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

NCT02151448 | Completed Phase 1 Results DMC

• 2 other identifiers: 12-1105P01CA132714-05
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (10)

• Time to Progression (TTP)

  Up to18 months

• Overall Survival (OS)

  Up to 5 years

• Progression-free Survival (PFS)

  Up to 5 years

• 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)

• 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)

Study Arms (1)

vaccine + chemokine modulatory regimen

EXPERIMENTAL

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 vaccine;Tues - Fri: Systemic Chemokine Modulation Regimen. Oral celecoxib, 200 mg, BID on vaccination days \& CKM. Celecoxib will be dced after CKM on Fri. Rintatolimod only administered on Wed \& Fri.; Week 5-7 -Rest; Week 8 (target) -Booster C2; Monday: αDC1 vaccine. Oral celecoxib, 200 mg, BID on days of vaccination and CKM. Tues - Fri:Systemic Chemokine Modulation Regimen. Rintatolimod only administered on Wed \& Fri. Celecoxib will be dced after CKM on Fri.; Week 9-11 -Rest; Week 12 (target) -Booster C3; Monday: αDC1 vaccine. Tues-Fri: Systemic Chemokine Modulation Regimen. Rintatolimod only administered on Wed \& Fri. Oral celecoxib, 200 mg, BID, given on days of vaccination and CKM. Celecoxib will be discontinued after CKM on Fri.

Biological: DC vaccine; Drug: Celecoxib; Drug: Interferon Alfa-2b; Biological: rintatolimod

Interventions

DC vaccine BIOLOGICAL

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)

Also known as: Alpha-type-1 polarized dendritic cells, alpha DC1, αDC1

vaccine + chemokine modulatory regimen

Celecoxib DRUG

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.

Also known as: Celebrex, Celebra, Onsenal

vaccine + chemokine modulatory regimen

Interferon Alfa-2b DRUG

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.

Also known as: Interferon-α2b, Intron A, IFN-α2b, IFNα, IFN, NSC #377523

vaccine + chemokine modulatory regimen

rintatolimod BIOLOGICAL

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.

Also known as: PolyIC12U, Ampligen®, poly I: polyC12U, Polyinosinic:polycytidylic-polyuridylic acid, polyriboinosinic/polyribocytidylic (uridylic) acid

vaccine + chemokine modulatory regimen

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• David Bartlett: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

MeSH Terms

Conditions

Peritoneal Neoplasms

Interventions

lentiviral minigene vaccine of COVID-19 coronavirus; AlkB Homolog 2, Alpha-Ketoglutarate-Dependent Dioxygenase; Celecoxib; Interferon alpha-2; Introns; poly(I).poly(c12,U); Acids

Condition Hierarchy (Ancestors)

Abdominal Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Peritoneal Diseases

Intervention Hierarchy (Ancestors)

AlkB Enzymes; DNA Repair Enzymes; Enzymes; Enzymes and Coenzymes; Dioxygenases; Oxygenases; Oxidoreductases; Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Interferon-alpha; Interferon Type I; Interferons; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; DNA, Intergenic; Genome Components; Genome; Genetic Structures; Genetic Phenomena; Gene Components; Genes; Inorganic Chemicals

Results Point of Contact

• Title: Barbara Stadterman, MPH, MCCR, Regulatory Supervisor, CRS
• Organization: UPMC Hillman Cancer Center

stadtermanbm@upmc.edu

412-647-5554

Study Officials

• David L Bartlett, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: May 28, 2014
• First Posted: May 30, 2014
• Study Start: July 1, 2014
• Primary Completion: February 18, 2019
• Study Completion: February 18, 2019
• Last Updated: July 20, 2020
• Results First Posted: January 28, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)