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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 : Recruiting
First Posted : June 19, 2017
Last Update Posted : May 15, 2018
Sponsor:
Collaborators:
Kom Op Tegen Kanker
Anticancer Fund, Belgium
Information provided by (Responsible Party):
University Hospital, Ghent

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.


Condition or disease Intervention/treatment Phase
Cervical Cancer Endometrial Cancer Uterine Cancer Drug: Pembrolizumab Radiation: Radiation Drug: Vitamin D Drug: Aspirin Drug: Lansoprazole Drug: Cyclophosphamide Dietary Supplement: Curcumin Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 43 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : July 1, 2017
Estimated Primary Completion Date : June 2021
Estimated Study Completion Date : June 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Uterine Cancer

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




Primary Outcome Measures :
  1. Objective response rate at week 26 [ Time Frame: week 26 ]
    Efficacy (objective response rate) at week 26 according to immune related response criteria (irRC)


Secondary Outcome Measures :
  1. 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).

  2. Objective response rate [ Time Frame: week 26 ]
    Objective response rate at week 26 according to RECIST criteria

  3. Best OR [ Time Frame: week 26 ]
    Best overall response

  4. 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.

  5. Median PFS [ Time Frame: up to 156 weeks ]
    At weeks 26, 52, 75, 104, 130 and 156 the median PFS will be calculated.

  6. 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.

  7. Median OS [ Time Frame: up to 156 weeks ]
    At weeks 26, 52, 75, 104, 130 and 156 the median survival will be calculated.

  8. 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03192059


Contacts
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Contact: Hannelore Denys, MD, PhD +32 9 332 2692 hannelore.denys@ugent.be
Contact: Katrien Vandecasteele, MD, PhD +32 9 332 5974 katrien.vandecasteele@ugent.be

Locations
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Belgium
University Hospital Antwerp Recruiting
Antwerp, Belgium
Contact: Peter Van Dam         
Institut Jules Bordet Recruiting
Brussels, Belgium, 1000
Contact: Alex De Caluwé         
University Hospital Gent Recruiting
Gent, Belgium, 9000
Contact: Hannelore Denys         
CMSE Namur Recruiting
Namur, Belgium
Contact: Peter Vuylsteke         
Sponsors and Collaborators
University Hospital, Ghent
Kom Op Tegen Kanker
Anticancer Fund, Belgium
Investigators
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Principal Investigator: Hannelore Denys, MD, PhD University Hospital, Ghent

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: University Hospital, Ghent
ClinicalTrials.gov Identifier: NCT03192059     History of Changes
Other Study ID Numbers: 2016-001569-97
First Posted: June 19, 2017    Key Record Dates
Last Update Posted: May 15, 2018
Last Verified: May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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

Keywords provided by University Hospital, Ghent:
Immunotherapy
Radiotherapy
Immune-modulatory cocktail

Additional relevant MeSH terms:
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Uterine Cervical Neoplasms
Endometrial Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Uterine Cervical Diseases
Uterine Diseases
Genital Diseases, Female
Vitamins
Vitamin D
Cyclophosphamide
Curcumin
Pembrolizumab
Lansoprazole
Dexlansoprazole
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Bone Density Conservation Agents