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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 : November 15, 2019
Sponsor:
Collaborator:
Clovis Oncology, Inc.
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

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.

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: Rucaparib Radiation: Radiotherapy Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Intervention Model: Single Group Assignment
Intervention Model Description: This is a single-arm Phase I study.
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : May 23, 2018
Estimated Primary Completion Date : May 2020
Estimated Study Completion Date : May 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Rucaparib

Arm Intervention/treatment
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.

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.




Primary Outcome Measures :
  1. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Breast cancer
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03542175


Contacts
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Contact: Atif Khan, MD 848-225-6334 khana7@mskcc.org
Contact: Simon Powell, MD, PhD 212-639-3639

Locations
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United States, New Jersey
Memorial Sloan Kettering at Basking Ridge Recruiting
Basking Ridge, New Jersey, United States, 07920
Contact: Atif Khan, MD    848-225-6334      
Memoral Sloan Kettering Monmouth Recruiting
Middletown, New Jersey, United States, 07748
Contact: Atif Khan, MD    848-225-6334      
Memorial Sloan Kettering Bergen Recruiting
Montvale, New Jersey, United States, 07645
Contact: Atif Khan, MD    848-225-6334      
United States, New York
Memorial Sloan Kettering Commack Recruiting
Commack, New York, United States, 11725
Contact: Atif Khan, MD    848-225-6334      
Memorial Sloan Kettering Westchester Recruiting
Harrison, New York, United States, 10604
Contact: Atif Khan, MD    848-225-6334      
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Atif Khan, MD    848-225-6334      
Contact: Simon Powell, MD, PhD    212-639-3639      
Memorial Sloan Kettering Nassau Recruiting
Uniondale, New York, United States, 11553
Contact: Atif Khan, MD    848-225-6334      
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
Clovis Oncology, Inc.
Investigators
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Principal Investigator: Atif Khan, MD Memorial Sloan Kettering Cancer Center

Additional Information:
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Responsible Party: Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT03542175     History of Changes
Other Study ID Numbers: 18-002
First Posted: May 31, 2018    Key Record Dates
Last Update Posted: November 15, 2019
Last Verified: November 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Memorial Sloan Kettering Cancer Center:
Rucaparib
Radiotherapy
Triple Negative Breast Cancer
18-002
Additional relevant MeSH terms:
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Breast Neoplasms
Triple Negative Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Rucaparib
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents