Phase 2
N=9
αDC1 Vaccine + Chemokine Modulatory Regimen (CKM) as Adjuvant Treatment of Peritoneal Surface Malignancies
Malignant Neoplasm of Pancreas Metastatic to Peritoneal Surface · Malignant Peritoneal Mesothelioma · Peritoneal Carcinomatosis
Bottom Line
View on ClinicalTrials.gov: NCT02151448 ↗Enrolled (actual)
9
Serious AEs
26.6%
Results posted
Jan 2020
Primary outcome: Primary: Recommended Phase 2 Dose (RP2D) (Phase 1) — 5; 0; 4 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- DC vaccine (Biological); Celecoxib (Drug); Interferon Alfa-2b (Drug); rintatolimod (Biological)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- David Bartlett
- Primary completion
- Feb 2019
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Recommended Phase 2 Dose (RP2D) (Phase 1) |
5; 0; 4 | — |
| PRIMARY Adverse Events Possibly, Probably or Definitely Related to Study Treatment |
3; 1; 1; 0; 1; 0 | — |
| SECONDARY Time to Progression (TTP) |
15.9 | — |
| SECONDARY Overall Survival (OS) |
52 | — |
| SECONDARY Progression-free Survival (PFS) |
19; 16; NA | — |
| SECONDARY CXCL10 (Interferon Gamma-induced Protein 10) Levels |
1221.5; 16335.0; 137.6 | — |
| SECONDARY CXCL11 (C-X-C Motif Chemokine 11) Levels |
359.4; 12893.2; 208.9 | — |
| SECONDARY Interleukin 10 (IL-10) Levels |
1.2; 7.9; 7.5 | — |
| SECONDARY Interleukin 6 (IL-6) Cytokine Levels |
15.2; 32.8; 11.1 | — |
| SECONDARY Interleukin-8 (IL-8) Cytokine Levels |
9.5; 16.9; 28.6 | — |
| SECONDARY Stromal Derived Factor 1 Alpha (SDF-1A/CXCL-12) Chemokine Levels |
1267.3; 2160.3; 510.0 | — |
| SECONDARY Tumor Necrosis Factor (TFNα) Cytokine Levels |
10.8; 31.0; 17.2 | — |
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.
Eligibility Criteria
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
Data sourced from ClinicalTrials.gov (NCT02151448). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.