2nd Line Treatment With Pemetrexed and Sorafenib for Recurrent or Metastatic Triple Negative Breast Cancer

NCT02624700 | Terminated Phase 2 Results DMC FDA Drug

• 3 other identifiers: MCC-14-10790HM20005967NCI-2015-02190
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

This phase 2 clinical trial will evaluate the efficacy of the combination of pemetrexed and sorafenib in patients with recurrent or metastatic Triple Negative Breast Cancer (TNBC). Candidate pharmacodynamic and predictive biomarkers will also be evaluated.

Conditions

Breast Cancer; Metastatic Breast Cancer; Recurrent Breast Cancer

Keywords

ER-negative; PgR-negative; Human epidermal growth factor receptor 2 (HER2-negative); Triple Negative Breast Cancer; HER2-negative

Outcome Measures

Primary Outcomes (1)

• The Percentage of Patients With Objective Response Either Partial Response (PR) or Complete Response(CR).

  The primary endpoint is the percentage of patients with HER2-negative metastatic breast cancer achieving an objective response (either PR or CR). Overall Response = CR+PR, based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1).

  2 years 3 months

Secondary Outcomes (3)

• The Duration of Progression-free Survival (PFS).

  2 years 3 months

• The 2-year Survival Rate After Initial Study Treatment.

  2 years 3 months

• Number of Participants at Risk and Affected by Adverse Events (AEs)

  2 years 3 months

Study Arms (2)

A: Pemetrexed + Sorafenib

EXPERIMENTAL

Pemetrexed 500 mg/m2 IV Day 1 + Sorafenib 400mg PO twice each day on Days 1-5 of each 14-day cycle

Drug: Experimental Arm A: Pemetrexed; Drug: Experimental Arm A: Sorafenib

B: Pemetrexed + Sorafenib

EXPERIMENTAL

Pemetrexed 375mg/m2 intravenously (IV) Day 1 + Sorafenib 200mg by mouth twice daily on days 1-5, every 21 days of each cycle.

Drug: Experimental Arm B: Pemetrexed; Drug: Experimental Arm B: Sorafenib

Interventions

Experimental Arm A: Pemetrexed DRUG

Treatment schedule is administered on day 1 of each 14-day cycle by Intravenous infusion over 10 minutes with a dose of 500 mg/m2. If necessary, the duration of the pemetrexed infusion may be extended to a maximum of 20 minutes.

Also known as: Alimta

A: Pemetrexed + Sorafenib

Experimental Arm A: Sorafenib DRUG

Treatment schedule is administered twice daily by mouth on an empty stomach on days 1-5 of each 14-day cycle with a dose of 400 mg.

Also known as: Nexavar

A: Pemetrexed + Sorafenib

Experimental Arm B: Pemetrexed DRUG

Treatment schedule is administered on day 1 of each 21-day cycle by Intravenous infusion over 10 minutes with a dose of 375 mg/m2. If necessary, the duration of the pemetrexed infusion may be extended to a maximum of 20 minutes.

Also known as: Alimta

B: Pemetrexed + Sorafenib

Experimental Arm B: Sorafenib DRUG

Treatment schedule is administered twice daily by mouth on an empty stomach on days 1-5 of each 21-day cycle with a dose of 200 mg.

Also known as: Nexavar

B: Pemetrexed + Sorafenib

Eligibility Criteria

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

You may qualify if:

• Unresectable adenocarcinoma of the breast involving chest wall, regional nodes, or distant site
• Breast cancer determined to be estrogen receptor (ER)-negative and progesterone receptor (PgR)-negative defined for this study as \< 10% tumor staining by immunohistochemistry (IHC) (Note: Eligibility should be based on the ER and PgR status reported at the time of the most recent biopsy or resection).
• Breast cancer determined to be HER2-negative per current American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) HER2 Guidelines (Note: Eligibility should be based on the HER2 status reported at the time of the most recent biopsy or resection).
• At least one prior regimen for treatment of recurrent or metastatic disease (Note: Prior regimen for recurrent or metastatic disease is not required if the patient had disease progression or recurrence during or within the first 6 months following completion of adjuvant or neoadjuvant chemotherapy.)
• Measurable disease per RECIST v1.1
• Age ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Ability to swallow oral medications
• Adequate bone marrow function as defined below:
• Absolute neutrophil count (ANC) ≥ 1,200/mm3
• Platelet count ≥ 100,000/mm3
• Hemoglobin ≥ 9.0 g/dL, which must be stable in the opinion of the investigator without a history of transfusion dependence.
• Adequate renal function as defined below:
• Calculated creatinine clearance ≥ 45 mL/min
• Adequate hepatic function as defined below:

You may not qualify if:

• Women who are not postmenopausal or have not undergone hysterectomy must have a documented negative serum pregnancy test within 7 days prior to initiating study treatment. Note: Postmenopausal is defined as one or more of the following:
• Age ≥ 60 years
• Age \< 60 years and amenorrheic for at least 1 year with follicle-stimulating hormone (FSH) and plasma estradiol levels in the postmenopausal range
• Bilateral oophorectomy
• A woman of child-bearing potential (WCBP) and a male patient with partner who is a WCBP must agree to use a medically accepted method for preventing pregnancy for the duration of study treatment and for 2 months following completion of study treatment.
• Ability to understand and willingness to sign the consent form written in English
• Any investigational agent within 4 weeks prior to initiating study treatment
• Anticancer therapy within 2 weeks prior to initiating study treatment
• Plans for concurrent anticancer therapy except as permitted in Section 6.7.11
• Known or presumed intolerance of pemetrexed or sorafenib
• Known or suspected malabsorption condition or obstruction
• Untreated brain metastases
• After completion of brain-directed therapy, the patient has not been able to tolerate discontinuation of steroids or a decrease in steroid dose
• Leptomeningeal metastasis
• Any documented history of clinically identifiable thrombotic, embolic, venous, or arterial events such as cerebrovascular accident, transient ischemic attack, deep vein thrombosis, or pulmonary embolism within 6 months prior to initiating study treatment (Note: Patients with an asymptomatic catheter-related thrombus or a tumor-associated thrombus of locally-involved vessels or with incidental asymptomatic filling defects identified on imaging are not excluded.)

Sponsors & Collaborators

• Virginia Commonwealth University: lead
• Eli Lilly and Company: collaborator
• Bayer: collaborator

Study Sites (1)

Virginia Commonwealth University/Massey Cancer Center

Richmond, Virginia, 23298, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Triple Negative Breast Neoplasms

Interventions

Pemetrexed; Sorafenib

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Pyridines; Heterocyclic Compounds, 1-Ring

Limitations and Caveats

Incomplete objectives due to early termination of trial. Amendment to allow more heavily pretreated subjects to be enrolled required a change in starting doses (Arm B) for all subsequently enrolled subjects.

Results Point of Contact

• Title: Andrew Poklepovic, MD
• Organization: Virginia Commonwealth University Massey Cancer Center

AskMassey@vcu.edu

(804) 828-0450

Study Officials

• Andrew S Poklepovic, MD

  Massey Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 3, 2015
• First Posted: December 8, 2015
• Study Start: January 28, 2016
• Primary Completion: July 10, 2019
• Study Completion: July 10, 2019
• Last Updated: July 14, 2020
• Results First Posted: July 14, 2020

Record last verified: 2020-06

Locations

US (1)