LY2157299 Monohydrate (LY2157299) and Radiotherapy in Metastatic Breast Cancer

NCT02538471 | Terminated Phase 2 Results DMC

• 1 other identifier: 1505016222
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

Patients with metastatic breast cancer receiving at least one single agent chemotherapy and demonstrating stable disease or disease progression at two consecutive clinical/radiological assessments (at an interval of at least 2 weeks). Transforming growth factor-beta (TGFΒ) blockade will enhance response of irradiated tumors and improve the function of Dendritic and T cells. Patients will receive 300 mg/day of study drug administered via oral drug tablet every day for 14 days on and 14 days off (=28 day cycle). Radiation to a metastatic site will be delivered at a dose of 7.5 Gy, given consecutively on days 1-3-5.

Conditions

Metastatic Breast Cancer

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Adverse Events

  Patients who have received at least one 14 days cycle of the study drug will be followed for toxicity (lack of grade 4 toxicity- primary safety end point). Physical exam (including labs) will be performed every 2 weeks while on the study. Patients will be followed with follow-up visits monthly for the first three months after completing therapy then annually for 5 years. Adverse Events will be monitored throughout the course of the study using the NCI CTCAE vers. 4.0.

  until end of study

• Number of Participants Non-irradiated Tumor Lesions That Had a Response.

  To determine if treatment with TGFΒ receptor I kinase inhibitor LY2157299 and localized RT achieves an abscopal tumor regression

  Until next progression up to 3 years

Secondary Outcomes (3)

• Number of Participants Who Received Radiation to the Tumor Who Had a Response.

  25 weeks

• Number of Participants Who Had a Change in Their T Regulatory Cell Numbers and Function Over the Course of the Study.

  2 years

• Number of Participants With Enhanced Tumor Specific Immunity.

  2 years

Study Arms (1)

Arm 1 - Study Drug & Radiation therapy

EXPERIMENTAL

Study Drug: Enrolled patients will receive 300 mg/day of LY2157299. LY2157299 will be administered as an oral drug tablet. The study drug will be administered orally on a 28-day cycle (1 cycle=28 days), every 2 weeks, or 14 days on / 14 days off. Blood samples will be obtained at baseline, and weeks 2, 6 and 15 for immune monitoring. Radiation therapy : Patients will receive Radiation therapy to a metastatic site at a dose of 7.5 Gy, given consecutively on days 1, 3 and 5, during Week 1 of their treatment.

Radiation: Radiation therapy; Drug: Study Drug

Interventions

Radiation therapy RADIATION

Imaging by PET/CT will be performed at baseline, 5 weeks and 15 weeks. The chosen metastatic sites will receive conformal external beam radiation 7.5 Gy/fraction x 3, to a total of 22.5 Gy over the course of one week.

Also known as: Radiation

Arm 1 - Study Drug & Radiation therapy

Study Drug DRUG

Patients will receive 300 mg/day of study drug administered via oral drug tablet every day for 14 days on and 14 days off (=28 day cycle) .

Also known as: Study Drug - oral

Arm 1 - Study Drug & Radiation therapy

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Biopsy proven breast carcinoma which is persistent and metastatic or recurrent and metastatic.
• Patients must have failed at least one line of chemotherapy for metastatic disease.
• Patients who are Human epidermal growth factor 2 +(HER2+) as defined by American Society of Clinical Oncology and College of American Pathologists (ASCO CAP) guidelines must have failed all prior therapy known to confer clinical benefit
• Patients must have at least 3 distinct metastatic sites with at least one measurable lesion which is at least 1 cm or larger in largest diameter
• At the time of enrollment, patients must be ≥ 4 weeks since all of the following treatments (and recovered from the toxicity of prior treatment to \<= Grade 1, exclusive of alopecia):
• major surgery; radiotherapy; chemotherapy (note: must be ≥ 6 weeks since therapy if treated with a nitrosourea, mitomycin, or monoclonal antibodies such as bevacizumab); immunotherapy; Biotherapy/targeted therapies.
• Patient ≥ 18 years of age. Patient life expectancy \> 6 months. Eastern cooperative group (ECOG) of 0 or 1
• Adequate organ function including:
• Marrow: Hemoglobin \>= 10.0 g/dL, absolute neutrophil count (ANC) \>=1,500/mm3, and platelets \>=100,000/mm3.
• Hepatic: Serum total bilirubin \<=1.5 x upper limit of normal (ULN) (Patients with Gilbert's Disease may be included if their total bilirubin is \<= 3.0 mg/dL), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) \<= 2.5 x ULN. If the patient has known liver metastases, an ALT and/or AST \<= 5 x ULN are allowed.
• Renal: Estimated or measured creatinine clearance \>= 60 mL/min.
• Other: Prothrombin time (PT) and partial thromboplastin time (PTT) \< ULN.
• Patients must have negative tests (antibody and/or antigen) for hepatitis viruses B and C unless the result is consistent with prior vaccination or prior infection with full recovery.
• Male and female patients of child-producing potential must agree to use effective contraception while enrolled on study and receiving the experimental drug, and for at least 3 months after the last treatment.

You may not qualify if:

• Patients diagnosed with another malignancy - unless following curative intent therapy, the patient has been disease free for at least 2 years and the probability of recurrence of the prior malignancy is \< 5%. Patients with curatively treated early-stage squamous cell carcinoma of the skin, basal cell carcinoma of the skin, or cervical intraepithelial neoplasia (CIN) are eligible for this study.
• Concurrent cancer therapy is not permitted.
• Uncontrolled central nervous system (CNS) metastases, meningeal carcinomatosis, malignant seizures, or a disease that either causes or threatens neurologic compromise (e.g., unstable vertebral metastases).
• History of ascites or pleural effusions, unless successfully treated.
• Patients with an organ transplant, including those that have received an allogeneic bone marrow transplant.
• Patients on immunosuppressive therapy including:
• Systemic corticosteroid therapy for any reason, including replacement therapy for hypoadrenalism. Patients receiving inhaled or topical corticosteroids may participate (if therapy is \< 5 days and is limited to systemic steroids as antiemetics).
• Patients receiving cyclosporine A, tacrolimus, or sirolimus are not eligible for this study.
• Use of investigational agents within 4 weeks prior to study enrollment (within 6 weeks if the treatment was with a long-acting agent such as a monoclonal antibody).
• Patients with moderate or severe cardiac disease:
• have the presence of cardiac disease, including a myocardial infarction within 6 months prior to study entry, unstable angina pectoris, New York Heart Association Class III/IV congestive heart failure, or uncontrolled hypertension.
• have documented major electrocardiogram (ECG) abnormalities (not responding to medical treatments) at the investigator's discretion (for example, symptomatic or sustained atrial or ventricular arrhythmias, second- or third-degree atrio ventricular block, complete bundle branch block, ventricular hypertrophy, or recent myocardial infarction).
• have major abnormalities documented by echocardiography (ECHO) with Doppler (for example, moderate or severe heart valve function defect and/or left ventricular ejection fraction \<50%, evaluation based on the institutional lower limit of normal). For additional details, refer to ECHO protocol.
• have predisposing conditions that are consistent with development of aneurysms of the ascending aorta or aortic stress (for example, family history of aneurysms, Marfan-Syndrome, bicuspid aortic valve, evidence of damage to the large vessels of the heart documented by computed tomography (CT) scan with contrast).
• B-type Natriuretic Peptide (BNP) above 3 times the baseline value and above the ULN that is sustained consecutive, scheduled blood draws. Troponin I above ULN, high sensitive C-reactive protein (hsCRP) above ULN or Cystatin above ULN.

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• University of California, Los Angeles: collaborator

Study Sites (1)

Weill Cornell Medical College

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Radiotherapy; Radiation; Drug Evaluation

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Physical Phenomena; Drug Development; Investigative Techniques; Evaluation Studies as Topic

Results Point of Contact

• Title: Dr. Silvia Formenti
• Organization: Weill Cornell Medicine

formenti@med.cornell.edu

212-746-3608

Study Officials

• Silvia Formenti, M.D

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 27, 2015
• First Posted: September 2, 2015
• Study Start: August 10, 2015
• Primary Completion: September 4, 2018
• Study Completion: February 20, 2019
• Last Updated: December 9, 2019
• Results First Posted: December 9, 2019

Record last verified: 2019-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)