A Phase 1/2 interventional study of Phase 1 : Regorafenib and Phase 1 : Avelumab in Colorectal Cancer Not MSI-H or MMR-deficient, GIST and Oesophageal or Gastric Carcinoma, sponsored by Institut Bergonié. Recruiting at 7 sites in France. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-03-03.
Sponsored by Institut Bergonié · Phase 1/2, Interventional, and Treatment
Assessment of the efficacy and safety of Regorafenib and Avelumab in patients with advanced or metastatic solid tumors (ten cohorts), once the Recommanded Phase II Dose (RP2D) has been determined (phase I trial).
Assessement of the efficacy and safety of a low-dose of regorafenib (80mg/day) with avelumab in patients with advanced or metastatic colorectal tumors.
This is a multicenter, prospective open-labeled phase Ib trial based on a dose escalation study design (3+3 traditional design) assessing three dose levels of Regorafenib given in combination with Avelumab (no dose escalation for Avelumab) in patients with advanced digestive solid tumors followed by independent phase II trials to evaluate the association of Regorafenib at the RP2D with Avelumab in 17cohorts of advanced or metastatic tumors :
In addition, to evaluate in a phase II trial, the association of a low-dose of regorafenib (80mg/day) with avelumab :
60 studies on the registry are indexed under Turcot syndrome; 29 are open to participants now.
This study's planned enrollment of 747 is above the median of 38 across 45 interventional studies indexed under Turcot syndrome.
Browse Turcot syndrome studies →Institut Bergonié is the lead sponsor of 119 studies on the registry; 16 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Histology:
Phase II trials : histologically confirmed
Adequate hematological, renal, metabolic and hepatic functions:
For patients with urothelial cancer (cohort J):
For HPV-associated cancer (cohort K), TMB-high solid tumors (cohort M) MSI-high solid tumors (cohort N), Non clear-cell renal carcinoma (cohort O):
o No previous line of PD(L)1 mAb containing regimen
For malignant pleural mesothelioma (Cohort P):
For triple-negative breast cancer patients (Cohort L)
For TMB-High cancer patients (Cohort M):
Exclusion Criteria:
Active disease that might deteriorate when receiving an immunostimulatory agent :
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
A score of how well the liver works in people with liver disease such as cirrhosis: class A is mild, B moderate and C severe.
The US National Cancer Institute’s scale of how severe an adverse event is — any unwanted medical event during a study, such as a symptom, an illness or an abnormal test result, whether or not a treatment caused it. Whether it did is judged separately.
“Side effects of earlier treatment resolved to grade 1 or less” means they have settled to mild or gone.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.
“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.
PD-1, PD-L1 and CTLA-4 are proteins that act as brakes on the immune system. Checkpoint inhibitors, such as pembrolizumab or nivolumab, block them so the immune system can attack a cancer.
PD-L1 can also be measured in a tumour sample. Some scores count stained tumour cells only (TPS); others also count certain immune cells (CPS). The study names the score and the minimum it uses.
Cancer that has spread to the leptomeninges, the thin layers covering the brain and spinal cord, and the fluid between them. It is not the same as brain metastases.
Criteria often treat it separately, and many studies leave it out even where treated brain metastases are allowed.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
A “mini-stroke”: temporary stroke-like symptoms caused by reduced blood flow to part of the brain, spinal cord or eye, without signs of a new stroke on a scan.
Stroke symptoms need emergency care at once, even if they go away.
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Stem cell (bone marrow) transplants. Allogeneic uses cells from a donor; autologous uses your own cells, collected earlier and given back.
Histologically or cytologically confirmed
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Relapsed and refractory
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Measurable disease
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
RECIST
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Life expectancy
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Absolute neutrophil count (ANC)
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Creatinine clearance (CrCl)
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
INR, PT and aPTT (clotting tests)
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Child-Pugh class
A score of how well the liver works in people with liver disease such as cirrhosis: class A is mild, B moderate and C severe.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CTCAE grade
The US National Cancer Institute’s scale of how severe an adverse event is — any unwanted medical event during a study, such as a symptom, an illness or an abnormal test result, whether or not a treatment caused it. Whether it did is judged separately.
“Side effects of earlier treatment resolved to grade 1 or less” means they have settled to mild or gone.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Line of therapy
A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.
“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
PD-1, PD-L1 and checkpoint inhibitors
PD-1, PD-L1 and CTLA-4 are proteins that act as brakes on the immune system. Checkpoint inhibitors, such as pembrolizumab or nivolumab, block them so the immune system can attack a cancer.
PD-L1 can also be measured in a tumour sample. Some scores count stained tumour cells only (TPS); others also count certain immune cells (CPS). The study names the score and the minimum it uses.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Leptomeningeal disease
Cancer that has spread to the leptomeninges, the thin layers covering the brain and spinal cord, and the fluid between them. It is not the same as brain metastases.
Criteria often treat it separately, and many studies leave it out even where treated brain metastases are allowed.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
TIA (transient ischaemic attack)
A “mini-stroke”: temporary stroke-like symptoms caused by reduced blood flow to part of the brain, spinal cord or eye, without signs of a new stroke on a scan.
Stroke symptoms need emergency care at once, even if they go away.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
NYHA class (heart failure)
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Allogeneic and autologous transplant
Stem cell (bone marrow) transplants. Allogeneic uses cells from a donor; autologous uses your own cells, collected earlier and given back.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Avelumab will be administrated by intravenous 1-hour infusion every 2 weeks starting at Cycle 1 Day 15. Regorafenib will be taken orally once daily for three weeks on/ one week off.
Drug: Phase 1 : Regorafenib · Drug: Phase 1 : Avelumab
Treatment by Avelumab + Regorafenib Avelumab will be administrated by intravenous 1-hour infusion every 2 weeks starting at Cycle 1 Day 15. Regorafenib will be taken orally once daily for three weeks on/ one week off.
Drug: Phase 2 : Regorafenib · Drug: Phase 2 : Avelumab
Treatment by Avelumab will be administrated by intravenous 1-hour infusion every 2 weeks starting at Cycle 1 Day 15. Regorafenib will be taken orally once daily for three weeks on/ one week off.
Drug: Phase 2 : Regorafenib · Drug: Phase 2 : Avelumab
Treatment by Avelumab will be administrated by intravenous 1-hour infusion every 2 weeks starting at Cycle 1 Day 15. Regorafenib will be taken orally once daily for three weeks on/ one week off.
Drug: Phase 2 : Regorafenib · Drug: Phase 2 : Avelumab
Treatment by Avelumab will be administrated by intravenous 1-hour infusion every 2 weeks starting at Cycle 1 Day 15. Regorafenib will be taken orally once daily for three weeks on/ one week off.
Drug: Phase 2 : Regorafenib · Drug: Phase 2 : Avelumab
Treatment by Avelumab will be administrated by intravenous 1-hour infusion every 2 weeks starting at Cycle 1 Day 15. Regorafenib will be taken orally once daily for three weeks on/ one week off.
Drug: Phase 2 : Regorafenib · Drug: Phase 2 : Avelumab
Treatment by Avelumab will be administrated by intravenous 1-hour infusion every 2 weeks starting at Cycle 1 Day 15. Regorafenib will be taken orally once daily for three weeks on/ one week off.
Drug: Phase 2 : Regorafenib · Drug: Phase 2 : Avelumab
Treatment by Avelumab will be administrated by intravenous 1-hour infusion every 2 weeks starting at Cycle 1 Day 15. Regorafenib will be taken orally once daily for three weeks on/ one week off.
Drug: Phase 2 : Regorafenib · Drug: Phase 2 : Avelumab
Treatment by Avelumab will be administrated by intravenous 1-hour infusion every 2 weeks starting at Cycle 1 Day 15. Regorafenib will be taken orally once daily for three weeks on/ one week off.
Drug: Phase 2 : Regorafenib · Drug: Phase 2 : Avelumab
Treatment by Avelumab will be administrated by intravenous 1-hour infusion every 2 weeks starting at Cycle 1 Day 15. Regorafenib will be taken orally once daily for three weeks on/ one week off.
Drug: Phase 2 : Regorafenib · Drug: Phase 2 : Avelumab
Treatment by Avelumab will be administrated by intravenous 1-hour infusion every 2 weeks starting at Cycle 1 Day 15. Regorafenib will be taken orally once daily for three weeks on/ one week off.
Drug: Phase 2 : Avelumab · Drug: Phase 2: low-dose Regorafenib
Treatment by Avelumab will be administrated by intravenous 1-hour infusion every 2 weeks starting at Cycle 1 Day 15. Regorafenib will be taken orally once daily for three weeks on/ one week off.
Drug: Phase 2 : Regorafenib · Drug: Phase 2 : Avelumab
Treatment by Avelumab will be administrated by intravenous 1-hour infusion every 2 weeks starting at Cycle 1 Day 15. Regorafenib will be taken orally once daily for three weeks on/ one week off.
Drug: Phase 2 : Regorafenib · Drug: Phase 2 : Avelumab
Treatment by Avelumab will be administrated by intravenous 1-hour infusion every 2 weeks starting at Cycle 1 Day 15. Regorafenib will be taken orally once daily for three weeks on/ one week off.
Drug: Phase 2 : Regorafenib · Drug: Phase 2 : Avelumab
Treatment by Avelumab will be administrated by intravenous 1-hour infusion every 2 weeks starting at Cycle 1 Day 15. Regorafenib will be taken orally once daily for three weeks on/ one week off.
Drug: Phase 2 : Regorafenib · Drug: Phase 2 : Avelumab
Treatment by Avelumab will be administrated by intravenous 1-hour infusion every 2 weeks starting at Cycle 1 Day 15. Regorafenib will be taken orally once daily for three weeks on/ one week off.
Drug: Phase 2 : Regorafenib · Drug: Phase 2 : Avelumab
Treatment by Avelumab will be administrated by intravenous 1-hour infusion every 2 weeks starting at Cycle 1 Day 15. Regorafenib will be taken orally once daily for three weeks on/ one week off.
Drug: Phase 2 : Regorafenib · Drug: Phase 2 : Avelumab
Treatment by Avelumab will be administrated by intravenous 1-hour infusion every 2 weeks starting at Cycle 1 Day 15. Regorafenib will be taken orally once daily for three weeks on/ one week off.
Drug: Phase 2 : Regorafenib · Drug: Phase 2 : Avelumab
A treatment cycle consists of 4 weeks. Treatment may continue until disease progression or study discontinuation (withdrawal of consent, intercurrent illness, unacceptable adverse event or any other changes unacceptable for further treatment, etc.). Patients will be allocated 3 dose levels of Regorafenib following a 3 + 3 design.
A treatment cycle consists of 4 weeks. Treatment may continue until disease progression or study discontinuation (withdrawal of consent, intercurrent illness, unacceptable adverse event or any other changes unacceptable for further treatment, etc.). Avelumab will be administered on cycle 1 Day 15 as a 1-hour intravenous (IV) infusion (10mg/kg), repeated every two weeks thereafter (ie. Day 1 and Day 15 of each subsequent cycle, as a 1-hour intravenous infusion).
Phase 2 : Regorafenib - All patients will be treated at the RP2D of regorafenib defined in the preliminary phase 1 trial with the same schedule as in the phase I.
Phase 2 : Avelumab - All patients will be treated with avelumab with the same schedule as in the phase 1 trial.
Phase 2 : Regorafenib - All patients will be treated at a fixed low-dose of regorafenib of 80 mg/day
PHASE I : Recommended phase II dose (RP2D)
Recommended phase II dose (RP2D) evaluated on the first cycle (Day 1 to Day 28) of regorafenib when prescribed in association with avelumab.
Time frame: During the first cycle (28 days)
PHASE II (7cohorts A, C, D, E, F and G) : Assessment of the antitumor activity of regorafenib
Assessment of the antitumor activity of regorafenib when prescribed in association with avelumab based on objective response under treatment defined as CR or PR following RECIST v1.1 criteria.
Time frame: Throughout the treatment period, an average of 6 months
Phase II (cohorts B, H, I, M, N, O and P): Assessment of the antitumor activity of regorafenib
Assessment of the antitumor activity of regorafenib when prescribed in association with avelumab based on 6-month progression-free rate, defined as CR, PR and SD following RECIST v1.1 criteria.
Time frame: 6 months
Phase II (cohort A'): Assessment of the antitumor activity of regorafenib
Assessment of the antitumor activity of regorafenib when prescribed in association with avelumab based on 4-months progression-free rate, defined as CR, PR and SD following RECIST v1.1 criteria.
Time frame: 4 months
PHASE I : Maximum Tolerated Dose (MTD)
Maximum Tolerated Dose (MTD) evaluated on the first cycle (Day 1 to Day 28) of regorafenib when prescribed in association with avelumab.
Time frame: During the first cycle (28 days)
PHASE I : Dose Limiting Toxicities (DLT)
Dose Limiting Toxicities (DLT) evaluated on the first cycle (Day 1 to Day 28) of regorafenib when prescribed in association with avelumab.
Time frame: During the first cycle (28 days)
PHASE I : Toxicity
Toxicity graded using the common toxicity criteria from the NCI v5.
Time frame: Throughout the treatment period, an average of 6 months
PHASE I : Assessment of the antitumor activity of regorafenib - Best overall response
Assessment of the antitumor activity of regorafenib when prescribed in association with avelumab in terms of best overall response as per RECIST v1.1.
Time frame: Throughout the treatment period, an average of 6 months
PHASE I :Assessment of the antitumor activity of regorafenib - objective response rate under treatment
Assessment of the antitumor activity of regorafenib when prescribed in association with avelumab in terms of objective response rate under treatment (ORR) defined as CR or PR as per RECIST v1.1.
Time frame: Throughout the treatment period, an average of 6 months
PHASE I :Assessment of the antitumor activity of regorafenib - objective response rate
Assessment of the antitumor activity of regorafenib when prescribed in association with avelumab in terms of objective response rate at 6-months (ORR) defined as CR or PR as per RECIST v1.1.
Time frame: Throughout the treatment period, an average of 6 months
PHASE I :Assessment of the antitumor activity of regorafenib - non-progression
Assessment of the antitumor activity of regorafenib when prescribed in association with avelumab in terms of 6-months non-progression defined as CR, PR or SD as per RECIST v1.1
Time frame: 6 months
PHASE I :Assessment of the antitumor activity of regorafenib - progression-free survival (PFS)
Assessment of the antitumor activity of regorafenib when prescribed in association with avelumab in terms of 1-year progression-free survival (PFS) as per RECIST v1.1.
Time frame: 1 year
PHASE I : Assessment of the antitumor activity of regorafenib - overall survival (OS)
Assessment of the antitumor activity of regorafenib when prescribed in association with avelumab in terms of 1-year overall survival (OS) as per RECIST v1.1.
Time frame: 1 year
PHASE I :Pharmacocinetics (PK) - Area Under Curve (AUC)
PK measurement expressed as Area Under Curve (AUC) for regorafenib.
Time frame: Day 15 of cycle 1 (Each cycle is 28 days)
PHASE I :Pharmacocinetics (PK) - Area Under Curve (AUC)
PK measurement expressed as Area Under Curve (AUC) for regorafenib.
Time frame: Day 1 of cycle 2 (Each cycle is 28 days)
PHASE I :Pharmacocinetics (PK) - Area Under Curve (AUC)
PK measurement expressed as Area Under Curve (AUC) for regorafenib.
Time frame: Day 15 of cycle 2 (Each cycle is 28 days)
PHASE I :Pharmacocinetics (PK) - half-life for regorafenib.
PK measurement expressed as half-life for regorafenib.
Time frame: Day 15 of cycle 1 (Each cycle is 28 days)
PHASE I :Pharmacocinetics (PK) - half-life for regorafenib.
PK measurement expressed as half-life for regorafenib.
Time frame: Day 1 of cycle 2 (Each cycle is 28 days)
PHASE I :Pharmacocinetics (PK) - half-life for regorafenib.
PK measurement expressed as half-life for regorafenib.
Time frame: Day 15 of cycle 2 (Each cycle is 28 days)
PHASE I :PK - concentration peak for regorafenib.
PK measurement expressed as concentration peak for regorafenib
Time frame: Day 15 of cycle 1 (Each cycle is 28 days)
PHASE I :PK - concentration peak for regorafenib.
PK measurement expressed as concentration peak for regorafenib
Time frame: Day 1 of cycle 2 (Each cycle is 28 days)
PHASE I :PK - concentration peak for regorafenib.
PK measurement expressed as concentration peak for regorafenib
Time frame: Day 15 of cycle 2 (Each cycle is 28 days)
Phase I: Predictive blood biomarkers analysis (cytokines levels) by ELISA.
levels of angiogenic and immunologic biomarkers in blood
Time frame: day 1 of cycles 1, 2, 4, 6 and at progression
Phase I: Predictive blood biomarkers analysis (lymphocytes) by flow cytmetry.
levels of angiogenic and immunologic biomarkers in blood
Time frame: day 1 of cycles 1, 2, 4, 6 and at progression
Phase I: Predictive tumor growth factor biomarkers analysis by immunohistochemistry.
levels of angiogenic and immunologic biomarkers in tissue
Time frame: day 1 of cycle 1 and day 1 of cycle 2
Phase I: Adverses events graded using the common toxicity criteria from the NCI v5 to determine the safety profile of regorafenib plus avelumab.
Toxicity graded using the common toxicity criteria from the NCI v5.
Time frame: throughouth the treatment period, an average of 6 months
PHASE II : Assessment of the antitumor activity of regorafenib - Best overall response
Assessment of the antitumor activity of regorafenib when prescribed in association with avelumab in terms of best overall response as per RECIST v1.1.
Time frame: Throughout the treatment period, an average of 6 months
PHASE II : Assessment of the antitumor activity of regorafenib - objective response rate
Assessment of the antitumor activity of regorafenib when prescribed in association with avelumab in terms of objective response rate at 6-months (ORR) defined as CR or PR as per RECIST v1.1.
Time frame: Throughout the treatment period, an average of 6 months
PHASE II :Assessment of the antitumor activity of regorafenib - non progression
Assessment of the antitumor activity of regorafenib when prescribed in association with avelumab in terms of 6-months non-progression defined as CR, PR or SD as per RECIST v1.1.
Time frame: 6 months
PHASE II : Assessment of the antitumor activity of regorafenib - Progression-Free Survival (PFS)
Assessment of the antitumor activity of regorafenib when prescribed in association with avelumab in terms of 1-year progression-free survival (PFS) as per RECIST v1.1.
Time frame: 1 year
PHASE II : Assessment of the antitumor activity of regorafenib - Overall Survival
Assessment of the antitumor activity of regorafenib when prescribed in association with avelumab in terms of 1-year overall survival (OS) as per RECIST v1.1.
Time frame: 1 year
Phase II: Predictive blood biomarkers analysis (cytokines levels) by ELISA.
levels of angiogenic and immunologic biomarkers in blood
Time frame: day 1 of cycles 1, 2, 4, 6 and at progression
Phase II: Predictive blood biomarkers analysis (lymphocytes) by flow cytometry.
levels of angiogenic and immunologic biomarkers in blood
Time frame: day 1 of cycles 1, 2, 4, 6 and at progression
Phase II: Predictive tumor growth factor biomarkers analysis by immunohistochemistry.
levels of angiogenic and immunologic biomarkers in tissue
Time frame: day 1 of cycle 1 and day 1 of cycle 2
Phase II: Adverses events graded using the common toxicity criteria from the NCI v5 to determine the safety profile of regorafenib plus avelumab
Toxicity graded using the common toxicity criteria from the NCI v5
Time frame: throughouth the treatment period, an average of 6 months
Predictive metabolomic analysis by liquid chromatography-mass spectrometry
Levels of metabolites in blood
Time frame: day 1 of cycles 1, 2, 4, 6 and at progression
Phase II (cohort B): assessment of the antitumor activity of regorafenib
Assessment of the antitumor activity of regorafenib when prescribed in association with avelumab based on CHOI criteria
Time frame: throughouth the treatment period, an average of 6 months
Started May 2018 (actual). Primary completion is estimated for Dec 2024, 79 months after the start.
How these figures are worked out, and which studies are left out of them.
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
Contact study teamGet an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Studies of the drugs tested here: Regorafenib · Avelumab