Clinical Trials /

Niraparib and Panitumumab in Patients With Advanced or Metastatic Colorectal Cancer

NCT03983993

Description:

This phase II trial studies the side effects and how well niraparib and panitumumab work in treating patients with colorectal cancer that has spread to other places in the body. Niraparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as panitumumab, may help the body's immune system attack the cancer and may interfere with the ability of tumor cells to grow and spread. Giving niraparib and panitumumab may work better in treating patients with colorectal cancer.

Related Conditions:
  • Colorectal Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Niraparib and Panitumumab in Patients With Advanced or Metastatic Colorectal Cancer
  • Official Title: A Phase II Study of Niraparib in Combination With EGFR Inhibitor Panitumumab in Patients With Advanced Colorectal Cancer

Clinical Trial IDs

  • ORG STUDY ID: IRB00107377
  • SECONDARY ID: NCI-2018-02757
  • SECONDARY ID: Winship4517-18
  • NCT ID: NCT03983993

Conditions

  • Advanced Microsatellite Stable Colorectal Carcinoma
  • Metastatic Microsatellite Stable Colorectal Carcinoma
  • Microsatellite Stable
  • RAS Wild Type
  • Stage IV Colorectal Cancer AJCC v8
  • MSI-H Colorectal Cancer

Interventions

DrugSynonymsArms
NiraparibMK-4827, ZejulaTreatment (niraparib, panitumumab)
PanitumumabABX-EGF, VectibixTreatment (niraparib, panitumumab)

Purpose

This phase II trial studies the side effects and how well niraparib and panitumumab work in treating patients with colorectal cancer that has spread to other places in the body. Niraparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as panitumumab, may help the body's immune system attack the cancer and may interfere with the ability of tumor cells to grow and spread. Giving niraparib and panitumumab may work better in treating patients with colorectal cancer.

Detailed Description

      PRIMARY OBJECTIVE:

      I. Evaluate the activity of the combination of niraparib with epidermal growth factor
      receptor (EGFR) inhibitor panitumumab in previously treated patients with rat sarcoma gene
      (RAS) wild type (WT) metastatic colorectal cancer.

      SECONDARY OBJECTIVES:

      I. Define the toxicity profile of the combination of niraparib and panitumumab.

      II. Evaluate the activity of the combination of niraparib and panitumumab in previously
      treated patients with metastatic colorectal cancer.

      OUTLINE:

      Patients receive niraparib orally (PO) once daily (QD) on days 1-28 and panitumumab
      intravenously (IV) over 60-90 minutes on days 1 and 15. Cycles repeat every 28 days in the
      absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up at 30 days, every 6 months for
      2 years, and then annually for up to 5 years.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (niraparib, panitumumab)ExperimentalPatients receive niraparib orally once daily on days 1-28 and panitumumab intravenously over 60-90 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Niraparib
  • Panitumumab

Eligibility Criteria

        Inclusion Criteria:

          -  Participant must have advanced, metastatic RAS wildtype colorectal cancer and must
             have received at least one line of systemic therapy. Both microsatellite (MSI) high
             and stable (MSS) patients are eligible

          -  Participants may have been intolerant of, progressed on, or failed at least one line
             of systemic chemotherapy. Patients who are currently on first line
             Oxaliplatin-containing chemotherapy regimen are allowed on the trial if they have
             remained stable or better ([partial response]PR or [complete response]CR) for at least
             4 months on that line of treatment and are being considered for maintenance therapy as
             standard of care

          -  Histologic or cytologic diagnosis of colorectal cancer

          -  Participant must have an Eastern Cooperative Oncology Group (ECOG) performance status
             of ≤ 1

          -  Absolute neutrophil count ≥ 1,500/µL

          -  Platelets ≥ 100,000/µL

          -  Hemoglobin ≥ 9 g/dL

          -  Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or calculated creatinine
             clearance ≥ 30 mL/min using the Cockcroft-Gault equation

          -  Total bilirubin ≤ 1.5 x ULN (≤ 2.0 in patients with known Gilberts syndrome) OR direct
             bilirubin ≤ 1 x ULN

          -  Aspartate aminotransferase and alanine aminotransferase ≤ 2.5 x ULN unless liver
             metastases are present, in which case they must be ≤ 5 x ULN

          -  Participant must agree to not donate blood during the study or for 90 days after the
             last dose of study treatment

          -  Female participant has a negative urine or serum pregnancy test within 7 days prior to
             taking study treatment if of childbearing potential and agrees to abstain from
             activities that could result in pregnancy from screening through 180 days after the
             last dose of study

          -  Male participant agrees to use an adequate method of contraception starting with the
             first dose of study treatment through 180 days after the last dose of study treatment

          -  Participant must be able to provide written informed consent

        Exclusion Criteria:

          -  Participant must not be simultaneously enrolled in any interventional clinical trial

          -  Prior therapy with poly ADP (adenosine diphosphate) ribose polymerase (PARP)
             inhibitors or with EGFR inhibitors approved for the treatment of colorectal cancer
             (cetuximab or panitumumab)

          -  Patients with a history of interstitial pneumonitis or pulmonary fibrosis, or evidence
             of interstitial pneumonitis or pulmonary fibrosis during screening

          -  Inability to take oral medications

          -  Participant has had radiation therapy encompassing > 20% of the bone marrow within 2
             weeks; or any radiation therapy within 1 week prior to day 1 of protocol therapy

          -  Participant must not have a known hypersensitivity to components or excipients of
             niraparib or panitumumab

          -  Participant must not have a serious, uncontrolled medical disorder, nonmalignant
             systemic disease, or active, uncontrolled infection. Examples include, but are not
             limited to, uncontrolled ventricular arrhythmia, recent (within 90 days) myocardial
             infarction, uncontrolled major seizure disorder, unstable spinal cord compression,
             superior vena cava syndrome, or any psychiatric disorder that prohibits obtaining
             informed consent

          -  Known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)

          -  Participant must not have had diagnosis, detection, or treatment of another type of
             cancer ≤ 2 years prior to initiating protocol therapy (except basal or squamous cell
             carcinoma of the skin and cervical cancer that has been definitively treated)

          -  Participant must not have known active, symptomatic brain or leptomeningeal
             metastases.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Clinical benefit rate (CBR)
Time Frame:Up to 5 years post treatment
Safety Issue:
Description:The efficacy, as measured by clinical benefit rate (CBR), will be assessed for the total number of patients enrolled. CBR = (Complete Response + Partial Response + Stable Disease [CR +PR + SD] rate. Response will be assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1 criteria using an independent review.

Secondary Outcome Measures

Measure:Objective response rate (ORR)
Time Frame:Up to 5 years post treatment
Safety Issue:
Description:Objective response rate (ORR) is defined as the percentage of patients with complete response (CR) or partial response (PR), as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1 criteria using an independent review.
Measure:Duration of response (DOR)
Time Frame:Up to 5 years post treatment
Safety Issue:
Description:Duration of response (DOR) is defined as the time from the initial response (complete response [CR] or partial response [PR]) until the time of first documentation of disease progression, as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1 criteria using an independent review.
Measure:Progression free survival (PFS)
Time Frame:Up to 5 years post treatment
Safety Issue:
Description:For progression free survival (PFS), progression or death from any cause will be defined as the event. Progression will be assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1 criteria using an independent review. Patients will be censored at time of last follow-up.
Measure:Overall survival (OS)
Time Frame:Up to 5 years post treatment
Safety Issue:
Description:For overall survival (OS), death from any cause will be defined as the event. Patients will be censored at time of last follow-up.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Emory University

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