Haematological MalignancyPhase 2/3DETERMINENCT05786716
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
A Phase 2/3 study testing Trastuzumab and Pertuzumab in people with Haematological Malignancy and Colorectal Neoplasms, run by Cancer Research UK at 27 sites in United Kingdom.
Trial 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). Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Haematological Malignancy, Colorectal Neoplasms, Urinary Bladder Neoplasm
- What is being tested?
- Trastuzumab and Pertuzumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 27 sitesUnited Kingdom
- Study dates
- 7 Mar 2023to Oct 2029
- Phase
- Phase 2/3
- Are there results?
- Not yet: the study is under way
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 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
- Age 12 years or above.
- 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:
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- combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal or transdermal):
- progestogen-only hormonal contraception associated with or without inhibition of ovulation (oral, injectable or implantable)
- intrauterine device (IUD)
- intrauterine hormone-releasing system (IUS)
- bilateral tubal occlusion
- vasectomised partner
- sexual abstinence
- male or female condom with or without spermicide
- cap, diaphragm or sponge with spermicide
- Effective from the first administration of trastuzumab or pertuzumab (whichever is first), throughout the trial and for seven months after the last administration of trastuzumab or pertuzumab (whichever is later).
- Male patients with partners who are women of childbearing potential are eligible provided that they agree to the following, from the first administration of trastuzumab or pertuzumab (whichever is first), throughout the trial and for seven months after the last administration of trastuzumab or pertuzumab (whichever is later):
- Agree to take measures not to father children by using a barrier method of contraception (condom plus spermicide) or to sexual abstinence.
- Non-vasectomised male patients with partners who are women of childbearing potential must also be willing to ensure that their partner uses an effective method of contraception as in C, above.
- Male patients with pregnant or lactating partners must be advised to use barrier method contraception (e.g. condom) to prevent drug exposure of the foetus or neonate.
- All male patients must refrain from donating sperm for the same period.
- Patients must be able and willing to undergo a fresh tissue biopsy at baseline and blood samples for translational research. Note that for patients with haematological malignancies or neuroblastomas, blood, bone marrow aspiration and/or trephine or lymph node biopsy samples may be taken.
- ADULT PATIENTS (≥18 years): Adequate organ function as per haematological and biochemical indices within the ranges defined in the protocol. These measurements should be performed to confirm the patient's eligibility.
- PAEDIATRIC PATIENTS (<18 years): Adequate organ function as per haematological and biochemical indices within the ranges defined in the protocol. These measurements should be performed to confirm the patient's eligibility.
Who cannot join
- Diagnosis of HER2-positive early or metastatic breast cancer.
- Female patients who are pregnant, breastfeeding or planning to become pregnant during the trial or within seven months following their last dose of trastuzumab or pertuzumab (whichever is later).
- Severe dyspnoea at rest due to complications of advanced malignancy or requiring supplementary oxygen therapy.
- Known hypersensitivity to trastuzumab or pertuzumab, murine proteins, or to any of the excipients.
- Patients who were administered a live, attenuated vaccine within 28 days prior to enrolment, or anticipation of need for such a vaccine during trastuzumab and pertuzumab treatment or within six months after the final dose of trastuzumab and pertuzumab.
- Patients with clinically significant pre-existing cardiac conditions, including uncontrolled or symptomatic angina, uncontrolled atrial or ventricular arrhythmias (within three months), NYHA class III or IV congestive heart failure.
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- Left Ventricular Ejection Fraction <55%.
- Patients with a cerebrovascular event (including stroke or transient ischaemic attack [TIA]) or cardiovascular event (including acute myocardial infarction [MI]) within three months before the first dose of trastuzumab and pertuzumab.
- Patients with primary CNS tumours may be considered unless intra-tumoural bleeding has occurred within 2 weeks of the first dose of trastuzumab and pertuzumab, and patients with punctate CNS haemorrhages <3 mm may be considered.
- Prior treatment with the same class of drug unless genetic profile demonstrates a mechanism of resistance known to be potentially sensitive to trastuzumab or pertuzumab.
- Any clinically significant concomitant disease or condition (or its treatment) that could interfere with the conduct of the trial or absorption of oral medications or that would, in the opinion of the Investigator, pose an unacceptable risk to the patient in this trial.
- Known active infections (bacterial, fungal or viral) that would interfere with the assessment of safety or efficacy of trastuzumab and pertuzumab, including human immunodeficiency virus (HIV) positivity. Patients with history of testing positive for HIV infection are eligible provided the each of the following conditions are met:
- CD4 count ≥350/μL;
- undetectable viral load;
- receiving antiretroviral therapy (ART) that does not interact with IMP (patients should be on established ART for at least four weeks); and
- no HIV/ acquired immune deficiency syndrome (AIDS)-associated opportunistic infection in the last 12 months.
Trial locations and contacts
27 sites in 1 country. Contact the study team or a site near you to ask about taking part.
27 sites in 1 country
United Kingdom27 sites, 27 recruiting
- Recruiting
Belfast City Hospital
Belfast, BT9 7AB
Vicky Coyle, Prof, V.Coyle@qub.ac.uk
Vicky Coyle, Prof
- Recruiting
University Hospital Birmingham
Birmingham, B15 2TT
Gary Middleton, Prof, 0121 371 3573, G.Middleton@bham.ac.uk
Gary Middleton, Prof
- Not yet recruiting
Birmingham Children's Hospital
Birmingham
Gerard Millen, Dr, 07921843607, g.millen@nhs.net
Gerard Millen, Dr
- Recruiting
Bristol Royal Hospital for Children
Bristol, BS2 8BJ
Antony Ng, Dr, 0117 342 8044, Antony.Ng@uhbw.nhs.uk
Antony Ng, Dr
- Recruiting
Bristol Haematology and Oncology Centre
Bristol, BS2 8ED
Antony Ng, Dr, 0117 342 8044, Antony.Ng@uhbw.nhs.uk
Antony Ng, Dr
- Recruiting
Addenbrooke's Hospital
Cambridge, CB2 OQQ
Bristi Basu, Dr, 01223 596105, bb313@medschl.cam.ac.uk
Bristi Basu, Dr
- Recruiting
Velindre Cancer Centre
Cardiff, CF14 2TL
Robert Jones, Dr, 02920 615888 ext. 6327, Robert.Hugh.Jones@wales.nhs.uk
Robert Jones, Dr
- Not yet recruiting
Cardiff Children's Hospital
Cardiff, CF14 4XW
Madeline Adams, Dr, +442921842285, madeline.adams@wales.nhs.uk
Madeline Adams, Dr
- Recruiting
Western General Hospital
Edinburgh, EH4 2XU
Stefan Symeonides, Dr
Stefan Symeonides, Dr
- Recruiting
The Beatson Hospital
Glasgow, G12 OYN
Patricia Roxburgh, Dr, 0141 301 7118, Patricia.Roxburgh@glasgow.ac.uk
Patricia Roxburgh, Dr
- Recruiting
Royal Hospital for Children Glasgow
Glasgow, G51 4TF
Milind Ronghe, Dr, 0141 452 6692, Milind.Ronghe@ggc.scot.nhs.uk
Milind Ronghe, Dr
- Recruiting
Leicester Royal Infirmary
Leicester, LE1 5WW
Olubukola Ayodele, Dr, 0116 2587601, olubukola.ayodele@uhl-tr.nhs.uk
Olubukola Ayodele, Dr
- Recruiting
Alder Hey Hospital
Liverpool, L14 5AB
Lisa Howell, Dr, 0151 293 3679, Lisa.Howell@alderhey.nhs.uk
Lisa Howell, Dr
- Recruiting
University College London Hospital
London, NW1 2BU
Martin Forster, Prof, 020 3447 5085, M.Forster@ucl.ac.uk
Martin Forster, Prof
- Recruiting
Guy's Hospital
London, SE1 9RT
James Spicer, Dr, 020 7188 4260, james.spicer@kcl.ac.uk
James Spicer, Dr
- Recruiting
Great Ormond Street Hospital
London, WC1N 3JH
Darren Hargrave, Dr, 0207 813 8525, Darren.hargrave@gosh.nhs.uk
Darren Hargrave, Dr
- Not yet recruiting
Royal Manchester Children's Hospital
Manchester, M13 9WL
Guy Makin, Dr, 0161 701 8419, Guy.Makin@mft.nhs.uk
Guy Makin, Dr
- Recruiting
The Christie Hospital
Manchester, M20 4BX
Matthew Krebs, Dr, 0161 918 7672, matthew.krebs@nhs.net
Matthew Krebs, Dr
- Recruiting
Clatterbridge Cancer Centre
Metropolitan Borough of Wirral, CH63 4JY
Dan Palmer, Dr, 0151 706 4172 / 0151 706 4177, daniel.palmer@liverpool.ac.uk
Dan Palmer, Dr
- Recruiting
Great North Children's Hospital
Newcastle, NE1 4LP
Alastair Greystoke, Dr, 0191 2138476, Alastair.Greystoke@newcastle.ac.uk
Alastair Greystoke, Dr
- Recruiting
Freeman Hospital
Newcastle, NE7 7DN
Alastair Greystoke, Dr, 0191 2138476, Greystoke@newcastle.ac.uk
Alastair Greystoke, Dr
- Recruiting
Churchill Hospital
Oxford, OX3 7LE
Sarah Pratap, Dr, 01865 235273, Sarah.Pratap@ouh.nhs.uk
Sarah Pratap, Dr
- Recruiting
John Radcliffe Hospital
Oxford, OX3 9DU
Sarah Pratap, Dr, 01865 235273, Sarah.Pratap@ouh.nhs.uk
Sarah Pratap, Dr
- Recruiting
Weston Park Hospital
Sheffield, S10 2SJ
Sarah Danson, Dr, 0114 226 5068, s.danson@sheffield.ac.uk
Sarah Danson, Dr
- Recruiting
Sheffield's Children's Hospital
Sheffield, S10 2TH
Daniel Yeomanson, Dr, 01142717366, danyeomanson@nhs.net
Daniel Yeomanson, Dr
- Recruiting
Southampton General Hospital
Southampton, SO16 6YD
Juliet Gray, Prof, 0238 120 6639, Juliet.Gray@uhs.nhs.uk
Juliet Gray, Prof
- Recruiting
The Royal Marsden Hospital
Sutton, SM2 5PT
Lynley Marshall, Dr, 0208 661 3678, LynleyVanessa.Marshall@icr.ac.uk
Lynley Marshall, Dr
About this study
Official title: 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.
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.
Read more
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.
Read the detailed description
DETERMINE Treatment Arm 04: Trastuzumab in combination with pertuzumab in Adult, Paediatric and TYA patients with rare* cancers with HER2 amplification or activating mutations and in common cancers where HER2 amplification or activating mutations are considered to be infrequent.
*Rare is defined generally as incidence less than 6 cases in 100,000 patients (includes paediatric and teenagers/young adult cancers) or common cancers with rare alterations.
This treatment arm has a target sample size of 30 evaluable patients. Sub-cohorts may be defined and further expanded to a target of 30 evaluable patients each.
The ultimate aim is to translate positive clinical findings to the NHS (Cancer Drugs Fund) to provide new treatment options for rare adult, paediatric and TYA cancers.
OUTLINE:
Pre-screening: The Molecular Tumour Board (MTB) makes a treatment recommendation for the patient based on molecularly-defined cohorts.
Screening: Consenting patients undergo biopsy and collection of blood samples for research purposes.
Treatment: Patients will receive trastuzumab and pertuzumab until disease progression without clinical benefit, unacceptable adverse events (AEs) or withdrawal of consent. Patients will also undergo collection of blood samples at various intervals while receiving treatment and at End of Treatment (EoT).
After completion of study treatment, patients are followed up every 3 months for 2 years.
THE DETERMINE TRIAL MASTER (SCREENING) PROTOCOL:
Please see DETERMINE Trial Master (Screening) Protocol record (NCT05722886) for information on the DETERMINE Trial Master Protocol and applicable documents.
- Conditions
- Haematological Malignancy, Colorectal Neoplasms, Urinary Bladder Neoplasm, Gallbladder Neoplasms, Salivary Gland Neoplasm, Lung Neoplasm
- Being tested
- Trastuzumab, Pertuzumab
- Keywords
- Adult, Antibodies, monoclonal, Cancer, Child, Molecular Targeted Therapy, Mutation, Paediatric, Pertuzumab, Precision Medicine, Rare, Receptor, ErbB-2, Targeted, Trastuzumab, Tumour-agnostic, Young adult
- Medical subject headings
- Hematologic Neoplasms, Colorectal Neoplasms, Urinary Bladder Neoplasms, Gallbladder Neoplasms, Salivary Gland Neoplasms, Lung Neoplasms, Pancreatic Neoplasms, Ovarian Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TrastuzumabDrug
Also called Herceptin
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.
PertuzumabDrug
Also called Perjeta
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.
| Study group | Role | What they receive |
|---|---|---|
| Treatment Arm 04: trastuzumab in combination with pertuzumab | Experimental | This trastuzumab and pertuzumab treatment arm is for adult, paediatric and TYA patients with cancers with HER2 amplification or activating mutations. Receives: Drug: Trastuzumab; Drug: Pertuzumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Disease assessments to be performed up to 24 weeks from the start of trial treatment.
Secondary outcomes (13)
Duration of response (DR)
DR is defined as the time from the date of the first confirmed CR or PR according to RECIST 1.1 or ir-RECIST or standard imaging criteria for specific disease (e.g. RANO criteria) to the date of disease progression. The trial will report the median DR and 95% credible interval.
Measured: 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)
PCSD is defined as the greatest decrease or least increase in the sum of target lesion diameters (RECIST) or index lesion diameters (irRECIST) as a percentage compared to the baseline measurement. The trial will report the mean PCSD and 95% credible interval.
Measured: 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)
TTD is defined as the time from date of starting trial treatment to date of discontinuing trial treatment, in days estimated by the median of the posterior inverse gamma probability distribution. The trial will report the median TTD and 95% credible interval.
Measured: From first dose of trastuzumab and pertuzumab to discontinuation of trial treatment up to 5 years.
Progression-Free Survival time (PFS)
PFS is defined as the time from date of starting trial treatment to date of progression or date of death without a previous progression recorded estimated by the median of the posterior inverse gamma probability distribution.
Measured: 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)
TTP is defined as the time from date of starting trial treatment to date of progression or date of death without recorded progression censored rather than events. The trial will report the median TTP and 95% credible interval.
Measured: 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.
Growth Modulation Index (GMI)
GMI is defined as the ratio of TTP with the trial protocol treatment to TTP on the most recent prior line of therapy. The trial will report the mean GMI and 95% credible interval.
Measured: 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.
Overall Survival time (OS)
OS is defined as the time from date of starting trial treatment to date of death from any cause estimated by the median of the posterior normal probability distribution.
Measured: Time of death or up to 2 years after the EoT visit.
Occurrence of at least one Suspected Unexpected Serious Adverse Reaction (SUSAR)
The trial will report the number of patients who experience at least one SUSAR to trastuzumab and/or pertuzumab.
Measured: From the time of consent until 28 days after last dose of trastuzumab and/or pertuzumab (up to 5 years) or until patient starts another anti-cancer therapy, whichever came first. An average time frame will be presented with results entry.
Occurrence of at least one Grade 3, 4 or 5 trastuzumab and/or pertuzumab related AE
Number of patients who experience at least one trastuzumab and/or pertuzumab related Grade 3, 4 or 5 AE according to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0.
Measured: From the time of consent until 28 days after last dose of trastuzumab or pertuzumab (up to 5 years) or until patient starts another anti-cancer therapy, whichever came first. An average time frame will be presented with results entry.
EORTC-QLQ-C30 Standardised Area Under Summary Score Curve (QLQSAUC) in adult patients
For adult populations, multiple measures of Quality of Life (QoL) will be generated from patient completion of the European Organisation for Research and Treatment of Cancer QLQ-C30 (EORTC-QLQ-C30) questionnaire (15 measures). For each patient the Summary Score from the questionnaire will be generated at each time point and the area under the curve generated by these scores over time will be calculated and standardised by the time frame. The trial will report the mean QLQSAUC and 95% credible interval.
Measured: QoL surveys performed prior to inclusion, every cycle (each cycle is 21 days) and at EoT visit (up to 5 years).
EQ-5D Standardised Area Under Index Value Curve (EQ5DSAUC) in adult patients
For adult populations, two measures of QoL will be generated from patient completion of the EQ-5D-5L questionnaire. For each measure, scores based on responses from the questionnaire will be generated at each time point and the area under the curve generated by these scores over time will be calculated and standardised by the time frame. The trial will report the mean EQ5DSAUC and 95% credible interval.
Measured: QoL surveys performed prior to inclusion, every cycle (each cycle is 21 days) and at EoT visit (up to 5 years).
Mean change from baseline in the PedsQL 4.0 Standardised Area Under total Scale Score Curve (PedsSAUC) in paediatric patients
For paediatric populations, multiple measures of QoL will be generated from patient completion of the PedsQL 4.0 (4 measures). The Summary Score from the questionnaire will be generated at each time point and the area under the curve generated by these scores over time will be calculated and standardised by the time frame. The trial will report the mean PedsSAUC and 95% credible interval.
Measured: QoL surveys performed prior to inclusion, every cycle (each cycle is 21 days) and at EoT visit (up to 5 years).
Mean change from baseline in the PedsQL 4.0 Standardised Area Under total Scale Score Curve (PedsSAUC) in parents of paediatric patients
For paediatric populations multiple measures of QoL will be generated from patient's parent completion of the PedsQL 4.0 (4 measures). The Summary Score from the questionnaire will be generated at each time point and the area under the curve generated by these scores over time will be calculated and standardised by the time frame. The trial will report the mean PedsSAUC and 95% credible interval.
Measured: QoL surveys performed prior to inclusion, every cycle (each cycle is 21 days) and at EoT visit (up to 5 years).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Mar 2023
- Study start7 Mar 2023
- Primary completionOct 2029 (estimated)
- Study completionOct 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Haematological MalignancyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2/3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Cancer Research UK
- Sponsor type
- University, hospital or other
- Collaborators
- University of Manchester, University of Birmingham, Royal Marsden NHS Foundation Trust, Hoffmann-La Roche
- Responsible party
- Sponsor
- Investigators
- Matthew Krebs, Dr, Principal investigator, The Christie Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05786716
- Sponsor's protocol ID
- CRUKD/21/004 - Treatment Arm 4
- Other IDs
- IRAS ID: 1004057
- Acronym
- DETERMINE
- Status last verified
- Nov 2025
- First submitted
- 22 Feb 2023
- Last updated
- 2 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Study at a glance
From the registry record, last updated by the sponsor on 2 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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.
- ClinicalTrials.gov ID
- NCT05786716
- Acronym / sponsor ID
- DETERMINE / CRUKD/21/004 - Treatment Arm 4
- Conditions
- Haematological Malignancy, Colorectal Neoplasms, Urinary Bladder Neoplasm, Gallbladder Neoplasms, Salivary Gland Neoplasm, Lung Neoplasm
- Keywords
- Adult, Antibodies, monoclonal, Cancer, Child, Molecular Targeted Therapy, Mutation, Paediatric, Pertuzumab
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Cancer Research UKUniversity, hospital or other
- Collaborators
- University of Manchester, University of Birmingham, Royal Marsden NHS Foundation Trust, Hoffmann-La Roche
- Study start
- 7 Mar 2023 (actual)
- Primary completion
- Oct 2029 (estimated)
- Study completion
- Oct 2029 (estimated)
- First posted
- 28 Mar 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
DETERMINE Treatment Arm 04: Trastuzumab in combination with pertuzumab in Adult, Paediatric and TYA patients with rare* cancers with HER2 amplification or activating mutations and in common cancers where HER2 amplification or activating mutations are considered to be infrequent.
*Rare is defined generally as incidence less than 6 cases in 100,000 patients (includes paediatric and teenagers/young adult cancers) or common cancers with rare alterations.
This treatment arm has a target sample size of 30 evaluable patients. Sub-cohorts may be defined and further expanded to a target of 30 evaluable patients each.
The ultimate aim is to translate positive clinical findings to the NHS (Cancer Drugs Fund) to provide new treatment options for rare adult, paediatric and TYA cancers.
OUTLINE:
Pre-screening: The Molecular Tumour Board (MTB) makes a treatment recommendation for the patient based on molecularly-defined cohorts.
Screening: Consenting patients undergo biopsy and collection of blood samples for research purposes.
Treatment: Patients will receive trastuzumab and pertuzumab until disease progression without clinical benefit, unacceptable adverse events (AEs) or withdrawal of consent. Patients will also undergo collection of blood samples at various intervals while receiving treatment and at End of Treatment (EoT).
After completion of study treatment, patients are followed up every 3 months for 2 years.
THE DETERMINE TRIAL MASTER (SCREENING) PROTOCOL:
Please see DETERMINE Trial Master (Screening) Protocol record (NCT05722886) for information on the DETERMINE Trial Master Protocol and applicable documents.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment Arm 04: trastuzumab in combination with pertuzumab | Experimental | Drug: Trastuzumab, Drug: PertuzumabThis trastuzumab and pertuzumab treatment arm is for adult, paediatric and TYA patients with cancers with HER2 amplification or activating mutations. |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (24 listed)
- 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.
- Age 12 years or above.
- Women of childbearing potential are eligible provided that they meet the following criteria:
- Have a negative serum or urine pregnancy test before enrolment and;
Key exclusion criteria (16 listed)
- Diagnosis of HER2-positive early or metastatic breast cancer.
- Female patients who are pregnant, breastfeeding or planning to become pregnant during the trial or within seven months following their last dose of trastuzumab or pertuzumab (whichever is later).
- Severe dyspnoea at rest due to complications of advanced malignancy or requiring supplementary oxygen therapy.
- Known hypersensitivity to trastuzumab or pertuzumab, murine proteins, or to any of the excipients.
- Patients who were administered a live, attenuated vaccine within 28 days prior to enrolment, or anticipation of need for such a vaccine during trastuzumab and pertuzumab treatment or within six months after the final dose of trastuzumab and pertuzumab.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TrastuzumabAlso: HerceptinAn 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. | Drug | Treatment Arm 04: trastuzumab in combination with pertuzumab |
| PertuzumabAlso: PerjetaAn 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. | Drug | Treatment Arm 04: trastuzumab in combination with pertuzumab |
Primary outcome
Objective Response (OR)
Time frame: Disease assessments to be performed up to 24 weeks from the start of trial treatment.
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.
Durable Clinical Benefit (DCB)
Time frame: Disease assessments to be performed up to 24 weeks from the start of trial treatment.
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.
13 secondary outcomes
Duration of response (DR)
Time frame: 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)
Time frame: 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)
Time frame: From first dose of trastuzumab and pertuzumab to discontinuation of trial treatment up to 5 years.
Progression-Free Survival time (PFS)
Time frame: 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)
Time frame: 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.
Growth Modulation Index (GMI)
Time frame: 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.
Overall Survival time (OS)
Time frame: Time of death or up to 2 years after the EoT visit.
Occurrence of at least one Suspected Unexpected Serious Adverse Reaction (SUSAR)
Time frame: From the time of consent until 28 days after last dose of trastuzumab and/or pertuzumab (up to 5 years) or until patient starts another anti-cancer therapy, whichever came first. An average time frame will be presented with results entry.
Occurrence of at least one Grade 3, 4 or 5 trastuzumab and/or pertuzumab related AE
Time frame: From the time of consent until 28 days after last dose of trastuzumab or pertuzumab (up to 5 years) or until patient starts another anti-cancer therapy, whichever came first. An average time frame will be presented with results entry.
EORTC-QLQ-C30 Standardised Area Under Summary Score Curve (QLQSAUC) in adult patients
Time frame: QoL surveys performed prior to inclusion, every cycle (each cycle is 21 days) and at EoT visit (up to 5 years).
EQ-5D Standardised Area Under Index Value Curve (EQ5DSAUC) in adult patients
Time frame: QoL surveys performed prior to inclusion, every cycle (each cycle is 21 days) and at EoT visit (up to 5 years).
Mean change from baseline in the PedsQL 4.0 Standardised Area Under total Scale Score Curve (PedsSAUC) in paediatric patients
Time frame: QoL surveys performed prior to inclusion, every cycle (each cycle is 21 days) and at EoT visit (up to 5 years).
Mean change from baseline in the PedsQL 4.0 Standardised Area Under total Scale Score Curve (PedsSAUC) in parents of paediatric patients
Time frame: QoL surveys performed prior to inclusion, every cycle (each cycle is 21 days) and at EoT visit (up to 5 years).
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Dec 2025.
- Overview of the DETERMINE trial.Link provided by the sponsor.
- ClinicalTrials.gov record for DETERMINE Trial Master Screening Protocol (NCT05722886).Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Matthew Krebs, Dr principal investigator
The Christie Hospital
27 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Trastuzumab and Pertuzumab in people with Haematological Malignancy and Colorectal Neoplasms, run by Cancer Research UK at 27 sites in United Kingdom.
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 24 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: looking for participants now, as of the sponsor's last update on 2 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 27 sites in United Kingdom. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Aida Sarmiento Castro (+44 207 242 0200, determine@cancer.org.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response (OR) (time frame: Disease assessments to be performed up to 24 weeks from the start of trial treatment.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 2 Dec 2025.