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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

ConditionsHaematological MalignancyColorectal NeoplasmsUrinary Bladder NeoplasmGallbladder NeoplasmsSalivary Gland NeoplasmLung NeoplasmPancreatic NeoplasmOvarian NeoplasmsProstatic NeoplasmSkin NeoplasmSolid Tumour
Trial statusRecruiting
Trial phasePhase 2, Phase 3
Trial typeInterventional
Biological sexAll
Age12+
SponsorCancer Research UK

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

None

Disqualifiers

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.

CD4 count ≥350/μL;

Trial design

Design model

Single group

Treatments tested in this trial

  • Trastuzumab

    Drug

    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.

  • Pertuzumab

    Drug

    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.

Treatment groups

30 Participants
are divided into 1 treatment group
Group A: Treatment Arm 04: trastuzumab in combination with pertuzumabExperimental treatment 2 interventions

Trial outcomes

Primary outcomes

1

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.

Time frame
Disease assessments to be performed up to 24 weeks from the start of trial treatment.
2

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.

Time frame
Disease assessments to be performed up to 24 weeks from the start of trial treatment.

Secondary outcomes

1

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.

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.
2

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.

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.
3

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.

Time frame
From first dose of trastuzumab and pertuzumab to discontinuation of trial treatment up to 5 years.
4

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.

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.

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Cancer Research UK

Lead sponsor

University of Manchester

Collaborator

University of Birmingham

Collaborator

Royal Marsden NHS Foundation Trust

Collaborator

Hoffmann-La Roche

Collaborator

Source ClinicalTrials.gov
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