← Back to Search

Checkpoint Inhibitor

Regorafenib + Immunotherapy for Colorectal Cancer

Phase 1

Waitlist Available

Led By Marwan G Fakih

Research Sponsored by City of Hope Medical Center

Eligibility Criteria Checklist

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

Must have

Microsatellite status should be performed per local standard of practice (e.g., immunohistochemistry [IHC] and/or polymerase chain reaction [PCR], or next-generation sequencing). Only participants with pMMR/MSS metastatic colorectal cancer (mCRC) are eligible

Histological or cytological confirmed advanced, metastatic, or progressive mismatch repair protein proficient (pMMR)/microsatellite stable (MSS) adenocarcinoma of colon or rectum

Must not have

Participants with microsatellite instability high (MSI-H) colorectal cancer

Prior therapy with regorafenib, anti-PD-1, PD-L1, or CTLA-4 inhibitors

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years post treatment

Awards & highlights

No Placebo-Only Group

Summary

This trial is studying regorafenib in combination with ipilimumab and nivolumab to see if it can help to treat patients with colorectal cancer that has spread and is resistant to chemotherapy.

Who is the study for?

This trial is for adults with metastatic colorectal cancer that's stable at the microsatellite level and hasn't responded to chemotherapy. Participants should have a good performance status, acceptable organ function tests, measurable disease, and no prior treatment with the study drugs. They must not be pregnant or breastfeeding and agree to use contraception.

What is being tested?

The trial is testing the combination of Regorafenib (a growth inhibitor), Ipilimumab, and Nivolumab (both immune system boosters) in patients whose colorectal cancer has spread and resisted chemotherapy. It aims to find the safest dose while observing how well these drugs work together against cancer.

What are the potential side effects?

Possible side effects include fatigue, high blood pressure, diarrhea, skin reactions, liver enzyme changes, immune-related conditions like inflammation in organs or glands (thyroiditis), potential infections due to lowered immunity, and infusion-related reactions.

Eligibility Criteria

Inclusion Criteria

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

Select...

My colorectal cancer is not microsatellite unstable.

Select...

My colon or rectum cancer is advanced, spreading, and not responsive to certain DNA repair errors.

Select...

I am fully active or restricted in physically strenuous activity but can do light work.

Select...

My cancer's RAS and BRAF gene status is known.

Select...

I can swallow and absorb pills.

Select...

I can provide a recent sample of my tumor for the study.

Select...

I agree to use birth control during the study and for some months after.

Exclusion Criteria

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

Select...

My colorectal cancer is MSI-H.

Select...

I have previously been treated with regorafenib or immune checkpoint inhibitors.

Select...

I have severe diarrhea or a major digestive disorder like Crohn's.

Select...

I have not had a heart attack or unstable chest pain in the last 6 months.

Select...

I haven't had cancer treatment within the last 14 days or 5 half-lives of the drug.

Select...

I don't have major side effects from previous treatments, except for anemia, hair loss, or skin changes.

Select...

I have a history of bleeding disorders, regardless of severity.

Select...

I have not had severe bleeding in the last 28 days.

Select...

I have an immune system disorder or am on high-dose steroids or other drugs that weaken my immune system.

Select...

I am currently receiving treatment for a serious infection.

Select...

I haven't had any blood clots or strokes in the last 3 months.

Select...

I do not have irregular heartbeats that are uncontrolled.

Select...

I have tested positive for hepatitis B or C.

Select...

I have been diagnosed with HIV.

Select...

My blood pressure is often over 150/90 mmHg, even with treatment.

Select...

I have not had major surgery or significant injury in the last 28 days.

Select...

My heart condition limits my physical activity.

Select...

I have a history of lung scarring or fibrosis.

Select...

I have had pneumonitis treated with steroids or have it now.

Select...

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

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years post treatment

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years post treatment

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years post treatment for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Recommended dose level of the combination

Secondary study objectives

Duration of response

Objective response rate (ORR)

Overall survival

+1 more

Other study objectives

Immune response

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

1Treatment groups

Experimental Treatment

Group I: Treatment (regorafenib, nivolumab, ipilimumab)Experimental Treatment3 Interventions

Patients receive regorafenib PO QD on days 1-21, nivolumab IV over 30 minutes Q2W, and ipilimumab IV over 30 minutes Q6W. Cycles repeat every 28 day for up to 2 years in the absence of disease progression or unacceptable toxicity.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Ipilimumab

2015

Completed Phase 3

~3070

Nivolumab

2015

Completed Phase 3

~4010