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AsiDNA (a DNA Repair Inhibitor) Administered IntraVenously in Advanced Solid Tumors (DRIIV-1)

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ClinicalTrials.gov Identifier: NCT03579628
Recruitment Status : Recruiting
First Posted : July 6, 2018
Last Update Posted : February 4, 2019
Sponsor:
Information provided by (Responsible Party):
Onxeo

Brief Summary:
This will be a phase I clinical trial escalating dose testing AsiDNA administered intravenously (iv) as monotherapy. The aim of the study is to assess the safety, pharmacokinetics and pharmacodynamics and preliminary efficacy of AsiDNA in patients with solid tumors.

Condition or disease Intervention/treatment Phase
Advanced Cancer Drug: AsiDNA Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-label, Dose-escalation Phase I Study to Assess the Safety, Pharmacokinetics and Pharmacodynamics of AsiDNA, a DNA Repair Inhibitor Administered Intravenously in Patients With Advanced Solid Tumors
Actual Study Start Date : April 5, 2018
Estimated Primary Completion Date : September 30, 2019
Estimated Study Completion Date : March 30, 2020

Arm Intervention/treatment
Experimental: AsiDNA

This phase 1 will follow a dose escalation "3 + 3" cohort design (with 6 dose levels).

All patients will receive a loading dose of AsiDNA for 3 consecutive days as iv infusion at Day 1 (D1), Day 2 (D2) and Day 3 (D3), followed by iv infusion once a week (at D8 and D15 of a 21 days treatment period (1 cycle = 21 days). Each subsequent cycle will be administered on a weekly basis (D1, D8, D15) of a 21 days treatment period.

Drug: AsiDNA

Patients will receive a loading dose of AsiDNA iv infusion (D1, D2, D3) followed by weekly iv administrations.

Patients will continue study treatment until disease progression, unacceptable toxicity or patient's refusal to continue, whichever occurs first.





Primary Outcome Measures :
  1. Determine dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of iv infusions of AsiDNA. [ Time Frame: At Cycle 1 (a cycle is 21 days) for all patients ]

    DLTs will be based on the toxicities observed during the first 3 weeks of study treatment (i.e, cycle 1: from Day 1 to Day 21).

    MTD is defined as the dose immediately below the unacceptable dose or defined as the highest tested dose if no DLT observed at this dose.



Secondary Outcome Measures :
  1. Collection of new Adverse Events and follow-up of all ongoing Adverse Events assessed [ Time Frame: 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 ]
    Adverse Events will be reported and graded based on the National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events (AE) [CTCAE] scale, version 4.03.

  2. Elimination half-life (t1/2) of iv infusions of AsiDNA [ Time Frame: At Cycle 1 (at Day 1; Day 3; Day 8; Day 15) and at cycle 2 (at Day 1) for all patients ]

    The following standard plasma PK parameter for IV AsiDNA will be analyzed:

    elimination half-life (t1/2) in hours


  3. ECG evaluation for safety assessment [ Time Frame: 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. ]
    12-lead ECG will be performed 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.

  4. Peak plasma concentration of iv infusions of AsiDNA [ Time Frame: At Cycle 1 (at Day 1; Day 3; Day 8; Day 15) and at cycle 2 (at Day 1) for all patients ]

    The following standard plasma PK parameter for IV AsiDNA will be analyzed:

    peak plasma concentration (Cmax) in ng/mL


  5. Time to peak plasma concentration of iv infusions of AsiDNA [ Time Frame: At Cycle 1 (at Day 1; Day 3; Day 8; Day 15) and at cycle 2 (at Day 1) for all patients ]

    The following standard plasma PK parameter for IV AsiDNA will be analyzed:

    time to peak plasma concentration (tmax) in hours


  6. Area under the curve of iv infusions of AsiDNA [ Time Frame: At Cycle 1 (at Day 1; Day 3; Day 8; Day 15) and at cycle 2 (at Day 1) for all patients ]

    The following standard plasma PK parameter for IV AsiDNA will be analyzed:

    area under the curve (AUC) in mg*h/L.


  7. Accumulation factor based on total plasma exposure of iv infusions of AsiDNA [ Time Frame: At Cycle 1 (at Day 1) and at cycle 2 (at Day 1) for all patients ]

    The following standard plasma PK parameter for IV AsiDNA will be analyzed:

    accumulation factor between Day 1 and Day 3 based on total plasma exposure.




Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  • Fresh tumor sample from a biopsy
  • 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

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03579628


Contacts
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Contact: Olivier DE BEAUMONT, MD +33 (0)1 45 58 76 00 o.debeaumont@onxeo.com

Locations
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Belgium
Institut Jules Bordet Recruiting
Bruxelles, Belgium, B-1000
Contact: Nuria KOTECKI, MD         
France
Centre Leon Berard Recruiting
Lyon, France, 69008
Contact: Philippe CASSIER, MD         
Institut Curie Recruiting
Paris, France, 75005
Contact: Christophe LE TOURNEAU, MD         
Centre Hospitalier Saint-Joseph Not yet recruiting
Paris, France, 75014
Contact: Chantal DREYER, MD         
Institut Claudius Regaud Recruiting
Toulouse, France, 31059
Contact: Jean-Pierre DELORD, MD         
Sponsors and Collaborators
Onxeo

Additional Information:
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Responsible Party: Onxeo
ClinicalTrials.gov Identifier: NCT03579628     History of Changes
Other Study ID Numbers: OX2016-203-01
First Posted: July 6, 2018    Key Record Dates
Last Update Posted: February 4, 2019
Last Verified: February 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No