Clinical Trials /

Study of Pembrolizumab, Radiation and Immune Modulatory Cocktail in Cervical/Uterine Cancer

NCT03192059

Description:

This is a Phase II study in patients with advanced and/refractory cervical cancer, endometrial carcinoma or uterine sarcoma. Patients will be treated with an immunomodulatory cocktail (Vitamin D, aspirin, Cyclophosphamide and Lansoprazole), followed by pembrolizumab, combined with radiation. In addition, patients will take Curcumin, a food supplement.

Related Conditions:
  • Cervical Carcinoma
  • Endometrial Carcinoma
  • Uterine Sarcoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of Pembrolizumab, Radiation and Immune Modulatory Cocktail in Cervical/Uterine Cancer
  • Official Title: A Phase II Investigation of Pembrolizumab (Keytruda) in Combination With Radiation and an Immune Modulatory Cocktail in Patients With Cervical and Uterine Cancer (PRIMMO Trial)

Clinical Trial IDs

  • ORG STUDY ID: 2016-001569-97
  • NCT ID: NCT03192059

Conditions

  • Cervical Cancer
  • Endometrial Cancer
  • Uterine Cancer

Interventions

DrugSynonymsArms
Pembrolizumabexperimental arm
Vitamin Dexperimental arm
Aspirinexperimental arm
Lansoprazoleexperimental arm
Cyclophosphamideexperimental arm

Purpose

This is a Phase II study in patients with advanced and/refractory cervical cancer, endometrial carcinoma or uterine sarcoma. Patients will be treated with an immunomodulatory cocktail (Vitamin D, aspirin, Cyclophosphamide and Lansoprazole), followed by pembrolizumab, combined with radiation. In addition, patients will take Curcumin, a food supplement.

Detailed Description

      This is a Phase II multi-center, open-label, non-randomized, 3-cohort study in patients with
      advanced and/or refractory cervical cancer, endometrial carcinoma or uterine sarcoma.
      Patients will be treated by an immunomodulatory cocktail (consisting of a daily intake of
      2000 IU Vitamin D, 325 mg aspirin, 50 mg Cyclophosphamide and 180 or 30 mg Lansoprazole
      alternating weekly), followed by pembrolizumab administered intravenously at 200 mg in 21-day
      treatment cycles, combined with radiation (3x 8Gy in 48h-intervals). In addition, patients
      will take Curcumin, a food supplement on a daily basis.
    

Trial Arms

NameTypeDescriptionInterventions
experimental armExperimentalPembrolizumab, immune modulatory cocktail composed of Vitamin D, Lansoprazole Teva, Cyclophosphamide and Aspirine, radiation and Curcumin
  • Pembrolizumab
  • Vitamin D
  • Aspirin
  • Lansoprazole
  • Cyclophosphamide

Eligibility Criteria

        Inclusion Criteria:

          -  Have histologically confirmed endometrial carcinoma, cervical carcinoma or uterine
             sarcoma, refractory or persistent to chemotherapy or recurrent disease after at least
             one line of chemotherapy.

          -  Presence of an index lesion amenable to hypofractionated stereotactic radiotherapy

          -  At least one lesion outside the radiation field that can be followed by imaging for
             clinical response according to RECIST and irRC

          -  Be willing to provide tissue from a newly obtained core or excisional biopsy of a
             tumor lesion before and after radiotherapy if technically feasible.

          -  Have a performance status of 0 or 1 or 2 on the ECOG Performance Scale.

          -  Demonstrate adequate organ function

        Exclusion Criteria:

          -  Currently participating and receiving study therapy or has participated in a study of
             an investigational agent and received study therapy or used an investigational device
             within 4 weeks of the first dose of treatment.

          -  Prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2 agent

          -  Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other
             form of immunosuppressive therapy within 2 weeks prior to the first dose of trial
             treatment,

          -  Known history of active TB (Bacillus Tuberculosis), Human Immunodeficiency Virus
             (HIV), HTLV or syphilis,non-infectious pneumonitis, has active autoimmune disease.

          -  Has active central nervous system metastases and/or carcinomatous meningitis
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective response rate at week 26
Time Frame:week 26
Safety Issue:
Description:Efficacy (objective response rate) at week 26 according to immune related response criteria (irRC)

Secondary Outcome Measures

Measure:Incidence of treatment-emergent adverse events (Safety according to CTCAE4.0).
Time Frame:up to 30 days post end of study treatment
Safety Issue:
Description:The number of unmanageable dose limiting toxicities will be reported for the run-in period and the main trial. This analysis will be performed for both the Full Analysis Set (FAS; evaluable patiënts) and extended FAS (eFAS; all patients included in the trial).
Measure:Objective response rate
Time Frame:week 26
Safety Issue:
Description:Objective response rate at week 26 according to RECIST criteria
Measure:Best OR
Time Frame:week 26
Safety Issue:
Description:Best overall response
Measure:PFS
Time Frame:up to 156 weeks
Safety Issue:
Description:At weeks 26, 52, 75, 104, 130 and 156 the proportion of progression-free patients will be estimated with a 95% confidence interval.
Measure:Median PFS
Time Frame:up to 156 weeks
Safety Issue:
Description:At weeks 26, 52, 75, 104, 130 and 156 the median PFS will be calculated.
Measure:OS
Time Frame:up to 156 weeks
Safety Issue:
Description:At weeks 26, 52, 75, 104, 130 and 156 the proportion of patients surviving will be estimated with a 95% confidence interval.
Measure:Median OS
Time Frame:up to 156 weeks
Safety Issue:
Description:At weeks 26, 52, 75, 104, 130 and 156 the median survival will be calculated.
Measure:Quality of life assessment
Time Frame:Quality of life questionnaires will be completed by the patients at baseline, after 3 months of therapy, after 6 months of treatment (end of treatment) and finally 3 months after therapy.
Safety Issue:
Description:Quality of life as measured by FACT-Cx questionnaire for the cervical cancer group and by the FACT-G questionnaire for the endometrial carcinoma and uterine sarcoma group. Descriptive statistics of the total score at each visit and the difference with the baseline visit for all other visits will be reported.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University Hospital, Ghent

Trial Keywords

  • Immunotherapy
  • Radiotherapy
  • Immune-modulatory cocktail

Last Updated

May 14, 2018