DETERMINE Trial Treatment Arm 04: Trastuzumab in Combination With Pertuzumab in Adult, Paediatric and Teenage/Young Adult Patients With Cancers With HER2 Amplification or Activating Mutations
DETERMINE
DETERMINE (Determining Extended Therapeutic Indications for Existing Drugs in Rare Molecularly Defined Indications Using a National Evaluation Platform Trial): An Umbrella-Basket Platform Trial to Evaluate the Efficacy of Targeted Therapies in Rare Adult, Paediatric and Teenage/Young Adult (TYA) Cancers With Actionable Genomic Alterations, Including Common Cancers With Rare Actionable Alterations. Treatment Arm 04: Trastuzumab in Combination With Pertuzumab in Adult, Paediatric and Teenage/Young Adult Patients With Cancers With HER2 Amplification or Activating Mutations.
2 other identifiers
interventional
30
1 country
27
Brief Summary
This clinical trial is looking at a combination of drugs called trastuzumab and pertuzumab. This combination of drugs is approved together as standard of care treatment for adult patients with breast cancer (often with other anti-cancer drugs). This means it has gone through clinical trials and been approved by the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK. Trastuzumab and pertuzumab work in patients with these types of cancers which have a molecular alteration called HER2 amplification or HER2 activating mutation. Investigators now wish to find out if it will be useful in treating patients with other cancer types which are also HER2 amplified or HER2 mutated. If the results are positive, the study team will work with the NHS and the Cancer Drugs Fund to see if these drugs can be routinely accessed for patients in the future. This trial is part of a trial programme called DETERMINE. The programme will also look at other anti-cancer drugs in the same way, through matching the drug to rare cancer types or ones with specific mutations.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Mar 2023
Longer than P75 for phase_2
27 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 22, 2023
CompletedStudy Start
First participant enrolled
March 7, 2023
CompletedFirst Posted
Study publicly available on registry
March 28, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 1, 2029
ExpectedStudy Completion
Last participant's last visit for all outcomes
October 1, 2029
December 2, 2025
November 1, 2025
6.6 years
February 22, 2023
November 25, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Objective Response (OR)
An OR is defined as the confirmed occurrence of either a Complete Response (CR) or Partial Response (PR) according to Response Evaluation Criteria in Solid Tumours (RECIST) Version 1.1 criteria (or immune related \[ir\]-RECIST or standard imaging criteria for specific disease e.g. Response Evaluation in Neuro Oncology criteria \[RANO\]). In patients with leukaemia, OR will be defined as the occurrence of CR, CRi (CR incomplete neutrophil recovery) or CRp (CR with incomplete platelet recovery). The trial will report the proportion of patients with an OR and 95% credible interval.
Disease assessments to be performed up to 24 weeks from the start of trial treatment.
Durable Clinical Benefit (DCB)
DCB is defined as the absence of disease progression for at least 24 weeks from the start of trial treatment according to RECIST Version 1.1 criteria (or ir-RECIST or standard imaging criteria for specific disease e.g. RANO criteria) and, where relevant (e.g. for haematological malignancies), by standard bone marrow response assessment criteria. Alternative definitions of DCB based on different time points may be pre-specified for particular sub-cohorts if 24 weeks is not clinically relevant. The trial will report the proportion of patients with a DCB and 95% credible interval.
Disease assessments to be performed up to 24 weeks from the start of trial treatment.
Secondary Outcomes (13)
Duration of response (DR)
Disease assessment every 2 cycles of trastuzumab and pertuzumab (each cycle is 21 days) and at EoT. After 24 weeks, it can be done every 12 weeks, on discussion with Sponsor. Follow-up visits are every 3 months after last dose for up to 2 years.
Best percentage change in sum of target lesion / index lesion diameters (PCSD)
Disease assessment every 2 cycles of trastuzumab and pertuzumab (each cycle is 21 days) and at EoT. After 24 weeks, it can be done every 12 weeks, on discussion with Sponsor. Follow-up visits are every 3 months after last dose for up to 2 years.
Time to treatment discontinuation (TTD)
From first dose of trastuzumab and pertuzumab to discontinuation of trial treatment up to 5 years.
Progression-Free Survival time (PFS)
Disease assessment every 2 cycles of trastuzumab and pertuzumab (each cycle is 21 days) and at EoT. After 24 weeks, it can be done every 12 weeks, on discussion with Sponsor. Follow-up visits are every 3 months after last dose for up to 2 years.
Time to Progression (TTP)
Disease assessment every 2 cycles of trastuzumab and pertuzumab (each cycle is 21 days) and at EoT. After 24 weeks, it can be done every 12 weeks, on discussion with Sponsor. Follow-up visits are every 3 months after last dose for up to 2 years.
- +8 more secondary outcomes
Study Arms (1)
Treatment Arm 04: trastuzumab in combination with pertuzumab
EXPERIMENTALThis trastuzumab and pertuzumab treatment arm is for adult, paediatric and TYA patients with cancers with HER2 amplification or activating mutations.
Interventions
An initial loading dose of 8 mg/kg body weight, followed thereafter by a maintenance dose of 6 mg/kg body weight administered intravenously every 21 days. Patients may continue until disease progression without clinical benefit, unacceptable AEs or withdrawal of consent.
An initial loading dose of 640 mg, followed thereafter by a maintenance dose of 420 mg administered intravenously every 21 days. Paediatric patients will receive an initial loading dose of 14 mg/kg (maximum 840 mg), followed thereafter by a maintenance dose of 7 mg/kg (maximum 420 mg) administered intravenously every 21 days. Patients may continue until disease progression without clinical benefit, unacceptable AEs or withdrawal of consent.
Eligibility Criteria
You may not qualify if:
- A. Confirmed diagnosis of a malignancy harbouring HER2 amplification, or an appropriate activating mutation as defined by the MTB, using an analytically validated next-generation sequencing method.
- A HER2 amplification copy number between 5-9 will require an MTB discussion. A HER2 amplification copy number ≥10 will be fast-tracked for an MTB recommendation, unless there are any patient-specific individualities (such as multiple gene amplifications) that require MTB discussion.
- B. Age 12 years or above.
- C. Women of childbearing potential are eligible provided that they meet the following criteria:
- Have a negative serum or urine pregnancy test before enrolment and;
- Agree to use one form of effective birth control method such as:
- I. combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal or transdermal):
- II. progestogen-only hormonal contraception associated with or without inhibition of ovulation (oral, injectable or implantable)
- III. intrauterine device (IUD)
- IV. intrauterine hormone-releasing system (IUS)
- V. bilateral tubal occlusion
- VI. vasectomised partner
- VII. sexual abstinence
- VIII. male or female condom with or without spermicide
- IX. cap, diaphragm or sponge with spermicide
- +25 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Cancer Research UKlead
- University of Manchestercollaborator
- University of Birminghamcollaborator
- Royal Marsden NHS Foundation Trustcollaborator
- Hoffmann-La Rochecollaborator
Study Sites (27)
Belfast City Hospital
Belfast, BT9 7AB, United Kingdom
University Hospital Birmingham
Birmingham, B15 2TT, United Kingdom
Birmingham Children's Hospital
Birmingham, United Kingdom
Bristol Royal Hospital for Children
Bristol, BS2 8BJ, United Kingdom
Bristol Haematology and Oncology Centre
Bristol, BS2 8ED, United Kingdom
Addenbrooke's Hospital
Cambridge, CB2 OQQ, United Kingdom
Velindre Cancer Centre
Cardiff, CF14 2TL, United Kingdom
Cardiff Children's Hospital
Cardiff, CF14 4XW, United Kingdom
Western General Hospital
Edinburgh, EH4 2XU, United Kingdom
The Beatson Hospital
Glasgow, G12 OYN, United Kingdom
Royal Hospital for Children Glasgow
Glasgow, G51 4TF, United Kingdom
Leicester Royal Infirmary
Leicester, LE1 5WW, United Kingdom
Alder Hey Hospital
Liverpool, L14 5AB, United Kingdom
University College London Hospital
London, NW1 2BU, United Kingdom
Guy's Hospital
London, SE1 9RT, United Kingdom
Great Ormond Street Hospital
London, WC1N 3JH, United Kingdom
Royal Manchester Children's Hospital
Manchester, M13 9WL, United Kingdom
The Christie Hospital
Manchester, M20 4BX, United Kingdom
Clatterbridge Cancer Centre
Metropolitan Borough of Wirral, CH63 4JY, United Kingdom
Great North Children's Hospital
Newcastle, NE1 4LP, United Kingdom
Freeman Hospital
Newcastle, NE7 7DN, United Kingdom
Churchill Hospital
Oxford, OX3 7LE, United Kingdom
John Radcliffe Hospital
Oxford, OX3 9DU, United Kingdom
Weston Park Hospital
Sheffield, S10 2SJ, United Kingdom
Sheffield's Children's Hospital
Sheffield, S10 2TH, United Kingdom
Southampton General Hospital
Southampton, SO16 6YD, United Kingdom
The Royal Marsden Hospital
Sutton, SM2 5PT, United Kingdom
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Matthew Krebs, Dr
The Christie Hospital
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 22, 2023
First Posted
March 28, 2023
Study Start
March 7, 2023
Primary Completion (Estimated)
October 1, 2029
Study Completion (Estimated)
October 1, 2029
Last Updated
December 2, 2025
Record last verified: 2025-11
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF
- Time Frame
- All requests for data relating to this treatment arm that are made within 5 years from last patient last visit for the trastuzumab and pertuzumab treatment arm will be considered; requests made subsequently will be considered where possible.
- Access Criteria
- When a request has been approved, Cancer Research UK will provide access to the de-identified individual patient-level data and appropriate supporting information. A signed Data Sharing Agreement must be in place before accessing requested information. Requests should be submitted to drugdev@cancer.org.uk.
Individual de-identified patient data will be shared with researchers whose proposed use of the data is approved by a review committee of the Sponsor.