Clinical Trials /

A Study of Rucaparib Administered With Radiation in Patients With Triple Negative Breast Cancer With an Incomplete Response Following Chemotherapy

NCT03542175

Description:

The purpose of this study is to test the safety of a study drug called Rucaparib, administered in combination with the type of radiation therapy that is usually given to women with your form of breast cancer.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of Rucaparib Administered With Radiation in Patients With Triple Negative Breast Cancer With an Incomplete Response Following Chemotherapy
  • Official Title: A Phase I Study of Rucaparib Administered Concurrently With Postoperative Radiotherapy in Patients With Triple Negative Breast Cancer With an Incomplete Pathologic Response Following Neoadjuvant Chemotherapy

Clinical Trial IDs

  • ORG STUDY ID: 18-002
  • NCT ID: NCT03542175

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
RucaparibRucaparib Administered With Radiation

Purpose

The purpose of this study is to test the safety of a study drug called Rucaparib, administered in combination with the type of radiation therapy that is usually given to women with your form of breast cancer.

Trial Arms

NameTypeDescriptionInterventions
Rucaparib Administered With RadiationExperimentalTreatment will consist of rucaparib at one dose level (300 mg BID, 400 mg BID, 500 mg BID or 600 mg BID) concurrently with a 6-week course of radiotherapy and 4 additional weeks of maintenance rucaparib at the same dose level. Radiotherapy will consist of 50 Gy in 2 Gy per fraction to the breast or chest wall with or without regional nodes plus a 10 Gy boost to the lumpectomy cavity, to a total dose of 60 Gy. A 10 Gy boost to the post-mastectomy scar is allowed at the discretion of the treating physician.
  • Rucaparib

Eligibility Criteria

        Inclusion Criteria:

          -  Female, ≥ 18 years of age.

          -  Non-metastatic, histologically or cytologically-confirmed TNBC (defined as ER <1%, PR
             <1%, her-2-neu 0-1+ by IHC or FISH-negative or as per MD discretion).

          -  Definitive surgical treatment with breast-conserving surgery or mastectomy and
             axillary lymph node evaluation.

          -  Residual disease in the breast or lymph nodes at the time of definitive surgical
             treatment.

          -  At least 6-month life expectancy, ECOG Performance status < 2.

          -  Willingness to discontinue any cytotoxic chemotherapeutic agents, immunotherapy and
             biologic therapy at least 2 weeks prior to the start of RT.

          -  Adequate organ function (assessed within 30 days prior to initiation of protocol
             treatment, unless otherwise indicated) as follows: Hematology

               -  Absolute Neutrophil Count (ANC) ≥1500/mm^3

               -  Platelet Count ≥100,000/mm^3

               -  Hemoglobin ≥9.0 g/dL (after transfusion if required) Renal Function

               -  Creatinine Serum ≤ 1.5 mg/dL or Creatinine Clearance ≥ 45 mL/min^a Hepatic
                  Function

               -  Bilirubin ≤ 1.5 mg/dL

               -  Aspartate Aminotransferase (AST) ≤ 2.5 x ULN^b

               -  Alanine Aminotransferase (ALT) ≤ 2.5 x ULN ULN = upper normal limit of
                  institution's normal range

                    1. If calculated creatinine clearance is < 45mL/min, a 24-hour urine collection
                       for creatinine clearance may be performed

                    2. Subjects with documented Gilbert's disease may have bilirubin up to 2.5
                       mg/dL

          -  Negative serum pregnancy test within 14 days prior to study treatment if a woman has
             child-bearing potential. Subjects of child bearing potential are those who have not
             been surgically sterilized or have not been free from menses for > 1 year.

          -  Ability to swallow and retain oral medications.

          -  Written informed consent obtained from subject and ability for subject to comply with
             the requirements of the study.

          -  Female subjects of childbearing potential should be willing to use 2 methods of birth
             control or be surgically sterile, or abstain from heterosexual activity for the
             duration of study participation. Should a woman become pregnant while participating on
             study, she should inform the treating physician immediately.

        Exclusion Criteria:

          -  Gross residual tumor or positive margins after surgery that is un-excised, as
             radiation dose in the study will be limited to 60 Gy.

          -  Complete pathologic response to NAC.

          -  Receipt of PARP inhibitor prior to RT.

          -  Pregnant or expecting to conceive within the projected duration of the trial, starting
             with screening visit through 180 days after the last dose of trial treatment.

          -  Prior history of radiation therapy to the ipsilateral breast and/or regional nodes is
             not allowed (prior RT to other sites is permitted).

          -  Patients with breast augmentation implants are excluded.

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to rucaparib.

          -  Concomitant anti-neoplastic treatment is not allowed during protocol treatment and
             should be completed at least 2 weeks prior to commencement of protocol treatment, with
             resolution of associated acute toxicities. Bisphosphonates are permitted without
             restriction even during protocol treatment.

          -  Significant comorbidity: Patients with clinically significant and uncontrolled major
             disease or disorder that could exacerbate potential toxicities, confound safety
             assessments, require excluded therapy for management, or limit study compliance.

          -  Ongoing therapy with other investigational agents. Patients may not be receiving any
             other investigational agents.

          -  Unresolved toxicity from other agents. Patients with unresolved CTCAE v4.03 Grade 3 or
             greater toxicity from prior administration of another investigational drug and/or
             anti-cancer treatment are not eligible.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:defining the maximum tolerated dose (MTD)
Time Frame:1 year
Safety Issue:
Description:proportion of subjects encountering toxicity at each dose level. The trial will be monitored using TITE-CRM. Assuming a model for the time to occurrence of toxic response as a function of dose, the method allows information from all enrolled patients to be used when allocating a new patient to a dose level.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Memorial Sloan Kettering Cancer Center

Trial Keywords

  • Rucaparib
  • Radiotherapy
  • Triple Negative Breast Cancer
  • 18-002

Last Updated

November 14, 2019