A Phase 1/1b Clinical Trial of Niraparib and Neratinib in Advanced Solid Tumors With an Expansion Cohort in Platinum-resistant Ovarian Cancer
Overview
- Phase
- Phase 1
- Intervention
- Neratinib 160 mg
- Conditions
- Advanced Solid Tumor
- Sponsor
- Virginia Commonwealth University
- Enrollment
- 18
- Locations
- 1
- Primary Endpoint
- Phase 1: To determine the Recommended phase 2 dose (RP2D) of niraparib and neratinib in patients with advanced solid tumors
- Status
- Active, not recruiting
- Last Updated
- 12 months ago
Overview
Brief Summary
To determine the recommended phase 2 dose (RP2D) of niraparib and neratinib in combination in patients with advanced solid tumors during Phase 1. To evaluate clinical benefit (≥4-month progression-free survival [PFS]) of niraparib and neratinib in patients with platinum-resistant ovarian cancer in Phase 1b.
Detailed Description
This study is a single-arm, open-label, phase 1/1b trial to determine the RP2D of neratinib and niraparib when given in combination to patients with advanced solid tumors. The RP2D will be identified during the phase 1 dose escalation portion of the study using a modified 3+3 design and evaluated in a phase 1b dose expansion cohort of up to 12 patients with platinum-resistant ovarian cancer.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Disease Characteristics
- •Phase 1: Patients with advanced solid tumors, excluding primary CNS and prostate tumors, that have progressed during or after treatment with approved therapies or for which there is no standard effective therapy available or
- •Phase 1b: Female patients with ovarian cancer who:
- •Are platinum resistant (progressed within 6 months of finishing platinum therapy) and
- •Have received at least 2 prior lines of therapy and
- •Do not have a BRCA germline mutation
- •Measurable or evaluable disease by RECIST 1.1
- •Age ≥ 18 years
- •ECOG performance status 0 or 1
- •Adequate bone marrow function as defined below:
Exclusion Criteria
- •Any investigational agent within 4 weeks, or within a time interval less than at least 5 half-lives of the investigational agent, whichever is shorter, prior to initiating study treatment
- •Simultaneous enrollment in any other interventional clinical trial
- •Active, uncontrolled diarrhea leading to dehydration or electrolyte disturbances not controlled with oral repletion
- •Serious (ie, grade ≥ 3) uncontrolled infection
- •Major surgery ≤ 3 weeks prior to initiating study treatment and patient must have recovered from any surgical effects.
- •Radiation encompassing \>20% of the bone marrow within 2 weeks, or any radiation therapy within 1 week, prior to initiating study treatment.
- •Transfusion of platelets or red blood cells ≤ 4 weeks prior to initiating study treatment
- •Receipt of colony-stimulating factors (e.g., granulocyte colony-stimulating factor \[GCSF\], granulocyte macrophage colony- stimulating factor \[GM-CSF\], or recombinant erythropoietin) within 4 weeks prior to initiating study treatment
- •Known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML)
- •Known brain or leptomeningeal metastasis
Arms & Interventions
Dose Level -1
Neratinib 160 mg and Niraparib 100 mg by mouth once daily for 28 day cycles.
Intervention: Neratinib 160 mg
Dose Level -1
Neratinib 160 mg and Niraparib 100 mg by mouth once daily for 28 day cycles.
Intervention: Niraparib 100 mg
Dose Level 1
Neratinib 160 mg and Niraparib 200 mg by mouth once daily for 28 day cycles.
Intervention: Neratinib 160 mg
Dose Level 1
Neratinib 160 mg and Niraparib 200 mg by mouth once daily for 28 day cycles.
Intervention: Niraparib 200 mg
Dose Level 2
Neratinib 200 mg and Niraparib 200 mg by mouth once daily for 28 day cycles.
Intervention: Neratinib 200 mg
Dose Level 2
Neratinib 200 mg and Niraparib 200 mg by mouth once daily for 28 day cycles.
Intervention: Niraparib 200 mg
Dose Level 3
Neratinib 240 mg and Niraparib 200 mg by mouth once daily for 28 day cycles.
Intervention: Neratinib 240 mg
Dose Level 3
Neratinib 240 mg and Niraparib 200 mg by mouth once daily for 28 day cycles.
Intervention: Niraparib 200 mg
Dose Level 4
Neratinib 240 mg and Niraparib 300 mg by mouth once daily for 28 day cycles.
Intervention: Neratinib 240 mg
Dose Level 4
Neratinib 240 mg and Niraparib 300 mg by mouth once daily for 28 day cycles.
Intervention: Niraparib 300 mg
Phase 1b: Platinum Resistant Expansion Cohort
This portion of the study provides for cohort expansion to observe for 4 month or greater progression-free survival in patients with platinum resistant ovarian cancer treated at the recommended phase 2 dose (RP2D) determined in Phase I.
Intervention: Niraparib at RP2D
Phase 1b: Platinum Resistant Expansion Cohort
This portion of the study provides for cohort expansion to observe for 4 month or greater progression-free survival in patients with platinum resistant ovarian cancer treated at the recommended phase 2 dose (RP2D) determined in Phase I.
Intervention: Neratinib at RP2D
Outcomes
Primary Outcomes
Phase 1: To determine the Recommended phase 2 dose (RP2D) of niraparib and neratinib in patients with advanced solid tumors
Time Frame: 4 Months
The RP2D will be identified during the phase 1 dose escalation portion of the study using a modified 3+3 design and evaluated in a phase 1b dose expansion cohort of up to 12 patients with platinum-resistant ovarian cancer.
Phase 1b: To evaluate clinical benefit (≥4-month progression-free survival [PFS]) of niraparib and neratinib in patients with platinum-resistant ovarian cancer.
Time Frame: 4 months
Phase 1b: To evaluate clinical benefit (≥4-month progression-free survival \[PFS\]) of niraparib and neratinib given at the RP2D to in patients with platinum-resistant ovarian cancer. To evaluate the clinical benefit, (defined as ≥4-month progression free survival (PFS), using Response Evaluation Criteria in Solid Tumors (RECIST 1.1) criteria in patients with platinum-resistant ovarian cancer.
Secondary Outcomes
- To assess the frequency of adverse events (AEs)(5 months)
- Preliminary efficacy (objective response rate [ORR]) of niraparib and neratinib in patients with advanced solid tumors.(5 years)