Advanced CancerPhase 1DRIIV-1NCT03579628
AsiDNA (a DNA Repair Inhibitor) Administered IntraVenously in Advanced Solid Tumors
A Phase 1 study testing AsiDNA in people with Advanced Cancer, run by Valerio Therapeutics at 5 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Cancer
- What is being tested?
- AsiDNA
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 5 sitesin 2 countries
- Study dates
- 5 Apr 2018to 20 Feb 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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:
- hematuria > 1+ on dipstick,
- proteinuria > 1+ on dipstick
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- 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.
Trial locations and contacts
5 sites in 2 countries.
5 sites in 2 countries
France3 sites
Centre Leon Berard
Lyon, 69008
Institut Curie
Paris, 75005
Institut Claudius Regaud
Toulouse, 31059
Belgium2 sites
Institut Jules Bordet
Brussels, B-1000
Grand Hôpital de Charleroi
Charleroi, 6000
About this study
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
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.
- Conditions
- Advanced Cancer
- Being tested
- AsiDNA
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AsiDNADrug
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.
| Study group | Role | What they receive |
|---|---|---|
| AsiDNA | Experimental | 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). Receives: Drug: AsiDNA |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of iv infusions of AsiDNA.
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.
Measured: At Cycle 1 (a cycle is 21 days for Part A and 28 days for Part B) for all patients
Secondary outcomes (7)
Collection of new Adverse Events and follow-up of all ongoing Adverse Events assessed
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.
Measured: 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
Elimination half-life (t1/2) of iv infusions of AsiDNA
The following standard plasma PK parameter for IV AsiDNA will be analyzed:
elimination half-life (t1/2) in hours
Measured: At Cycle 1 (at Day 1; Day 3; Day 8; Day 15) and at cycle 2 (at Day 1) for all patients
ECG evaluation for safety assessment
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.
Measured: 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.
Peak plasma concentration of iv infusions of AsiDNA
The following standard plasma PK parameter for IV AsiDNA will be analyzed:
peak plasma concentration (Cmax) in ng/mL
Measured: At Cycle 1 (at Day 1; Day 3; Day 8; Day 15) and at cycle 2 (at Day 1) for all patients
Time to peak plasma concentration of iv infusions of AsiDNA
The following standard plasma PK parameter for IV AsiDNA will be analyzed:
time to peak plasma concentration (tmax) in hours
Measured: At Cycle 1 (at Day 1; Day 3; Day 8; Day 15) and at cycle 2 (at Day 1) for all patients
Area under the curve of iv infusions of AsiDNA
The following standard plasma PK parameter for IV AsiDNA will be analyzed:
area under the curve (AUC) in mg*h/L.
Measured: At Cycle 1 (at Day 1; Day 3; Day 8; Day 15) and at cycle 2 (at Day 1) for all patients
Accumulation factor based on total plasma exposure of iv infusions of AsiDNA
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.
Measured: At Cycle 1 (at Day 1) and at cycle 2 (at Day 1) for all patients
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jul 2018
- Study start5 Apr 2018
- Primary completion24 Feb 2021
- Study completion20 Feb 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Advanced CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- Valerio Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03579628
- Sponsor's protocol ID
- OX2016-203-01
- Acronym
- DRIIV-1
- Status last verified
- Mar 2022
- First submitted
- 6 Apr 2018
- Last updated
- 24 Mar 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 32839491
Study at a glance
From the registry record, last updated by the sponsor on 24 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03579628
- Acronym / sponsor ID
- DRIIV-1 / OX2016-203-01
- Conditions
- Advanced Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- Valerio TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 5 Apr 2018 (actual)
- Primary completion
- 24 Feb 2021 (actual)
- Study completion
- 20 Feb 2022 (actual)
- First posted
- 6 Jul 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| AsiDNA | Experimental | Drug: AsiDNAPart 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). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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).
Key exclusion criteria (11 listed)
- 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:
- Patient with uncontrolled congestive heart failure defined as New York Heart Association (NYHA) class III or IV, uncontrolled hypertension, unstable heart disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AsiDNAAll 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. | Drug | AsiDNA |
Primary outcome
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.
7 secondary outcomes
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
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
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.
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
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
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
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Mar 2022.
- Derived from this study: PubMed 32839491Le 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.
- Sponsor websiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
5 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AsiDNA in people with Advanced Cancer, run by Valerio Therapeutics at 5 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in France, Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03579628, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Mar 2022.