NCT05786716

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 (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.

• Status: Recruiting
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 30 (estimated)
• Sponsor: Cancer Research UK · Academic / Other
• Sex: All
• Age: 12 Years
• Healthy volunteers: Not accepted

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.

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
• Pancreatic Neoplasm
• Ovarian Neoplasms
• Prostatic Neoplasm
• Skin Neoplasm
• Solid Tumour

Interventions

Type	Name	Description
DRUG	Trastuzumab	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.
DRUG	Pertuzumab	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.

Timeline

• Start date: 2023-03-07
• Primary completion: 2029-10-01
• Completion: 2029-10-01
• First posted: 2023-03-28
• Last updated: 2025-12-02

Locations

27 sites across 1 country: United Kingdom