A Study of Pembrolizumab And Platinum With Radiotherapy in Cervix Cancer

Launched by ROYAL MARSDEN NHS FOUNDATION TRUST · May 5, 2017

Keywords

ClinConnect Summary

The study is designed to determine the safest dosage of pembrolizumab to be given in combination with chemoradiotherapy and brachytherapy for patients with locally advanced cervix cancer. The study will be run at the Royal Marsden Hospital only and is open label so both patient and doctor will know what treatment patients are receiving. Patients will receive pembrolizumab in combination with chemoradiotherapy and brachytherapy. Patients will be tested against 2 dose escalation levels (Dose Level 1/2). An initial dose of 100mg of pembrolizumab will be implemented. If dose limiting toxicity i...

Gender

FEMALE

Eligibility criteria

• Inclusion Criteria:
• • 1. Histologically confirmed FIGO stage 1B - IVA carcinoma of the cervix planned to receive radical radiotherapy with concomitant cisplatin and brachytherapy. Pelvic lymph node but not para-aortic lymph node involvement is permitted.
• • 2. ECOG PS 0-1
• • 3. Be willing and able to provide written informed consent for the trial.
• • 4. Be \>= 18 years of age on day of signing informed consent.
• • 5. Have measurable disease based on RECIST 1.1.
• • 6. Demonstrate adequate organ function (as defined in Table 1 of the trial protocol) all screening tests should be performed within 10 days prior to confirmation of study eligibility.
• • 7. Female patient of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to confirmation of study eligibility. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• • 8. Female patients of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Patients of childbearing potential are those who have not been surgically sterilized or have not been free from menses for \> 1 year.
• • 9. For Concomitant cisplatin GFR\>50ml/min, no contraindications to cisplatin (pre-existing tinnitus or neuropathy)
• Exclusion Criteria:
• • 1. Requires para-aortic radiotherapy
• • 2. Has had previous pelvic radiotherapy
• • 3. Has had bowel resection, history of inflammatory bowel disease or autoimmune condition
• • 4. Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment.
• • 5. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• • 6. Has had a prior monoclonal antibody, chemotherapy, targeted small molecule therapy, or radiation therapy. Note: If patient received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• • 7. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
• • 8. Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Patients with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Patients that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Patients with hypothyroidism stable on hormone replacement or Sjorgen's syndrome will not be excluded from the study.
• • 9. Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
• • 10. Has an active infection requiring systemic therapy.
• • 11. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating investigator.
• • 12. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• • 13. Is pregnant or breastfeeding, or expecting to conceive children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
• • 14. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137.
• • 15. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
• • 16. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA \[qualitative\] is detected).
• • 17. Has received a live vaccine within 30 days prior to the first dose of trial treatment.