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| Name | Class |
|---|---|
| Lombardi Comprehensive Cancer Center | OTHER |
| Medstar Health Research Institute | OTHER |
| Genentech, Inc. | INDUSTRY |
| Napo Pharmaceuticals, Inc. |
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Chemotherapy induced diarrhea is seen in up to 40-80% of patients receiving this treatment for HER2 positive locally advanced or metastatic breast cancer. This diarrhea can significantly impact a patient's quality of life and ability to tolerate chemo/anti-HER2 therapy. This study will look at the efficacy of the drug crofelemer in preventing diarrhea in breast cancer patients.
Various anti-diarrheal agents, such as loperamide, codeine, octreotide, are available for diarrhea management, but few are used in the prophylactic setting and none provide a targeted approach for treating chemotherapy induced diarrhea (CID).
Pre-clinical studies have suggested that blocking EGFR results in excess chloride secretion and thus diarrhea. Crofelemer is an extract from the blood red bark of Croton lechleri that inhibits luminal chloride efflux by blocking the calcium activated chloride channel (CaCC) and cystic fibrosis transmembrane regulator (CFTR) chloride channels. Due to its size and polarity, it acts only luminally and is not systemically absorbed. It is currently FDA approved for use in preventing diarrhea in HIV/AIDS patients on anti-retroviral therapy.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Crofelemer | Experimental | Patients on the treatment arm will take one tablet of crofelemer twice a day (each tablet is 125 mg), to be swallowed whole without chewing or crushing, during cycles 1-2 of chemotherapy with THP or TCHP. Patient will be monitored off crofelemer during cycle 3 of chemotherapy. |
|
| Control | No Intervention | Patients on the control arm will be on the study for cycles 1-3 of THP or TCHP. Patients on the control arm will not receive crofelemer at any time on this study. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Crofelemer | Drug | Crofelemer 125 mg BID during cycles 1-2 of THP or TCHP |
|
| Measure | Description | Time Frame |
|---|---|---|
| Diarrhea for >= 2 Consecutive Days | Percentage of participants with any grade (based on CTCAE 4.0) diarrhea lasting 2 or more consecutive days during cycles 1 and 2 of chemotherapy. | Cycle 1, Cycle 2 (each cycle is 21 days) |
| Measure | Description | Time Frame |
|---|---|---|
| Diarrhea Any Grade | Incidence of diarrhea of any grade, as measured by CTCAE v4.0, by cycle | Cycle 1, Cycle 2 (each cycle is 21 days) |
| Grade 3-4 Diarrhea | number of patients with diarrhea of grade 3 or grade 4, as measured by CTCAE v4.0, by cycle and by stratum |
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Inclusion Criteria:
Exclusion Criteria:
Pregnant and/or breastfeeding;
Ongoing irritable bowel syndrome (IBS) or colitis (including but not limited to ulcerative colitis, Crohn's disease, microscopic colitis, etc.);
Use of investigational drugs within 3 weeks of signing consent or foreseen use during the study;
Use of chemotherapy, trastuzumab, or pertuzumab within the past 3 weeks;
Use of antibiotics within the past 7 days (up to 2 prophylactic doses of antibiotics for procedures including, but not limited to port placement, is permitted);
Any type of ostomy;
Total colectomy;
Fecal incontinence;
Ongoing radiation induced diarrhea or constipation or planned radiotherapy to the abdomen or pelvis while on study;
Active systemic infection requiring ongoing intervention, including but not limited to oral and intravenous antibiotics, anti-fungals, anti-parasites, anti-virals;
Abdominal or pelvic surgery without recovery of bowel function;
Inadequate organ function for starting THP or TCHP, which may include the following laboratory results within 28 days prior to signing consent:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Lombardi Comprehensive Cancer Center | Washington D.C. | District of Columbia | 20007 | United States | ||
| MedStar Franklin Square Cancer Center at Loch Raven Campus |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27692565 | Background | Gao JJ, Tan M, Pohlmann PR, Swain SM. HALT-D: A Phase II Evaluation of Crofelemer for the Prevention and Prophylaxis of Diarrhea in Patients With Breast Cancer on Pertuzumab-Based Regimens. Clin Breast Cancer. 2017 Feb;17(1):76-78. doi: 10.1016/j.clbc.2016.08.005. Epub 2016 Aug 27. | |
| 36280642 | Derived | Pohlmann PR, Graham D, Wu T, Ottaviano Y, Mohebtash M, Kurian S, McNamara D, Lynce F, Warren R, Dilawari A, Rao S, Mainor C, Swanson N, Tan M, Isaacs C, Swain SM. HALT-D: a randomized open-label phase II study of crofelemer for the prevention of chemotherapy-induced diarrhea in patients with HER2-positive breast cancer receiving trastuzumab, pertuzumab, and a taxane. Breast Cancer Res Treat. 2022 Dec;196(3):571-581. doi: 10.1007/s10549-022-06743-9. Epub 2022 Oct 25. |
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No plan to make individual participant data available
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| ID | Title | Description |
|---|---|---|
| FG000 | Crofelemer | Patients on the treatment arm will take one tablet of crofelemer twice a day (each tablet is 125 mg), to be swallowed whole without chewing or crushing, during cycles 1-2 of chemotherapy with THP or TCHP. Patient will be monitored off crofelemer during cycle 3 of chemotherapy. Crofelemer: Crofelemer 125 mg BID during cycles 1-2 of THP or TCHP |
| FG001 | Control | Patients on the control arm will be on the study for cycles 1-3 of THP or TCHP. Patients on the control arm will not receive crofelemer at any time on this study. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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|
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| ID | Title | Description |
|---|---|---|
| BG000 | Treatment | Patients on the treatment arm will take one tablet of crofelemer twice a day (each tablet is 125 mg), to be swallowed whole without chewing or crushing, during cycles 1-2 of chemotherapy with THP or TCHP. Patient will be monitored off crofelemer during cycle 3 of chemotherapy. Crofelemer: Crofelemer 125 mg BID during cycles 1-2 of THP or TCHP |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Diarrhea for >= 2 Consecutive Days | Percentage of participants with any grade (based on CTCAE 4.0) diarrhea lasting 2 or more consecutive days during cycles 1 and 2 of chemotherapy. | Posted | Number | percentage of patients | Cycle 1, Cycle 2 (each cycle is 21 days) |
|
Adverse events were collected from signing consent to 30 days after completing study or 30 days after last dose of crofelemer, whichever occurs later (until cycle 4 day 1).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Crofelemer | Patients on the treatment arm will take one tablet of crofelemer twice a day (each tablet is 125 mg), to be swallowed whole without chewing or crushing, during cycles 1-2 of chemotherapy with THP or TCHP. Patient will be monitored off crofelemer during cycle 3 of chemotherapy. Crofelemer: Crofelemer 125 mg BID during cycles 1-2 of THP or TCHP |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Neutrophil count decreased | Investigations | CTCAE (4.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anemia | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Sandra M. Swain, MD, FACP, FASCO | Georgetown University | 202-687-4600 | Sandra.Swain@georgetown.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jun 7, 2021 | May 11, 2022 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
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| ID | Term |
|---|---|
| C546704 | crofelemer |
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| INDUSTRY |
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| Cycle 1, Cycle 2 (each cycle is 21 days) |
| Diarrhea Onset | Time to onset of first episode of diarrhea of any grade, overall | from baseline through Cycle 3 (21 day cycles) |
| Diarrhea Duration | Duration (days) of any grade diarrhea, defined from day 1 to day 21, by cycle in which the episode started | Cycle 1, Cycle 2 (each cycle is 21 days) |
| Duration Grade 3-4 Diarrhea | Duration (days) of grade 3-4 diarrhea during cycle 1 through the end of cycle 2, defined from cycle day 1 to cycle 2 day 21 | End of Cycle 2 (each cycle is 21 days) |
| Anti-diarrheal Medications | Use of anti-diarrheal medications (other than study drug), by cycle and arm | Cycle 1, Cycle 2 (each cycle is 21 days) |
| FACIT-D Total Score | Quantitative FACIT-D (FACIT-D Functional Assessment of Chronic Illness Therapy for Patients With Diarrhea) total score, collected day 1 of each cycle and at the time of study completion, cycles 1 and 2 reported; The higher the score the better the QOL; Score range 0-152. | Cycle 1, Cycle 2 (each cycle is 21 days) |
| FACIT-D Diarrhea Score | Quantitative FACIT-D (FACIT-D Functional Assessment of Chronic Illness Therapy for Patients With Diarrhea) diarrhea subscale (DS) score, by cycle; Score Range 0-44; the higher the score, the better the QOL. | Cycle 1, Cycle 2 (each cycle is 21 days) |
| Stool Frequency Based on Consistency (Bristol Stool Scale) | Frequency of stool consistency of 6-7, as measured by the Bristol Stool scale (minimum 1-separate hard lumps, maximum 7-watery, no solid pieces), by cycle; Median in watery bowel movements (Bristol Stool Form Scale 6-7). | Cycle 1, Cycle 2 (each cycle is 21 days) |
| Baltimore |
| Maryland |
| 21218 |
| United States |
| Harry and Jeanette Weinberg Cancer Institute | Baltimore | Maryland | 21237 | United States |
| John Theurer Cancer Center at Hackensack Univ | Hackensack | New Jersey | 07601 | United States |
| BG001 |
| Control |
Patients on the control arm will be on the study for cycles 1-3 of THP or TCHP. Patients on the control arm will not receive crofelemer at any time on this study. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
|
|
| Secondary | Diarrhea Any Grade | Incidence of diarrhea of any grade, as measured by CTCAE v4.0, by cycle | The number analyzed is different from overall number due to early treatment discontinuation. | Posted | Count of Participants | Participants | Cycle 1, Cycle 2 (each cycle is 21 days) |
|
|
|
| Secondary | Grade 3-4 Diarrhea | number of patients with diarrhea of grade 3 or grade 4, as measured by CTCAE v4.0, by cycle and by stratum | The number analyzed is different from overall number due to early treatment discontinuation. | Posted | Count of Participants | Participants | Cycle 1, Cycle 2 (each cycle is 21 days) |
|
|
|
| Secondary | Diarrhea Onset | Time to onset of first episode of diarrhea of any grade, overall | The number analyzed is different from overall number due to missing data. | Posted | Median | 95% Confidence Interval | days | from baseline through Cycle 3 (21 day cycles) |
|
|
|
| Secondary | Diarrhea Duration | Duration (days) of any grade diarrhea, defined from day 1 to day 21, by cycle in which the episode started | Duration of the "FIRST day of diarrhea" to the "LAST day of diarrhea" based on patient diary. Only Cycle 1 and Cycle 2 analyzed. The number analyzed is different from overall number due to missing data. | Posted | Median | 95% Confidence Interval | days | Cycle 1, Cycle 2 (each cycle is 21 days) |
|
|
|
| Secondary | Duration Grade 3-4 Diarrhea | Duration (days) of grade 3-4 diarrhea during cycle 1 through the end of cycle 2, defined from cycle day 1 to cycle 2 day 21 | Posted | Mean | Full Range | days | End of Cycle 2 (each cycle is 21 days) |
|
|
|
| Secondary | Anti-diarrheal Medications | Use of anti-diarrheal medications (other than study drug), by cycle and arm | Only cycle 1 and cycle 2 analyzed. Total amount of Loperamide, Diphenoxylate Atropine and Octreotide; No subjects in the Crofelemer arm received octreotide in either cycle 1 or 2. | Posted | Mean | Standard Deviation | units | Cycle 1, Cycle 2 (each cycle is 21 days) |
|
|
|
| Secondary | FACIT-D Total Score | Quantitative FACIT-D (FACIT-D Functional Assessment of Chronic Illness Therapy for Patients With Diarrhea) total score, collected day 1 of each cycle and at the time of study completion, cycles 1 and 2 reported; The higher the score the better the QOL; Score range 0-152. | The number analyzed is different from overall number due to early treatment discontinuation. | Posted | Mean | Standard Deviation | score on a scale | Cycle 1, Cycle 2 (each cycle is 21 days) |
|
|
|
| Secondary | FACIT-D Diarrhea Score | Quantitative FACIT-D (FACIT-D Functional Assessment of Chronic Illness Therapy for Patients With Diarrhea) diarrhea subscale (DS) score, by cycle; Score Range 0-44; the higher the score, the better the QOL. | The number analyzed is different from overall number due to early treatment discontinuation. | Posted | Mean | Standard Deviation | score on a scale | Cycle 1, Cycle 2 (each cycle is 21 days) |
|
|
|
| Secondary | Stool Frequency Based on Consistency (Bristol Stool Scale) | Frequency of stool consistency of 6-7, as measured by the Bristol Stool scale (minimum 1-separate hard lumps, maximum 7-watery, no solid pieces), by cycle; Median in watery bowel movements (Bristol Stool Form Scale 6-7). | The number analyzed is different from overall number due to early treatment discontinuation. | Posted | Median | Full Range | number of bowel movements | Cycle 1, Cycle 2 (each cycle is 21 days) |
|
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|
| 0 |
| 26 |
| 1 |
| 26 |
| 26 |
| 26 |
| EG001 | Control | Patients on the control arm will be on the study for cycles 1-3 of THP or TCHP. Patients on the control arm will not receive crofelemer at any time on this study. | 0 | 25 | 7 | 25 | 24 | 25 |
| Infections and infestations - Other, specify | Infections and infestations | CTCAE (4.0) | Systematic Assessment | port-a-cath infection |
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| Obstruction gastric | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
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| Infections and infestations - Other, specify | Infections and infestations | CTCAE (4.0) | Systematic Assessment | Cellulitis |
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| Hyperglycemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
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| Dehydration | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
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| Hyperkalemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
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| Acidosis | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
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| Confusion | Psychiatric disorders | CTCAE (4.0) | Systematic Assessment |
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| Fatigue | General disorders | CTCAE (4.0) | Systematic Assessment |
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| Urinary Tract Infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| chest pain | Cardiac disorders | CTCAE (4.0) | Systematic Assessment |
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| Atrial Flutter | Cardiac disorders | CTCAE (4.0) | Systematic Assessment |
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| Fever | General disorders | CTCAE (4.0) | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
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| Diarrhea | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
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| Gastroesophageal reflux disease | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
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| Mucositis oral | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
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| Fatigue | General disorders | CTCAE (4.0) | Systematic Assessment |
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| Infusion related reaction | General disorders | CTCAE (4.0) | Systematic Assessment |
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| Pain | General disorders | CTCAE (4.0) | Systematic Assessment |
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| Alanine aminotransferase increased | Investigations | CTCAE (4.0) | Systematic Assessment |
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| Aspartate aminotransferase increased | Investigations | CTCAE (4.0) | Systematic Assessment |
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| Anorexia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
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| Dehydration | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
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| Hypoalbuminemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
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| Hypokalemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
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| Dysgeusia | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
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| Headache | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
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| Peripheral sensory neuropathy | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
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| Anxiety | Psychiatric disorders | CTCAE (4.0) | Systematic Assessment |
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| Dyspnea | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
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| Alopecia | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
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| Rash acneiform | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
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| Rash maculo-papular | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
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| Weight loss | Investigations | CTCAE (4.0) | Systematic Assessment |
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| Hypertension | Vascular disorders | CTCAE (4.0) | Systematic Assessment |
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| D017437 |
| Skin and Connective Tissue Diseases |
| Cycle 2 (investigator-assessed) |
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| Cycle 2 |
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| Cycle 2 |
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| Cycle 2-Loperamide |
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| Cycle 1-Diphenoxylate Atropine |
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| Cycle 2- Diophnoxylate Atropine |
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| Cycle 1- Octreotide |
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| Cycle 2- Octreotide |
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| Cycle 2 |
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| Cycle 2 |
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| Cycle 2 |
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