AsiDNA (a DNA Repair Inhibitor) Administered IntraVenousl... | NCT03579628

NCT03579628

Protocol Section

Identification Module

Results Section

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Annotation Section

Annotation Module

Unposted Annotation

Document Section

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No data is available for this block.

Derived Section

Miscellaneous Info Module

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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).	Drug: AsiDNA

Interventions

Name	Type	Description	Arm Group Labels	Other Names
AsiDNA	Drug	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.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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.	At Cycle 1 (a cycle is 21 days for Part A and 28 days for Part B) for all patients

Secondary Outcomes

Measure	Description	Time Frame
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.	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

Eligibility Module

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.

Facility	Status	City	State	ZIP	Country	Contacts
Institut Jules Bordet		Brussels		B-1000	Belgium
Grand Hôpital de Charleroi

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
32839491	Derived	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.

Type	Date	Date Unknown
Release	Jan 19, 2023
Reset	Nov 6, 2023