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

Cervical Cancer Clinical Trial

— 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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03192059
• Other study ID #: 2016-001569-97
• Status: Completed
• Phase: Phase 2
• Start date: July 1, 2017
• Est. completion date: June 30, 2021

Study information

• Verified date: May 2018
• Source: University Hospital, Ghent
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 43
• Est. completion date: June 30, 2021
• Est. primary completion date: June 30, 2021
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cervical Cancer
• Endometrial Cancer
• Endometrial Neoplasms
• Uterine Cancer
• Uterine Neoplasms

Intervention

Drug:
• Pembrolizumab
Efficacy of the combined treatment

Radiation:
• Radiation
Efficacy of the combined treatment

Drug:
• Vitamin D
Efficacy of the combined treatment
• Aspirin
Efficacy of the combined treatment
• Lansoprazole
Efficacy of the combined treatment
• Cyclophosphamide
Efficacy of the combined treatment

Dietary Supplement:
• Curcumin
Efficacy of the combined treatment

Locations

Country	Name	City	State
Belgium	University Hospital Antwerp	Antwerp
Belgium	Institut Jules Bordet	Brussels
Belgium	University Hospital Gent	Gent
Belgium	CMSE Namur	Namur

Sponsors (3)

Lead Sponsor	Collaborator
University Hospital, Ghent	Anticancer Fund, Belgium, Kom Op Tegen Kanker

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective response rate at week 26	Efficacy (objective response rate) at week 26 according to immune related response criteria (irRC)	week 26
Secondary	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
Secondary	Objective response rate	Objective response rate at week 26 according to RECIST criteria	week 26
Secondary	Best OR	Best overall response	week 26
Secondary	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
Secondary	Median PFS	At weeks 26, 52, 75, 104, 130 and 156 the median PFS will be calculated.	up to 156 weeks
Secondary	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
Secondary	Median OS	At weeks 26, 52, 75, 104, 130 and 156 the median survival will be calculated.	up to 156 weeks
Secondary	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.