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

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

Tracking Information

• First Submitted Date: May 29, 2017
• First Posted Date: June 19, 2017
• Last Update Posted Date: September 8, 2021
• Actual Study Start Date: July 1, 2017
• Actual Primary Completion Date: June 30, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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 (submitted: June 15, 2017)

Efficacy [ Time Frame: week 26 ]

Efficacy (objective response rate) at week 26 according to immune related response criteria (irRC)

Current Secondary Outcome Measures (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: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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)

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: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Cervical Cancer
• Endometrial Cancer
• Uterine Cancer

Intervention

• 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

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 *

• 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.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 15, 2017): 43
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: June 30, 2021
• Actual Primary Completion Date: June 30, 2021 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium

Administrative Information

• NCT Number: NCT03192059
• Other Study ID Numbers: 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

• Plan to Share IPD: No

• Current Responsible Party: University Hospital, Ghent
• Original Responsible Party: Same as current
• Current Study Sponsor: University Hospital, Ghent
• Original Study Sponsor: Same as current

Collaborators

• Kom Op Tegen Kanker
• Anticancer Fund, Belgium

Investigators

• Principal Investigator: Hannelore Denys, MD, PhD; University Hospital, Ghent

• PRS Account: University Hospital, Ghent
• Verification Date: May 2018