A Phase III Study of Pembrolizumab in Subjects with Gastric Cancer
- Conditions
- Gastric or Gastroesophageal Junction AdenocarcinomaMedDRA version: 20.0Level: PTClassification code 10001150Term: Adenocarcinoma gastricSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2014-005241-45-PL
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 720
1. Be willing and able to provide written informed consent/assent for the trial. The subject may also provide consent for Future Biomedical Research. However, the subject may participate in the main trial without participating in Future Biomedical Research.
2. Be 18 years of age on day of signing informed consent (or acceptable age according to local regulations, whichever is older).
3. Have histologically or cytologically-confirmed diagnosis of gastric or GEJ adenocarcinoma.
4. Have metastatic disease or locally advanced, unresectable disease.
5. Have measurable disease as defined by RECIST 1.1 as determined by the investigator. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
6. Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
7. Has experienced documented objective radiographic or clinical disease progression during or after first-line therapy containing any platinum/fluoropyrimidine doublet.
i. To be considered as second-line, the subject needs to have the documentation of disease progression on first-line treatment. The disease progression can be confirmed by CT scan or by clinical evidence (such as cytology report from newly developed ascites and plural effusion).
ii. Any new or worsening malignant effusion (documented by ultrasound) may be confirmed by pathologic criteria (histology and/or cytology) if appropriate.
iii. A subject experiencing clinical disease progression during or within 6 months following the last dose of adjuvant therapy will be eligible for enrollment provided they received a platinum/fluoropyrimidine doublet as required.
iv. To be eligible, the subject is required to have received at least one dose of platinum and fluoropyrimidine therapy.
8. Be willing to provide tissue for PD-L1 biomarker analysis and, based on the adequacy
of the tissue sample quality for assessment of PD-L1 status, received permission for enrollment from the Core Lab. Repeat samples may be required if adequate tissue is not provided. Newly-obtained biopsy specimens are preferred to archived samples and formalin-fixed, paraffin-embedded (FFPE) block specimens are preferred to slides.
As of 20 March 2016, subjects must be PD-L1 positive to be enrolled.
9. Subjects with HER-2/neu negative tumors are eligible. For subjects with HER2/neu positive tumors or have an unknown tumor status, need to match the following:
i. If HER2/neu positive, subject must have documentation of disease progression on treatment containing trastuzumab.
ii. Subjects with unknown status must have their HER2/neu status determined locally.
10. Female subjects 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.
Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.
11. Demonstrate adequate organ function
12. Female subjects of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number
1. Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigation device within 4 weeks of the first dose of treatment.
2. Has squamous cell or undifferentiated gastric cancer.
3. Has active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
4. 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. The use of physiologic doses of corticosteroids may be approved after consultation with the Sponsor.
5. Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., = Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
6. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., = Grade 1 or at baseline) from adverse events due to a previously administered agent. Note: Subjects with = Grade 2 neuropathy or = Grade 2 alopecia are an exception to this criterion and may qualify for the study.
a. If subject 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 known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
9. Has history of (non-infectious) pneumonitis that required steroids or current penumonitis.
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 subject’s participation for the full duration of the trial, or is not in the best interest of the subject 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 or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of trial treatment.
14. Has received prior immunotherapy including anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or if the subject has previously participa
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