Lung CancerPhase 1NCT03891615
Niraparib in Combination With Osimertinib in EGFR-Mutated Advanced Lung Cancer
A Phase 1 study testing Niraparib and Osimertinib in people with Lung Cancer, run by Massachusetts General Hospital at 3 sites in United States.
Trial summary
This research study is studying a combination of drugs as a possible treatment for EGFR-Mutated Advanced Lung Cancer. The names of the study drugs involved in this study are Niraparib and Osimertinib. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lung Cancer
- What is being tested?
- Niraparib and Osimertinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 3 sitesUnited States
- Study dates
- 6 Jun 2019to 7 Nov 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- Participants must have histologically or cytologically confirmed stage IV (AJCC 8th ed.) NSCLC with an activating EGFR mutation as identified in a CLIA-approved laboratory.
- Presence of evaluable disease, either measure or non-measurable, in accordance with RECIST 1.1 criteria.
- Participants must have had clinical progression on osimertinib at any prior time, i.e., intervening therapy between osimertinib and study enrollment is allowed.
- Participants must have access to commercial osimertinib.
- Participants must not have received any prior PARP inhibitor therapy.
- Age minimum 18 years.
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- ECOG performance status ≤1 (Karnofsky ≥70%, see Appendix A).
- Life expectancy of greater than 6 months.
- Participants must have normal organ and marrow function as defined below:
- absolute neutrophil count ≥1,500/mcL
- platelets ≥100,000/mcL
- hemoglobin ≥ 9 g/dL
- bilirubin total bilirubin ≤ 1.5 x upper limit of normal (ULN) (≤2.0 in patients with known Gilberts syndrome or liver metastases) OR direct bilirubin ≤ 1 x ULN
- AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal, unless liver metastases are present, in which case they must be ≤ 5 x ULN
- creatinine ≤ 1.5 x institutional ULN OR
- creatinine clearance ≥50 mL/min using the Cockcroft-Gault equation
- Participants must have undergone a prior tumor biopsy upon clinical progression on osimertinib. If it was not feasible or medically safe to undergo a biopsy a patient may enroll with permission of the PI.
- The effects of Niraparib on the developing human fetus are unknown but based on its mechanism of action Niraparib may cause fetal harm when administered to a pregnant woman. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry through 180 days after the last dose of study treatment. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of Niraparib administration.
- Female participant must have a negative urine or serum pregnancy test within 7 days prior to taking study treatment if of childbearing potential, or is of nonchildbearing potential. Nonchildbearing 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 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. See Section 4.4 for a list of acceptable birth control methods. 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.
- Ability to take oral medications whole.
- Participant receiving corticosteroids may continue as long as their dose is stable for least 4 weeks prior to initiating protocol therapy.
- Participant must agree to not donate blood during the study or for 90 days after the last dose of study treatment
- Participant must agree not to breastfeed during the study or for 180 days after the last dose of study treatment.
- Ability to understand and the willingness to sign a written informed consent document.
Who cannot join
- Participants must not be simultaneously enrolled in any interventional clinical trial.
- Participants receiving any systemic standard of care or investigational therapy within 4 weeks from the last dose prior to planned study treatment, with the exception of osimertinib. This time frame may be shortened for participants depending on the characteristics of the individual therapy, after discussion with the Study PI. For investigational therapy, the time frame will not be shortened to less than at least 5 half-lives of the investigational agent.
- Patients receiving radiation therapy encompassing > 20% of the bone marrow by investigator's estimate within 14 days, or any radiation therapy within 7 days from the last treatment prior to planned study treatment. However, small volume palliative radiation therapy with no or little bone marrow exposure is allowed at the investigator's discretion.
- Participants may receive a stable dose of bisphosphonates for bone metastases, before and during the study as long as these were started at least 4 weeks prior to treatment.
- Participants who had any major surgery within the past 3 weeks (excluding vascular access placement, mediastinoscopy, or biopsies performed by an interventional service) and participant must have recovered from any surgical effects.
- Participants with symptomatic uncontrolled brain or leptomeningeal metastases. Participants with brain metastases that have been treated with prior radiation therapy and are stable on a subsequent scan are allowed. Participants with untreated possible brain metastases that are ≤ 1 cm and asymptomatic are allowed.
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- Participants who received a transfusion (platelets, red blood cells) or hematopoetic growth factors within 4 weeks of study treatment.
- Presence of any of the following cardiac criteria/factors:
- Resting QT interval of >470 msec.
- Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG, such as complete left bundle branch block, third degree heart block, or second degree heart block.
- Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age in first degree relatives, or any concomitant medication known to prolong the QT interval.
- Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required corticosteroid treatment, or any evidence of clinically active interstitial lung disease.
- Participants with known hypersensitivity to the components or excipients of niraparib or osimertinib.
- Participants may not have received prior treatment with anti-PD1, -PDL1, or -CTLA4 inhibitors.
- Participants with a second, clinically active, malignancy. Participants must not have known history or current diagnosis of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, myocardial infarction, major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, or psychiatric illness/social situations that would limit compliance with study requirements.
- Participants must not have had any known Grade 3 or 4 anemia, neutropenia or thrombocytopenia due to prior chemotherapy that persisted > 4 weeks and was related to the most recent treatment.
- Participants must not have current evidence of any condition, therapy, or laboratory abnormality (including active or uncontrolled myelosuppression [ie, anemia, leukopenia, neutropenia, thrombocytopenia]) that might confound the results of the study or interfere with the patient's participation for the full duration of the study treatment or that makes it not in the best interest of the patient to participate in the opinion of the investigator or sponsor.
- Patients must not have known, active hepatitis B/C.
- Known disorder affecting gastrointestinal absorption.
- Patients must not be pregnant or breastfeeding, or expecting to conceive children, within the projected duration of the study treatment, or for 180 days after the last dose of study treatment.
- Known HIV-positive participants are ineligible because of the potential for pharmacokinetic interactions with Niraparib. In addition, these participants may be at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in participants receiving combination antiretroviral therapy when indicated, However, HIV testing is not required.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Dana Farber Cancer Institute
Boston, Massachusetts, 02114
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114
Beth Israel Deaconess
Boston, Massachusetts, 02115
About this study
Official title: Phase 1 Study of Niraparib in Combination With Osimertinib in EGFR-Mutated Advanced Lung Cancer
This research study is studying a combination of drugs as a possible treatment for EGFR-Mutated Advanced Lung Cancer.
The names of the study drugs involved in this study are Niraparib and Osimertinib.
Read the detailed description
This research study is a Phase I clinical trial, which tests the safety of an investigational drug and also tries to define the appropriate dose of the investigational drug to use for further studies. "Investigational" means that the drug is being studied.
The FDA (the U.S. Food and Drug Administration) has not approved niraparib for this specific disease but it has been approved for other uses.
The FDA has approved osimertinib as a treatment option for this disease.
Niraparib is a type of drug called a "PARP inhibitor", which blocks DNA (the genetic material of cells) damage from being repaired or may prevent damage from occurring in the first place. In cancer treatment, inhibiting PARP may help kill cancer cells through deadly DNA damage. PARP inhibition may be a treatment option for participants with this type of cancer due to altered repair and protection of tumor DNA.
Osimertinib is an inhibitor of the epidermal growth factor receptor (EGFR). In this type of cancer there is a mutation in the EGFR which is allowing the cancer to grow when it is not supposed to. Osimertinib blocks mutated EGFR, which may cause tumor regression (when the tumor starts to shrink) and prevent the spread of the cancer.
In this research study, the investigators are looking to see whether the combination of niraparib and osimertinib is safe and well tolerated and what the best dose of niraparib is in participants with EGFR-Mutated Advanced Lung Cancer. The investigators also hope that the combination of niraparib and osimertinib will stop the cancer from growing and spreading.
- Conditions
- Lung Cancer
- Being tested
- Niraparib, Osimertinib
- Keywords
- Lung Cancer
- Medical subject headings
- Lung Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NiraparibDrug
Also called ZEJULA
Niraparib is a type of drug called a "PARP inhibitor", which blocks DNA (the genetic material of cells) damage from being repaired or may prevent damage from occurring in the first place. In cancer treatment, inhibiting PARP may help kill cancer cells through deadly DNA damage.
OsimertinibDrug
Also called Tagrisso
Osimertinib blocks mutated EGFR, which may cause tumor regression (when the tumor starts to shrink) and prevent the spread of the cancer.
| Study group | Role | What they receive |
|---|---|---|
| Niraparib + Osimertinib | Experimental | * Niraparib will be administered orally once daily
* Osimertinib will be administered by mouth once daily Receives: Drug: Niraparib; Drug: Osimertinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose of Niraparib
Measured: 2 years
Secondary outcomes (3)
Rate of toxicity of combined niraparib and osimertinib
Measured: 2 years
Objective response rate of niraparib
Measured: 2 years
Median Progression Free Survival time of Niraparib
Measured: 2 Years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2019
- Study start6 Jun 2019
- Primary completion3 Jul 2024
- Study completion7 Nov 2024
Why it stopped: Slow accrual.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Lung CancerStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Tesaro, Inc.
- Responsible party
- Principal investigator, Zofia Piotrowska, Massachusetts General Hospital
- Investigators
- Zofia Piotrowska, MD, MPH, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03891615
- Sponsor's protocol ID
- 18-613
- Status last verified
- Sep 2026
- First submitted
- 25 Mar 2019
- Last updated
- 21 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research
Study at a glance
From the registry record, last updated by the sponsor on 21 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 Study of Niraparib in Combination With Osimertinib in EGFR-Mutated Advanced Lung Cancer
- ClinicalTrials.gov ID
- NCT03891615
- Acronym / sponsor ID
- 18-613
- Conditions
- Lung Cancer
- Keywords
- Lung Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow accrual.
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- Tesaro, Inc.
- Study start
- 6 Jun 2019 (actual)
- Primary completion
- 3 Jul 2024 (actual)
- Study completion
- 7 Nov 2024 (actual)
- First posted
- 27 Mar 2019 (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.
This research study is studying a combination of drugs as a possible treatment for EGFR-Mutated Advanced Lung Cancer.
The names of the study drugs involved in this study are Niraparib and Osimertinib.
Detailed description
This research study is a Phase I clinical trial, which tests the safety of an investigational drug and also tries to define the appropriate dose of the investigational drug to use for further studies. "Investigational" means that the drug is being studied.
The FDA (the U.S. Food and Drug Administration) has not approved niraparib for this specific disease but it has been approved for other uses.
The FDA has approved osimertinib as a treatment option for this disease.
Niraparib is a type of drug called a "PARP inhibitor", which blocks DNA (the genetic material of cells) damage from being repaired or may prevent damage from occurring in the first place. In cancer treatment, inhibiting PARP may help kill cancer cells through deadly DNA damage. PARP inhibition may be a treatment option for participants with this type of cancer due to altered repair and protection of tumor DNA.
Osimertinib is an inhibitor of the epidermal growth factor receptor (EGFR). In this type of cancer there is a mutation in the EGFR which is allowing the cancer to grow when it is not supposed to. Osimertinib blocks mutated EGFR, which may cause tumor regression (when the tumor starts to shrink) and prevent the spread of the cancer.
In this research study, the investigators are looking to see whether the combination of niraparib and osimertinib is safe and well tolerated and what the best dose of niraparib is in participants with EGFR-Mutated Advanced Lung Cancer. The investigators also hope that the combination of niraparib and osimertinib will stop the cancer from growing and spreading.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Niraparib + Osimertinib | Experimental | Drug: Niraparib, Drug: Osimertinib* Niraparib will be administered orally once daily * Osimertinib will be administered by mouth once daily |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (27 listed)
- Participants must have histologically or cytologically confirmed stage IV (AJCC 8th ed.) NSCLC with an activating EGFR mutation as identified in a CLIA-approved laboratory.
- Presence of evaluable disease, either measure or non-measurable, in accordance with RECIST 1.1 criteria.
- Participants must have had clinical progression on osimertinib at any prior time, i.e., intervening therapy between osimertinib and study enrollment is allowed.
- Participants must have access to commercial osimertinib.
- Participants must not have received any prior PARP inhibitor therapy.
Key exclusion criteria (22 listed)
- Participants must not be simultaneously enrolled in any interventional clinical trial.
- Participants receiving any systemic standard of care or investigational therapy within 4 weeks from the last dose prior to planned study treatment, with the exception of osimertinib. This time frame may be shortened for participants depending on the characteristics of the individual therapy, after discussion with the Study PI. For investigational therapy, the time frame will not be shortened to less than at least 5 half-lives of the investigational agent.
- Patients receiving radiation therapy encompassing > 20% of the bone marrow by investigator's estimate within 14 days, or any radiation therapy within 7 days from the last treatment prior to planned study treatment. However, small volume palliative radiation therapy with no or little bone marrow exposure is allowed at the investigator's discretion.
- Participants may receive a stable dose of bisphosphonates for bone metastases, before and during the study as long as these were started at least 4 weeks prior to treatment.
- Participants who had any major surgery within the past 3 weeks (excluding vascular access placement, mediastinoscopy, or biopsies performed by an interventional service) and participant 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 |
|---|---|---|
| NiraparibAlso: ZEJULANiraparib is a type of drug called a "PARP inhibitor", which blocks DNA (the genetic material of cells) damage from being repaired or may prevent damage from occurring in the first place. In cancer treatment, inhibiting PARP may help kill cancer cells through deadly DNA damage. | Drug | Niraparib + Osimertinib |
| OsimertinibAlso: TagrissoOsimertinib blocks mutated EGFR, which may cause tumor regression (when the tumor starts to shrink) and prevent the spread of the cancer. | Drug | Niraparib + Osimertinib |
Primary outcome
Maximum Tolerated Dose of Niraparib
Time frame: 2 years
3 secondary outcomes
Rate of toxicity of combined niraparib and osimertinib
Time frame: 2 years
Objective response rate of niraparib
Time frame: 2 years
Median Progression Free Survival time of Niraparib
Time frame: 2 Years
Results and safety
The study was stopped early (reason given: Slow accrual.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Sep 2026.
- Individual participant dataSharing planned: Yes. The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: [contact information for Sponsor Investigator or designee]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research
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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.
Zofia Piotrowska, MD, MPH principal investigator
Dana-Farber Cancer Institute
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Niraparib and Osimertinib in people with Lung Cancer, run by Massachusetts General Hospital at 3 sites 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 27 inclusion and 22 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: stopped early, as of the sponsor's last update on 21 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites 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?
The study was stopped early (reason given: Slow accrual.). Results are not available in the source record.
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?
Maximum Tolerated Dose of Niraparib (time frame: 2 years). 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 21 Sep 2026.