Clinical trial NCT03192059: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cervical Cancer
Endometrial Cancer
Uterine Cancer
Keywords: Immunotherapy
Radiotherapy
Immune-modulatory cocktail
Lead sponsor: University Hospital, Ghent
Sponsor class: OTHER
Collaborators: name: Kom Op Tegen Kanker
name: Anticancer Fund, Belgium
First posted: 2017-06-19
Enrollment: 43
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Objective response rate at week 26
timeFrame: week 26
Secondary outcomes:
measure: Incidence of treatment-emergent adverse events (Safety according to CTCAE4.0).
timeFrame: up to 30 days post end of study treatment
measure: Objective response rate
timeFrame: week 26
measure: Best OR
timeFrame: week 26
measure: PFS
timeFrame: up to 156 weeks
measure: Median PFS
timeFrame: up to 156 weeks
measure: OS
timeFrame: up to 156 weeks
measure: Median OS
timeFrame: up to 156 weeks
measure: Quality of life assessment
timeFrame: 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.
Other outcomes:
Locations:
city: Antwerp
country: Belgium
facility: University Hospital Antwerp
city: Brussels
country: Belgium
facility: Institut Jules Bordet
city: Gent
country: Belgium
facility: University Hospital Gent
city: Namur
country: Belgium
facility: CMSE Namur
Study officials:
affiliation: University Hospital, Ghent
name: Hannelore Denys, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.