PROACT: Can we Prevent Chemotherapy-related Heart Damage in Patients With Breast Cancer and Lymphoma?

NCT03265574 | Completed Phase 3 DMC

• 1 other identifier: 2016152
• Study Type: interventional
• Target: 111
• Locations: 1 country
• Sites: 1

Brief Summary

PROACT will establish the effectiveness of the angiotensin-converting enzyme inhibitor (ACEI) enalapril maleate (enalapril) in preventing cardiotoxicity in patients with breast cancer and non-Hodgkin lymphoma undergoing adjuvant epirubicin-based chemotherapy.

Conditions

Breast Cancer; Non Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (1)

• Cardiac troponin T release

  Cardiac troponin T release during anthracycline treatment

  One month after last dose of anthracycline

Secondary Outcomes (6)

• Cardiac function

  One month after last dose of anthracycline

• Adherence to enalapril

  One month after last dose of anthracycline

• Adverse Events / Reactions

  One month after last dose of anthracycline

• Anxiety or distress related to trial participation

  One month after last dose of anthracycline

• Cancer and chemotherapy outcomes

  One month after last dose of anthracycline

Study Arms (2)

Intervention

EXPERIMENTAL

Drug: Enalapril

Standard care

NO INTERVENTION

Interventions

Enalapril DRUG

Enalapril is an Angiotensin Converting Enzyme (ACE) inhibitor which supresses the reninangiotensin-aldosterone system resulting in increased plasma renin activity and decreased aldosterone secretion

Intervention

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent.
• Adult patients with histopathologically confirmed non-Hodgkin lymphoma (NHL), planned to receive 6 cycles of R-CHOP or CHOP (total planned dose 300mg/m2 doxorubicin) chemotherapy\*\*

You may not qualify if:

• Positive baseline cardiac troponin T (≥14ng/L);
• known contraindication to ACE inhibitor e.g. renal artery stenosis, severe aortic stenosis;
• are taking, or have a previous intolerance to ACEI (e.g. angioedema);
• patient already taking other agents acting on the renin-angiotensin-aldosterone system e.g. Aliskiren, angiotensin receptor blockers (ARBs), Entresto (sacubitril/valsartan), spironolactone, eplerenone;
• LVEF \<50%\*;
• estimated GFR \< 30 mL/min/1.73m2 at baseline;
• hyperkalaemia defined as serum potassium ≥5.5mmol/L;
• symptomatic hypotension, or Systolic Blood Pressure \<100mmHg;
• poorly-controlled hypertension (Blood Pressure \>160/100mmHg\*\*, or ambulatory BP of 150/95mmHg);
• previous myocardial infarction;
• known metastatic breast cancer;
• previous exposure to anthracycline chemotherapy;
• are pregnant or breastfeeding;
• previous Herceptin treatment or planned Herceptin treatment within four weeks following anthracycline chemotherapy;
• for patients of childbearing potential: refusal to use adequate contraception throughout the trial;\*\*\*

Sponsors & Collaborators

• South Tees Hospitals NHS Foundation Trust: lead
• Newcastle University: collaborator
• University of Durham: collaborator
• Newcastle-upon-Tyne Hospitals NHS Trust: collaborator

Study Sites (1)

South Tees Hospitals NHS FT

Middlesbrough, Teesside, TS4 3BW, United Kingdom

Location

Related Publications (2)

• Austin D, Maier RH, Akhter N, Sayari M, Ogundimu E, Maddox JM, Vahabi S, Humphreys AC, Graham J, Oxenham H, Haney S, Cresti N, Verrill M, Osborne W, Wright KL, Goranova R, Bailey JR, Kalakonda N, Macheta M, Kilner MF, Young ME, Morley NJ, Neelakantan P, Gilbert G, Thomas BK, Graham RJ, Fujisawa T, Mills NL, Hildreth V, Prichard J, Kasim AS, Hancock HC, Plummer C. Preventing Cardiac Damage in Patients Treated for Breast Cancer and Lymphoma: The PROACT Clinical Trial. JACC CardioOncol. 2024 Aug 27;6(5):684-696. doi: 10.1016/j.jaccao.2024.07.010. eCollection 2024 Oct.

  PMID: 39479329 DERIVED

• Maier RH, Plummer C, Kasim AS, Akhter N, Ogundimu E, Maddox J, Graham J, Stewart M, Wardley A, Haney S, Vahabi S, Oxenham H, Humphreys A, Cresti N, Verrill M, Graham R, Chang L, Hancock HC, Austin D. Preventing cardiotoxicity in patients with breast cancer and lymphoma: protocol for a multicentre randomised controlled trial (PROACT). BMJ Open. 2022 Dec 30;12(12):e066252. doi: 10.1136/bmjopen-2022-066252.

  PMID: 36585130 DERIVED

MeSH Terms

Conditions

Breast Neoplasms; Lymphoma, Non-Hodgkin

Interventions

Enalapril

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Lymphoma; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Dipeptides; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Victoria Hildreth

  Study Chair

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 24, 2017
• First Posted: August 29, 2017
• Study Start: October 4, 2017
• Primary Completion: August 4, 2023
• Study Completion: August 4, 2023
• Last Updated: February 20, 2024

Record last verified: 2024-02

Locations

GB (1)