Back to resultsStudy of Pembrolizumab, Radiation and Immune Modulatory Cocktail in Cervical/Uterine Cancer (PRIMMO)
Primary Purpose
Cervical Cancer, Endometrial Cancer, Uterine Cancer
Status
Completed
Phase
Phase 2
Locations
Belgium
Study Type
Interventional
Intervention
Pembrolizumab
Radiation
Vitamin D
Aspirin
Lansoprazole
Cyclophosphamide
Curcumin
Sponsored by
About this trial
This is an interventional treatment trial for Cervical Cancer focused on measuring Immunotherapy, Radiotherapy, Immune-modulatory cocktail
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
Sites / Locations
- University Hospital Antwerp
- Institut Jules Bordet
- University Hospital Gent
- CMSE Namur
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
experimental arm
Arm Description
Pembrolizumab, immune modulatory cocktail composed of Vitamin D, Lansoprazole Teva, Cyclophosphamide and Aspirine, radiation and Curcumin
Outcomes
Primary Outcome Measures
Objective response rate at week 26
Efficacy (objective response rate) at week 26 according to immune related response criteria (irRC)
Secondary Outcome Measures
Incidence of treatment-emergent adverse events (Safety according to CTCAE4.0).
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
Objective response rate at week 26 according to RECIST criteria
Best OR
Best overall response
PFS
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
At weeks 26, 52, 75, 104, 130 and 156 the median PFS will be calculated.
OS
At weeks 26, 52, 75, 104, 130 and 156 the proportion of patients surviving will be estimated with a 95% confidence interval.
Median OS
At weeks 26, 52, 75, 104, 130 and 156 the median survival will be calculated.
Quality of life assessment
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.
Full Information
NCT ID
NCT03192059
First Posted
May 29, 2017
Last Updated
September 6, 2021
Sponsor
University Hospital, Ghent
Collaborators
Kom Op Tegen Kanker, Anticancer Fund, Belgium
1. Study Identification
Unique Protocol Identification Number
NCT03192059
Brief Title
Study of Pembrolizumab, Radiation and Immune Modulatory Cocktail in Cervical/Uterine Cancer
Acronym
PRIMMO
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)
Study Type
Interventional
2. Study Status
Record Verification Date
May 2018
Overall Recruitment Status
Completed
Study Start Date
July 1, 2017 (Actual)
Primary Completion Date
June 30, 2021 (Actual)
Study Completion Date
June 30, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Ghent
Collaborators
Kom Op Tegen Kanker, Anticancer Fund, Belgium
4. Oversight
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
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cervical Cancer, Endometrial Cancer, Uterine Cancer
Keywords
Immunotherapy, Radiotherapy, Immune-modulatory cocktail
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
43 (Actual)
8. Arms, Groups, and Interventions
Arm Title
experimental arm
Arm Type
Experimental
Arm Description
Pembrolizumab, immune modulatory cocktail composed of Vitamin D, Lansoprazole Teva, Cyclophosphamide and Aspirine, radiation and Curcumin
Intervention Type
Drug
Intervention Name(s)
Pembrolizumab
Intervention Description
Efficacy of the combined treatment
Intervention Type
Radiation
Intervention Name(s)
Radiation
Intervention Description
Efficacy of the combined treatment
Intervention Type
Drug
Intervention Name(s)
Vitamin D
Intervention Description
Efficacy of the combined treatment
Intervention Type
Drug
Intervention Name(s)
Aspirin
Intervention Description
Efficacy of the combined treatment
Intervention Type
Drug
Intervention Name(s)
Lansoprazole
Intervention Description
Efficacy of the combined treatment
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Intervention Description
Efficacy of the combined treatment
Intervention Type
Dietary Supplement
Intervention Name(s)
Curcumin
Intervention Description
Efficacy of the combined treatment
Primary Outcome Measure Information:
Title
Objective response rate at week 26
Description
Efficacy (objective response rate) at week 26 according to immune related response criteria (irRC)
Time Frame
week 26
Secondary Outcome Measure Information:
Title
Incidence of treatment-emergent adverse events (Safety according to CTCAE4.0).
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).
Time Frame
up to 30 days post end of study treatment
Title
Objective response rate
Description
Objective response rate at week 26 according to RECIST criteria
Time Frame
week 26
Title
Best OR
Description
Best overall response
Time Frame
week 26
Title
PFS
Description
At weeks 26, 52, 75, 104, 130 and 156 the proportion of progression-free patients will be estimated with a 95% confidence interval.
Time Frame
up to 156 weeks
Title
Median PFS
Description
At weeks 26, 52, 75, 104, 130 and 156 the median PFS will be calculated.
Time Frame
up to 156 weeks
Title
OS
Description
At weeks 26, 52, 75, 104, 130 and 156 the proportion of patients surviving will be estimated with a 95% confidence interval.
Time Frame
up to 156 weeks
Title
Median OS
Description
At weeks 26, 52, 75, 104, 130 and 156 the median survival will be calculated.
Time Frame
up to 156 weeks
Title
Quality of life assessment
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.
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.
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hannelore Denys, MD, PhD
Organizational Affiliation
University Hospital, Ghent
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospital Antwerp
City
Antwerp
Country
Belgium
Facility Name
Institut Jules Bordet
City
Brussels
ZIP/Postal Code
1000
Country
Belgium
Facility Name
University Hospital Gent
City
Gent
ZIP/Postal Code
9000
Country
Belgium
Facility Name
CMSE Namur
City
Namur
Country
Belgium
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
35960332
Citation
De Jaeghere EA, Tuyaerts S, Van Nuffel AMT, Belmans A, Bogaerts K, Baiden-Amissah R, Lippens L, Vuylsteke P, Henry S, Trinh XB, van Dam PA, Aspeslagh S, De Caluwe A, Naert E, Lambrechts D, Hendrix A, De Wever O, Van de Vijver KK, Amant F, Vandecasteele K, Denys HG. Pembrolizumab, radiotherapy, and an immunomodulatory five-drug cocktail in pretreated patients with persistent, recurrent, or metastatic cervical or endometrial carcinoma: Results of the phase II PRIMMO study. Cancer Immunol Immunother. 2023 Feb;72(2):475-491. doi: 10.1007/s00262-022-03253-x. Epub 2022 Aug 12.
Results Reference
derived
PubMed Identifier
31138229
Citation
Tuyaerts S, Van Nuffel AMT, Naert E, Van Dam PA, Vuylsteke P, De Caluwe 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.
Results Reference
derived
Learn more about this trial
Study of Pembrolizumab, Radiation and Immune Modulatory Cocktail in Cervical/Uterine Cancer
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