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

Valerio Therapeutics

Status and phase: Completed; Phase 1

Conditions: Advanced Cancer

Treatments: Drug: AsiDNA

Study type: Interventional

Funder types: Industry

Identifiers

NCT03579628

OX2016-203-01

Details and patient eligibility

About

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.

Enrollment: 33 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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33 participants in 1 patient group

AsiDNA

Experimental group

Description:

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).

Treatment:

Drug: AsiDNA