PTC299 and Hormonal Agent for Treatment of Metastatic Breast Cancer

Sponsor

PTC Therapeutics (Industry)

Overall Status

Completed

CT.gov ID

NCT00508586

Collaborator

United States Department of Defense (U.S. Fed)

Enrollment

Locations

Arm

Duration (Months)

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Breast Cancer	Drug: PTC299	Phase 1

Detailed Description

The study will be conducted in 2 stages. In Stage 1 of the study, successive groups of 3 to 6 patients will receive progressively higher PTC299 dose levels; in this stage, treatment will be given in repeated 6-week cycles consisting of 4 weeks of oral PTC299 twice per day followed by a 2-week, no-drug period. During Stage 2, study candidates must be women with natural or induced suppression of ovarian function to post-menopausal levels who are receiving or are candidates for hormonal therapy. These subjects will receive continuous administration of PTC299, 100 mg/dose BID, in repeated 6-week cycles in combination with continuous administration of one of 3 hormonal agents. All planned PTC299 dose levels in all stages are expected to achieve circulating blood levels of PTC299 known to be active in animal models of human cancer. Treatment for each patient can continue as long as the therapy appears to be safely offering tumor control to that patient. Up to 36 evaluable patients will be accrued across both stages.

Study Design

Study Type:

Interventional

Actual Enrollment :

33 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1b Study to Assess the Safety, Feasibility, Pharmacokinetics, and Activity of PTC299 Monotherapy or Combination Therapy With Hormonal Agents in Patients With Metastatic Breast Cancer

Study Start Date :

Nov 1, 2007

Actual Primary Completion Date :

Mar 1, 2012

Actual Study Completion Date :

Mar 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 PTC299 with an aromatase inhibitor	Drug: PTC299 PTC299 orally administered twice per day given in combination with anastrozole (Arimidex®), letrazole (Femara®), or exemestane (Aromasin®)

Arm

Intervention/Treatment

Experimental: 1

PTC299 with an aromatase inhibitor

Drug: PTC299

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

Outcome Measures

Primary Outcome Measures

Maximum Tolerated Dose (MTD) within the tested dose range. [6 Weeks]

Secondary Outcome Measures

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]
Tumor metabolism as assessed by fluorodeoxyglucose positron emission tomography (FDG-PET) [6 Weeks]
Antitumor activity as assessed by computed tomography (CT) scans and tumor markers [6 Weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Major Eligibility Criteria:

Female sex.
Age ≥18 years.
Body weight 40-100 kg.
ECOG performance status of 0 or 1.
Histologically or cytologically confirmed adenocarcinoma of the breast.
Presence of metastatic disease not amenable to surgery, radiation therapy, or chemoradiotherapy with curative intent.
No active second metastatic malignancy other than breast cancer.
No unstable brain or leptomeningeal disease.
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.
Adequate bone marrow, liver, and kidney function.
No uncontrolled hypertension, major bleeding, HIV infection or recent acute cardiovascular event.
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.
No pregnancy or breast-feeding.
Willingness and ability to comply with scheduled visits, drug administration plan, laboratory tests, other study procedures, and study restrictions.
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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Indiana University Simon Cancer Center	Indianapolis	Indiana	United States	46202
2	New York University Clinical Cancer Center	New York	New York	United States	10016
3	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10065