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

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)

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.

Study Overview

• Status: Completed
• Conditions: Cervical Cancer; Endometrial Cancer; Uterine Cancer
• Intervention / Treatment: Drug: Pembrolizumab; Radiation: Radiation; Drug: Vitamin D; Drug: Aspirin; Drug: Lansoprazole; Drug: Cyclophosphamide; Dietary supplement: Curcumin

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
• Enrollment (Actual): 43
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Antwerp, Belgium
    • University Hospital Antwerp
  • Brussels, Belgium, 1000
    • Institut Jules Bordet
  • Gent, Belgium, 9000
    • University Hospital Gent
  • Namur, Belgium
    • CMSE Namur

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: experimental arm; Pembrolizumab, immune modulatory cocktail composed of Vitamin D, Lansoprazole Teva, Cyclophosphamide and Aspirine, radiation and Curcumin	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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	up to 30 days post end of study treatment
Objective response rate	Objective response rate at week 26 according to RECIST criteria	week 26
Best OR	Best overall response	week 26
PFS	At weeks 26, 52, 75, 104, 130 and 156 the proportion of progression-free patients will be estimated with a 95% confidence interval.	up to 156 weeks
Median PFS	At weeks 26, 52, 75, 104, 130 and 156 the median PFS will be calculated.	up to 156 weeks
OS	At weeks 26, 52, 75, 104, 130 and 156 the proportion of patients surviving will be estimated with a 95% confidence interval.	up to 156 weeks
Median OS	At weeks 26, 52, 75, 104, 130 and 156 the median survival will be calculated.	up to 156 weeks
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.	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.

Collaborators and Investigators

• Sponsor: University Hospital, Ghent
• Collaborators: Kom Op Tegen Kanker; Anticancer Fund, Belgium
• Investigators: Principal Investigator: Hannelore Denys, MD, PhD, University Hospital, Ghent

Publications and helpful links

General 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. 2022 Aug 12. doi: 10.1007/s00262-022-03253-x. Online ahead of print.
• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 1, 2017
• Primary Completion (ACTUAL): June 30, 2021
• Study Completion (ACTUAL): June 30, 2021

Study Registration Dates

• First Submitted: May 29, 2017
• First Submitted That Met QC Criteria: June 15, 2017
• First Posted (ACTUAL): June 19, 2017

Study Record Updates

• Last Update Posted (ACTUAL): September 8, 2021
• Last Update Submitted That Met QC Criteria: September 6, 2021
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: Immunotherapy; Radiotherapy; Immune-modulatory cocktail
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Female; Uterine Diseases; Endometrial Neoplasms; Uterine Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Gastrointestinal Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Immunological; Micronutrients; Vitamins; Bone Density Conservation Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Aspirin; Cyclophosphamide; Vitamin D; Dexlansoprazole; Lansoprazole; Pembrolizumab; Curcumin
• Other Study ID Numbers: 2016-001569-97

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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