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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 : December 3, 2019
Sponsor:
Information provided by (Responsible Party):
Onxeo

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.

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
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : April 5, 2018
Estimated Primary Completion Date : March 30, 2020
Estimated Study Completion Date : September 30, 2020

Arm Intervention/treatment
Experimental: AsiDNA

Part A: AsiDNA as a single agent:

The study 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.

Part B: AsiDNA combination with Carboplatin with or without Paclitaxel (Background treatments):

  • Part B1: Combination cohort of AsiDNA at DL3 (600mg) with Carboplatin AUC 5.
  • Part B2: Combination cohort of AsiDNA at DL3 (600mg) with Carboplatin AUC 5 and weekly Paclitaxel: 80 mg/m2 (full dose).
Drug: AsiDNA

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

At cycle 1: Part B1: Carboplatin will be administered by a 1 hour IV infusion at D8, 1 hour after the end of AsiDNA infusion. Part B2: Carboplatin will be administered by a 1 hour IV infusion at D8, 1 hour after the end of AsiDNA infusion and Paclitaxel will be administered by a 1 hour IV infusion at D8, D15, D22 or 1 hour after the end of AsiDNA infusion for weekly administrations.

At each other cycle: AsiDNA will be administered on a weekly basis. Part B1: Carboplatin will be administered by a 1 hour IV infusion at D1, 1 hour after the end of AsiDNA infusion. Part B2; Carboplatin will be administered by a 1 hour IV infusion at D1, 1 hour after the end of AsiDNA infusion and Paclitaxel will be administered on a weekly basis by a 1 hour IV infusion.

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





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 Part A and 28 days for Part B) 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) for Part A and during the 4 weeks of study treatment (i.e, cycle 1: from Day 1 to Day 28) for Part B.

    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 (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.

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         
Grand Hôpital de Charleroi Recruiting
Charleroi, Belgium, 6000
Contact: Jean-Luc CANON, MD         
France
Centre Leon Berard Active, not recruiting
Lyon, France, 69008
Institut Curie Active, not recruiting
Paris, France, 75005
Centre Hospitalier Saint-Joseph Active, not recruiting
Paris, France, 75014
Institut Claudius Regaud Active, not recruiting
Toulouse, France, 31059
Sponsors and Collaborators
Onxeo
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Onxeo
ClinicalTrials.gov Identifier: NCT03579628    
Other Study ID Numbers: OX2016-203-01
First Posted: July 6, 2018    Key Record Dates
Last Update Posted: December 3, 2019
Last Verified: December 2019

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