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A Study of Propranolol to Treat Kaposi Sarcoma

Primary Purpose

Kaposi Sarcoma

Status
Not yet recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Propranolol
Sponsored by
AIDS Malignancy Consortium
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Kaposi Sarcoma focused on measuring Kaposi Sarcoma, Propranolol

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Pediatric (< 18 years) and adult (≥ 18 years) participants with biopsy-proven and measurable Kaposi Sarcoma (KS) as defined in the KS Manual of Procedures (MOP). No urgent clinical indication for immediate cytotoxic chemotherapy. Participants who have received cytotoxic chemotherapy > 4 weeks prior to screening are eligible. KS stage: < 18 years: 1A (Mild): disease limited to skin, flat oral mucosal lesions, and/or flesh colored subcutaneous nodules, total <10 lesions. 1B (Moderate): having any of the following features, alone or in combination: a total of 10-19 hyperpigmented skin/oral lesions, nodular oral involvement, conjunctival eye involvement, or exophytic mass. ≥ 18 years: T0: confined to skin and/or lymph nodes and/or minimal oral lesions. T1: limited to tumor-associated edema of cutaneous lesions without functional impairment or flat oral lesions. Performance Status: < 18 years: Lansky performance status > 70% ≥ 18 years: Easter Cooperative Oncology Group (ECOG) performance status ≤ 2 Participants must have adequate organ function, as defined by the following: Bilirubin (direct or total) within normal range, or total bilirubin <3.0 mg/dl for participants with Gilbert syndrome. Calculated creatinine clearance ≥ 30 mL/min for participants ≥ 12 years (see Appendix III); creatinine <1.5 Upper Limit Normal (ULN) for participants < 12 years. Hemoglobin > 9 g/dL; Platelets > 100 × 109/L; ANC > 1000 cells/mm3 Human Immunodeficiency Virus (HIV) positive participants must be on antiretroviral therapy (ART) that conforms to local standards of care. Participants will have been on ART for at least 12 weeks. Participants will not be excluded based on CD4 count or HIV viral load. HIV positive participants must not show recent improvement on ART that may confound response evaluation: If on ART 12 to 24 weeks, participants must show evidence of KS progression requiring further systemic treatment. If on ART for >24 weeks, must show no evidence of regression in the last eight weeks. HIV-negative participants must not show evidence of improvement in the three months prior to enrollment. No history of asthma or diabetes mellitus (as it is a risk factor for hypoglycemia). No clinically significant cardiovascular disease other than hypertension, which is permitted. No use of beta-adrenergic antagonists for other indications. Not pregnant or planning to become pregnant. Propranolol is United Stats Food and Drug Administration (US FDA) pregnancy category C. At this time, the study team has determined that the unknown risk to a developing fetus is greater than the potential benefit of treatment. Use of effective contraception for women of childbearing potential, defined as a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months. Women of child bearing potential (WOCBP) must agree to use adequate contraception (oral contraceptive pills, intrauterine device, Nexplanon, Depo-Provera, or permanent sterilization, etc., or another acceptable method as determined by the investigator) prior to study entry, for the duration of study participation. Not breast feeding. Exclusion Criteria: • Participants who do not fulfill the criteria as listed in Section 3.1 above, are ineligible. Additionally, the presence of any of the following conditions will exclude a participant from study enrollment: Children and adolescents with lymph node or visceral disease, woody edema, or ≥ 20 cutaneous lesions. Children and adolescents with heart rate or systolic blood pressure <10th percentile for age. Adults with visceral disease or tumor-associated edema causing functional impairment. Shortness of breath, hemoptysis, or moderate/severe cough not attributable to causes other than KS. Bleeding from the mouth or rectum not attributable to causes other than KS. Treatment for active and serious infection. Children with severe acute malnutrition based on World Health Organization (WHO) criteria (Mid-upper arm circumference <11.5 cm, weight-for height Z-score <-3 or presence of symmetrical pitting edema). Given the risk of hypotension and hypoglycemia, participants must take the study drug with food. If needed, the study team will pursue additional funding to support providing supplemental food for participants who experience food insecurity. Patients who experienced hypersensitivity to propranolol during initiation phase of treatment or had previous known allergy to propranolol or allergy to other β-blockers. Patients with a history of uncompensated heart failure; severe sinus bradycardia; sick sinus syndrome; or heart block greater than first-degree. Patients with diagnosed obstructive airway disease such as asthma, chronic obstructive pulmonary disease (COPD), or bronchiolitis. History of diabetes mellitus (as it is a risk factor for hypoglycemia) Patients receiving concurrent treatment with an anticancer therapy. Patients must not have received any anticancer therapies within 30 days prior to receiving the first dose of investigational treatment. Patients with concern for Kaposi Sarcoma herpesvirus (KSHV) inflammatory cytokine syndrome.

Sites / Locations

  • Fundación Huésped
  • Instituto Nacional de Câncer José de Alencar
  • Complexo Hospitalar Universitário Professor Edgard Santos
  • Moi University School of Medicine
  • UNC Project Malawi
  • Instituto Nacional de Cancerologia
  • African Cancer Institute at Stellenbosch
  • Uganda Cancer Institute
  • University of Zimbabwe College of Health Sciences

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Propranolol

Arm Description

Propranolol Twice Daily (BID) x 12 weeks Dosage: For ages ≤ 12 years: 3mg/kg/day divided BID; for ages > 12 years, 120 mg BID.

Outcomes

Primary Outcome Measures

Objective Response Rate
ORR is defined as the proportion of participants with complete response (CR), or partial response (PR) based on AIDS Malignancy Consortium Kaposi Sarcoma (AMC KS) Response Criteria.

Secondary Outcome Measures

Number of dose-limiting toxicities
To evaluate the number of dose-limiting toxicities. The dose-limiting toxicities will be based on the National Cancer Institute's Common Terminology Criteria for Adverse Events
Number of treatment-emergent adverse events
To evaluate the number of treatment-emergent adverse events. The treatment-emergent adverse events will be based on the National Cancer Institute's Common Terminology Criteria for Adverse Events
Complete and Partial Response rates in children and adults
Proportion of children and adults with a Complete Response or Partial Response.
Time to recurrence among children
Time to recurrence among responders overall in children. Recurrent disease is defined as the appearance of tumor following documentation of a complete remission.
Time to recurrence among adults
Time to recurrence among responders overall in adults. Recurrent disease is defined as the appearance of tumor following documentation of a complete remission.
Time to progression among children
Time to progression among responders overall in children. Time to progression is defined as time from initiation of propranolol to documentation of first progression.
Time to progression among adults
Time to progression among responders overall in adults. Time to progression is defined as time from initiation of propranolol to documentation of first progression.

Full Information

First Posted
March 22, 2023
Last Updated
April 13, 2023
Sponsor
AIDS Malignancy Consortium
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT05797662
Brief Title
A Study of Propranolol to Treat Kaposi Sarcoma
Official Title
A Phase II Study of Propranolol for the Treatment of Kaposi Sarcoma in Children and Adults
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
July 1, 2024 (Anticipated)
Primary Completion Date
August 1, 2026 (Anticipated)
Study Completion Date
August 1, 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AIDS Malignancy Consortium
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
A clinical study of propranolol for the treatment of Kaposi Sarcoma in children and adults. This study will be an open-label single armed treatment trial that will test the effectiveness and the safety of treating Kaposi Sarcoma with propranolol.
Detailed Description
Eligible study participants will receive propanolol twice daily for an initial 12-week period. At the conclusion of 12-weeks, response will be assessed. Participants who achieve a complete or partial response will continue propanolol for an additional 6 weeks or 12 weeks, respectively.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Kaposi Sarcoma
Keywords
Kaposi Sarcoma, Propranolol

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
25 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Propranolol
Arm Type
Experimental
Arm Description
Propranolol Twice Daily (BID) x 12 weeks Dosage: For ages ≤ 12 years: 3mg/kg/day divided BID; for ages > 12 years, 120 mg BID.
Intervention Type
Drug
Intervention Name(s)
Propranolol
Intervention Description
Adults: Propanolol 120 mg tablets by mouth twice daily for up to 24 weeks Children: Propanolol 3 mg/kg suspension, divided dose twice daily for up to 24 weeks
Primary Outcome Measure Information:
Title
Objective Response Rate
Description
ORR is defined as the proportion of participants with complete response (CR), or partial response (PR) based on AIDS Malignancy Consortium Kaposi Sarcoma (AMC KS) Response Criteria.
Time Frame
At one year
Secondary Outcome Measure Information:
Title
Number of dose-limiting toxicities
Description
To evaluate the number of dose-limiting toxicities. The dose-limiting toxicities will be based on the National Cancer Institute's Common Terminology Criteria for Adverse Events
Time Frame
At one year
Title
Number of treatment-emergent adverse events
Description
To evaluate the number of treatment-emergent adverse events. The treatment-emergent adverse events will be based on the National Cancer Institute's Common Terminology Criteria for Adverse Events
Time Frame
At one year
Title
Complete and Partial Response rates in children and adults
Description
Proportion of children and adults with a Complete Response or Partial Response.
Time Frame
At one year
Title
Time to recurrence among children
Description
Time to recurrence among responders overall in children. Recurrent disease is defined as the appearance of tumor following documentation of a complete remission.
Time Frame
At one year
Title
Time to recurrence among adults
Description
Time to recurrence among responders overall in adults. Recurrent disease is defined as the appearance of tumor following documentation of a complete remission.
Time Frame
At one year
Title
Time to progression among children
Description
Time to progression among responders overall in children. Time to progression is defined as time from initiation of propranolol to documentation of first progression.
Time Frame
At one year
Title
Time to progression among adults
Description
Time to progression among responders overall in adults. Time to progression is defined as time from initiation of propranolol to documentation of first progression.
Time Frame
At one year

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Pediatric (< 18 years) and adult (≥ 18 years) participants with biopsy-proven and measurable Kaposi Sarcoma (KS) as defined in the KS Manual of Procedures (MOP). No urgent clinical indication for immediate cytotoxic chemotherapy. Participants who have received cytotoxic chemotherapy > 4 weeks prior to screening are eligible. KS stage: < 18 years: 1A (Mild): disease limited to skin, flat oral mucosal lesions, and/or flesh colored subcutaneous nodules, total <10 lesions. 1B (Moderate): having any of the following features, alone or in combination: a total of 10-19 hyperpigmented skin/oral lesions, nodular oral involvement, conjunctival eye involvement, or exophytic mass. ≥ 18 years: T0: confined to skin and/or lymph nodes and/or minimal oral lesions. T1: limited to tumor-associated edema of cutaneous lesions without functional impairment or flat oral lesions. Performance Status: < 18 years: Lansky performance status > 70% ≥ 18 years: Easter Cooperative Oncology Group (ECOG) performance status ≤ 2 Participants must have adequate organ function, as defined by the following: Bilirubin (direct or total) within normal range, or total bilirubin <3.0 mg/dl for participants with Gilbert syndrome. Calculated creatinine clearance ≥ 30 mL/min for participants ≥ 12 years (see Appendix III); creatinine <1.5 Upper Limit Normal (ULN) for participants < 12 years. Hemoglobin > 9 g/dL; Platelets > 100 × 109/L; ANC > 1000 cells/mm3 Human Immunodeficiency Virus (HIV) positive participants must be on antiretroviral therapy (ART) that conforms to local standards of care. Participants will have been on ART for at least 12 weeks. Participants will not be excluded based on CD4 count or HIV viral load. HIV positive participants must not show recent improvement on ART that may confound response evaluation: If on ART 12 to 24 weeks, participants must show evidence of KS progression requiring further systemic treatment. If on ART for >24 weeks, must show no evidence of regression in the last eight weeks. HIV-negative participants must not show evidence of improvement in the three months prior to enrollment. No history of asthma or diabetes mellitus (as it is a risk factor for hypoglycemia). No clinically significant cardiovascular disease other than hypertension, which is permitted. No use of beta-adrenergic antagonists for other indications. Not pregnant or planning to become pregnant. Propranolol is United Stats Food and Drug Administration (US FDA) pregnancy category C. At this time, the study team has determined that the unknown risk to a developing fetus is greater than the potential benefit of treatment. Use of effective contraception for women of childbearing potential, defined as a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months. Women of child bearing potential (WOCBP) must agree to use adequate contraception (oral contraceptive pills, intrauterine device, Nexplanon, Depo-Provera, or permanent sterilization, etc., or another acceptable method as determined by the investigator) prior to study entry, for the duration of study participation. Not breast feeding. Exclusion Criteria: • Participants who do not fulfill the criteria as listed in Section 3.1 above, are ineligible. Additionally, the presence of any of the following conditions will exclude a participant from study enrollment: Children and adolescents with lymph node or visceral disease, woody edema, or ≥ 20 cutaneous lesions. Children and adolescents with heart rate or systolic blood pressure <10th percentile for age. Adults with visceral disease or tumor-associated edema causing functional impairment. Shortness of breath, hemoptysis, or moderate/severe cough not attributable to causes other than KS. Bleeding from the mouth or rectum not attributable to causes other than KS. Treatment for active and serious infection. Children with severe acute malnutrition based on World Health Organization (WHO) criteria (Mid-upper arm circumference <11.5 cm, weight-for height Z-score <-3 or presence of symmetrical pitting edema). Given the risk of hypotension and hypoglycemia, participants must take the study drug with food. If needed, the study team will pursue additional funding to support providing supplemental food for participants who experience food insecurity. Patients who experienced hypersensitivity to propranolol during initiation phase of treatment or had previous known allergy to propranolol or allergy to other β-blockers. Patients with a history of uncompensated heart failure; severe sinus bradycardia; sick sinus syndrome; or heart block greater than first-degree. Patients with diagnosed obstructive airway disease such as asthma, chronic obstructive pulmonary disease (COPD), or bronchiolitis. History of diabetes mellitus (as it is a risk factor for hypoglycemia) Patients receiving concurrent treatment with an anticancer therapy. Patients must not have received any anticancer therapies within 30 days prior to receiving the first dose of investigational treatment. Patients with concern for Kaposi Sarcoma herpesvirus (KSHV) inflammatory cytokine syndrome.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Shane McAllister, Md, Phd
Phone
612-301-2205
Email
smcallis@umn.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Shane McAllister, Md, PhD
Organizational Affiliation
University of Minnesota Medical School Department of Pediatrics
Official's Role
Study Chair
Facility Information:
Facility Name
Fundación Huésped
City
Buenos Aires
Country
Argentina
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Pedro Cahn, PhD
Phone
54 (11) 4981-7777
Email
pedro.cahn@huesped.org.ar
Facility Name
Instituto Nacional de Câncer José de Alencar
City
Rio De Janeiro
ZIP/Postal Code
20231-050
Country
Brazil
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Fabio Leal, MD, PhD
Phone
552132076557
Email
fabio.leal@inca.gov.br
Facility Name
Complexo Hospitalar Universitário Professor Edgard Santos
City
Salvador
Country
Brazil
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Carlos Brites, PhD
Phone
55 (71) 3283-8123
Email
crbrites@gmail.com
Facility Name
Moi University School of Medicine
City
Eldoret
Country
Kenya
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Naftali Busakhala
Phone
254-722-496-933
Email
nbusakhala@yahoo.com
First Name & Middle Initial & Last Name & Degree
Naftali Busakhala, MBChB MMed
Facility Name
UNC Project Malawi
City
Lilongwe
Country
Malawi
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lameck Chinula
Phone
265 88 248 3220
Email
lchinula@unclilongwe.org
First Name & Middle Initial & Last Name & Degree
Lameck Chinula
Facility Name
Instituto Nacional de Cancerologia
City
Ciudad de Mexico
ZIP/Postal Code
14080
Country
Mexico
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Patricia Volkow, MD
Phone
5255 51026450
Email
pvolkowf@gmail.com
First Name & Middle Initial & Last Name & Degree
Patricia Volkow, MD
Facility Name
African Cancer Institute at Stellenbosch
City
Cape Town
Country
South Africa
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hennie Botha, MMed PhD
Phone
+27 (21) 938-9209
Email
mhbotha@sun.ac.za
First Name & Middle Initial & Last Name & Degree
Hennie Botha
Facility Name
Uganda Cancer Institute
City
Kampala
Country
Uganda
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jackson Orem, MD
Phone
+256 414540 410
Email
jacksonorem@yahoo.co.uk
First Name & Middle Initial & Last Name & Degree
Jackson Orem, MD
Facility Name
University of Zimbabwe College of Health Sciences
City
Harare
Country
Zimbabwe
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Margaret Borok, MBChB, FRCP
Phone
+263 (242) 791-631
Email
mborok@mweb.co.zw
First Name & Middle Initial & Last Name & Degree
Margaret Borok, MBChB (Hons) FRCP(UK)

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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A Study of Propranolol to Treat Kaposi Sarcoma

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