A phase I, open label, multicenter, dose-escalation study of oral HDM201 in adult patients with advanced solid and hematological tumors characterized by wild-type TP53
- Conditions
- Solid and hematologic tumors1002765510024324
- Registration Number
- NL-OMON46915
- Lead Sponsor
- ovartis
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 24
- ECOG performance status 0-2
- Locally advanced or metastatic solid malignancy, that has progressed despite standardtherapy, or for which no effective standard therapy exists. Lymphomas are excluded.
- Refractory/relapse non-M3 AML ,
- High and very high risk MDS - IPSS-R (International Prognostic Scoring System ) score of > 4.5
- Acute Lymphoblastic Leukemia (B-ALL or T-ALL) including Ph+ ALL, or previously untreated patients who are considered inappropriate candidates for standard induction therapy
* Tumor of the patient is TP53wt (minimum no mutations in exons 5, 6, 7 and 8)
For solid tumor the TP53 status was obtained from a tumor sample collected no longer than 36 months before screening.
for hematologic tumors the TP53 status was obtained from a bone-marrow aspirate or extra medullary site, collected no longer than 3 months before screening.;* Tumor of the patient is TP53wt (minimum no mutations in exons 5, 6, 7 and 8):
For solid tumor the TP53 status was obtained from a tumor sample collected no longer than 36 months before screening except if HDM2 amplification is documented (irrespectively the date) or EBV positive gastric cancer. ;For hematologic tumors the TP53 status was obtained from a bone-marrow aspirate or extra medullary site, collected no longer than 3 months before screening.
* Prior treatment with compounds with the same mode of action as proposed for HDM201,
* Symptomatic CNS metastasis (NB: Patients with CNS metastases are eligible for thisstudy only if they are asymptomatic, off corticosteroids, and radiographically stable for at least 2 months).
* Concurrent other malignancy. Exceptions to this exclusion criteria include: adequately treated basal cell or squamous cell skin cancer; in situ carcinoma of the cervix
* Patients with significant or uncontrolled cardiovascular disease (e.g. uncontrolled hypertension, peripheral vascular disease, congestive heart failure, cardiac arrhythmia, or acute coronary syndrome) within 6 months of starting study treatment or heart attack within 12 months of starting study treatment
* History of thromboembolic or cerebrovascular events within the last 6 months, including transient ischemic attack, cerebrovascular accident, deep vein thrombosis, or pulmonary embolism
* Diagnosis of acute or chronic pancreatitis
* Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral HDM201
* Previous therapy that precludes enrollment < 2 weeks prior tostudy start: for details see protocol section 5.3 exclusion criteria #8.
Patients with hematological tumors
* WBC > 30 x109/L
* Platelets < 25 000/*L = 25 x 109 /L
* Hemoglobin < 8.0 g/dL = 4,96 mmol/L;Specific exclusion criteria for patients receiving eltrombopag
QTc <450msec or <480msec for patients with bundle branch block.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>To determine the MTD and/or to identify the RDE of HDM201 in one or more of the<br /><br>pre-defined regimens as measured by Incidence of Dose Limiting Toxicities<br /><br>(DLTs) during the first cycle of treatment.</p><br>
- Secondary Outcome Measures
Name Time Method