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Alkylating agents

Genotype-Directed Chemotherapy for Colorectal Cancer

Phase 2

Waitlist Available

Led By Hanna Sannoff, MD

Research Sponsored by UNC Lineberger Comprehensive Cancer Center

Eligibility Criteria Checklist

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

Must have

Metastatic disease not amenable to surgical resection with curative intent

Age ≥ 18 years

Must not have

Prior history of hypertensive encephalopathy

History of hemoptysis (≥ 1/2 teaspoon of bright red blood per episode) within 1 month prior to Day 1 of FOLFIRI + bevacizumab initiation

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 8 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new way to give colon cancer patients a standard combination chemotherapy treatment, which includes the anti-cancer drugs 5-Fluorouracil (5FU), leucovorin and irinotecan (known as FOLFIRI), plus the anti-angiogenesis drug bevacizumab (Avastin). The study is designed to test the FOLFIRI regimen based on certain characteristics of a person's genetic makeup or "genes".

Who is the study for?

Adults with measurable metastatic colorectal cancer who haven't had chemotherapy for it yet. They must be in fairly good health, willing to have their UGT1A1 gene tested, and able to use effective birth control. People can't join if they have certain heart conditions, uncontrolled high blood pressure, severe proteinuria, recent major surgeries or injuries, a history of significant bleeding disorders or stroke within the past 6 months.

What is being tested?

The trial is testing different doses of irinotecan (180 mg/m2, 260 mg/m2, or 310 mg/m2) combined with standard chemo drugs (5FU and leucovorin) plus bevacizumab for colon cancer treatment. The dose depends on the patient's genotype which affects how well they process the drug. This could make treatment more effective and safer.

What are the potential side effects?

Possible side effects include diarrhea from irinotecan; mouth sores, low blood counts from 5FU; nerve damage from leucovorin; and hypertension or increased risk of bleeding from bevacizumab. Side effects vary based on individual reactions to these medications.

Eligibility Criteria

Inclusion Criteria

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

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My cancer has spread and cannot be removed by surgery to cure it.

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I am 18 years old or older.

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I am able to get out of my bed or chair and move around.

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My cancer is confirmed to be adenocarcinoma of the colon or rectum.

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I haven't had chemotherapy for cancer that has spread.

Exclusion Criteria

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

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I have had hypertensive encephalopathy in the past.

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I have coughed up a noticeable amount of blood recently.

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I haven't had any stomach or intestine tears in the last 6 months.

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I do not have a bleeding disorder or significant blood clotting issues.

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I haven't had a stroke or mini-stroke in the last 6 months.

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I haven't had major surgery or serious injuries in the last 28 days and don't expect to need major surgery during the study.

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I haven't had major blood vessel problems like aneurysms or clots in the last 6 months.

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I am not taking any other cancer treatments or experimental drugs while on this study therapy.

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I have a heart condition.

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

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

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I have a known DPD deficiency.

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My heart condition is at least moderate in severity.

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My UGT1A1 genotype does not match *1/*1, *1/*28, or *28/*28.

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I do not have any serious health issues that would stop me from following the treatment plan.

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I have been treated with irinotecan and/or bevacizumab before.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 8 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~8 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and 8 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

Progression Free Survival

Secondary study objectives

Number of Participants with adverse events

Overall Response

Overall Survival

Side effects data

From 2020 Phase 2 & 3 trial • 483 Patients • NCT03098030

66%

Anaemia

51%

Neutropenia

28%

Asthenia

26%

Decreased appetite

26%

Neutrophil count decreased

25%

Nausea

25%

Thrombocytopenia

20%

Platelet count decreased

18%

Fatigue

16%

White blood cell count decreased

15%

Diarrhoea

15%

Pyrexia

15%

Constipation

15%

Dyspnoea

14%

Leukopenia

11%

Alopecia

10%

Hyperglycaemia

10%

Abdominal pain

10%

Cough

10%

Pneumonia

Weight decreased

Alanine aminotransferase increased

Aspartate aminotransferase increased

Stomatitis

Vomiting

Back pain

Anemia

Dizziness

Non-cardiac chest pain

Lymphocyte count decreased

Abdominal pain upper

Blood alkaline phosphatase increased

Blood lactate dehydrogenase increased

Hypotension

Hypokalaemia

Hypomagnesaemia

Headache

Arthralgia

Febrile neutropenia

Productive cough

Muscular weakness

Pain in extremity

Bronchitis

Musculoskeletal chest pain

Hypertension

Small cell lung cancer

Chronic obstructive pulmonary disease

Neck pain

Myalgia

Confusional state

Anxiety

Upper respiratory tract infection

Musculoskeletal pain

Pleural effusion

Haemoglobin decreased

Hyponatraemia

Pulmonary embolism

Hypocalcaemia

Dysphonia

Respiratory tract infection

Hypertriglyceridaemia

Diarrhea

Rash

Klebsiella sepsis

Blood creatinine increased

Dyskinesia

Hypoxia

Dehydration

Acute coronary syndrome

Cardiac failure

Febrile bone marrow aplasia

Ejection fraction decreased

Epistaxis

Pyelonephritis

Atrial flutter

Dry mouth

Acute kidney injury

Death

Acute myocardial infarction

Supraventricular tachycardia

Gastrooesophageal reflux disease

Neutropenic colitis

Herpes zoster

Pain

Hypercholesterolaemia

Leukocytosis

Troponin I increased

Chest pain

Pleuritic pain

Malignant pleural effusion

Metastases to central nervous system

100%

80%

60%

40%

20%

Study treatment Arm

Part 2: Topotecan

Part 2: Dinutuximab + Irinotecan

Part 1: Dinutuximab + Irinotecan

Part 2: Irinotecan

Awards & Highlights

No Placebo-Only Group

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

Trial Design

3Treatment groups

Experimental Treatment

Group I: *28/*28Experimental Treatment4 Interventions

FOLFIRI (5-fluorouracil (5-FU), leucovorin, irinotecan) Irinotecan dose 180 mg/m2, FOLFIRI (IV, Day 1, 15); Bevacizumab (IV, Day 1, 15), repeat treatment cycle every 28 days.

Group II: *1/*28 GenotypeExperimental Treatment4 Interventions

FOLFIRI (5-fluorouracil (5-FU), leucovorin, irinotecan) Irinotecan dose 260 mg/m2, FOLFIRI (IV, Day 1, 15); Bevacizumab (IV, Day 1, 15), repeat treatment cycle every 28 days.

Group III: *1/*1 GenotypeExperimental Treatment4 Interventions

FOLFIRI (5-fluorouracil (5-FU), leucovorin, irinotecan) Irinotecan dose 310 mg/m2,(IV, Day 1, 15); Bevacizumab (IV, Day 1, 15), repeat treatment cycle every 28 days.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Bevacizumab

2013

Completed Phase 4

~5540

5-Fluorouracil

2012

Completed Phase 3

~7800