E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with gastrointestinal stromal tumor (GIST) harboring activating mutations of CKIT or PDGFRA pre/post surgery or pre/under treatment with a Tyrokinase Inhibitors or progressive disease irrespective of current or planned treatment. |
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E.1.1.1 | Medical condition in easily understood language |
Gastrointestinal stromal tumor (GIST)
GIST is the most common non-epithelial tumor of the gastrointestinal tract |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Goal of the study is to investigate whether tumor-specific CKIT or PDGFRA DNA fragments can be detected and quantified in the plasma of patients with active GIST as defined as GIST lesions that can be measured by diagnostic imaging. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are:
• To assess the correlation of test results with the amount of tumor
• To investigate whether the test result correlates with response to therapy
• To investigate whether the test result correlates with relapse or progression of disease
• To determine whether medical treatment results in a transient increase of CKIT or PDGFA DNA in the plasma
• To determine the test sensitivity of L-PCR, ddPCR and NGS for specific CKIT or PGDFRA mutations
• To determine whether tumor clonal heterogeneity can be de-tected in plasma DNA using L-PCR, NGS or ddPCR
• To examine whether clonal heterogeneity of tumor specific mutations in plasma samples correlates with response, re-lapse and progression
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Signed written informed consent
• Male or female patients aged >18 years
• Histologically confirmed GIST
• Known activating mutation of CKIT or PDGFRA and tissue sample can be provided for central mutation analysis or mutation status unknown and tissue sample can be provided for central mutation analysis at baseline
• Routinely planned follow-up visits in no longer than three months intervals (+ 14 days) including local standard of care diagnostic imaging (CT, PET-CT, or MRI)
• At least one GIST lesion that can be measured by CT, PET-CT, or MRI
• Planned surgery of one or more disease manifestations or planned TKI treatment (such as imatinib or sunitinib) in neoadjuvant or palliative intention or disease progression ir-respective of current/planned treatment
• Life expectancy of at least three months |
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E.4 | Principal exclusion criteria |
• Wild type sequence for CKIT exon 9, 11, 13, 14, 17, 18 and PDGFRA exon 18
• Tissue sample can not be provided for central mutation analysis
• Surgery of primary or progressive lesions already completed and currently no evidence of progressive lesions
• Patients currently receiving adjuvant TKI treatment after sur-gery and no evidence of progressive lesions
• Patients currently receiving palliative TKI treatment and no evidence of progressive lesions
• Planned follow-up intervals including CT, PET-CT or MRI at more than three months intervals (+ 14 days)
• Coexisting medical condition or treatment that could interfere with the ability of the patient to comply with planned treatment interventions (surgery or TKI treatment) or regular follow-up visits
• Patients unwilling to or unable to comply with the planned therapeutic intervention (surgery or TKI treatment) or to comply with the regular follow-up visits including blood sam-ple collection
• Pregnancy and lactation
• Presence of chronic inflammatory diseases, autoimmune dis-eases, or liver cirrhosis
• Known HIV and/or hepatitis B or C infection
• Other malignancies within the past 3 years except for ade-quately treated carcinoma of the cervix and basal or squamous cell carcinoma of the skin |
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E.5 End points |
E.5.1 | Primary end point(s) |
Percentage of patients with histologically proven GIST, measurable lesion in imaging and activating CKIT and PDGFRA mutation, where detection of tumor specific DNA encoding for mutated CKIT or PDGFA is possible in the plasma at least at one timepoint |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Detection of tumor specific DNA encoding for mutated CKIT or PDGFA in the plasma at least at one timepoint |
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E.5.2 | Secondary end point(s) |
• Correlation between the amount of tumor specific CKIT or PDGFRA DNA in plasma samples and the amount of tumor as assessed by diagnostic imaging
• Correlation between the amount of tumor specific CKIT or PDGFRA DNA in plasma samples and the response to ther-apy (surgery and/or therapy with a TKI) as assessed by di-agnostic imaging
• Correlation between the amount of tumor specific CKIT or PDGFRA DNA in plasma samples and relapse or progression of disease as assessed by diagnostic imaging
• Percentage of patients with transient increase of tumor spe-cific CKIT or PDGFRA DNA in the plasma („tumor flare“) af-ter starting a medical treatment with a TKI
• Comparison of the sensitivity of L-PCR, ddPCR and NGS for specific CKIT or PGDFRA mutations
• Percentage of patients with more than one GIST-specific mu-tation in plasma DNA
• Correlation between detection of more than one GIST-specific mutation in plasma DNA and the response to therapy (surgery and/or therapy with a TKI) as assessed by diagnostic imaging
• Correlation between detection of more than one GIST-specific mutation in plasma samples and relapse or progres-sion of disease as assessed by diagnostic imaging
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Patients with GIST receiving standard medical care according to hospital routine will be included. For the purpose of this clinical trial blood samples will be taken at baseline and during the patient's regular follow-up visits in the clinic in 3-months intervals in order to detect circulating tumor DNA in the plasma. The amount of circulating mutated CKIT or PDGFRA DNA will be correlated with the clinical course of disease as assessed by imaging, which will be performed according to the clinical centre's routine follow-up of the patient. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The trial will end after 25 patients evaluable for the primary endpoint were included.
It is estimated that all patients can be included within 1 year. Each patient will be followed-up (blood will be withdrawn) for 2 years. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |