Evaluation of Regorafenib, Vemurafenib, and Dacomitinib in Advanced Solid Tumors, Multiple Myeloma, and Non-Hodgkin Lymphoma with Targetable Genomic Variants
- Trial ID
- 2023-509152-33-00
- Protocol
- M15DRU
Trial statistics
Diseases & Conditions
Objectives
The primary objective of the DRUP trial is to evaluate the **anti-tumor activity** and toxicity of commercially available, targeted anti-cancer drugs in patients with advanced solid tumors, multiple myeloma, or non-Hodgkin lymphoma. These patients have tumors that harbor genomic or protein expression variants known to be drug targets or predictive of drug sensitivity. This objective is clinically relevant as it aims to provide insights into the efficacy and safety of targeted therapies in a personalized treatment approach, potentially improving outcomes for patients with these advanced cancers.
Secondary objectives include performing **biomarker analyses**, such as next-generation sequencing on fresh tumor biopsy specimens. This analysis is crucial for understanding the molecular characteristics of tumors, which can guide the selection of targeted therapies and further personalize treatment strategies.
Participants
The clinical trial involves a study population comprising **adult** patients aged over 18 years, including both **male** and **female** subjects. The trial does not include a vulnerable population. Participants are individuals diagnosed with **non-Hodgkin lymphoma**, **advanced solid tumors**, or **multiple myeloma**. The sponsor has not provided the total number of participants. Selection criteria include patients with symptomatic disease progression or progression according to RECIST criteria after standard anti-cancer treatment, or for whom no such treatment is available or indicated. Participants must have an **ECOG performance status** of 0-2 and acceptable organ function. Lifestyle considerations such as diet and physical activity are not specified. The trial requires participants to have a tumor profile that suggests potential clinical benefit from targeted anti-cancer drugs, with results from genomic or protein expression tests available. The study does not specify any particular lifestyle habits or restrictions beyond the medical criteria outlined.
Plans and Procedures
The clinical trial is designed to evaluate the **anti-tumor** activity and toxicity of targeted anti-cancer drugs in patients with advanced solid tumors, multiple myeloma, or non-Hodgkin lymphoma. This trial is a Phase II, prospective, open-label, non-randomized basket- and umbrella trial. The study aims to facilitate patient access to commercially available drugs that target specific genomic or protein expression variants known to predict drug sensitivity. The trial is expected to run until December 31, 2030, with recruitment having started on August 19, 2016.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, disease progression, and organ function. Follow-up visits will be scheduled to monitor treatment response and adverse events, with assessments conducted according to RECIST v1.1 for solid tumors or other relevant criteria for multiple myeloma and non-Hodgkin lymphoma. The end-of-study visit will conclude the participant's involvement, which is anticipated to last up to 999 days, depending on individual response and drug tolerance.
Participants may be withdrawn from the study early if they experience unacceptable toxicity, disease progression, or if they withdraw consent. The primary endpoints include the percentage of patients treated based on their molecular tumor profile, objective tumor response, and disease control at 16 weeks post-treatment initiation. Secondary endpoints focus on progression-free and overall survival, as well as the duration of treatment on study. The trial's methodology ensures rigorous monitoring and data collection to assess the efficacy and safety of the investigational drugs.
Treatment
The clinical trial involves the administration of **Stivarga** (regorafenib) 40 mg film-coated tablets. This medication is administered orally with a maximum daily dose of 160 mg. The treatment period can extend up to 999 days. Compliance with the dosing schedule is monitored to ensure adherence to the prescribed regimen.
**Zelboraf** (vemurafenib) 240 mg film-coated tablets are also used in the trial. This medication is administered orally with a maximum daily dose of 1920 mg. The treatment duration is set for a maximum of 999 days, and participant compliance is closely monitored.
**Vizimpro** (dacomitinib) 45 mg film-coated tablets are administered orally with a maximum daily dose of 45 mg. The treatment period is up to 999 days, and adherence to the dosing schedule is monitored.
**Cotellic** (cobimetinib) 20 mg film-coated tablets are administered orally with a maximum daily dose of 60 mg. The treatment duration is up to 999 days, with compliance monitoring in place.
**Tecentriq** (atezolizumab) 1200 mg concentrate for solution for infusion is administered intravenously. The maximum daily dose is 1200 mg, and the treatment period can last up to 999 days. Participant compliance is monitored throughout the trial.
**Tarceva** (erlotinib) 100 mg film-coated tablets are administered orally with a maximum daily dose of 150 mg. The treatment period is up to 999 days, and adherence to the dosing schedule is monitored.
**Rozlytrek** (entrectinib) 100 mg hard capsules are administered orally with a maximum daily dose of 600 mg. The treatment duration is up to 999 days, with compliance monitoring in place.
**Erivedge** (vismodegib) 150 mg hard capsules are administered orally with a maximum daily dose of 150 mg. The treatment period is up to 999 days, and adherence to the dosing schedule is monitored.
**Talzenna** (talazoparib) 0.25 mg hard capsules are administered orally with a maximum daily dose of 1 mg. The treatment duration is up to 999 days, with compliance monitoring in place.
**Rubraca** (rucaparib) 250 mg film-coated tablets are administered orally with a maximum daily dose of 1200 mg. The treatment period is up to 999 days, and adherence to the dosing schedule is monitored.
**Tasigna** (nilotinib) 200 mg hard capsules are administered orally with a maximum daily dose of 800 mg. The treatment duration is up to 999 days, with compliance monitoring in place.
**JNJ-42756493** (erdafitinib) film-coated tablets are administered orally with a maximum daily dose of 9 mg. The treatment period is up to 999 days, and adherence to the dosing schedule is monitored.
**Inlyta** (axitinib) 1 mg film-coated tablets are administered orally with a maximum daily dose of 20 mg. The treatment duration is up to 999 days, with compliance monitoring in place.
**KEYTRUDA** (pembrolizumab) 25 mg/mL concentrate for solution for infusion is administered intravenously. The maximum daily dose is 200 mg, and the treatment period can last up to 999 days. Participant compliance is monitored throughout the trial.
**Lorviqua** (lorlatinib) 100 mg film-coated tablets are administered orally with a maximum daily dose of 100 mg. The treatment period is up to 999 days, and adherence to the dosing schedule is monitored.
**Avastin** (bevacizumab) 25 mg/mL concentrate for solution for infusion is administered intravenously. The maximum daily dose is 15 mg/kg, and the treatment period can last up to 999 days. Participant compliance is monitored throughout the trial.
**LENVIMA** (lenvatinib) 10 mg hard capsules are administered orally with a maximum daily dose of 24 mg. The treatment duration is up to 999 days, with compliance monitoring in place.
**Lynparza** (olaparib) 100 mg film-coated tablets are administered orally with a maximum daily dose of 600 mg. The treatment period is up to 999 days, and adherence to the dosing schedule is monitored.
**Retsevmo** (selpercatinib) 80 mg hard capsules are administered orally with a maximum daily dose of 320 mg. The treatment duration is up to 999 days, with compliance monitoring in place.
**Sutent** (sunitinib) 25 mg hard capsules are administered orally with a maximum daily dose of 50 mg. The treatment period is up to 999 days, and adherence to the dosing schedule is monitored.
**XALKORI** (crizotinib) 250 mg hard capsules are administered orally with a maximum daily dose of 500 mg. The treatment duration is up to 999 days, with compliance monitoring in place.
**OPDIVO** (nivolumab) 10 mg/mL concentrate for solution for infusion is administered intravenously. The maximum daily dose is 480 mg, and the treatment period can last up to 999 days. Participant compliance is monitored throughout the trial.
**Vectibix** (panitumumab) 20 mg/mL concentrate for solution for infusion is administered intravenously. The maximum daily dose is 6 mg/kg, and the treatment period can last up to 999 days. Participant compliance is monitored throughout the trial.
**Verzenios** (abemaciclib) 50 mg film-coated tablets are administered orally with a maximum daily dose of 400 mg. The treatment period is up to 999 days, and adherence to the dosing schedule is monitored.
**CABOMETYX** (cabozantinib) 20 mg film-coated tablets are administered orally with a maximum daily dose of 60 mg. The treatment duration is up to 999 days, with compliance monitoring in place.
**IMFINZI** (durvalumab) 50 mg/mL concentrate for solution for infusion is administered intravenously. The maximum daily dose is 1500 mg, and the treatment period can last up to 999 days. Participant compliance is monitored throughout the trial.
**Herceptin** (trastuzumab) 150 mg powder for concentrate for solution for infusion is administered intravenously. The maximum daily dose is 8 mg/kg, and the treatment period can last up to 999 days. Participant compliance is monitored throughout the trial.
**Mekinist** (trametinib) 2 mg film-coated tablets are administered orally with a maximum daily dose of 2 mg. The treatment duration is up to 999 days, with compliance monitoring in place.
**Pemazyre** (pemigatinib) 4.5 mg tablets are administered orally with a maximum daily dose of 13.5 mg. The treatment period is up to 999 days, and adherence to the dosing schedule is monitored.
**Zejula** (niraparib tosilate monohydrate) 100 mg hard capsules are administered orally with a maximum daily dose of 300 mg. The treatment duration is up to 999 days, with compliance monitoring in place.
**Perjeta** (pertuzumab) 420 mg concentrate for solution for infusion is administered intravenously. The maximum daily dose is 840 mg, and the treatment period can last up to 999 days. Participant compliance is monitored throughout the trial.
**TEPMETKO** (tepotinib) 225 mg film-coated tablets are administered orally with a maximum daily dose of 450 mg. The treatment duration is up to 999 days, with compliance monitoring in place.
**Piqray** (alpelisib) 50 mg and 200 mg film-coated tablets are administered orally with a maximum daily dose of 300 mg. The treatment period is up to 999 days, and adherence to the dosing schedule is monitored.
**Alecensa** (alectinib) 150 mg hard capsules are administered orally with a maximum daily dose of 1200 mg. The treatment duration is up to 999 days, with compliance monitoring in place.
**YERVOY** (ipilimumab) 5 mg/mL concentrate for solution for infusion is administered intravenously. The maximum daily dose is 1 mg/kg, with a total dose of 4 mg/kg over a treatment period of 12 weeks. Participant compliance is monitored throughout the trial.
Efficacy
The efficacy of the clinical trial will be assessed using several primary and secondary endpoints. The primary endpoints include the percentage of patients treated based on their molecular tumor profile, objective tumor response, disease control defined as Stable Disease (SD) at 16 weeks after treatment initiation, and treatment-related grade ≥3 and serious adverse events. Secondary endpoints will focus on progression-free and overall survival, as well as the duration of treatment on study (time on drug).
These endpoints will be measured and analyzed to evaluate the anti-tumor activity and toxicity of commercially available, targeted anti-cancer drugs used for the treatment of patients with advanced solid tumors, multiple myeloma, or non-Hodgkin lymphoma. The trial aims to facilitate patient access to these drugs, which are selected based on the presence of a genomic or protein expression variant known to be a drug target or to predict sensitivity to a drug. The trial is designed as a Phase II, prospective, open-label, non-randomized basket- and umbrella trial, allowing for a comprehensive assessment of the drugs' efficacy across different cancer types with known molecular profiles.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Adult (age >18 years) patient with a histologically-proven locally advanced or metastatic solid tumor, multiple myeloma, non-Hodgkin lymphoma or T-cell prolymphocytic leukemia with symptomatic or radiological disease progression after standard anti-cancer treatment or for whom no such treatment is available or indicated. For patients with a primary brain tumor: Histologically confirmed recurrent or de novo primary brain tumor, with unequivocal progression after prior therapy, at least 3 months after radiotherapy (either first line chemo-radiotherapy or re-irradiation), and with stable or decreasing dosage of steroids for at least 7 days prior to the baseline MRI scan.
- ECOG performance status 0-2
- Patients must have acceptable organ function as defined below. However, specific inclusion/exclusion criteria specified in the drug-specific study manual will take precedence: a. Absolute neutrophil count ≥ 1.5 x 109/l b. Hemoglobin > 5.6 mmol/l c. Platelets > 75 x 109/l d. Total bilirubin < 2 x ULN e. AST (SGOT) and ALT (SGPT) < 2.5 x institutional ULN (or < 5 x ULN in patients with known hepatic metastases) f. Serum creatinine ≤ 1.5 × ULN or calculated or measured creatinine clearance ≥ 50 mL/min/1.73 m2
- Patients must have objectively measurable disease (by physical or radiographic examination, according to RECIST v1.1 for patients with solid tumors, or according to IMWG, Lugano, RANO or GCIG criteria, resp., for patients with multiple myeloma, non-Hodgkin lymphoma, and T-cell prolymphocytic leukemia, primary brain tumors or ovarian cancer in case of CA125-based evaluation
- Results must be available from a tumor genomic or protein expression test. Eligible tests may include any of the following technologies: fluorescence in situ hybridization (FISH), polymerase chain reaction (PCR), comparative genomic hybridization (CGH), next generation sequencing (NGS), immunohistochemistry (IHC) or RNA sequencing (RNAseq). The test may have been performed on the primary tumor or a metastatic deposit, in a diagnostic laboratory or within the context of another CPCT study, and must reveal a potentially actionable variant as defined in Section 5. The test results (full pathology or molecular diagnostics report) must be uploaded in the eCRF.
- Patients must have a tumor profile for which treatment with one of the FDA and / or EMA approved (or under revision for approval) targeted anti-cancer drugs included in this study has potential clinical benefit based on preclinical data or clinical information
- A new (obtained ≤2 months before inclusion, and without any type of anti-cancer therapy within those ≤2 months) fresh frozen tumor biopsy specimen for extensive biomarker testing is mandatory before the start of treatment with a targeted agent included in the protocol. Alternatively, fresh frozen tumor tissue acquired in the context of a standard care procedure may be used, provided that no systemic anti-cancer treatment was given between the procedure and start of study treatment within DRUP. Exceptions are made for: a) patients with a primary brain tumor or other tumor types with only intracerebral lesions, only if the mandatory DRUP pre-treatment biopsy for biomarker analysis cannot safely be obtained; b) In case WGS is performed on tumor tissue outside the context of a clinical trial before inclusion, and without any type of anti-cancer therapy between the collection of tissue and inclusion in DRUP, this can replace the DRUP pre-treatment biopsy; c) patients that underwent an allogeneic hematopoietic stem cell transplantation prior to study enrollment, since this will prevent a correct WGS analysis due to a mismatch between the biopsy specimen and the required blood sample
- Ability to understand and the willingness to sign a written informed consent document
- For orally administered drugs, the patient must be able to swallow and tolerate oral medication and must have no known malabsorption syndrome.
- Because of the risks of drug treatment to the developing foetus, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) for the duration of study participation, and for four months following completion of study therapy. Male patients should avoid impregnating a female partner. Male patients, even if surgically sterilized, (i.e. post-vasectomy) must agree to one of the following: practice effective barrier contraception during the entire study treatment period and through 4 months after the last dose of study drug, or completely abstain from sexual intercourse.
Exclusion Criteria
- Ongoing toxicity > grade 2, other than alopecia or grade 2 peripheral neuropathy.
- Patient is receiving any other anti-cancer therapy (cytotoxic, biologic, radiation, or hormonal other than for replacement). Required wash out period prior to starting study treatment is at least two weeks. An exception is made for patients suffering from CRPC are allowed to continue androgen deprivation therapy
- Patient is pregnant or nursing
- Patients with brain metastases. Patients with previously treated brain metastases are eligible, provided that the patient has not experienced a seizure or had a clinically significant change in neurological status within the 3 months prior to registration. All patients with previously treated brain metastases must be stable for at least 1 month after completion of treatment and off steroid treatment prior to study enrollment. Specific exclusion criteria for patients with primary brain tumors: a. Patients who require anti-convulsant therapy must be taking non-enzyme inducing antiepileptic drugs (non-EIAED). EIAED are prohibited. Patients previously on EIAED must be switched to non-EIAED at least 2 weeks prior to randomization. b. No radiotherapy within the three months prior to the diagnosis of progression. c. No radiotherapy with a dose over 65 Gy, stereotactic radiosurgery or brachytherapy unless the recurrence is histologically proven.
- Patients with clinically significant preexisting cardiac conditions, including uncontrolled or symptomatic angina, uncontrolled atrial or ventricular arrhythmias, or symptomatic congestive heart failure
- Patients with known left ventricular ejection fraction (LVEF) < 40%
- Patients with stroke (including TIA) or acute myocardial infarction within 3 months before the first dose of study treatment
- Patients with any other clinically significant medical condition which, in the opinion of the treating physician, makes it undesirable for the patient to participate in the study or which could jeopardize compliance with study requirements including, but not limited to: ongoing or active infection, significant uncontrolled hypertension, or severe psychiatric illness/social situations
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 The Netherlands | Recruiting | 19 Aug 2016 | — |
| Netherlands | — | — | 3000 |
Sites & Investigators
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 |
|---|---|---|---|---|---|---|
Zejula 100 mg film-coated tablets | Test | FILM-COATED TABLETS | ORAL | 300 | 999 | PRD9709366 |
Zelboraf 240 mg film-coated tablets | Test | FILM-COATED TABLETS | ORAL | 1920 | 999 | PRD366907 |
Inlyta 1 mg film-coated tablets | Test | FILM-COATED TABLETS | ORAL | 20 | 999 | PRD6541011 |
Verzenios 50 mg film-coated tablets | Test | FILM-COATED TABLETS | ORAL | 400 | 999 | PRD6841633 |
Lorviqua 100 mg film-coated tablets | Test | FILM-COATED TABLETS | ORAL | 100 | 999 | PRD7271630 |
Tarceva 100 mg film-coated tablets | Test | FILM-COATED TABLETS | ORAL | 150 | 999 | PRD366726 |
Tasigna 200 mg hard capsules | Test | HARD CAPSULES | ORAL | 800 | 999 | PRD4299866 |
Stivarga 40 mg film-coated tablets | Test | FILM-COATED TABLETS | ORAL | 160 | 999 | PRD3438601 |
Tafinlar 75 mg hard capsules | Test | HARD CAPSULES | ORAL | 300 | 999 | PRD4300053 |
Zejula 100 mg hard capsules | Test | HARD CAPSULE | ORAL | 300 | 999 | PRD7912570 |