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

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ClinicalTrials.gov Identifier: NCT03542175
Recruitment Status : Recruiting
First Posted : May 31, 2018
Last Update Posted : February 21, 2021
Sponsor:
Collaborator:
Clovis Oncology, Inc.
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

Tracking Information
First Submitted Date  ICMJE May 18, 2018
First Posted Date  ICMJE May 31, 2018
Last Update Posted Date February 21, 2021
Actual Study Start Date  ICMJE May 23, 2018
Estimated Primary Completion Date May 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 18, 2018)
defining the maximum tolerated dose (MTD) [ Time Frame: 1 year ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Rucaparib Administered With Radiation in Patients With Triple Negative Breast Cancer With an Incomplete Response Following Chemotherapy
Official Title  ICMJE 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
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:
This is a single-arm Phase I study.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Breast Cancer
Intervention  ICMJE
  • Drug: Rucaparib
    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.
  • Radiation: Radiotherapy
    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.
Study Arms  ICMJE Experimental: Rucaparib Administered With Radiation

Treatment 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.

Interventions:
  • Drug: Rucaparib
  • Radiation: Radiotherapy
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 18, 2018)
30
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 2023
Estimated Primary Completion Date May 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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), with evidence of residual disease in the breast or lymph nodes after neoadjuvant chemotherapy, at the time of definitive surgical treatment.
  • Non-metastatic, histologically or cytologically-confirmed hormone-receptor positive, Her2/neu negative breast cancer (defined as ER >1% or PR >1% AND Her-2/neu 0-1+ by IHC or FISH-negative, or as per MD discretion), with evidence of residual grade 3 invasive breast cancer AND either 1) >5 cm of residual disease in the breast OR 2) ≥ 4 axillary LNs in the axilla after neoadjuvant chemotherapy, at the time of definitive surgical treatment.
  • Definitive surgical treatment with breast-conserving surgery or mastectomy and axillary lymph node evaluation.
  • 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Gender Based Eligibility: Yes
Gender Eligibility Description: Breast cancer
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Atif Khan, MD 848-225-6334 khana7@mskcc.org
Contact: Simon Powell, MD, PhD 212-639-3639
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03542175
Other Study ID Numbers  ICMJE 18-002
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Memorial Sloan Kettering Cancer Center
Study Sponsor  ICMJE Memorial Sloan Kettering Cancer Center
Collaborators  ICMJE Clovis Oncology, Inc.
Investigators  ICMJE
Principal Investigator: Atif Khan, MD Memorial Sloan Kettering Cancer Center
PRS Account Memorial Sloan Kettering Cancer Center
Verification Date February 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP