Clinical trial NCT02143635: Study to Determine and Evaluate a Safe and Tolerated Dose of HDM201 in Patients With Selected Advanced Tumors That Are TP53wt
Official title: A Phase I, Open Label, Multicenter, Dose-escalation Study of HDM201 in Adult Patients With Advanced Solid and Hematological Tumors Characterized by Wild-type TP53
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid and Hematological TP53wt Tumors
Keywords: HDM201,TP53wt, p53, MDM2, HDM2, advanced tumors, BLRM (Bayesian logistic regression model)
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2014-05-21
Enrollment: 208
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To determine and evaluate a safe and tolerated dose of HDM201 in adult patients with selected advanced tumors characterized by wild-type TP53.


Eligibility criteria: Inclusion Criteria:

* Patient with a TP53wt locally advanced or metastatic solid malignancy and with measurable or non-measurable (but evaluable) disease as determined by RECIST 1.1 criteria.
* Patients with the TP53wt hematological tumors (AML, ALL, HR-MDS) who have failed prior therapies or who are considered inappropriate candidates for standard induction therapy.

Other protocol-defined inclusion criteria may apply

Exclusion Criteria:

* Prior treatment with compounds with the same mode of action
* Subjects with significant or uncontrolled cardiovascular disease
* History of thromboembolic or cerebrovascular events within the last 6 months, including transient ischemic attack, cerebrovascular accident, deep vein thrombosis, or pulmonary embolism
* Previous and concomitant therapy that precludes enrollment, as defined in the protocol
* Known Human Immunodeficiency Virus (HIV) infection and/or active Hepatitis B or Hepatitis C infection
* Patients who have undergone major surgery within the 2 weeks prior to starting study treatment or who have not fully recovered from previous surgery
* Women of child-bearing potential, unless they are using highly effective methods of contraception during dosing and for 2 weeks after study drug discontinuation
* Pregnant or nursing women

Other protocol-defined inclusion/exclusion criteria may apply

Primary outcomes:
measure: Incidence of dose limiting toxicities (DLTs)
timeFrame: up to 28 days
Secondary outcomes:
measure: Number of patients with adverse events (AEs)
timeFrame: For the duration of treatment, an average of 16 weeks
measure: Pharmacokinetics (PK) parameters of HDM201
timeFrame: Up to 42 days
measure: Changes from baseline of Pharmacodynamics markers
timeFrame: Baseline, up to 28 days
measure: Tumor response
timeFrame: Every 8 weeks (for solid tumors), every cycle (for hematological tumors) until end of treatment
Other outcomes:
Locations:
city: Boston
country: United States
facility: Dana Farber Cancer Institute SC-6
state: Massachusetts
city: New York
country: United States
facility: Memorial Sloan Kettering Onc. Dep
state: New York
city: Lyon Cedex
country: France
facility: Novartis Investigative Site
city: Paris
country: France
facility: Novartis Investigative Site
city: Essen
country: Germany
facility: Novartis Investigative Site
city: Frankfurt
country: Germany
facility: Novartis Investigative Site
city: Wuerzburg
country: Germany
facility: Novartis Investigative Site
city: Kobe-shi
country: Japan
facility: Novartis Investigative Site
state: Hyogo
city: Chuo ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Amsterdam
country: Netherlands
facility: Novartis Investigative Site
city: Utrecht
country: Netherlands
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
state: Taiwan ROC
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: