NCT02151448

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

A Phase 1/2 Trial Evaluating αDC1 Vaccines Combined With Tumor-Selective Chemokine Modulation as Adjuvant Therapy After Surgical Resection of Peritoneal Surface Malignancies

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 64 (actual)
• Sponsor: David Bartlett · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Malignant Neoplasm of Pancreas Metastatic to Peritoneal Surface
• Malignant Peritoneal Mesothelioma
• Peritoneal Carcinomatosis

Interventions

Type	Name	Description
BIOLOGICAL	DC 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)
DRUG	Celecoxib	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.
DRUG	Interferon 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.
BIOLOGICAL	rintatolimod	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.

Timeline

• Start date: 2014-07-01
• Primary completion: 2019-02-18
• Completion: 2019-02-18
• First posted: 2014-05-30
• Last updated: 2020-07-20
• Results posted: 2020-01-28

Locations

1 site across 1 country: United States