BridgeMD
CAIRE : COMBINING EPIGENETIC AND IMMUNE THERAPY TO BEAT CANCER
EU CTIS ID: 2023-509501-72-00
What this study is testing
To investigate the antitumor activity of durvalumab when prescribed in association with tazemetostat independently for 4 populations of participants : o [Cohort A] Participants with pancreatic cancer, o [Cohort B] Participants with colorectal cancer not MSI-H or MMR-deficient, o [Cohort C] Participants with metastatic solid tumors with positive interferon gamma signature and/or tertiary lymphoid structure positive, o [Cohort D] Participants with soft-tissue sarcoma. Antitumor activity will be assessed in terms of: o [Cohorts A, B] Disease control rate within 24 weeks of treatment onset. o [Cohort C] Objective response rate within 24 weeks of treatment onset. o [Cohort D] 6-month progression-free rate.
- Therapeutic exploratory (Phase II)
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- Histology: histologically confirmed pancreatic cancer (cohort A), non MSI-H or MMR-deficient colorectal cancer (cohort B), solid tumor with positive IFNG gene expression signature and/or tertiary lymphoid structure positive (cohort C), soft-tissue sarcomas (Cohort D). Other solid tumor types may be included through future amendment of the current version of the study protocol. Note: for cohort C, IFNG gene expression and/or presence of tertiary lymphoid structure will be centrally assessed. Cohort D, diagnosis must be confirmed and reviewed by the RRePS Network.as recommended by the French NCI (Inca).
- No prior or concurrent malignant disease diagnosed or treated in the last 2 years except for adequately treated in situ carcinoma of the cervix, basal or squamous skin cell carcinoma, or in situ transitional bladder cell carcinoma.
- At least three weeks since last chemotherapy, immunotherapy or any other pharmacological treatment and/or radiotherapy.
- Recovery to grade ≤ 1 from any adverse event (AE) derived from previous treatment, excluding alopecia of any grade and non-painful peripheral neuropathy grade ≤ 2 (according to the National Cancer Institute Common Terminology Criteria for Adverse Event - NCI-CTCAE, v5).
- Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to inclusion. Note that pregnancy test must be repeated within 72 hours prior to receiving the first dose of study medication.
- Both women and men must agree to use a highly effective method of contraception throughout the treatment period and for at least nine months after discontinuation of treatment for women and six months after discontinuation of treatment for men. Acceptable methods for contraception are described in protocol.
You likely can't join if
- Previous treatment with durvalumab or tazemetostat.
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 14 days prior to the first dose of trial treatment.
- History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia, or evidence of active pneumonitis on screening chest CT scan or interstitial lung disease with ongoing signs and symptoms at inclusion. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
- Has known active tuberculosis, hepatitis B or hepatitis C.
- Has a known history of Human Immunodeficiency Virus (HIV) (HIV1/2 antibodies) or known acquired immunodeficiency syndrome (AIDS).
- Persistent proteinuria > 3.5 g/24 hours measured by urine protein-creatinine ratio from a random urine sample (≥ Grade 3, NCI-CTCAE v5).
See the full eligibility criteria
Who can join
- Histology: histologically confirmed pancreatic cancer (cohort A), non MSI-H or MMR-deficient colorectal cancer (cohort B), solid tumor with positive IFNG gene expression signature and/or tertiary lymphoid structure positive (cohort C), soft-tissue sarcomas (Cohort D). Other solid tumor types may be included through future amendment of the current version of the study protocol. Note: for cohort C, IFNG gene expression and/or presence of tertiary lymphoid structure will be centrally assessed. Cohort D, diagnosis must be confirmed and reviewed by the RRePS Network.as recommended by the French NCI (Inca).
- No prior or concurrent malignant disease diagnosed or treated in the last 2 years except for adequately treated in situ carcinoma of the cervix, basal or squamous skin cell carcinoma, or in situ transitional bladder cell carcinoma.
- At least three weeks since last chemotherapy, immunotherapy or any other pharmacological treatment and/or radiotherapy.
- Recovery to grade ≤ 1 from any adverse event (AE) derived from previous treatment, excluding alopecia of any grade and non-painful peripheral neuropathy grade ≤ 2 (according to the National Cancer Institute Common Terminology Criteria for Adverse Event - NCI-CTCAE, v5).
- Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to inclusion. Note that pregnancy test must be repeated within 72 hours prior to receiving the first dose of study medication.
- Both women and men must agree to use a highly effective method of contraception throughout the treatment period and for at least nine months after discontinuation of treatment for women and six months after discontinuation of treatment for men. Acceptable methods for contraception are described in protocol.
- Voluntary signed and dated written informed consents prior to any specific study procedure.
- Participants with a social security in compliance with the French law.
- For cohort C, availability of archived FFPE (Formalin-Fixed Paraffin-Embedded) tumor tissue sample for IFNG gene expression assessment and/or determination of the presence of tertiary lymphoid structure.
- Advanced disease defined as metastatic or unresectable locally advanced disease.
- Age ≥ 18 years.
- ECOG, Performance status ≤ 1.
- Measurable disease according to RECIST (lesion in previously irradiated field can be considered as measurable if progressive at inclusion according to RECIST v1.1). At least one site of disease must be uni-dimensionally ≥ 10 mm.
- Life expectancy > 3 months.
- Participants must have advanced disease and must not be a candidate for other approved therapeutic regimen known to provide significant clinical benefit based on investigator judgment.
- Adequate hematological, renal, metabolic and hepatic functions: a. Hemoglobin ≥ 9 g/dl (participants may have received prior red blood cell [RBC] transfusion, if clinically indicated); absolute neutrophil count (ANC) ≥ 1.5 G/l and platelet count ≥ 100 G/l, b. Alkaline phosphatase (AP), alanine aminotransferase (ALT) and aspartate aminotransferase (ASP) ≤ 2.5 x upper limit of normality (ULN) (≤ 5 in case of extensive skeletal involvement and/or liver metastasis for AP exclusively and ≤ 5 x ULN in case of liver metastasis for AST and ALT). c. Total serum bilirubin ≤ 1.5 x ULN d. Albumin ≥ 25 g/l e. Calculated creatinine clearance (CrCl) ≥ 30 ml/min (according to Cockroft and Gault formula) f. Deleted at MSA 1. g. Lipase ≤ 1.5 X ULN.
What rules you out
- Previous treatment with durvalumab or tazemetostat.
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 14 days prior to the first dose of trial treatment.
- History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia, or evidence of active pneumonitis on screening chest CT scan or interstitial lung disease with ongoing signs and symptoms at inclusion. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
- Has known active tuberculosis, hepatitis B or hepatitis C.
- Has a known history of Human Immunodeficiency Virus (HIV) (HIV1/2 antibodies) or known acquired immunodeficiency syndrome (AIDS).
- Persistent proteinuria > 3.5 g/24 hours measured by urine protein-creatinine ratio from a random urine sample (≥ Grade 3, NCI-CTCAE v5).
- Major surgical procedure or significant traumatic injury within 28 days before inclusion.
- Non-healing wound, non-healing ulcer, or non-healing bone fracture.
- Participants with evidence or history of any bleeding diathesis, irrespective of severity.
- Any hemorrhage or bleeding event ≥ CTCAE Grade 3 within 4 weeks prior to inclusion.
- Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 6 months before inclusion (except for adequately treated catheter-related venous thrombosis occurring more than one month before inclusion).
- Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
- Ongoing infection > Grade 2 as per NCI CTCAE v5.
- Uncontrolled hypertension (Systolic blood pressure > 140 mmHg or diastolic pressure > 90 mmHg) despite optimal medical management.
- Congestive heart failure ≥ New York Heart Association (NHYA) class 2.
- Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months).
- Myocardial infarction less than 6 months before inclusion.
- Uncontrolled cardiac arrhythmias.
- Pregnant or breast-feeding participants.
- Individuals deprived of liberty or placed under legal guardianship.
- Prior organ transplantation, including allogeneic stem cell transplantation.
- Known alcohol or drug abuse.
- EGFR/ALK/ROS mutated NSCLC.
- Participants with any condition that impairs their ability to swallow and retain tablets.
- Other severe acute or chronic medical conditions including immune inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study
- Participant with anti-Vitamine K oral anticoagulation therapy.
- Suspected or known intraabdominal fistula.
- Screening QTc interval > 480 msec is excluded (corrected by Fredericia or Bazett formula). In the event that a single QTc is > 480 msec, the subject may enroll if the average QTc for the 3 ECGs is < 480 msec.
- Has received a live vaccine within 30 days prior to the first dose of trial treatment. Note: the killed virus vaccines used for seasonal influenza vaccines for injection are allowed; however intranasal influenza vaccines (e.g., FluMistR) are live attenuated vaccines and are not allowed.
- Participants with a prior history of myeloid malignancies, including myelodysplastic syndromes (MDS), acute myeloid leukemia (AML) or myeloproliferative neoplasm (MPN).
- Participants with a prior history of T-cell lymphoblastic lymphoma (T-LBL) / T-cell lymphoblastic leukemia (T-ALL).
- Evidence of progressive or symptomatic central nervous system (CNS) or leptomeningeal metastases.
- Participation to a study involving a medical or therapeutic intervention in the last 30 days.
- Previous enrolment in the present study.
- Participant unable to follow and comply with the study procedures because of any geographical, familial, social or psychological reasons.
- Known hypersensitivity to any involved study drug or of its formulation components.
- Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent: a.Subjects with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible b. Subjects requiring hormone replacement with corticosteroids are eligible if the steroids are administered only for the purpose of hormonal replacement and at doses ≤ 10 mg or 10 mg equivalent prednisone per day c. Administration of steroids through a route known to result in a minimal systemic exposure (topical, intranasal, intro-ocular, or inhalation) are acceptable.
The study team makes the final eligibility decision.
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18-64 years, 65+ years. The study team makes the final eligibility decision.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.