Clinical trial NCT03579628: AsiDNA (a DNA Repair Inhibitor) Administered IntraVenously in Advanced Solid Tumors
Official title: An Open-label, Dose-escalation Phase I/Ib Study to Assess the Safety, Pharmacokinetics and Pharmacodynamics of AsiDNA, a DNA Repair Inhibitor Administered Intravenously, as Single Agent and to Assess the Safety and the Efficacy of AsiDNA in Combination With Carboplatin With or Without Paclitaxel, in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Cancer
Lead sponsor: Valerio Therapeutics
Sponsor class: INDUSTRY
First posted: 2018-07-06
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The aim of the study is to assess:

* Part A: the safety, pharmacokinetics, pharmacodynamics and preliminary efficacy of AsiDNA in patients with advanced solid tumors.
* Part B: the safety and preliminary efficacy of AsiDNA in combination with Carboplatin with or without Paclitaxel in patients with Advanced solid tumors.


Eligibility criteria: Key Inclusion Criteria:

* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* Life expectancy of at least 3 months.
* Patient with histologically or cytologically documented advanced/metastatic primary or recurrent solid tumors who failed or are not eligible to standard therapy (Part A) and who are candidate to Carboplatin (Part B1) and to Carboplatin and Paclitaxel (Part B2).
* Part A: Fresh tumor sample from a biopsy
* Part B: A most recent available tumor sample from a biopsy for all patients will be collected for retrospective analysis of 6 genes expression profile for validation of further stratification approach (exploratory purpose).
* Prior anticancer therapies (chemotherapy, radiation therapy, hormonal therapy, immunotherapy, biological therapy) are allowed under conditions
* At least one measurable lesion according to RECIST 1.1; Patient with no measurable lesion can be enrolled, if the tumor evaluation can be properly documented
* Must meet select hematological and biochemical laboratory indices

Part B only:

* Patient must be eligible to Carboplatin (Part B1) and to Carboplatin + weekly Paclitaxel (Part B2).
* Patients must not have received more than 6 prior cycles of platinum-based chemotherapy.

Key Exclusion Criteria:

* Patient with symptomatic/active central nervous system (CNS) metastases
* Other tumor location necessitating an urgent therapeutic intervention
* Patient with uncontrolled disease-related metabolic disorder
* Patient presenting the following abnormal laboratory values at screening:

  1. hematuria \> 1+ on dipstick,
  2. proteinuria \> 1+ on dipstick
* Patient with uncontrolled congestive heart failure defined as New York Heart Association (NYHA) class III or IV, uncontrolled hypertension, unstable heart disease
* Patient with significant ECG abnormalities defined as any cardiac dysrhythmia (\> grade 2)
* Patient with significant chronic liver disease or active HBV or HCV infection
* Patients with HIV infection or an active infection requiring specific anti-infective therapy
* Participation in another clinical trial with any investigational drug within 28 days prior to first study drug administration.

Primary outcomes:
measure: Determine dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of iv infusions of AsiDNA.
timeFrame: At Cycle 1 (a cycle is 21 days for Part A and 28 days for Part B) for all patients
Secondary outcomes:
measure: Collection of new Adverse Events and follow-up of all ongoing Adverse Events assessed
timeFrame: At Cycle 1 (at Day 1; Day 3; Day 8; Day 15) and at Cycle 2 (at Day 1; Day 8; Day 15) and at each subsequent cycles in any (at Day 1; Day 8; Day 15) for all patients
measure: Elimination half-life (t1/2) of iv infusions of AsiDNA
timeFrame: At Cycle 1 (at Day 1; Day 3; Day 8; Day 15) and at cycle 2 (at Day 1) for all patients
measure: ECG evaluation for safety assessment
timeFrame: Before each cycle (e.g at Day 1 of cycle 1; Day 1 of cycle 2 and Day 1 of each subsequent cycles if any) per usual center's practice.
measure: Peak plasma concentration of iv infusions of AsiDNA
timeFrame: At Cycle 1 (at Day 1; Day 3; Day 8; Day 15) and at cycle 2 (at Day 1) for all patients
measure: Time to peak plasma concentration of iv infusions of AsiDNA
timeFrame: At Cycle 1 (at Day 1; Day 3; Day 8; Day 15) and at cycle 2 (at Day 1) for all patients
measure: Area under the curve of iv infusions of AsiDNA
timeFrame: At Cycle 1 (at Day 1; Day 3; Day 8; Day 15) and at cycle 2 (at Day 1) for all patients
measure: Accumulation factor based on total plasma exposure of iv infusions of AsiDNA
timeFrame: At Cycle 1 (at Day 1) and at cycle 2 (at Day 1) for all patients
Other outcomes:
Locations:
city: Bruxelles
country: Belgium
facility: Institut Jules Bordet
city: Charleroi
country: Belgium
facility: Grand Hôpital de Charleroi
city: Lyon
country: France
facility: Centre Leon Berard
city: Paris
country: France
facility: Institut Curie
city: Toulouse
country: France
facility: Institut Claudius Regaud
Study officials:
References:
citation: Le Tourneau C, Delord JP, Kotecki N, Borcoman E, Gomez-Roca C, Hescot S, Jungels C, Vincent-Salomon A, Cockenpot V, Eberst L, Mole A, Jdey W, Bono F, Trochon-Joseph V, Toussaint H, Zandanel C, Adamiec O, de Beaumont O, Cassier PA. A Phase 1 dose-escalation study to evaluate safety, pharmacokinetics and pharmacodynamics of AsiDNA, a first-in-class DNA repair inhibitor, administered intravenously in patients with advanced solid tumours. Br J Cancer. 2020 Nov;123(10):1481-1489. doi: 10.1038/s41416-020-01028-8. Epub 2020 Aug 25.