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

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ClinicalTrials.gov Identifier: NCT03192059
Recruitment Status : Completed
First Posted : June 19, 2017
Last Update Posted : September 8, 2021
Sponsor:
Collaborators:
Kom Op Tegen Kanker
Anticancer Fund, Belgium
Information provided by (Responsible Party):
University Hospital, Ghent

Tracking Information
First Submitted Date  ICMJE May 29, 2017
First Posted Date  ICMJE June 19, 2017
Last Update Posted Date September 8, 2021
Actual Study Start Date  ICMJE July 1, 2017
Actual Primary Completion Date June 30, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 19, 2017)
Objective response rate at week 26 [ Time Frame: week 26 ]
Efficacy (objective response rate) at week 26 according to immune related response criteria (irRC)
Original Primary Outcome Measures  ICMJE
 (submitted: June 15, 2017)
Efficacy [ Time Frame: week 26 ]
Efficacy (objective response rate) at week 26 according to immune related response criteria (irRC)
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 15, 2017)
  • Incidence of treatment-emergent adverse events (Safety according to CTCAE4.0). [ Time Frame: up to 30 days post end of study treatment ]
    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).
  • Objective response rate [ Time Frame: week 26 ]
    Objective response rate at week 26 according to RECIST criteria
  • Best OR [ Time Frame: week 26 ]
    Best overall response
  • PFS [ Time Frame: up to 156 weeks ]
    At weeks 26, 52, 75, 104, 130 and 156 the proportion of progression-free patients will be estimated with a 95% confidence interval.
  • Median PFS [ Time Frame: up to 156 weeks ]
    At weeks 26, 52, 75, 104, 130 and 156 the median PFS will be calculated.
  • OS [ Time Frame: up to 156 weeks ]
    At weeks 26, 52, 75, 104, 130 and 156 the proportion of patients surviving will be estimated with a 95% confidence interval.
  • Median OS [ Time Frame: up to 156 weeks ]
    At weeks 26, 52, 75, 104, 130 and 156 the median survival will be calculated.
  • 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. ]
    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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Pembrolizumab, Radiation and Immune Modulatory Cocktail in Cervical/Uterine Cancer
Official Title  ICMJE 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)
Brief Summary

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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Cervical Cancer
  • Endometrial Cancer
  • Uterine Cancer
Intervention  ICMJE
  • Drug: Pembrolizumab
    Efficacy of the combined treatment
  • Radiation: Radiation
    Efficacy of the combined treatment
  • Drug: Vitamin D
    Efficacy of the combined treatment
  • Drug: Aspirin
    Efficacy of the combined treatment
  • Drug: Lansoprazole
    Efficacy of the combined treatment
  • Drug: Cyclophosphamide
    Efficacy of the combined treatment
  • Dietary Supplement: Curcumin
    Efficacy of the combined treatment
Study Arms  ICMJE Experimental: experimental arm
Pembrolizumab, immune modulatory cocktail composed of Vitamin D, Lansoprazole Teva, Cyclophosphamide and Aspirine, radiation and Curcumin
Interventions:
  • Drug: Pembrolizumab
  • Radiation: Radiation
  • Drug: Vitamin D
  • Drug: Aspirin
  • Drug: Lansoprazole
  • Drug: Cyclophosphamide
  • Dietary Supplement: Curcumin
Publications * Tuyaerts S, Van Nuffel AMT, Naert E, Van Dam PA, Vuylsteke P, De Caluwé A, Aspeslagh S, Dirix P, Lippens L, De Jaeghere E, Amant F, Vandecasteele K, Denys H. PRIMMO study protocol: a phase II study combining PD-1 blockade, radiation and immunomodulation to tackle cervical and uterine cancer. BMC Cancer. 2019 May 28;19(1):506. doi: 10.1186/s12885-019-5676-3.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 15, 2017)
43
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE June 30, 2021
Actual Primary Completion Date June 30, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03192059
Other Study ID Numbers  ICMJE 2016-001569-97
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party University Hospital, Ghent
Study Sponsor  ICMJE University Hospital, Ghent
Collaborators  ICMJE
  • Kom Op Tegen Kanker
  • Anticancer Fund, Belgium
Investigators  ICMJE
Principal Investigator: Hannelore Denys, MD, PhD University Hospital, Ghent
PRS Account University Hospital, Ghent
Verification Date May 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP