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Cancer Therapy-Related DiarrheaPhase 3OnTARGETNCT04538625

Prophylaxis of Diarrhea in Adult Cancer Patients Receiving Targeted Cancer Therapy

A Phase 3 study testing Crofelemer 125 MG [Mytesi] in people with Cancer Therapy-Related Diarrhea and Chemotherapy-related Diarrhea, run by Napo Pharmaceuticals, Inc. at 52 sites in 5 countries.

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

A 24-week, (two 12-week stages), randomized, placebo-controlled, double-blind study to evaluate the safety and efficacy of crofelemer in providing prophylaxis of diarrhea in adult patients with solid tumors treated with targeted cancer therapy-containing treatment regimens. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Crofelemer 125 MG [Mytesi]
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
287 participants
Where
52 sitesin 5 countries
Study dates
7 Oct 2020to 30 Oct 2023
Phase
Phase 3
Are there results?
None posted in the registry

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

  • 1. Patients to receive targeted cancer therapy drugs that have a reported an all grade diarrhea incidence of 50% or higher (e.g., tyrosine kinase inhibitors, cdk inhibitors, anti-EGFR, etc., for treatment of solid tumors.
  • 2. Patients able to provide written informed consent.
  • 3. Men and women ≥ 18 years of age.
  • 4. Pathologically and/or radiologically confirmed diagnosis of solid tumors scheduled to receive targeted cancer therapy.
  • 5. Patients eligible to receive targeted cancer therapy per NCCN (National Comprehensive Cancer Network) guidelines and/or standard-of-care practice, with or without cycle chemotherapy.
  • 6. Patient can receive concomitant cycle [standard] chemotherapy agents together with their targeted cancer therapy treatment regimens.
  • 7. ECOG (Eastern Cooperative Oncology Group) performance status 0-2 and expected to survive a 12-week course of targeted therapy with or without chemotherapy
  • 8. Negative urine pregnancy test at time of informed consent for women of childbearing potential.

Who cannot join

  • 1. Patients receiving any type of immunotherapy including but not limited to immune checkpoint inhibitors that inhibit negative regulatory components of immune response such as cytotoxic T-lymphocyte associated antigen 4 (CTLA-4) and the programmed cell death protein-1 and its ligand (PD1/ PDL1) and IL-2 cancer immunotherapy.
  • 2. Any cancer therapy for which antidiarrheal (antimotility) medications in the prophylaxis setting is mandatory, including but not limited to patients receiving neratinib and irinotecan.
  • 3. Ongoing irritable bowel syndrome (IBS) or colitis (including but not limited to ulcerative colitis, Crohn's disease, microscopic colitis, etc.).
  • 4. Ongoing diarrhea and/or diarrheal episodes within the previous 7 days prior to randomization into the study.
  • 5. Laxative use within 7 days prior to randomization or a history of constipation requiring the use of laxatives for more than ≥ 30 consecutive days.
  • 6. Inadequate organ function, which may include, but is not limited to, the following laboratory results within 28 days prior to signing consent: Total bilirubin > upper limit of normal (ULN), AST (SGOT) and ALT (SPGT) > 2.5 ULN (unless the participant has documented Gilbert's syndrome, hepatocellular carcinoma or hepatic metastases), serum creatinine > 2.0 mg/dL or 177 μmol/L.
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  • NOTE: Investigator discretion will determine continued eligibility after randomization occurs, in the event the liver function test results are greater than (>) the proposed upper limit of normal.
  • 7. Use of other investigational drugs within 4 weeks of signed informed consent or foreseen use during the study.
  • 8. Use of antibiotics within the past 7 days (up to 2 prophylactic doses of antibiotic for procedures, including but not limited to port placement, is permitted) prior to randomization.
  • 9. Total colectomy and/or any type of gastrointestinal ostomy.
  • 10. Major abdominal or pelvic surgery within the past 3 months.
  • 11. Previous (within 1 month) or planned abdominal and/or pelvic radiation.
  • 12. Fecal incontinence from ongoing radiation-induced diarrhea or constipation
  • 13. Active systemic infection requiring ongoing intervention, including but not limited to oral and intravenous antibiotics, anti-fungals, anti-parasitics, and anti-viral drugs.
  • 14. Inability to comply with study requirements as judged by the Investigator.
  • 15. Pregnant and/or breastfeeding.

Trial locations and contacts

52 sites in 5 countries.

52 sites in 5 countries

United States27 sites

  • Pacific Cancer Medical Center Inc

    Anaheim, California, 92801

  • GenesisCare USA

    Aventura, Florida, 33180

  • American Oncology Partners of Maryland

    Bethesda, Maryland, 20817

  • Gabrail Cancer Research

    Canton, Ohio, 44718

  • The Oncology Institute of Hope and Innovation

    Corona, California, 92882

  • Texas Oncology - Denison

    Denison, Texas, 75020

  • Inova Schar Cancer Institute

    Fairfax, Virginia, 22031

  • Texas Oncology, P.A. - Flower Mound

    Flower Mound, Texas, 75028

  • The West Clinic Research

    Germantown, Tennessee, 38138

  • The Oncology Institute of Hope and Innovation

    Glendale, California, 91204

  • MD Anderson Cancer Center

    Houston, Texas, 77030

  • SCL Health Research Institute

    Lafayette, Colorado, 80218

  • Minnesota Oncology Hematology, P.A.

    Minneapolis, Minnesota, 55404

  • Texas Oncology - New Braunfels

    New Braunfels, Texas, 78130

  • Nebraska Methodist Hospital

    Omaha, Nebraska, 68114

  • Cancer Care Centers of Brevard, Inc.

    Palm Bay, Florida, 32909

  • Texas Oncology - Plano East

    Plano, Texas, 75075-7787

  • BRCR Global

    Plantation, Florida, 33322

  • North Shore Hematology Oncology Associates dba New York Cancer and Blood Specialists

    Port Jefferson Station, New York, 11776

  • Oregon Health & Science University (OHSU) Knight Cancer Institute

    Portland, Oregon, 97239

  • Arizona Oncology Associates PC - HAL

    Prescott, Arizona, 86314

  • Advanced Research Institute

    St. Petersburg, Florida, 33710

  • MultiCare Institute for Research and Innovation

    Tacoma, Washington, 98405

  • Jacobi Medical Center

    The Bronx, New York, 10461

  • Texas Oncology - Gulf Coast

    Webster, Texas, 77598

  • PIH Health Whittier Hospital

    Whittier, California, 90602

  • Shenandoah Oncology Associates

    Winchester, Virginia, 22601

Other trials in United States

Argentina8 sites

  • Fleischer Medical Center

    Buenos Aires, 1414

  • Medical Center Austral

    Buenos Aires, C1019ABS

  • Buenos Aires British Hospital

    Buenos Aires

  • Cordoba Oncology Institute (IONC)

    Córdoba

  • Center of Nuclear and Molecular Medicine of Entre Rios (CEMENER)

    Paraná, 3100

  • CEDIT Diagnostic and Treatment Center

    Salta

  • 9 of July Sanatorium

    San Miguel de Tucumán, 4000

  • Isis Specialized Clinic

    Santa Fe, S3000FFV

Other trials in Argentina

Serbia6 sites

  • Clinical Hospital Center Bezanijska Kosa

    Belgrade, 11 080

  • National Cancer Research Center

    Belgrade, 11000

  • Institute of Pulmonary Diseases of Vojvodina

    Kamenitz, 21204

  • Oncology Institute of Vojvodina (IOV)

    Kamenitz, 21204

  • University Clinical Center Kragujevac

    Kragujevac, 34 000

  • University Clinical Center Nis

    Niš, 18 000

Other trials in Serbia

Taiwan6 sites

  • Changhua Christian Hospital

    Changhua, 500

  • Kaohsiung Chang Gung Memorial Hospital

    Kaohsiung City

  • China Medical University Hospital

    Taichung, 404332

  • Chi Mei Medical Center - LiouYing Branch

    Tainan, 736402

  • National Taiwan University Hospital

    Taipei, 100226

  • Taipei Veterans General Hospital

    Taipei, 112201

Other trials in Taiwan

Georgia5 sites

  • LLC "Todua Clinic"

    Tbilisi, 0112

  • Archangel St. Michael Multiprofile Clinical Hospital LTD

    Tbilisi, 0159

  • JSC K. Eristavi National Center of Experimental and Clinical Surgery

    Tbilisi, 0159

  • Malkhaz Katsiashvili Multiprofile Emergency Medicine Center LLC

    Tbilisi, 0172

  • LTD Caucasus Medical Centre

    Tbilisi, 0186

Other trials in Georgia

About this study

Official title: A Phase 3 Multicenter, Randomized, Double-blind Placebo-controlled Trial Evaluating Crofelemer for the Prophylaxis of Diarrhea in Adult Patients With Solid Tumors Receiving Targeted-cancer Therapies With or Without Standard Chemotherapy

A 24-week, (two 12-week stages), randomized, placebo-controlled, double-blind study to evaluate the safety and efficacy of crofelemer in providing prophylaxis of diarrhea in adult patients with solid tumors treated with targeted cancer therapy-containing treatment regimens. Diarrhea grading will be done according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0.

Patients will be randomized 1:1 to placebo or crofelemer and will be stratified by the type of targeted cancer therapy and the tumor type. Placebo and/or crofelemer will be dispensed at Visit 1/Day 1 with the concurrent start of the targeted cancer therapy regimen. The initial Stage I double-blind placebo-controlled primary treatment phase will occur over a 12-week period to accommodate approximately 3 cycle chemotherapy cancer treatment dosing-cycles. The Primary and Secondary Endpoints will be analyzed after the last patient last visit (LPLV) of Stage I.

After completing the Stage I double-blind, placebo-controlled primary treatment phase, the subjects will have the option to remain on their assigned treatment arm and reconsented to enter into the Stage II extension phase. Reconsent will be required to enter into Stage II. For subjects who do not reconsent, visit 5 will be the last study visit.

Read the detailed description

A randomized, placebo controlled, double blind study to evaluate the safety and efficacy of crofelemer in providing prophylaxis of diarrhea in adult patients with solid tumors receiving targeted cancer therapy containing regimens. Diarrhea grading will be done according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE Ver. 5.0).

Randomization will be at a 1:1 ratio with subjects randomized either to crofelemer 125 mg delayed-release tablets or matching placebo tablets administered orally twice daily with or without food. Randomization will be stratified by the type of targeted cancer therapy and by tumor type. Placebo and crofelemer treatment will be initiated concomitantly with the administration of targeted cancer therapy-containing regimens.

The Stage I double-blind placebo-controlled primary treatment phase will be the first 12-week period to accommodate targeted cancer therapy with approximately three (3) cycle chemotherapy regimens (if needed) over the inclusive 12-week period after initiation of crofelemer or placebo treatment in Stage I.

After completing the Stage I treatment phase (12 weeks), and after the LPLV of the primary Stage I treatment phase, the primary and secondary endpoints will be analyzed. The subjects will have the option to remain on their assigned treatment arm and reconsented to enter into the Stage II extension phase. Reconsent will be required to enter into Stage II. For subjects who do not reconsent, Visit 5 will be the last study visit. Subjects who enter into the Stage II extension phase will continue on their originally assigned study treatment commenced at the beginning of Stage I.

Being tested
Crofelemer 125 MG [Mytesi], Placebo

What participants receive

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

  • Crofelemer 125 MG [Mytesi]Drug

    Randomized, Double-blind, Placebo-controlled, two arm trial

  • PlaceboDrug

    Matching placebo tablets

Study groups in NCT04538625
Study groupRoleWhat they receive
PlaceboPlacebo comparatorSubjects randomized to the placebo arm, will receive oral doses of matching placebo tablets twice daily with or without food.
Receives: Drug: Placebo
CrofelemerExperimentalSubjects randomized to the crofelemer arm, will receive oral doses of crofelemer 125mg delayed-release tablets twice daily with or without food.
Receives: Drug: Crofelemer 125 MG [Mytesi]

What is being measured

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

  1. Frequency of Number of Loose/watery Stools

    The frequency of diarrhea as measured by the average number of loose/watery stools per week will be evaluated as a continuous endpoint.

    Measured: For the entire 12-week double-blind placebo-controlled treatment period (The Stage 1 Primary Treatment Phase).

Secondary outcomes (3)

  1. Proportion of Durable, Clinical Responders

    Proportion of "durable responders" defined as the proportion of subjects with ≤7 loose and/or watery bowel movements per week for at least 50% of the time over the Stage 1 double-blind placebo-controlled primary treatment period (Stage 1).

    Measured: Initial 12-week (Stage 1) period of the study.

  2. Maximum Number of Weekly Loose/Watery Stools

    Maximum number of weekly unformed (loose and/or watery) bowel movements from Week 1 through end of Week 12.

    Measured: Initial 12-week (Stage 1) period of the study.

  3. Fecal Incontinence

    Mean number of fecal incontinence episodes from Week 1 through end of Week 12

    Measured: Initial 12-week (Stage 1) period of the study.

Timeline

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

  1. First posted4 Sep 2020
  2. Study start7 Oct 2020
  3. Primary completion7 Aug 2023
  4. Study completion30 Oct 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 3
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Model description
A randomized, placebo controlled, double blind study to evaluate the safety and efficacy of crofelemer in providing prophylaxis of diarrhea in adult patients with solid tumors receiving targeted cancer therapy containing regimens. Diarrhea grading will be done according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE Ver. 5.0).
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
287 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04538625
Sponsor's protocol ID
NP 303-102
Acronym
OnTARGET
Status last verified
Nov 2023
First submitted
28 Aug 2020
Last updated
26 Jul 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Hirsh V, Blais N, Burkes R, Verma S, Croitoru K. Management of diarrhea induced by epidermal growth factor receptor tyrosine kinase inhibitors. Curr Oncol. 2014 Dec;21(6):329-36. doi: 10.3747/co.21.2241.

    PubMed 25489260

  • Davila M, Bresalier RS. Gastrointestinal complications of oncologic therapy. Nat Clin Pract Gastroenterol Hepatol. 2008 Dec;5(12):682-96. doi: 10.1038/ncpgasthep1277. Epub 2008 Oct 21.

    PubMed 18941434

  • Gibson RJ, Keefe DM. Cancer chemotherapy-induced diarrhoea and constipation: mechanisms of damage and prevention strategies. Support Care Cancer. 2006 Sep;14(9):890-900. doi: 10.1007/s00520-006-0040-y. Epub 2006 Apr 8.

    PubMed 16604351

  • Stein A, Voigt W, Jordan K. Chemotherapy-induced diarrhea: pathophysiology, frequency and guideline-based management. Ther Adv Med Oncol. 2010 Jan;2(1):51-63. doi: 10.1177/1758834009355164.

    PubMed 21789126

  • Engelking C, Rutledge DN, Ippoliti C, Neumann J, Hogan CM. Cancer-related diarrhea: a neglected cause of cancer-related symptom distress. Oncol Nurs Forum. 1998 Jun;25(5):859-60. No abstract available.

    PubMed 9644701

  • Benson AB 3rd, Ajani JA, Catalano RB, Engelking C, Kornblau SM, Martenson JA Jr, McCallum R, Mitchell EP, O'Dorisio TM, Vokes EE, Wadler S. Recommended guidelines for the treatment of cancer treatment-induced diarrhea. J Clin Oncol. 2004 Jul 15;22(14):2918-26. doi: 10.1200/JCO.2004.04.132.

    PubMed 15254061

  • Di Fiore F, Van Cutsem E. Acute and long-term gastrointestinal consequences of chemotherapy. Best Pract Res Clin Gastroenterol. 2009;23(1):113-24. doi: 10.1016/j.bpg.2008.11.016.

    PubMed 19258191

  • Carlotto A, Hogsett VL, Maiorini EM, Razulis JG, Sonis ST. The economic burden of toxicities associated with cancer treatment: review of the literature and analysis of nausea and vomiting, diarrhoea, oral mucositis and fatigue. Pharmacoeconomics. 2013 Sep;31(9):753-66. doi: 10.1007/s40273-013-0081-2.

    PubMed 23963867

  • Bowen JM. Mechanisms of TKI-induced diarrhea in cancer patients. Curr Opin Support Palliat Care. 2013 Jun;7(2):162-7. doi: 10.1097/SPC.0b013e32835ec861.

    PubMed 23399616

  • Crutchley RD, Miller J, Garey KW. Crofelemer, a novel agent for treatment of secretory diarrhea. Ann Pharmacother. 2010 May;44(5):878-84. doi: 10.1345/aph.1M658. Epub 2010 Apr 13.

    PubMed 20388859

  • Cottreau J, Tucker A, Crutchley R, Garey KW. Crofelemer for the treatment of secretory diarrhea. Expert Rev Gastroenterol Hepatol. 2012 Feb;6(1):17-23. doi: 10.1586/egh.11.87.

    PubMed 22149578

  • Tradtrantip L, Namkung W, Verkman AS. Crofelemer, an antisecretory antidiarrheal proanthocyanidin oligomer extracted from Croton lechleri, targets two distinct intestinal chloride channels. Mol Pharmacol. 2010 Jan;77(1):69-78. doi: 10.1124/mol.109.061051. Epub 2009 Oct 6.

    PubMed 19808995

  • Holodniy M, Koch J, Mistal M, Schmidt JM, Khandwala A, Pennington JE, Porter SB. A double blind, randomized, placebo-controlled phase II study to assess the safety and efficacy of orally administered SP-303 for the symptomatic treatment of diarrhea in patients with AIDS. Am J Gastroenterol. 1999 Nov;94(11):3267-73. doi: 10.1111/j.1572-0241.1999.01535.x.

    PubMed 10566728

  • DiCesare D, DuPont HL, Mathewson JJ, Ashley D, Martinez-Sandoval F, Pennington JE, Porter SB. A double blind, randomized, placebo-controlled study of SP-303 (Provir) in the symptomatic treatment of acute diarrhea among travelers to Jamaica and Mexico. Am J Gastroenterol. 2002 Oct;97(10):2585-8. doi: 10.1111/j.1572-0241.2002.06027.x.

    PubMed 12385443

  • Mangel AW, Chaturvedi P. Evaluation of crofelemer in the treatment of diarrhea-predominant irritable bowel syndrome patients. Digestion. 2008;78(4):180-6. doi: 10.1159/000185719. Epub 2008 Dec 18.

    PubMed 19092244

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Crofelemer 125 MG [Mytesi] in people with Cancer Therapy-Related Diarrhea and Chemotherapy-related Diarrhea, run by Napo Pharmaceuticals, Inc. at 52 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 52 sites in United States, Argentina, Serbia, Taiwan, Georgia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Frequency of Number of Loose/watery Stools (time frame: For the entire 12-week double-blind placebo-controlled treatment period (The Stage 1 Primary Treatment Phase).). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04538625, which also lists 18 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jul 2024.

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