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

NCT03192059 | Completed Phase 2 DMC

• 1 other identifier: 2016-001569-97
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 4

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.

Conditions

Cervical Cancer; Endometrial Cancer; Uterine Cancer

Keywords

Immunotherapy; Radiotherapy; Immune-modulatory cocktail

Outcome Measures

Primary Outcomes (1)

• Objective response rate at week 26

  Efficacy (objective response rate) at week 26 according to immune related response criteria (irRC)

  week 26

Secondary Outcomes (8)

• Incidence of treatment-emergent adverse events (Safety according to CTCAE4.0).

  up to 30 days post end of study treatment

• Objective response rate

  week 26

• Best OR

  week 26

• PFS

  up to 156 weeks

• Median PFS

  up to 156 weeks

Study Arms (1)

experimental arm

EXPERIMENTAL

Pembrolizumab, immune modulatory cocktail composed of Vitamin D, Lansoprazole Teva, Cyclophosphamide and Aspirine, radiation and Curcumin

Drug: Pembrolizumab; Radiation: Radiation; Drug: Vitamin D; Drug: Aspirin; Drug: Lansoprazole; Drug: Cyclophosphamide; Dietary Supplement: Curcumin

Interventions

Pembrolizumab DRUG

Efficacy of the combined treatment

experimental arm

Radiation RADIATION

Efficacy of the combined treatment

experimental arm

Vitamin D DRUG

Efficacy of the combined treatment

experimental arm

Aspirin DRUG

Efficacy of the combined treatment

experimental arm

Lansoprazole DRUG

Efficacy of the combined treatment

experimental arm

Cyclophosphamide DRUG

Efficacy of the combined treatment

experimental arm

Curcumin DIETARY_SUPPLEMENT

Efficacy of the combined treatment

experimental arm

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Ghent: lead
• Kom Op Tegen Kanker: collaborator
• Anticancer Fund, Belgium: collaborator

Study Sites (4)

University Hospital Antwerp

Antwerp, Belgium

Location

Institut Jules Bordet

Brussels, 1000, Belgium

Location

University Hospital Gent

Ghent, 9000, Belgium

Location

CMSE Namur

Namur, Belgium

Location

Related Publications (3)

• De Jaeghere EA, Hamerlinck H, Tuyaerts S, Lippens L, Van Nuffel AMT, Baiden-Amissah R, 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, Verhasselt B, Denys HG. Associations of the gut microbiome with outcomes in cervical and endometrial cancer patients treated with pembrolizumab: Insights from the phase II PRIMMO trial. Gynecol Oncol. 2024 Dec;191:275-286. doi: 10.1016/j.ygyno.2024.10.020. Epub 2024 Nov 7.

  PMID: 39515198 DERIVED

• 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.

  PMID: 35960332 DERIVED

• 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.

  PMID: 31138229 DERIVED

MeSH Terms

Conditions

Uterine Cervical Neoplasms; Endometrial Neoplasms; Uterine Neoplasms

Interventions

pembrolizumab; Radiation; Vitamin D; Aspirin; Lansoprazole; Cyclophosphamide; Curcumin

Condition Hierarchy (Ancestors)

Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Physical Phenomena; Secosteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Diarylheptanoids; Heptanes; Alkanes; Hydrocarbons, Acyclic; Catechols

Study Officials

• Hannelore Denys, MD, PhD

  University Hospital, Ghent

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 29, 2017
• First Posted: June 19, 2017
• Study Start: July 1, 2017
• Primary Completion: June 30, 2021
• Study Completion: June 30, 2021
• Last Updated: September 8, 2021

Record last verified: 2018-05

Data Sharing

• IPD Sharing: Will not share

Locations

BE (4)