 |
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Stromal Derived Factor 1 Alpha (SDF-1A/CXCL-12) Chemokine Levels | Prior to vaccine booster (Week 4) | 2160.3 pg/mL | Standard Deviation 476.8 |
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Stromal Derived Factor 1 Alpha (SDF-1A/CXCL-12) Chemokine Levels | After vaccine booster (Week 8) | 510.0 pg/mL | Standard Deviation 852.2 |
Secondary
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).
Time frame: Up to18 months
Population: Patients treated with at least 1 course of α DC1 vaccine + 1 cycle of chemokine modulatory regimen who were evaluable for for completing surgery and response to treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Time to Progression (TTP) | 15.9 months |
Secondary
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.
Time frame: Prior to vaccine administration (Week 1), prior to vaccine booster (Week 4) and after vaccine booster (Week 8)
Population: Patients treated with at least 1 course of α DC1 vaccine + 1 cycle of chemokine modulatory regimen who were evaluable for completing surgery and response to treatment, and with ≥80% of samples available with measurable cytokine profiles via peripheral blood assay.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Tumor Necrosis Factor (TFNα) Cytokine Levels | Prior to vaccine administration (Week 1) | 10.8 pg/mL | Standard Deviation 12.2 |
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Tumor Necrosis Factor (TFNα) Cytokine Levels | Prior to vaccine booster (Week 4) | 31.0 pg/mL | Standard Deviation 5 |
| Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen | Tumor Necrosis Factor (TFNα) Cytokine Levels | After vaccine booster (Week 8) | 17.2 pg/mL | Standard Deviation 25.4 |