Clinical Trials /

Frontline Immunotherapy Combined With Radiation and Chemotherapy in High Risk Endometrial Cancer

NCT03932409

Description:

The purpose of this single arm, open label study is to evaluate the feasibility of pembrolizumab combined with radiation administered to the upper part of the vagina (vaginal cuff brachytherapy) followed by three cycles of pembrolizumab and chemotherapy in patients with endometrial cancer.

Related Conditions:
  • Endometrial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Frontline Immunotherapy Combined With Radiation and Chemotherapy in High Risk Endometrial Cancer
  • Official Title: A Phase Ib Trial of Vaginal Cuff Brachytherapy + Pembrolizumab (MK3475) Followed by 3 Cycles of Dose Dense Paclitaxel/q 21 Day Carboplatin + Pembrolizumab (MK3475) in High Intermediate Risk Endometrial Cancer

Clinical Trial IDs

  • ORG STUDY ID: OUSCC-FIERCE
  • NCT ID: NCT03932409

Conditions

  • Endometrial Cancer

Interventions

DrugSynonymsArms
PembrolizumabMK3475Pembrolizumab + Radiation Therapy

Purpose

The purpose of this single arm, open label study is to evaluate the feasibility of pembrolizumab combined with radiation administered to the upper part of the vagina (vaginal cuff brachytherapy) followed by three cycles of pembrolizumab and chemotherapy in patients with endometrial cancer.

Detailed Description

      Before the patient begins the study:

      Endometrial cancer is commonly treated with surgery. The patient must have already had
      surgery including hysterectomy (removal of the uterus) prior to being considered eligible for
      this study. The surgery may also include removal of the ovaries, and removal of pelvic and
      para-aortic lymph nodes. Following the surgery, the doctor will identify if the patient has
      factors related to the cancer which places the patient at a greater risk for the cancer
      returning.

      Prior to participating in this study there are exams, tests or procedures to find out if the
      patient can be treated in the study. Most are part of regular cancer care. Tumor tissue will
      need to be collected for study tests to see if the patient is eligible for to take part on
      the study.

      TREATMENT If the patient is eligible, pembrolizumab will be given 7 days before radiation
      therapy. After radiation therapy, three cycles of pembrolizumab and chemotherapy will be
      given.

      Study participation will be up to two years.
    

Trial Arms

NameTypeDescriptionInterventions
Pembrolizumab + Radiation TherapyExperimentalPembrolizumab given 7 days prior to radiation therapy (e.g., vaginal cuff brachytherapy)
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          1. All patients must have undergone hysterectomy. Bilateral salpingooophorectomy is
             strongly encouraged but not mandatory.

          2. Pelvic and para-aortic lymphadenectomy are optional, but strongly encouraged.

          3. If either a bilateral salpingo-oophorectomy or nodal dissection was not performed,
             post-operative pre-treatment CT/MRI is required and must not demonstrate evidence
             suggestive of metastatic disease (adnexa, nodes, intraperitoneal disease).
             Post-operative, pre-treatment CT/MRI must be performed if a pelvic and para-aortic
             nodal dissection was not performed.

          4. Tissue from an archival sample or newly obtained core or excisional biopsy of a tumor
             lesion within 10 weeks confirming diagnosis.

          5. All patients will be staged according to the FIGO 2009 staging system and with
             endometrial carcinoma (endometrioid types) confined to the corpus uteri or with
             endocervical glandular involvement fitting one of the following high-intermediate risk
             factor categories:

               -  age ≥18 years with 3 risk factors

               -  Risk factors: Grade 2 or 3 tumor, (+) lymphovascular space invasion, outer ½
                  myometrial invasion. Patients with these risk criteria may be enrolled with
                  either positive or negative cytology.

          6. Patients with Stage II endometrial carcinoma (any histology) with cervical stromal
             invasion (occult or gross involvement), with or without high-intermediate risk
             factors.

          7. Patients with serous or clear cell histology (with or without other high-intermediate
             risk factors) are eligible provided the disease is Stage I or II (with or without
             cervical stromal invasion or endocervical glandular involvement). Eligibility for
             clear cell and serous histology is not based on presence of lymphovascular space
             invasion or depth of invasion.

          8. Patients must have ECOG performance status 0 or 1.

          9. The participant (or legally acceptable representative if applicable) provides written
             informed consent for the trial and authorization permitting release of personal health
             information.

         10. Neuropathy (sensory and motor) ≤ Grade 1.

         11. Have adequate organ function as defined per Protocol. Specimens must be collected
             within 10 days prior to the start of study treatment.

        Exclusion Criteria:

          1. Patients with recurrent disease.

          2. Greater than 12 weeks elapsed from surgery to enrollment

          3. Patients have prior pelvic or abdominal radiation therapy

          4. Known hypersensitivity to any component of study treatments that resulted in drug
             discontinuation

          5. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with
             an agent directed to another stimulatory or co-inhibitory T-cell receptor

          6. Has received prior systemic anti-cancer therapy including investigational agents
             within 4 weeks [could consider shorter interval for kinase inhibitors or other short
             half-life drugs] prior to allocation.

          7. Has received prior radiotherapy within 2 weeks of start of study treatment.
             Participants must have recovered from all radiation-related toxicities, not require
             corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted
             for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.

          8. Has received a live vaccine within 30 days prior to the first dose of study drug.

          9. Is currently participating in or has participated in a study of an investigational
             agent or has used an investigational device within 4 weeks prior to the first dose of
             study treatment.

         10. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
             (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of
             immunosuppressive therapy within 7 days prior to the first dose of study drug.

         11. Has a known additional malignancy that is progressing or has required active treatment
             within the past 3 years. Note: Participants with basal cell carcinoma of the skin,
             squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma,
             cervical cancer in situ) that have undergone potentially curative therapy are not
             excluded.

         12. Has known active CNS metastases and/or carcinomatous meningitis.

         13. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.

         14. Has active autoimmune disease that has required systemic treatment in the past 2 years
             (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive
             drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid
             replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
             form of systemic treatment.

         15. Has a history of (non-infectious) pneumonitis that required steroids or has current
             pneumonitis.

         16. Has an active infection requiring systemic therapy. This excludes grade 2 urinary
             track infections or grade 1-2 skin infections.

         17. Has a known history of Human Immunodeficiency Virus (HIV).

         18. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg]
             reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is
             detected) infection.

         19. Has a known history of active TB (Bacillus Tuberculosis).

         20. Has a history or current evidence of any condition, therapy, or laboratory abnormality
             that might confound the results of the study, interfere with the subject's
             participation for the full duration of the study, or is not in the best interest of
             the subject to participate, in the opinion of the treating investigator.

         21. Has known psychiatric or substance abuse disorders that would interfere with
             cooperation with the requirements of the trial.

         22. Is pregnant or breastfeeding
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Proportion of patients completing three cycles
Time Frame:36 months
Safety Issue:
Description:defined as completion of 3 cycles of pembrolizumab combined with dose dense paclitaxel and carboplatin chemotherapy

Secondary Outcome Measures

Measure:progression free survival
Time Frame:up to 3 years
Safety Issue:
Description:time from study entry to the first tumor progression
Measure:progression free survival
Time Frame:6 months
Safety Issue:
Description:progression free survival rate at 6 months
Measure:Overall survival
Time Frame:up to 3 years
Safety Issue:
Description:time from study entry to death
Measure:Frequency of adverse events
Time Frame:up to 3 years
Safety Issue:
Description:frequency and severity of adverse events as assessed by the CTCAE v5

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:University of Oklahoma

Trial Keywords

  • pembrolizumab
  • radiation therapy

Last Updated