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

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.

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.

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