Clinical Trials /

Niraparib in Combination With Osimertinib in EGFR-Mutated Advanced Lung Cancer

NCT03891615

Description:

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.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Phase 1 Study of Niraparib in Combination With Osimertinib in EGFR-Mutated Advanced Lung Cancer
  • Official Title: Phase 1 Study of Niraparib in Combination With Osimertinib in EGFR-Mutated Advanced Lung Cancer

Clinical Trial IDs

  • ORG STUDY ID: 18-613
  • NCT ID: NCT03891615

Conditions

  • Lung Cancer

Interventions

DrugSynonymsArms
NiraparibZEJULANiraparib + Osimertinib
OsimertinibTagrissoNiraparib + Osimertinib

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Niraparib + OsimertinibExperimentalNiraparib will be administered orally once daily Osimertinib will be administered by mouth once daily
  • Niraparib
  • Osimertinib

Eligibility Criteria

        Inclusion Criteria:

          -  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.

          -  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.

        Exclusion Criteria:

          -  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.

          -  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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum Tolerated Dose of Niraparib
Time Frame:2 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Rate of toxicity of combined niraparib and osimertinib
Time Frame:2 years
Safety Issue:
Description:
Measure:Objective response rate of niraparib
Time Frame:2 years
Safety Issue:
Description:
Measure:Median Progression Free Survival time of Niraparib
Time Frame:2 Years
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Massachusetts General Hospital

Trial Keywords

  • Lung Cancer

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