Anti-Inflammatory Agents

Antineoplastic Agents

Antiemetics

Gastrointestinal Agents

All Drugs and Chemicals

Dexamethasone

Docetaxel

Dexamethasone acetate

Tubulin Modulators

Antimitotic Agents

In Stage 1, PTC299 will be given orally twice a day (BID) each day at about the same time each day for the first 28 days of each cycle. Each cycle will constitute a 4-week (28 days) period followed by a ≥2-week (14-day) washout period. Participants will be assigned to 0.3 milligrams (mg)/kilograms (kg)/dose BID, 0.6 mg/kg/dose BID, or 1.2 mg/kg/dose BID sequentially based on safety evaluations by the Sponsor's medical monitor in Cycle 1. Treatment cycles can continue if therapy appears to be safely offering tumor control to participant.

In Stage 2, PTC299 will be given BID or 3 times a day (TID) orally each day at about the same time each day; therefore, 84 (for BID) or 126 (for TID) doses of PTC299 will be delivered during the 6-week (42-day) period in each cycle. Each participant will be assigned to 100 mg/dose BID, 100 mg/dose TID, 120 mg/dose TID, 160 mg/dose TID, or 200 mg/dose TID sequentially based on safety evaluations by the Sponsor's medical monitor in Cycle 1. Treatment cycles can continue if therapy appears to be safely offering tumor control to participant.

In Stage 3, PTC299 will be given BID or TID (for total of 42 \[for BID\] or 63 \[for TID\] doses) orally about same time per day starting on Day 1 in each 3-week (21-day) cycle. Starting dose will be 1 dose level below maximum tolerated dose (MTD) from Stage 2 or 80 mg/dose BID if 100 mg/dose TID in Stage 2 exceeds MTD. Dose escalation will be based on safety evaluations by Sponsor's medical monitor in Cycle 1. Treatment cycles can continue if therapy appears to be safely offering tumor control to participant. Participants will also receive docetaxel as a 1-hour IV infusion on Day 1 per cycle at starting dose of 75 mg/m\^2 with body surface area calculation based on body weight. Dose will be sequentially reduced to 60 and 50 mg/m\^2 in participants with a docetaxel-related dose-limiting toxicity (DLT). Participants will be medicated with oral corticosteroids with docetaxel administration. Recommended dose is 8 mg BID dexamethasone for 3 days starting 1 day prior to docetaxel administration.

In Stage 4, PTC299 will be given orally each day continuously starting on first day of each cycle at about same time per day; so, 42 doses of PTC299 will be delivered for 3 weeks (21-day) in Cycle 1 (BID dosing), and 84 doses will be delivered for 3-weeks (21-day) in Cycle 2 and beyond (TID dosing). For Cycle 1, participants will be assigned to 600, 800, or 1000 mg/dose BID sequentially based on safety evaluations by Sponsor's medical monitor at enrollment. For Cycle 2 and beyond, participants will receive PTC299 160 mg/dose TID. During Cycle 1, Cohort 1 participants will eat a meal containing of ≤15 grams (g) of dietary fat and Cohort 2 participants will eat a meal containing of ≤25 g of dietary fat prior to each dose of PTC299. If ≤2 of 6 participants had experienced DLT during Cycle 1 in either diet plan, then the dose will be escalated to 800 mg BID in Cohort 3 at the optimal diet. Treatment cycles can continue if therapy appears to be safely offering tumor control to participant.

PTC299

Gary Schwartz, MD

Formation of new blood vessels (angiogenesis) is important for tumor growth in advanced cancer. It is known that tumors make a protein called vascular endothelial growth factor (VEGF). VEGF stimulates the formation of blood vessels that supply the tumor with nutrients and oxygen. PTC299 is an oral investigational new 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. When given in combination with the chemotherapeutic drug, docetaxel, PTC299 increases the antitumor activity over use of docetaxel alone. 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 anti-VEGF and antitumor activity when administered orally to participants with cancer.

The study will be conducted in 3 stages. In Stage 1 of the study, successive groups of 3 to 6 participants 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. In Stage 2, additional groups of 3 to 6 participants will be enrolled at tolerable dose levels to receive treatment in repeated 6-week cycles consisting of oral PTC299 administered 2 or 3 times per day continuously (that is, without the 2-week no-drug period as in Stage 1). In Stage 3, additional groups of 3 to 6 participants will be enrolled at tolerable dose levels to receive treatment in repeated 3-week cycles consisting of oral PTC299 administered 2 or 3 times per day continuously in combination with docetaxel (75 milligrams/meter squared \[mg/m\^2\] intravenously \[IV\] every 3 weeks). All planned 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 participant can continue as long as the therapy appears to be safely offering tumor control to that participant. Up to 76 evaluable participants will be accrued across the 3 stages.

PTC299 for Treatment of Advanced Cancer

A Phase 1b Study to Assess the Safety Profile, Pharmacokinetics, and Anti-VEGF Activity of PTC299 in Patients With Advanced Cancer

To analyze the MTD of PTC299 within the tested dose range for use in further clinical trials in participants with advanced cancer.

The relationship of TEAEs and SAEs to the study drugs will be assessed as: definite related, probable related, possible related, unlikely related, and unrelated. The severity of TEAEs will be graded using the Common Terminology Criteria for Adverse Events, Version 3.0 as: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (life-threatening), or Grade 5 (fatal). A summary of serious and all other non-serious adverse events, regardless of causality, will be located in the Reported Adverse Events module.

Number of participants with an abnormal clinical laboratory parameter considered clinically relevant by the Investigator will be reported. Clinical laboratory tests will include hematology, coagulation, biochemistry, and urinalysis. A summary of serious and all other non-serious adverse events, regardless of causality, will be located in the Reported Adverse Events module.

Number of participants with an abnormal ECG considered clinically significant by the Investigator will be reported. A summary of serious and all other non-serious adverse events, regardless of causality, will be located in the Reported Adverse Events module.

DLT defined as occurrence of any of the following considered related to PTC299 administration:

Stage 1

* Other Grade ≥3 PTC299-related toxicities.
* Failure to complete ≥80% (that is, ≥45 doses) of planned 56 doses of PTC299 treatment course due to PTC299-related toxicities.

Stages 2, 3, 4

* Grade ≥3 serum bilirubin (\>3.0\*upper limits of normal \[ULN\]), whether or not serum ALT or AST is elevated
* Other Grade ≥3 PTC299-related toxicities.
* Change in serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) from baseline (Grade 0) to Grade ≥2 (\>2.5\*ULN).

Stages 1, 2, 3, 4

* Grade ≥2 PTC299-related vomiting despite maximal oral antiemetic therapy, or requirement for intravenous antiemetics to control the nausea and vomiting.
* Grade ≥2 proteinuria.
* On-treatment serum ALT or AST of Grade ≥3 (\>5.0\*ULN).
* Failure to recover from PTC299-related AEs to baseline AE levels by Days 42, 49, 28, and 22 of cycle for Stages 1, 2, 3, and 4, respectively.

Two blood samples (6 milliliters \[mL\] of venous blood for plasma and 4 mL of venous blood for serum) are to be obtained for assessment of circulating VEGF. Participants can be evaluated for up to 14 cycles per Stage.

VEGF-A response is defined as ≥25% decrease relative to the baseline concentration at any time during study treatment. Two blood samples (6 mL of venous blood for plasma and 4 mL of venous blood for serum) are to be obtained for assessment of circulating VEGF. Participants can be evaluated for up to 14 cycles per Stage.

Ktrans defined as volume transfer constant between blood plasma and extra-cellular extra-vascular space.

AUCBN90 defined as blood-normalized area under the tumor enhancement curve over the first 90 seconds post-injection.

Change in tumor metabolism as assessed by changes in FDG-PET standardized uptake value (SUV) in a target tumor lesion.

The change in tumor size from baseline is to be described by dose at each assessment and the greatest change during the study will be computed.

Tumor response defined by Response Evaluation Criteria in Solid Tumors (RECIST). Definitions of tumor lesion responses: Complete response (CR) - disappearance of all target lesions; Partial response (PR) - ≥30% decrease in the sum of the longest dimensions of the target lesions, taking as a reference the baseline sum of the longest dimensions; Progressive disease (PD) - ≥20% increase in the sum of the longest dimensions of the target lesions taking as a reference the smallest sum of the longest dimensions recorded since the treatment started, or the appearance of 1 or more new lesions; Stable disease (SD) - neither sufficient shrinkage to qualify for PR, nor sufficient increase to qualify for PD, taking as a reference the smallest sum of the longest dimensions since the treatment started.

Tumor marker response defined as a reduction by ≥50% in the tumor marker value relative to baseline.

PTC Therapeutics

Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

Exemestane

Anastrozole

Aromatase Inhibitors

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

Jay Barth, MD

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.

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.

PTC299 and Hormonal Agent for Treatment of Metastatic Breast Cancer

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

United States Department of Defense

Nervous System Diseases

Diseases and Abnormalities at or Before Birth

Ear, Nose, and Throat Diseases

Symptoms and General Pathology

Rare Diseases

Neurofibromatoses

Neurofibromatosis 1

Neurofibroma

Neurofibromatosis 2

Nerve Sheath Neoplasms

Neoplasms, Nerve Tissue

Neoplasms by Histologic Type

Syndrome

Neoplastic Syndromes, Hereditary

Neurocutaneous Syndromes

Heredodegenerative Disorders, Nervous System

Neurodegenerative Diseases

Genetic Diseases, Inborn

Peripheral Nervous System Diseases

Neuromuscular Diseases

Nervous System Neoplasms

Peripheral Nervous System Neoplasms

Neuroma

Neuroma, Acoustic

Neurilemmoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Vestibulocochlear Nerve Diseases

Retrocochlear Diseases

Ear Diseases

Otorhinolaryngologic Diseases

Otorhinolaryngologic Neoplasms

Cranial Nerve Diseases

Neurofibromatosis

Neurofibromatosis Type 1

Neurofibromatosis Type 2

Schwannoma

Neuroendocrine Tumor

Neuroepithelioma

PTC299 administered at 100 mg/dose twice per day

PTC299 will be administered orally at 100 mg/dose twice per day for up to 1 year or until tumor progression

Formation of new blood vessels (angiogenesis) is important for tumor growth in neurofibromatosis type 2 (NF2). 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 patients with NF2. 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 tumor. This Phase 2 study is designed to test the hypothesis that PTC299 will be tolerable and will show evidence of VEGF reduction, antitumor activity, and hearing improvement when administered orally to patients with NF2.

The study will be conducted in 2 stages. In Stage 1 of the study, 11 patients will receive daily treatment with PTC299 administered at 100 mg/dose twice per day for up to 1 year or until tumor progression. If no subject responds with tumor shrinkage or an improvement in hearing, then the study will be stopped. If ≥1 out of 11 subjects respond, then the study will proceed to Stage 2 to enroll an additional 14 subjects for a total of 25 subjects.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
PTC299 for Treatment of Advanced Cancer	NCT00704821	Advanced Cancer	PTC299 Docetaxel	18 Years -	PTC Therapeutics
PTC299 and Hormonal Agent for Treatment of Metastatic Breast Cancer	NCT00508586	Metastatic Brea...	PTC299	18 Years -	PTC Therapeutics
PTC299 for Treatment of Neurofibromatosis Type 2	NCT00911248	Neurofibromatos...	PTC299	18 Years -	PTC Therapeutics
PTC299 and Hormonal Agent for Treatment of Metastatic Breast Cancer	NCT00508586	Metastatic Brea...	PTC299	18 Years -	PTC Therapeutics
PTC299 for Treatment of Neurofibromatosis Type 2	NCT00911248	Neurofibromatos...	PTC299	18 Years -	PTC Therapeutics

Spots Global Cancer Trial Database for ptc299

Every month we try and update this database with for ptc299 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for ptc299

Every month we try and update this database with for ptc299 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for ptc299 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.