αDC1 Vaccine + Chemokine Modulatory Regimen (CKM) as Adjuvant Treatment of Peritoneal Surface Malignancies

Brief summary public domain (ClinicalTrials.gov)

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 public domain (ClinicalTrials.gov)

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.

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Recommended Phase 2 Dose (RP2D) (Phase 1) [Up to 24 weeks]. Count Of Participants, Participants. 5 MU/M^2IFN alpha: Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen (n=9): 5. 10 MU/M^2 IFN alpha: Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen (n=9): 0. 20 MU/M^2IFN alpha (RP2D): Phase 1- αDC1 Vaccine +1 Cycle of Chemokine Modulatory Regimen (n=9): 4.

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Adverse Events Possibly, Probably or Definitely Related to Study Treatment [Up to 24 weeks]. Count Of Participants, Participants. Anemia : Grade 1-2: α DC1 Vaccine + 1 Cycle of Chemokine Modulatory Regimen (n=38): 3. Anemia : Grade 3-4: α DC1 Vaccine + 1 Cycle of Chemokine Modulatory Regimen (n=38): 1. Blurred vision : Grade 1-2: α DC1 Vaccine + 1 Cycle of Chemokine Modulatory Regimen (n=38): 1. Blurred vision : Grade 3-4: α DC1 Vaccine + 1 Cycle of Chemokine Modulatory Regimen (n=38): 0. Bruising : Grade 1-2: α DC1 Vaccine + 1 Cycle of Chemokine Modulatory Regimen (n=38): 1. Bruising : Grade 3-4: α DC1 Vaccine + 1 Cycle of Chemokine Modulatory Regimen (n=38): 0. Chills : Grade 1-2: α DC1 Vaccine + 1 Cycle of Chemokine Modulatory Regimen (n=38): 34. Chills : Grade 3-4: α DC1 Vaccine + 1 Cycle of Chemokine Modulatory Regimen (n=38): 0. Diarrhea : Grade 1-2: α DC1 Vaccine + 1 Cycle of Chemokine Modulatory Regimen (n=38): 7. Diarrhea : Grade 3-4: α DC1 Vaccine + 1 Cycle of Chemokine Modulatory Regimen (n=38): 1. Dizziness : Grade 1-2: α DC1 Vaccine + 1 Cycle of Chemokine Modulatory Regimen (n=38): 1. Dizziness : Grade 3-4: α DC1 Vaccine + 1 Cycle of Chemokine Modulatory Regimen (n=38): 0. Eye disorders - Other, specify : Grade 1-2: α DC1 Vaccine + 1 Cycle of Chemokine Modulatory Regimen (n=38): 0. Eye disorders - Other, specify : Grade 3-4: α DC1 Vaccine + 1 Cycle of Chemokine Modulatory Regimen (n=38): 1. Fatigue : Grade 1-2: α DC1 Vaccine + 1 Cycle of Chemokine Modulatory Regimen (n=38): 15. Fatigue : Grade 3-4: α DC1 Vaccine + 1 Cycle of Chemokine Modulatory Regimen (n=38): 0. Fever : Grade 1-2: α DC1 Vaccine + 1 Cycle of Chemokine Modulatory Regimen (n=38): 7. Fever : Grade 3-4: α DC1 Vaccine + 1 Cycle of Chemokine Modulatory Regimen (n=38): 0. Flu like symptoms : Grade 1-2: α DC1 Vaccine + 1 Cycle of Chemokine Modulatory Regimen (n=38): 5. Flu like symptoms : Grade 3-4: α DC1 Vaccine + 1 Cycle of Chemokine Modulatory Regimen (n=38): 0. Flushing : Grade 1-2: α DC1 Vaccine + 1 Cycle of Chemokine Modulatory Regimen (n=38): 3. Flushing : Grade 3-4: α DC1 Vaccine + 1 Cycle of Chemokine Modulatory Regimen (n=38): 0. General disorders and administration : Grade 1-2: α DC1 Vaccine + 1 Cycle of Chemokine Modulatory Regimen (n=38): 7. General disorders and administration: Grade 3-4: α DC1 Vaccine + 1 Cycle of Chemokine Modulatory Regimen (n=38): 0. Headache : Grade 1-2: α DC1 Vaccine + 1 Cycle of Chemokine Modulatory Regimen (n=38): 10. Headache : Grade 3-4: α DC1 Vaccine + 1 Cycle of Chemokine Modulatory Regimen (n=38): 0. Heart failure : Grade 1-2: α DC1 Vaccine + 1 Cycle of Chemokine Modulatory Regimen (n=38): 0. Heart failure : Grade 3-4: α DC1 Vaccine + 1 Cycle of Chemokine Modulatory Regimen (n=38): 1. Hypotension : Grade 1-2: α DC1 Vaccine + 1 Cycle of Chemokine Modulatory Regimen (n=38): 1. Hypotension : Grade 3-4: α DC1 Vaccine + 1 Cycle of Chemokine Modulatory Regimen (n=38): 0. Hypothyroidism : Grade 1-2: α DC1 Vaccine + 1 Cycle of Chemokine M

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Time to Progression (TTP) [Up to18 months]. Median, months (95% Confidence Interval). α DC1 Vaccine + Chemokine Modulatory Regimen (n=55): 15.9 (13.6 to NA) [Upper bound not reached for 95% CI].

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Overall Survival (OS) [Up to 5 years]. Median, months (95% Confidence Interval). α DC1 Vaccine + Chemokine Modulatory Regimen (n=64): 52 (44 to NA) [Upper bound of 95% CI not reached.].

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Progression-free Survival (PFS) [Up to 5 years]. Median, months (95% Confidence Interval). colon cancer: α DC1 Vaccine + Chemokine Modulatory Regimen (n=20): 19 (9 to NA) [Upper bound not reached for 95% CI]. appendiceal cancer: α DC1 Vaccine + Chemokine Modulatory Regimen (n=20): 16 (14 to NA) [Upper bound not reached for 95% CI]. Mesothelioma: α DC1 Vaccine + Chemokine Modulatory Regimen (n=20): NA (NA to NA) [Median not reached.].

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

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)]. Mean, pg/mL (Standard Deviation). Prior to vaccine administration (Week 1): α DC1 Vaccine + Chemokine Modulatory Regimen (n=41): 1221.5 (135.4). Prior to vaccine booster (Week 4): α DC1 Vaccine + Chemokine Modulatory Regimen (n=41): 16335.0 (59.3). After vaccine booster (Week 8): α DC1 Vaccine + Chemokine Modulatory Regimen (n=41): 137.6 (17098.5).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

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)]. Mean, pg/mL (Standard Deviation). Prior to vaccine administration (Week 1): α DC1 Vaccine + Chemokine Modulatory Regimen (n=41): 359.4 (340.2). Prior to vaccine booster (Week 4): α DC1 Vaccine + Chemokine Modulatory Regimen (n=41): 12893.2 (190.3). After vaccine booster (Week 8): α DC1 Vaccine + Chemokine Modulatory Regimen (n=41): 208.9 (5717.1).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Interleukin 10 (IL-10) Levels [Prior to vaccine administration (Week 1), prior to vaccine booster (Week 4) and after vaccine booster (Week 8)]. Mean, pg/ml (Standard Deviation). Prior to vaccine administration (Week 1): α DC1 Vaccine + Chemokine Modulatory Regimen (n=41): 1.2 (2.4). Prior to vaccine booster (Week 4): α DC1 Vaccine + Chemokine Modulatory Regimen (n=41): 7.9 (1.4). After vaccine booster (Week 8): α DC1 Vaccine + Chemokine Modulatory Regimen (n=41): 7.5 (12.6).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Interleukin 6 (IL-6) Cytokine Levels [Prior to vaccine administration (Week 1), prior to vaccine booster (Week 4) and after vaccine booster (Week 8)]. Mean, pg/mL (Standard Deviation). Prior to vaccine administration (Week 1): α DC1 Vaccine + 1 Cycle of Chemokine Modulatory Regimen (n=41): 15.2 (10.7). Prior to vaccine booster (Week 4): α DC1 Vaccine + 1 Cycle of Chemokine Modulatory Regimen (n=41): 32.8 (19.0). After vaccine booster (Week 8): α DC1 Vaccine + 1 Cycle of Chemokine Modulatory Regimen (n=41): 11.1 (32.7).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Interleukin-8 (IL-8) Cytokine Levels [Prior to vaccine administration (Week 1), prior to vaccine booster (Week 4) and after vaccine booster (Week 8)]. Mean, pg/mL (Standard Deviation). Prior to vaccine administration (Week 1): α DC1 Vaccine + 1 Cycle of Chemokine Modulatory Regimen (n=41): 9.5 (15.7). Prior to vaccine booster (Week 4): α DC1 Vaccine + 1 Cycle of Chemokine Modulatory Regimen (n=41): 16.9 (5.4). After vaccine booster (Week 8): α DC1 Vaccine + 1 Cycle of Chemokine Modulatory Regimen (n=41): 28.6 (12.7).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

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)]. Mean, pg/mL (Standard Deviation). Prior to vaccine administration (Week 1): α DC1 Vaccine + 1 Cycle of Chemokine Modulatory Regimen (n=41): 1267.3 (5.0). Prior to vaccine booster (Week 4): α DC1 Vaccine + 1 Cycle of Chemokine Modulatory Regimen (n=41): 2160.3 (476.8). After vaccine booster (Week 8): α DC1 Vaccine + 1 Cycle of Chemokine Modulatory Regimen (n=41): 510.0 (852.2).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Tumor Necrosis Factor (TFNα) Cytokine Levels [Prior to vaccine administration (Week 1), prior to vaccine booster (Week 4) and after vaccine booster (Week 8)]. Mean, pg/mL (Standard Deviation). Prior to vaccine administration (Week 1): α DC1 Vaccine + 1 Cycle of Chemokine Modulatory Regimen (n=40): 10.8 (12.2). Prior to vaccine booster (Week 4): α DC1 Vaccine + 1 Cycle of Chemokine Modulatory Regimen (n=40): 31.0 (5.0). After vaccine booster (Week 8): α DC1 Vaccine + 1 Cycle of Chemokine Modulatory Regimen (n=40): 17.2 (25.4).