Advanced Solid TumorPhase 1iNNOVATENCT04502602
Niraparib and Neratinib in Advanced Solid Tumors With Expansion Cohort in Advanced Ovarian Cancer
A Phase 1 study testing Neratinib 160 mg, Neratinib 200 mg and Neratinib 240 mg in people with Advanced Solid Tumor and Ovarian Cancer, run by Virginia Commonwealth University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Solid Tumor, Ovarian Cancer
- What is being tested?
- Neratinib 160 mg, Neratinib 200 mg and Neratinib 240 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Aug 2020to 31 Oct 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
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
- 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
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- 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
- Or actual creatinine clearance ≥ 30 mL/min (see Appendix 2 for the Cockcroft-Gault formula for calculating creatinine clearance)
- Adequate hepatic function as defined below:
- Total bilirubin ≤ 1.5 x ULN for the laboratory OR direct bilirubin ≤ 1.0 x ULN
- Aspartate aminotransferase and alanine aminotransferase ≤ 2.5 x ULN (≤ 3x ULN when liver metastases are present)
- Patients receiving corticosteroids may continue as long as their dose is stable for least 4 weeks prior to initiating protocol therapy
- Patients must agree not to donate blood during the study or for 90 days after the last dose of study treatment
- A woman of childbearing potential (WCBP) must have a documented negative serum pregnancy test within 7 days prior to initiating study treatment and agree to abstain from activities that could result in pregnancy from screening through 90 days after the last dose of study treatment. Non Childbearing potential is defined as follows (by other than medical reasons):
- ≥45 years of age and has not had menses for >1 year
- Patients who have been amenorrhoeic for <2 years without history of a hysterectomy and oophorectomy must have a follicle stimulating hormone (FSH) value in the postmenopausal range upon screening evaluation
- Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation. Documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by an ultrasound. Tubal ligation must be confirmed with medical records of the actual procedure, otherwise the patient must be willing to use 2 adequate barrier methods throughout the study, starting with the screening visit through 180 days after the last dose of study treatment. Information must be captured appropriately within the site's source documents. Note: Abstinence is acceptable if this is the established and preferred contraception for the patient.
- Participant must agree to not breastfeed during the study or for 30 days after the last dose of study treatment.
- Male participant agrees to use an adequate method of contraception starting with the first dose of study treatment through 90 days after the last dose of study treatment. Note: Abstinence is acceptable if this is the established and preferred contraception for the patient.
- Participant must agree to not donate sperm during the study or for 90 days after the last dose of study treatment
- Ability to understand and the willingness to sign a written informed consent document
Who cannot join
- 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.
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- 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
- Uncontrolled hypertension
- Inability to swallow medication
- Known hypersensitivity to niraparib or neratinib components or excipients
- Known or suspected malabsorption condition or obstruction Note: Use of pancreatic enzyme supplements is allowed to control malabsorption
- Inability to shift medications as follows:
- Antacids (eg, calcium carbonate): dose at least 3 hours after dosing with neratinib
- H2 receptor antagonists: dose must be taken at least 2 hours after or 10 hours before dosing with neratinib
- Planned ongoing treatment with other drugs thought to potentially have adverse interactions with either of the medications included in the study treatment:
- Proton pump inhibitors (PPIs). Must discontinue use 10 days prior to initiating study therapy.
- High-risk P-glycoprotein (P-gp) substrates (eg, digoxin, dabigatran).
- Strong or moderate CYP3A4 inhibitors and/or Strong or moderate CYP3A4 inducers. Examples of clinical inhibitors and clinical inducers for P450-mediated metabolism and classification of strong, moderate, and weak interactions are available through the FDA website: http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractionsLabeling/ucm093664.htm
- If such medications have been used, patients must have discontinued these agents ≥ 2 weeks prior to initiating study treatment.
- Pregnancy or breastfeeding
- Medical, psychological, or social condition that, in the opinion of the investigator, may increase the patient's risk or limit the patient's adherence with study requirements
Trial locations and contacts
1 site in 1 country.
United States1 site
Virginia Commonwealth University
Richmond, Virginia, 23298
About this study
Official title: A Phase 1/1b Clinical Trial of Niraparib and Neratinib in Advanced Solid Tumors With an Expansion Cohort in Platinum-resistant Ovarian Cancer
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.
Read the 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.
- Conditions
- Advanced Solid Tumor, Ovarian Cancer
- Being tested
- Neratinib 160 mg, Neratinib 200 mg, Neratinib 240 mg, Niraparib 100 mg, Niraparib 200 mg
- Medical subject headings
- Ovarian Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Neratinib 160 mgDrug
Escalating doses to determine recommended phase 2 dose (RP2D)
Neratinib 200 mgDrug
Determined RP2D dose
Neratinib 240 mgDrug
Escalating doses to determine recommended phase 2 dose (RP2D)
Niraparib 100 mgDrug
Escalating doses to determine recommended phase 2 dose (RP2D)
Niraparib 200 mgDrug
Escalating doses to determine recommended phase 2 dose (RP2D)
Niraparib 300 mgDrug
Phase 1: Escalating doses to determine recommended phase 2 dose (RP2D)
Niraparib at RP2DDrug
Phase 1b: Determined dose
Neratinib at RP2DDrug
Phase 1b: Determined dose
| Study group | Role | What they receive |
|---|---|---|
| Dose Level -1 | Experimental | Neratinib 160 mg and Niraparib 100 mg by mouth once daily for 28 day cycles. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: Niraparib at RP2D; Drug: Neratinib at RP2D |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 4 months
Secondary outcomes (2)
To assess the frequency of adverse events (AEs)
To assess adverse events (AEs) characterized and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE V 5.0) to determine safety and toxicity of the combination of neratinib and niraparib
Measured: 5 months
Preliminary efficacy (objective response rate [ORR]) of niraparib and neratinib in patients with advanced solid tumors.
To evaluate the objective response rate (ORR): The percentage of patients with objective response either partial response (PR) or complete response(CR), by analysis using RECIST 1.1 criteria
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Aug 2020
- Study start24 Aug 2020
- Primary completion30 Oct 2024
- Study completion31 Oct 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Solid TumorStudies 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
- Non-randomised
- Intervention model
- Sequential
- Model description
- Dose escalation will proceed within each cohort. Phase 1b is the expansion cohort at the recommended phase 2 dose found in phase 1.
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Virginia Commonwealth University
- Sponsor type
- University, hospital or other
- Collaborators
- Puma Biotechnology, Inc., GlaxoSmithKline
- Responsible party
- Sponsor
- Investigators
- Andrew Poklepovic, MD, Principal investigator, Massey Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04502602
- Sponsor's protocol ID
- MCC-18-14152
- Other IDs
- NCI-2020-05315
- Acronym
- iNNOVATE
- Status last verified
- May 2026
- First submitted
- 4 Aug 2020
- Last updated
- 11 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/1b Clinical Trial of Niraparib and Neratinib in Advanced Solid Tumors With an Expansion Cohort in Platinum-resistant Ovarian Cancer
- ClinicalTrials.gov ID
- NCT04502602
- Acronym / sponsor ID
- iNNOVATE / MCC-18-14152
- Conditions
- Advanced Solid Tumor, Ovarian Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Virginia Commonwealth UniversityUniversity, hospital or other
- Collaborators
- Puma Biotechnology, Inc., GlaxoSmithKline
- Study start
- 24 Aug 2020 (actual)
- Primary completion
- 30 Oct 2024 (actual)
- Study completion
- 31 Oct 2027 (estimated)
- First posted
- 6 Aug 2020 (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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 6
- Model description
- Dose escalation will proceed within each cohort. Phase 1b is the expansion cohort at the recommended phase 2 dose found in phase 1.
| Arm | Type | Receives |
|---|---|---|
| Dose Level -1 | Experimental | Drug: Neratinib 160 mg, Drug: Niraparib 100 mgNeratinib 160 mg and Niraparib 100 mg by mouth once daily for 28 day cycles. |
| Dose Level 1 | Experimental | Drug: Neratinib 160 mg, Drug: Niraparib 200 mgNeratinib 160 mg and Niraparib 200 mg by mouth once daily for 28 day cycles. |
| Dose Level 2 | Experimental | Drug: Neratinib 200 mg, Drug: Niraparib 200 mgNeratinib 200 mg and Niraparib 200 mg by mouth once daily for 28 day cycles. |
| Dose Level 3 | Experimental | Drug: Neratinib 240 mg, Drug: Niraparib 200 mgNeratinib 240 mg and Niraparib 200 mg by mouth once daily for 28 day cycles. |
| Dose Level 4 | Experimental | Drug: Neratinib 240 mg, Drug: Niraparib 300 mgNeratinib 240 mg and Niraparib 300 mg by mouth once daily for 28 day cycles. |
| Phase 1b: Platinum Resistant Expansion Cohort | Experimental | Drug: Niraparib at RP2D, Drug: Neratinib at RP2DThis 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (29 listed)
- 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
Key exclusion criteria (29 listed)
- 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.
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 |
|---|---|---|
| Neratinib 160 mgEscalating doses to determine recommended phase 2 dose (RP2D) | Drug | Dose Level -1, Dose Level 1 |
| Neratinib 200 mgDetermined RP2D dose | Drug | Dose Level 2 |
| Neratinib 240 mgEscalating doses to determine recommended phase 2 dose (RP2D) | Drug | Dose Level 3, Dose Level 4 |
| Niraparib 100 mgEscalating doses to determine recommended phase 2 dose (RP2D) | Drug | Dose Level -1 |
| Niraparib 200 mgEscalating doses to determine recommended phase 2 dose (RP2D) | Drug | Dose Level 1, Dose Level 2, Dose Level 3 |
| Niraparib 300 mgPhase 1: Escalating doses to determine recommended phase 2 dose (RP2D) | Drug | Dose Level 4 |
| Niraparib at RP2DPhase 1b: Determined dose | Drug | Phase 1b: Platinum Resistant Expansion Cohort |
| Neratinib at RP2DPhase 1b: Determined dose | Drug | Phase 1b: Platinum Resistant Expansion Cohort |
Primary outcome
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.
2 secondary outcomes
To assess the frequency of adverse events (AEs)
Time frame: 5 months
Preliminary efficacy (objective response rate [ORR]) of niraparib and neratinib in patients with advanced solid tumors.
Time frame: 5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 May 2026.
- Individual participant dataSharing planned: No
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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.
Andrew Poklepovic, MD principal investigator
Massey Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Neratinib 160 mg, Neratinib 200 mg and Neratinib 240 mg in people with Advanced Solid Tumor and Ovarian Cancer, run by Virginia Commonwealth University at 1 site in United States.
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 29 inclusion and 29 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: under way, not looking for participants, as of the sponsor's last update on 11 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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?
This study is still under way. Results are not available in the source record yet.
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?
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 study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 11 May 2026.