A Phase II Study of Pembrolizumab in Subjects with Gastric Cancer
- Conditions
- Gastric CancerTherapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2014-003574-16-EE
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 253
For potential subjects in Cohort 1 (3L+ cohort):
1.Have received, and progressed on, at least two prior chemotherapy regimens. For the purposes of this study, perioperative, neoadjuvant, adjuvant chemotherapy regimens will not count as a prior regimen, unless the subject progressed while receiving adjuvant therapy or within 6 months of receiving adjuvant treatment. The date of progression and how progression was determined must be known with documentation available confirming progression on or after treatment. Previous treatment regimens must have included a fluoropyrimidine and platinum doublet (as part of either a line of therapy or adjuvant treatment.
2.Be HER-2/neu negative, or, if HER2/neu positive, must have previously received treatment with trastuzumab (Note: If HER2/neu status was previously determined, that result is acceptable but documentation of status must be available; subjects with unknown status will have their HER2/neu status determined locally. Documentation of previous treatment with trastuzumab must also be provided.)
For potential subjects in Cohorts 2 or 3 (1L cohorts):
3.Is HER2/neu negative
4.Have not received prior systemic anti-cancer therapy for their metastatic or advanced gastric or gastroesophageal junction adenocarcinoma. For the purposes of this study, perioperative, neoadjuvant, adjuvant chemotherapy regimens will not count as a prior regimen, unless disease progression has occurred during or within 6 months of adjuvant chemotherapy.
For all potential subjects:
5.Be willing and able to provide written informed consent 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.
6.Be =18 years of age on day of signing informed consent.
7.Have histologically or cytologically-confirmed recurrent or metastatic gastric or gastroesophageal junction adenocarcinoma that is considered incurable by local therapies.
8.Be willing to provide newly-obtained or archived tissue for PD-L1 biomarker analysis
and, based on the adequacy of the tissue sample quality for assessment of PD -L1 status,
have received notice of eligibility prior to non-random allocation. Newly-obtained tissue
will be from the stomach and/or gastroesophageal junction (endoscopic tumor biopsy) or a metastatic location IF obtained as part of normal clinical practice. Repeat samples may
be required if adequate tissue is not provided.
9.Be PD-L1 positive, if the subject is being allocated to a cohort which, at the time of enrollment, is only enrolling PD-L1 positive subjects.
10.Have measurable disease based on RECIST 1.1 as determined by central imaging vendor. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
11.Have a performance status of 0 or 1 on the ECOG Performance Scale within 3 days prior to the first dose of study therapy.
12. Life expectancy of at least 3 months.
13.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 or 180 days after the last dose of study medication (Reference Section 5.7.2). Duration of use will be determined when the subject is assigned to treatment. Subjects of childbearing potential are those who have not been surgically sterilized
1. Experienced weight loss >10% over 2 months prior to first dose of study therapy.
2. Has clinical evidence of ascites by physical exam.
3. 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.
4. 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.
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. The use of physiologic doses of corticosteroids (prednisone 10 mg or
equivalent) may be approved after consultation with the Sponsor.
6. 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.
7. 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.
8. 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 that has undergone potentially curative therapy or in situ cervical cancer.
9. 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.
10. Has known history of, or any evidence of active, non-infectious pneumonitis.
11. Has an active infection requiring systemic therapy.
12. Has a history or current evidence of any condition (e.g. known deficiency of the enzyme dihydropyrimidine dehydrogenase [DPD]), 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 (e.g. any contraindication to the use of cisplatin, 5-FU, or capecitabine for subjects in Japan, in the opinion of the treating investigator.
13. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
14. 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 or 180 days after the last dose of trial treatment. Duration of use will be determined when the subject is assigned to treatment.
15. Has received prior therapy with an anti-PD-1, anti-PD-L1, or ant
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