Cervical Cancer, Endometrial Cancer, Uterine Cancer
Conditions
Keywords
Immunotherapy, Radiotherapy, Immune-modulatory cocktail
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.
Interventions
DRUGCyclophosphamide
Efficacy of the combined treatment
DIETARY_SUPPLEMENTCurcumin
Efficacy of the combined treatment
DRUGAspirin
Efficacy of the combined treatment
DRUGLansoprazole
Efficacy of the combined treatment
DRUGPembrolizumab
Efficacy of the combined treatment
RADIATIONRadiation
Efficacy of the combined treatment
DRUGVitamin D
Efficacy of the combined treatment
Sponsors
Kom Op Tegen Kanker
Anticancer Fund, Belgium
University Hospital, Ghent
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate at week 26 | week 26 | Efficacy (objective response rate) at week 26 according to immune related response criteria (irRC) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate | week 26 | Objective response rate at week 26 according to RECIST criteria |
| Best OR | week 26 | Best overall response |
| PFS | 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. |
| Incidence of treatment-emergent adverse events (Safety according to CTCAE4.0). | 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). |
| OS | 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. |
| Median OS | up to 156 weeks | At weeks 26, 52, 75, 104, 130 and 156 the median survival will be calculated. |
| Quality of life assessment | 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. |
| Median PFS | up to 156 weeks | At weeks 26, 52, 75, 104, 130 and 156 the median PFS will be calculated. |
Countries
Belgium
Outcome results
None listed