Niraparib and Neratinib in Advanced Solid Tumors With Expansion Cohort in Advanced Ovarian Cancer

NCT04502602 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: MCC-18-14152NCI-2020-05315
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

Advanced Solid Tumor; Ovarian Cancer

Outcome Measures

Primary Outcomes (2)

• Phase 1: To determine the Recommended phase 2 dose (RP2D) of niraparib and neratinib in 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.

  4 Months

• Phase 1b: To evaluate clinical benefit (≥4-month progression-free survival [PFS]) of niraparib and neratinib in patients with platinum-resistant ovarian cancer.

  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.

  4 months

Secondary Outcomes (2)

• 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

Study Arms (6)

Dose Level -1

EXPERIMENTAL

Neratinib 160 mg and Niraparib 100 mg by mouth once daily for 28 day cycles.

Drug: Neratinib 160 mg; Drug: Niraparib 100 mg

Dose Level 1

EXPERIMENTAL

Neratinib 160 mg and Niraparib 200 mg by mouth once daily for 28 day cycles.

Drug: Neratinib 160 mg; Drug: Niraparib 200 mg

Dose Level 2

EXPERIMENTAL

Neratinib 200 mg and Niraparib 200 mg by mouth once daily for 28 day cycles.

Drug: Neratinib 200 mg; Drug: Niraparib 200 mg

Dose Level 3

EXPERIMENTAL

Neratinib 240 mg and Niraparib 200 mg by mouth once daily for 28 day cycles.

Drug: Neratinib 240 mg; Drug: Niraparib 200 mg

Dose Level 4

EXPERIMENTAL

Neratinib 240 mg and Niraparib 300 mg by mouth once daily for 28 day cycles.

Drug: Neratinib 240 mg; Drug: Niraparib 300 mg

Phase 1b: Platinum Resistant Expansion Cohort

EXPERIMENTAL

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.

Drug: Niraparib at RP2D; Drug: Neratinib at RP2D

Interventions

Neratinib 160 mg DRUG

Escalating doses to determine recommended phase 2 dose (RP2D)

Dose Level -1; Dose Level 1

Neratinib 200 mg DRUG

Determined RP2D dose

Dose Level 2

Neratinib 240 mg DRUG

Escalating doses to determine recommended phase 2 dose (RP2D)

Dose Level 3; Dose Level 4

Niraparib 100 mg DRUG

Escalating doses to determine recommended phase 2 dose (RP2D)

Dose Level -1

Niraparib 200 mg DRUG

Escalating doses to determine recommended phase 2 dose (RP2D)

Dose Level 1; Dose Level 2; Dose Level 3

Niraparib 300 mg DRUG

Phase 1: Escalating doses to determine recommended phase 2 dose (RP2D)

Dose Level 4

Niraparib at RP2D DRUG

Phase 1b: Determined dose

Phase 1b: Platinum Resistant Expansion Cohort

Neratinib at RP2D DRUG

Phase 1b: Determined dose

Phase 1b: Platinum Resistant Expansion Cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Absolute neutrophil count (ANC) ≥ 1,500/mm3
• Platelets ≥ 100,000/mm3 (untransfused)
• Hemoglobin ≥9 g/dL (untransfused)
• Adequate renal function as defined below:
• Serum creatinine ≤ 1.5 x upper limit of normal (ULN) for the laboratory OR calculated

You may not qualify if:

• 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
• Diagnosis, detection, or treatment of another type of invasive cancer ≤ 2 years prior to initiating study treatment
• Active or clinically significant cardiac disease including any of the following;
• Unstable angina (eg, angina symptoms at rest) or onset of angina within 3 months prior to initiating study treatment
• Myocardial infarction diagnoses within 6 months prior to initiating study treatment
• New York Heart Association (NYHA) class III or IV congestive heart failure

Sponsors & Collaborators

• Virginia Commonwealth University: lead
• Puma Biotechnology, Inc.: collaborator
• GlaxoSmithKline: collaborator

Study Sites (1)

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

neratinib; niraparib

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Study Officials

• Andrew Poklepovic, MD

  Massey Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Dose escalation will proceed within each cohort. Phase 1b is the expansion cohort at the recommended phase 2 dose found in phase 1.

Study Record Dates

• First Submitted: August 4, 2020
• First Posted: August 6, 2020
• Study Start: August 24, 2020
• Primary Completion (Estimated): August 27, 2026
• Study Completion (Estimated): May 31, 2029
• Last Updated: May 4, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)