Phase 2 Study on the Efficacy of Alpelisib and Drug Combinations in Advanced Cancer with Genomic or Protein Expression Variants in Norway
- Trial ID
- 2023-507894-16-00
- Sponsor
- Oslo University Hospital HF
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the **anti-tumour activity** and toxicity of commercially available, targeted anti-cancer drugs in patients with advanced malignancy. These malignancies harbor a genomic or protein expression variant that is either a known drug target or predicts sensitivity to a drug. This objective is clinically relevant as it aims to optimize treatment strategies for patients with advanced cancer by utilizing precision medicine approaches, potentially improving patient outcomes and expanding therapeutic options.
Secondary objectives include further describing the **tumour response** to treatment. This will provide additional insights into the efficacy of the targeted therapies and help refine treatment protocols for better management of advanced cancer cases.
Participants
The clinical trial involves participants diagnosed with **cancer**, specifically those with advanced malignancies that exhibit genomic or protein expression variants targeted by specific anti-cancer drugs. The study population includes both male and female subjects, with an age range that encompasses adults and older adults. Participants are selected based on their **ECOG performance status** of 0-2, a minimum life expectancy of three months, and a pathology-proven locally advanced or metastatic malignant disease. They must have acceptable organ function and be able to swallow oral medications. The trial includes individuals who are no longer benefiting from standard treatments or for whom no standard treatment is available. Participants must have a genomic profile indicating potential clinical benefit from the targeted therapies under investigation. The sponsor has not provided the total number of participants involved in the trial.
Plans and Procedures
The clinical trial is designed to evaluate the **anti-tumour** activity and toxicity of commercially available, targeted anti-cancer drugs in patients with advanced cancer. This trial is a multi-cohort, phase II study, employing a randomized, double-blind, controlled design. The trial is expected to run from April 2021 to December 2032, with the primary objective of assessing the efficacy of these drugs in patients whose tumors harbor genomic or protein expression variants that are known drug targets or predict drug sensitivity.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to determine eligibility based on criteria such as an **ECOG performance status** of 0-2, a minimum life expectancy of three months, and acceptable organ function. Following the screening, eligible participants will be enrolled and randomized to receive one of the study drugs. The trial includes regular follow-up visits to monitor treatment response and adverse events, with the primary endpoints being the percentage of patients treated based on their molecular tumor profile and the occurrence of treatment-related grade ≥3 adverse events. Secondary endpoints include progression-free survival and overall survival.
The expected length of participant involvement is up to 100 weeks, depending on the specific drug regimen and individual response to treatment. Conditions that may lead to early termination from the study include significant adverse events, disease progression, or withdrawal of consent. The trial aims to facilitate patient access to potentially effective targeted therapies, thereby improving outcomes for individuals with advanced malignancies.
Treatment
The clinical trial involves the administration of several experimental medications, each with specific pharmaceutical forms, dosages, and administration routes. **Piqray** (alpelisib) is provided in film-coated tablets with a dosage of 150 mg, 50 mg, and 200 mg. The maximum daily dose is 300 mg, administered orally. The treatment period is up to 100 days. **Mekinist** (trametinib) is available in 0.5 mg and 2 mg film-coated tablets, with a maximum daily dose of 2 mg, also administered orally for up to 100 days.
**Retsevmo** (selpercatinib) is supplied in hard capsules of 40 mg and 80 mg, with a maximum daily dose of 320 mg, administered orally for a maximum of 100 days. **Imatinib Teva** is available in 100 mg and 400 mg film-coated tablets, with a maximum daily dose of 400 mg, administered orally for up to 100 days. **Bortezomib** is provided as a powder for solution for injection, with a maximum daily dose of 1.3 mg/m², administered subcutaneously for up to 100 days.
**Tepmetko** (tepotinib) is available in 225 mg film-coated tablets, with a maximum daily dose of 450 mg, administered orally for up to 100 days. **Tecentriq** (atezolizumab) is provided in two forms: a 1,875 mg solution for injection and an 840 mg and 1,200 mg concentrate for solution for infusion, with a maximum daily dose of 1,680 mg, administered subcutaneously or intravenously for up to 24 days.
**Lynparza** (olaparib) is available in 100 mg and 150 mg film-coated tablets, with a maximum daily dose of 600 mg, administered orally for up to 100 days. **Dostarlimab** is provided as a concentrate for solution for infusion, with a maximum daily dose of 500 mg, administered intravenously for up to 24 days. **Avastin** (bevacizumab) is available as a 25 mg/ml concentrate for solution for infusion, with a maximum daily dose of 7.5 mg/kg, administered intravenously for up to 100 days.
**Fulvestrant SUN** is provided as a 250 mg solution for injection, with a maximum daily dose of 500 mg, administered intramuscularly for up to 100 days. **Rozlytrek** (entrectinib) is available in 100 mg and 200 mg hard capsules, with a maximum daily dose of 600 mg, administered orally for up to 100 days. **Tabrecta** (capmatinib) is available in 150 mg and 200 mg film-coated tablets, with a maximum daily dose of 800 mg, administered orally for up to 100 days.
**Niraparib** is provided in tablet form, with a maximum daily dose of 300 mg, administered orally for up to 100 days. **Phesgo** (trastuzumab, pertuzumab) is available as a 600 mg/600 mg and 1,200 mg/600 mg solution for injection, with a maximum daily dose of 1,200 mg, administered subcutaneously for up to 100 days. **Zelboraf** (vemurafenib) is available in 240 mg film-coated tablets, with a maximum daily dose of 1,920 mg, administered orally for up to 100 days.
**Tafinlar** (dabrafenib) is available in 50 mg and 75 mg hard capsules, with a maximum daily dose of 300 mg, administered orally for up to 100 days. **Dactinomycin** is provided as a solution for injection, with a maximum daily dose of 15 µg/kg, administered intravenously for up to 30 days. **Alecensa** (alectinib hydrochloride) is available in 150 mg hard capsules, with a maximum daily dose of 1,200 mg, administered orally for up to 100 days.
**Cotellic** (cobimetinib) is available in 20 mg film-coated tablets, with a maximum daily dose of 600 mg, administered orally for up to 100 days. **Hydroxycarbamide** is provided in hard capsules, with a maximum daily dose of 500 mg, administered orally for up to 6 days. **Erivedge** (vismodegib) is available in 150 mg hard capsules, with a maximum daily dose of 150 mg, administered orally for up to 100 days.
**Melphalan** is provided in film-coated tablets, with a maximum daily dose of 2 mg, administered orally for up to 8 days. **Amivantamab** is available as a solution for injection, with a maximum daily dose of 1,400 mg, administered intravenously for up to 100 days. Participant compliance is monitored through regular assessments and adherence checks throughout the trial duration.
Efficacy
The efficacy of the clinical trial will be assessed using both primary and secondary endpoints. The primary endpoints include the percentage of patients included and treated based on their molecular tumor profile, as well as the occurrence of treatment-related grade ≥3 and serious adverse events. Secondary endpoints will focus on progression-free and overall survival, along with the duration of time on the drug.
These endpoints will be evaluated to determine the anti-tumor activity and toxicity of commercially available, targeted anti-cancer drugs used in patients with advanced malignancy. The trial aims to assess the potential efficacy of these drugs in treating advanced malignancies that harbor genomic or protein expression variants known to be drug targets or predictors of drug sensitivity. The trial is designed to facilitate patient access to these targeted therapies, with the ultimate goal of improving treatment outcomes for patients with advanced cancer.
Inclusion and Exclusion Criteria
Inclusion Criteria
- ECOG performance status 0-2
- Life expectancy minimum 3 months
- Patient with a pathology-proven locally advanced or metastatic malignant disease who is no longer benefitting from standard anti-cancer treatment or for whom, in the opinion of the investigator, no such treatment is available or indicated.
- Patients must have acceptable organ function as defined below (exceptions for haematological diagnoses): a) Absolute neutrophil count ≥ 1.5 x109 / L b) Hemoglobin > 9 g/dl c) Platelets > 75,000/µl d) Total bilirubin < 1.5 x institutional upper limit of normal (ULN) e) AST (SGOT) and ALT(SGPT) < 2.5 x institutional upper limit of normal (ULN) (or < 5 x ULN in patients with known hepatic metastases) f) Calculated or measured creatinine clearance ≥ 40 mL/min/1.73 m2
- For orally administered drugs, the patient must be able to swallow and tolerate oral medication and must have no known malabsorption syndrome.
- Results must be available from a genomic / molecular test performed in a preapproved laboratory (Section 10.1). The test used to qualify a patient for participation in IMPRESS-Norway may have been performed on any specimen of the patient’s tumour obtained at any point during the patient’s care at the discretion of the patient’s treating physician. Genomic assays performed on cell-free DNA in plasma (“liquid biopsies”) will also be acceptable if the genomic analysis is performed as defined in Section 10.5. NGS analyses will be performed on a newly sampled biopsy if possible. Information from these analyses might be used upon progression, for evaluation of possible new cohort-inclusion.
- Have a genomic profile for which treatment with one of the approved targeted anti-cancer therapies included in this study has potential clinical benefit
Exclusion Criteria
- Patients eligible to enter other ongoing trials which have the potential to benefit the patients equally or more than a IMPRESS-Norway cohort, and for
- Ongoing toxicity > CTCAE grade 2, other than peripheral neuropathy, related to anti-tumour treatment that was completed within 4 weeks prior to treatment initiation. Patients with ongoing peripheral neuropathy of ≥ CTCAE grade 3.Patients with known allergy/hypersensitivity to the study drug (active substance or to any of the excipients).
- Patients with acute gastrointestinal bleeding within 1 month of start of treatment
- Patients with stroke (including TIA) or acute myocardial infarction within 4 months before the first dose of study treatment
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Norway | Recruiting | 01 Apr 2021 | 1000 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Zelboraf 240 mg film-coated tablets | Test | FILM-COATED TABLETS | ORAL USE | 1920 | 100 | PRD2154737 |
Tecentriq 1 875 mg solution for injection | Test | SOLUTION FOR INJECTION | SUBCUTANEOUS USE | 1875 | 24 | PRD11048644 |
HYDROXYCARBAMIDE | Test | — | ORAL | 500 | 6 | SUB08076MIG |
Tafinlar 75 mg hard capsules | Test | HARD CAPSULES | ORAL USE | 300 | 100 | PRD3045797 |
Retsevmo 80 mg hard capsules | Test | HARD CAPSULES | ORAL USE | 320 | 100 | PRD9027391 |
Lynparza 100 mg film-coated tablets | Test | FILM-COATED TABLETS | ORAL | 600 | 100 | PRD6163467 |
Erivedge 150 mg hard capsules | Test | HARD CAPSULES | ORAL USE | 150 | 100 | PRD2153970 |
Fulvestrant SUN 250 mg injeksjonsvæske, oppløsning i ferdigfylt sprøyte | Test | INJEKSJONSVÆSKE, OPPLØSNING I FERDIGFYLT SPRØYTE | INTRAMUSCULAR | 500 | 100 | PRD7874426 |
Rozlytrek 200 mg hard capsules | Test | HARD CAPSULES | ORAL USE | 600 | 100 | PRD8236755 |
DEXAMETHASONE | Test | — | ORAL | 20 | 100 | SUB07017MIG |