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Tyrosine Kinase Inhibitor

Sunitinib + Regorafenib for GIST

Phase 2

Recruiting

Led By Jonathan Trent, MD, PhD

Research Sponsored by University of Miami

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patients who have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 2

Patients who have histologically confirmed metastatic or unresectable GIST. Unresectable GIST must be confirmed to be unresectable by an experienced surgeon

Must not have

Patients who have poor organ function as defined by one or more of the following laboratory parameters: Persistent proteinuria of NCI-CTCAE version 4.03 Grade 3 or higher, Alanine aminotransferase and aspartate aminotransferase (AST) > 3 × upper limit of normal (ULN) if no hepatic metastases are present; > 5 × ULN if hepatic metastases are present, Total bilirubin >1.5 × ULN; and in presence of Gilbert's syndrome, total bilirubin > 3 × ULN or direct bilirubin > 1.5 × ULN, Estimated (Cockcroft-Gault formula) or measured creatinine clearance < 40 mL/min, Platelet count < 90 × 10^9/L and absolute neutrophil count (ANC) < 1.0 × 10^9/L, Hemoglobin < 9 g/dL. Transfusion and erythropoietin may be used to reach at least 9 g/dL, but must have been administered at least 2 weeks before screening, Patients who have received neutrophil growth factor support within 14 days of screening, Patients who require therapy with a concomitant medication that is a strong inhibitor or strong inducer of CYP3A4, Patients who have had a major surgical procedure (minor surgical procedures such as central venous catheter placement, tumor needle biopsy, and feeding tube placement are not considered major surgical procedures) within 14 days of screening. Patient has significant traumatic injury within 28 days before screening, Patients who have a history of another primary malignancy that has been diagnosed or required therapy within 2 years before screening. (The following are exempt from the 2-year limit: completely resected basal cell and squamous cell skin cancer, curatively treated localized prostate cancer, and completely resected carcinoma in situ of any site), Patients who have a history of a seizure disorder requiring anti-seizure medication, Patients who have metastases to the brain, Patients who are unwilling or unable to comply with scheduled visits, drug administration plan, laboratory tests, or other study procedures and study restrictions, Patients who have a QT interval corrected using Fridericia's formula (QTcF) of > 450 msec, Women who are unwilling, if not postmenopausal or surgically sterile, to abstain from sexual intercourse or employ highly effective contraception from the time of randomization and for at least 30 days after the last dose of study drug. Men who are unwilling, if not surgically sterile, to abstain from sexual intercourse or employ highly effective contraception from the time of randomization and for at least 90 days after the last dose of study drug. Refer to Appendix G for acceptable methods of contraception, Women who are pregnant, as documented by a serum beta human chorionic gonadotropin (β-hCG) pregnancy test consistent with pregnancy, obtained within 7 days before the treatment assignment. Females with β-hCG values that are within the range for pregnancy but are not pregnant (false positives) may be enrolled with written consent of the investigator, after pregnancy has been ruled out. Females of non-childbearing potential (postmenopausal for more than 1 year; bilateral tubal ligation; bilateral oophorectomy; hysterectomy) do not require a serum β-hCG test, Women who are breastfeeding, Patients who have prior or ongoing clinically significant illness, medical condition, surgical history, physical finding, or laboratory abnormality that, in the Investigator's opinion, could affect the safety of the patient; alter the absorption, distribution, metabolism, or excretion of the study drug; or impair the assessment of study results, Patients with impaired decision-making capacity

Patients who have a non-healing wound, ulcer, or bone fracture

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 3 years

Awards & highlights

No Placebo-Only Group

Summary

This trial will test if changes to the KIT gene can help predict how well a patient will respond to a standard treatment.

Who is the study for?

Adults with advanced or inoperable Gastrointestinal Stromal Tumors (GIST) who have previously been treated with imatinib but didn't respond well or couldn't tolerate it. They must be able to perform daily activities with minimal assistance (ECOG PS 0-2) and have specific mutations in the KIT gene, which will be checked through a blood test or biopsy.

What is being tested?

The trial is testing whether changes in certain parts of the DNA of the KIT gene can predict how well patients respond to Sunitinib and Regorafenib, which are standard treatments for GIST. The study aims to guide therapy choices based on individual genetic profiles.

What are the potential side effects?

Sunitinib and Regorafenib may cause side effects like fatigue, high blood pressure, bleeding problems, skin reactions, digestive issues such as diarrhea and liver function changes. Heart problems are also possible but less common.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am able to care for myself and up to being unable to work but can still move around.

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My GIST cannot be removed by surgery as confirmed by a surgeon.

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I am 18 years old or older.

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My cancer has a specific mutation in the KIT gene, found through a blood test or biopsy.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have a wound, ulcer, or bone fracture that is not healing.

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I do not have serious heart problems or uncontrolled high blood pressure.

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I have a risk of brain bleeding or had a brain bleed in the last year.

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I have been treated with sunitinib or regorafenib before.

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I have been treated with more than 2 different TKI medications.

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My cancer is not caused by a KIT gene mutation.

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I have not had severe bleeding in the last 4 weeks.

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I haven't had a stroke, mini-stroke, or blood clots in my lungs or legs in the past 6 months.

Select...

I haven't had cancer treatment or major organ radiation in the last 2 weeks.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 3 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 3 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 3 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Number of Participants Achieving Overall Response

Secondary study objectives

Incidence of Treatment-Related Toxicity and Adverse Events

Number of Participants Achieving Clinical Benefit

Overall Survival (OS)

+1 more

Side effects data

From 2019 Phase 1 & 2 trial • 495 Patients • NCT02024607

82%

Diarrhoea

76%

Nausea

71%

Fatigue

57%

Vomiting

53%

Abdominal pain

30%

Neuropathy peripheral

27%

Dyspnoea

25%

Anaemia

23%

Neutrophil count decreased

23%

Constipation

22%

Weight decreased

21%

Hypokalaemia

20%

Oedema peripheral

18%

Dehydration

17%

Cough

17%

Neutropenia

17%

Pyrexia

17%

Peripheral sensory neuropathy

16%

Thrombocytopenia

15%

Platelet count decreased

15%

Back pain

13%

Mucosal inflammation

13%

Temperature intolerance

13%

Dysgeusia

13%

Chromaturia

12%

White blood cell count decreased

12%

Urinary tract infection

11%

Dizziness

11%

Depression

10%

Hyponatraemia

10%

Stomatitis

10%

Ascites

10%

Dysphagia

10%

Anxiety

Headache

Abdominal distension

Insomnia

Arthralgia

Asthenia

Pain in extremity

Alopecia

Urine ketone body present

Blood alkaline phosphatase increased

Pulmonary embolism

Lymphopenia

Leukopenia

Blood bilirubin increased

Dyspepsia

Sepsis

Palmar-plantar erythrodysaesthesia syndrome

Hypertension

Urine leukocyte esterase positive

Abdominal pain upper

Gastrooesophageal reflux disease

Proteinuria

Rash

Flatulence

Chills

Dry mouth

Myalgia

Epistaxis

Muscle spasms

Pneumonia

pelvic fracture

Haematemesis

Disease progression

Pleural effusion

Confusional state

Mental status changes

malignant neoplasm progression

Large intestine perforation

Oesophagitis

Lung abscess

embolism

pancreatic carcinoma

fall

Death

Haemorrhage intranial

Atrial fibrillation

Colitis

Enterocutaneous fistula

Gastrointestinal haemorrhage

Upper gastrointestinal haemorrhage

Chest pain

somnolence

syncope

Febrile neutropenia

Acute kidney injury

Acute respiratory failure

Hypoxia

Pneumonia aspiration

Clostridium difficile colitis

Influenza

Perirectal abscess

Salmonella sepsis

Septic shock

hip fracture

deep vein thrombosis

haematoma

pelvic venous thrombosis

Cholangitis

Ischaemic cerebral infarction

Hyperglycaemia

subdural haematoma

100%

80%

60%

40%

20%

Study treatment Arm

Napabucasin Plus FOLFOX6

Napabucasin Plus FOLFOX6 Plus Bevacizumab

Napabucasin Plus FOLFIRI Plus Bevacizumab

Napabucasin Plus Regorafenib

Napabucasin Plus FOLFIRI

Napabucasin Plus Irinotecan

Napabucasin Plus CAPOX

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: Group B: KIT Exon 17 receiving RegorafenibExperimental Treatment2 Interventions

Participants with KIT mutation on exon 17 will receive Regorafenib. Participants showing disease progression after first-assigned Regorafenib therapy have the option to receive Sunitinib therapy. Total allotted time for treatment is up to 12 months.

Group II: Group A: KIT Exon 13 receiving SunitinibExperimental Treatment2 Interventions

Participants with KIT mutation on exon 13 will receive Sunitinib. Participants showing disease progression after first-assigned Sunitinib therapy have the option to receive Regorafenib therapy. Total allotted time for treatment is up to 12 months.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Regorafenib

2014

Completed Phase 2

~1600

Sunitinib

2014

Completed Phase 3

~4380