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Advanced Colorectal CarcinomaPhase 1NCT04164069

Dasatinib for the Prevention of Oxaliplatin-Induced Neuropathy in Patients With Metastatic Gastrointestinal Cancer Receiving FOLFOX Chemotherapy With or Without Bevacizumab

A Phase 1 study testing Bevacizumab, Dasatinib and Fluorouracil in people with Advanced Colorectal Carcinoma and Metastatic Colorectal Carcinoma, run by Anne Noonan at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This phase Ib trial studies side effects and best dose of dasatinib in preventing oxaliplatin-induced peripheral neuropathy in patients with gastrointestinal cancers who are receiving FOLFOX regimen with or without bevacizumab. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Bevacizumab, Dasatinib and Fluorouracil
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
9 participants
Where
1 siteUnited States
Study dates
2 Sep 2020to 22 Jun 2023
Phase
Phase 1

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Confirmed confirmed stage II, III or IV colon or rectal cancer and other gastrointestinal (GI) cancers (e.g. pancreas, esophagogastric, bile duct, small bowel cancers etc) who are candidates for mFOLFOX6, with or without bevacizumab therapy. Pathological confirmation of colon,rectal or other GI cancer is required. Patients may have had prior therapy for GI cancer.
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
  • Platelets >= 100 x 10^9/L
  • International normalized ratio (INR) or prothrombin time (PT) =< 1.5 x upper limit of normal (ULN) unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants
  • Activated partial thromboplastin time (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
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  • Serum creatinine: =< 1.5 x upper limit of normal (ULN), or measured or calculated creatinine clearance (estimated by Cockcroft-Gault formula or measured ) >= 50 mL/min urine protein:creatinine (UPC) < 2
  • Total bilirubin =< 2 x ULN
  • Aspartate aminotransferase (AST, serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT, serum glutamate pyruvate transaminase [SGPT]) =< 3 x ULN, unless evidence of liver metastases, then AST/alanine aminotransferase (ALT) =< 5 x ULN
  • Blood pressure (if receiving bevacizumab): systolic blood pressure (SBP) > 150 or diastolic blood pressure (DBP) > 100
  • Serum potassium and magnesium within the institution normal range.
  • Corrected QT (QTc) interval =< 450 mSec
  • Women of child-bearing potential must agree to use adequate contraception prior to study entry, for the duration of study participation and for 3 months after completion of study treatment administration
  • Prior chemotherapy in the adjuvant or metastatic setting is allowed including prior exposure to oxaliplatin in the adjuvant setting for colorectal cancer or other GI cancer as long as neuropathy is grade 1 or less.
  • Pre-existing neuropathy is allowed as long as it is grade 1 or less.

Who cannot join

  • Treatment with any other investigational agents within 4 weeks or 5 half-lives (whichever is longer) prior to the first dose of dasatinib
  • Gastrointestinal (GI) disease or impairment of GI function that is likely to significantly alter the absorption of dasatinib
  • Use of potent OCT2 and/or CYP3A4 inhibitors if treatment cannot be either safely discontinued or switched to a different medication prior to starting dasatinib
  • Concurrent cetuximab panitumumab or any other biological/targeted agent.
  • Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, known human immunodeficiency virus (HIV) diagnosis if receiving combination antiretroviral therapy, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations, including psychotic disorders, dementia and substance use disorders, that would limit compliance with study requirements
  • Because there is an unknown potential risk for adverse events in nursing infants secondary to treatment of the mother with dasatinib and/or oxaliplatin, breastfeeding should be discontinued
  • Inability to understand and sign informed consent
  • Any other condition that in the opinion of the investigators would make the study therapy unsafe

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

Other trials in United States

About this study

Official title: A Phase Ib Adaptive Study Dasatinib for the Prevention of Oxaliplatin-Induced Neuropathy in Patients With Metastatic Gastrointestinal Cancer Receiving FOLFOX Chemotherapy With or Without Bevacizumab

This phase Ib trial studies side effects and best dose of dasatinib in preventing oxaliplatin-induced peripheral neuropathy in patients with gastrointestinal cancers who are receiving FOLFOX regimen with or without bevacizumab. Drugs used in chemotherapy, such as leucovorin, fluorouracil, and oxaliplatin (FOLFOX regimen), work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. However, the buildup of oxaliplatin in the cranial nerves can result in damage or the nerves. Dasatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Blocking these enzymes may reduce oxaliplatin-induced peripheral neuropathy.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the recommended phase 2 dose (RP2D) of dasatinib in combination with oxaliplatin and fluorouracil (5FU) (modified version 6 regimen of leucovorin, fluorouracil and oxaliplatin [mFOLFOX6]) with or without bevacizumab in patients with colon, rectal or other GI cancer, defined as the lowest intermittent dose of dasatinib that affects serum biomarkers of OCT2 without influencing the pharmacokinetic properties of oxaliplatin.

II. To determine the toxicity profile (based on Chemotherapy-Induced Peripheral Neuropathy [CIPN]20 and Common Terminology Criteria for Adverse Events [CTCAE] version [v.] 5.0) of dasatinib in combination with oxaliplatin/5-FU/bevacizumab in patients with colorectal cancer or other GI cancer.

SECONDARY OBJECTIVES:

  1. To evaluate the influence of dasatinib on the pharmacokinetics of oxaliplatin and vice versa in these patients.

OUTLINE: This is a dose-escalation study of dasatinib.

Patients receive oxaliplatin intravenously (IV) over 2 hours, leucovorin IV over 2 hours, fluorouracil slow IV push over 2-4 minutes followed by continuous infusion over 46 hours on days 1 and 15. Patients also receive dasatinib orally (PO) once daily (QD) on days 14, 15, and 28 of cycle 1 and day 1 of cycle 2. Patients may receive bevacizumab IV over 30 minutes on days 1 and 15. Treatment repeats every 28 days for up to cycle 3 day 1 in the absence of disease progression or unacceptable toxicity.

Medical subject headings
Colorectal Neoplasms, Colonic Neoplasms, Rectal Neoplasms, Esophageal Neoplasms, Pancreatic Neoplasms, Bile Duct Neoplasms, Stomach Neoplasms, Gallbladder Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BevacizumabBiological

    Also called Anti-VEGF, Anti-VEGF Humanized Monoclonal Antibody, Anti-VEGF rhuMAb, Avastin

    Given IV

  • DasatinibDrug

    Also called BMS-354825, Dasatinib Hydrate, Dasatinib Monohydrate, Sprycel

    Given PO

  • FluorouracilDrug

    Also called 5 Fluorouracil, 5 Fluorouracilum, 5 FU, 5-Fluoro-2,4(1H, 3H)-pyrimidinedione

    Given IV

  • LeucovorinDrug

    Also called Folinic acid

    Given IV

  • Leucovorin CalciumDrug

    Also called Adinepar, Calcifolin, Calcium (6S)-Folinate, Calcium Folinate

    Given IV

  • OxaliplatinDrug

    Also called 1-OHP, Ai Heng, Aiheng, Dacotin

    Given IV

  • Quality-of-Life AssessmentOther

    Also called Quality of Life Assessment

    Ancillary studies

Study groups in NCT04164069
Study groupRoleWhat they receive
Prevention (dasatinib, mFOLFOX, bevacizumab)ExperimentalPatients receive oxaliplatin IV over 2 hours, leucovorin IV over 2 hours, fluorouracil slow IV push over 2-4 minutes followed by continuous infusion over 46 hours on days 1 and 15. Patients also receive dasatinib PO QD on days 14, 15, and 28 of cycle 1 and day 1 of cycle 2. Patients may receive bevacizumab IV over 30 minutes on days 1 and 15. Treatment repeats every 28 days for up to cycle 3 day 1 in the absence of disease progression or unacceptable toxicity.
Receives: Biological: Bevacizumab; Drug: Dasatinib; Drug: Fluorouracil; Drug: Leucovorin; Drug: Leucovorin Calcium; Drug: Oxaliplatin; Other: Quality-of-Life Assessment

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Recommended phase II dose (RP2D) of dasatinib

    The RP2D will be defined as the lowest intermittent dose of dasatinib that affects serum biomarkers of OCT2 without influencing the pharmacokinetic properties of oxaliplatin.

    Measured: Up to 14 days

  2. Incidence of adverse events

    The dose-limiting toxicity and toxicity profile will be based using the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 and Chemotherapy-Induced Peripheral Neuropathy (CIPN) 20. Toxicity will be defined as adverse events deemed to be at least possibly related to dasatinib treatment. Adverse events and toxicities will be summarized by dose level, and will tabulate these events by type and severity. Will summarize the numbers of patients who required dose reductions in dasatinib or oxaliplatin and the cumulative doses received. The CIPN20 will be measured in these subjects, and will be summarized within and across dose levels, and will be used to support and inform assumptions for a subsequent phase 2 trial.

    Measured: At the end of Cycle 1 (cycle length is 28 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Nov 2019
  2. Study start2 Sep 2020
  3. Primary completion22 Jun 2023
  4. Study completion22 Jun 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Prevention
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04164069
Sponsor's protocol ID
OSU-19067
Other IDs
NCI-2019-04723
Status last verified
Apr 2024
First submitted
11 Oct 2019
Last updated
27 Dec 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Stage TB, Hu S, Sparreboom A, Kroetz DL. Role for Drug Transporters in Chemotherapy-Induced Peripheral Neuropathy. Clin Transl Sci. 2021 Mar;14(2):460-467. doi: 10.1111/cts.12915. Epub 2020 Nov 9.

    PubMed 33142018

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