PTC299 and Hormonal Agent for Treatment of Metastatic Breast Cancer

NCT00508586 | Completed Phase 1

• 2 other identifiers: PTC299-ONC-003-BRCBC050203
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 3

Brief Summary

Formation of new blood vessels (angiogenesis) is important for tumor growth in metastatic breast cancer. It is known that tumors make a protein called vascular endothelial growth factor (VEGF) and there are higher levels of VEGF in the tumors and blood of many women with metastatic breast cancer. VEGF stimulates the formation of blood vessels that supply the tumor with nutrients and oxygen. PTC299 is an oral drug that has been shown to decrease production of VEGF in animal models of human cancer. In these animal models, oral PTC299 administration decreases VEGF levels in the tumor and in the bloodstream, decreases blood vessel numbers in the tumor, and significantly slows or halts tumor growth. Safety studies in research animals indicate good tolerability at doses and drug levels that are higher than those planned for the clinical studies. Results from Phase 1a studies in healthy volunteers indicate that PTC299 achieves levels of PTC299 in the bloodstream that are known to be active in animal models of human cancer. This Phase 1b study is designed to test the hypothesis that PTC299 will be tolerable and will show evidence of VEGF reduction and antitumor activity when administered orally in combination with anastrozole (Arimidex®), letrozole (Femara®), or exemestane (Aromasin®) to women with metastatic breast cancer.

Conditions

Metastatic Breast Cancer

Keywords

Breast cancer; PTC299; VEGF; Angiogenesis; Post-transcriptional control; Aromatase inhibitors

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) within the tested dose range.

  6 Weeks

Secondary Outcomes (7)

• Overall safety profile

  6 Weeks

• Study drug compliance

  6 Weeks

• Pharmacokinetics

  6 Weeks

• Circulating angiogenic markers

  6 Weeks

• Tumor perfusion as assessed by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI)

  6 Weeks

Study Arms (1)

1

EXPERIMENTAL

PTC299 with an aromatase inhibitor

Drug: PTC299

Interventions

PTC299 DRUG

PTC299 orally administered twice per day given in combination with anastrozole (Arimidex®), letrazole (Femara®), or exemestane (Aromasin®)

1

Eligibility Criteria

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

Major Eligibility Criteria: 1. Female sex. 2. Age ≥18 years. 3. Body weight 40-100 kg. 4. ECOG performance status of 0 or 1. 5. Histologically or cytologically confirmed adenocarcinoma of the breast. 6. Presence of metastatic disease not amenable to surgery, radiation therapy, or chemoradiotherapy with curative intent. 7. No active second metastatic malignancy other than breast cancer. 8. No unstable brain or leptomeningeal disease. 9. Discontinuation of other therapies (except for anastrozole, letrozole, or exemestane) for the treatment of breast cancer and resolution of any acute toxic effects of prior therapies. 10. Adequate bone marrow, liver, and kidney function. 11. No uncontrolled hypertension, major bleeding, HIV infection or recent acute cardiovascular event. 12. If sexually active and not postmenopausal or surgically sterile, willingness to abstain from sexual intercourse or employ an effective barrier method of contraception during the study drug administration and follow-up periods. 13. No pregnancy or breast-feeding. 14. Willingness and ability to comply with scheduled visits, drug administration plan, laboratory tests, other study procedures, and study restrictions. 15. Willingness to provide informed consent. In addition to the criteria noted above, Stage 2 subjects must also have natural or induced suppression of ovarian function to post-menopausal levels and be receiving or be a candidate for hormonal therapy.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• PTC Therapeutics: lead
• United States Department of Defense: collaborator

Study Sites (3)

Indiana University Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

New York University Clinical Cancer Center

New York, New York, 10016, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Links

• PTC Therapeutics, Inc. web site

MeSH Terms

Conditions

Breast Neoplasms

Interventions

emvododstat

Condition Hierarchy (Ancestors)

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

Study Officials

• Jay Barth, MD

  PTC Therapeutics, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 26, 2007
• First Posted: July 30, 2007
• Study Start: November 1, 2007
• Primary Completion: March 1, 2012
• Study Completion: March 1, 2012
• Last Updated: March 3, 2016

Record last verified: 2012-04

Locations

US (3)