Chemoradiotherapy With or Without Pembrolizumab for the Treatment of High-risk, Locally Advanced Cervical Cancer
- Conditions
- High-risk locally advanced cervical cancerMedDRA version: 21.1Level: LLTClassification code 10008229Term: Cervical cancerSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-003152-37-IT
- Lead Sponsor
- MERCK SHARP & DOHME CORP. UNA SUSSIDIARIA DI MERCK & CO. INC.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Female
- Target Recruitment
- 980
1. Has high-risk LACC (a or b below):
a. FIGO 2014 Stage IB2-IIB (with node-positive disease) – must meet criteria below for positive pelvic lymph node OR para-aortic lymph node involvement
Pelvic lymph node involvement as assessed by one of the following criteria:
- Histopathologic, biopsy-proven pelvic node involvement, or
- 2 or more positive pelvic nodes by MRI or CT (>=1.5 cm shortest dimension), or
- 2 or more positive pelvic nodes by PET / CT with SUV >=2.5 Para-aortic lymph node involvement as assessed by one of the following criteria:
- Histopathologic, biopsy-proven para-aortic node involvement, or
- 1 or more positive para-aortic nodes by MRI or CT (>=1.5 cm shortest dimension), or
- 1 or more positive para-aortic nodes by PET / CT with SUV >=2.5
b. FIGO 2014 Stages III-IVA (either node-positive or node-negative disease)
2. Has histologically-confirmed squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the cervix.
3. Has not previously received any definitive surgical, radiation, or systemic therapy for cervical cancer and is immunotherapy-naïve.
4. Has an ECOG performance status of 0 or 1 within 7 days prior to the first dose of study intervention
5. Is female, at least 18 years of age at the time of signing the informed consent.
6. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
- Is not a WOCBP
OR
- Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis), during the intervention period and for at least 120 days after the last dose of
pembrolizumab or placebo and 180 days following the end of chemoradiotherapy. The investigator should evaluate the potential for contraceptive method failure (ie, noncompliance, recently initiated) in relationship to the first dose of study intervention.
- A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 24 hours before the first dose of study intervention
- If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive
- The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy
7. The participant (or legally acceptable representative if applicable) provides written informed consent for the study. The participant may also provide consent for future biomedical research. However, the participant may participate in the main study without participating in future biomedical research.
8. Has radiographically evaluable disease, either measurable or nonmeasurable per RECIST 1.1, as assessed by the local site investigator/radiology
9. Has provided a tissue sample from a core or excisional biopsy of a tumor lesion for confirmation of adequacy by the central vendor prior to randomization. Formalin-fixed, paraffin embedded tissue blocks are preferred to slides
10. Has adequate organ function. Specimens must be collected within 7 days prior to the start of study intervention
Are the trial subjects under 18? no
Number of subjects for
1. Has histological subtypes other than those allowed per inclusion criterion 2 (eg, sarcoma, small cell carcinoma with neuroendocrine differentiation, non-epithelial cancer).
2. Has FIGO 2014 Stage IVB disease.
3. Has undergone a previous hysterectomy defined as removal of the entire uterus or will have a hysterectomy as part of their initial cervical cancer therapy.
4. Has bilateral hydronephrosis, unless at least one side has been stented or resolved by positioning of nephrostomy
5. Has anatomy or tumor geometry or any other reason or contraindication that cannot be treated with intracavitary brachytherapy or a combination of intracavitary and interstitial brachytherapy
6. Has received a live vaccine within 30 days prior to the first dose of study intervention. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, BCG, and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
7. Has received treatment with systemic immunostimulatory agents such as bacterial or viral vaccines, colony stimulating factors, interferons, interleukins and vaccine combinations within 6 weeks or 5 half-lives of the drug, whichever is shorter, prior to Cycle 1, Day 1.
8. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PDL2 agent or with an agent directed to another stimulatory or coinhibitory T-cell recepto (eg, CTLA-4, OX-40, CD137).
9. Has received prior systemic anticancer therapy including investigational agents within 4 weeks prior to randomization.
10. 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 randomization
11. Has any contraindication to the use of cisplatin.
12. 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 the first dose of study medication.
13. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
14. Has severe hypersensitivity (=Grade 3) to pembrolizumab and/or any of its excipients.
15. Has an active autoimmune disease that has required systemic treatment in past 2 years (ie, 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) is not considered a form of systemic
treatment and is allowed.
16. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
17. Has an active infection requiring systemic therapy.
18. Has a known history of HIV infection.
19. Has a known history of Hepatitis B (defined as HBsAg reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection.
20. Has a known history of active tuberculosis (TB; Bacillus tuberculosis).
For remaining criteria refer to protocol
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method