A phase I/II study of Regorafenib plus Avelumab in digestive tumors
- Conditions
- Adult patients with advanced or metastatic digestive solid tumorsMedDRA version: 20.0Level: PTClassification code 10061451Term: Colorectal cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: PTClassification code 10051066Term: Gastrointestinal stromal tumourSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: HLGTClassification code 10017991Term: Gastrointestinal neoplasms malignant and unspecifiedSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: PTClassification code 10073073Term: Hepatobiliary cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2016-005175-27-FR
- Lead Sponsor
- Institut Bergonié
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 212
1. Histology:
- Dose escalation part: histologically confirmed non MSI-H or MMR-deficient colorectal cancer, or GIST, or oesophageal or gastric carcinoma or hepatobiliary cancers,
- Expansion cohort : histologically confirmed non MSI-H or MMR-deficient colorectal cancer (cohort A), or GIST (cohort B), or oesophageal or gastric carcinoma (cohort C) or hepatobiliary cancers (cohort D),
As recommended by INCa, patients with GIST must have diagnosis histologically confirmed by central review, except if it has been already confirmed by the RRePS Network.
2. Advanced non resectable / metastatic disease,
3. Age = 18 years,
4. ECOG, Performance status = 1,
5. Measurable disease according to RECIST (outside any previously irradiated field). At least one site of disease must be uni-dimensionally = 10 mm,
6. Life expectancy > 3 months,
7. = 1 previous line (s) of systemic therapy
8. Adequate hematological, renal, metabolic and hepatic functions:
a. Hemoglobin = 9 g/dl (patients may have received prior red blood cell [RBC] transfusion, if clinically indicated); absolute neutrophil count (ANC) = 1.5 x 109/l and platelet count = 100 x 109/l, lymphocytes = 1000/mm3.
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 for AP exclusively and = 5 x ULN in case of liver metastasis for AST and ALT).
c. Total bilirubin = 1.5 x ULN.
d.Albumin = 25g/l.
e. Calculated creatinine clearance (CrCl) = 30 ml/min (according to Cockroft and Gault formula).
f. Creatine phosphokinase (CPK) = 2.5 x ULN
g. INR < 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
h. aPTT = 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants.
i. Lipase = 1.5 X ULN
j. Cohort specific criteria: Patients with hepatocellular carcinoma must have a correct hepatocellular function, id est Child-Pugh A.
9. 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,
10. At least three weeks since last chemotherapy, immunotherapy or any other pharmacological treatment and/or radiotherapy,
11. 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, version 4.0)),
12. Women of childbearing potential must have a negative serum pregnancy test within 72 hours prior to receiving the first dose of study medication.
13. Both women and men must agree to use an highly effective method of contraception throughout the treatment period and for eight weeks after discontinuation of treatment. Acceptable methods for contraception include intrauterine device (IUD), oral contraceptive, subdermal implant and double barrier. Subjects of childbearing potential are those who have not been surgically sterilized (e.g., vasectomy for males and hysterectomy for females) or have not been free from menses for = 1 year.
14. Voluntary signed and dated written informed consents prior to any specific study procedure,
15.
1. Previous treatment with Avelumab or Regorafenib,
2. 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 costimulation or checkpoint pathways),
3. Evidence of progressive or symptomatic central nervous system (CNS) or leptomeningeal metastases,
4. Men or women of childbearing potential who are not using an effective method of contraception as previously described; women who are pregnant or breast feeding,
5. Participation to a study involving a medical or therapeutic intervention in the last 30 days,
6. Previous enrolment in the present study,
7. Patient unable to follow and comply with the study procedures because of any geographical, familial, social or psychological reasons,
8. Known hypersensitivity to any involved study drug or of its formulation components,
9. 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
10. 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,
11. 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,
12. Has known active hepatitis B or hepatitis C,
13. Has a known history of Human Immunodeficiency Virus (HIV) (HIV1/2 antibodies) or known acquired immunodeficiency syndrome (AIDS)
14. Persistent proteinuria < 3.5 g/24 hours measured by urine protein-creatinine ratio from a random urine sample (= Grade 3, NCI-CTCCAE v 4.0),
15. Major surgical procedure or significant traumatic injury within 28 days before start of study medication,
16. Non-healing wound, non-healing ulcer, or non-healing bone fracture,
17. Patients with evidence or history of any bleeding diathesis, irrespective of severity,
18. Any hemorrhage or bleeding event = CTCAE Grade 3 within 4 weeks prior to the start of study medication,
19.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 the start of study medication (except for adequately treated catheter-related venous thrombosis occurring more than one month before the start of study medication),
20. Ongoing infection > Grade 2 as per NCI CTCAE v4.0,
21. Uncontrolled hypertension (Systolic blood pressure > 140 mmHg or diastolic pressure > 90 mmHg) despite optimal medical management,
22. Congestive heart failure = New York Heart Association (NHYA) class 2,
23. Unstable angina (angina symptoms at rest), new-onset ang
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