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Imetelstat

Motesanib diphosphate

Protein Kinase Inhibitors

Enzyme Inhibitors

Single oral dose of 125 mg AMG 706 (motesanib) containing 100 μCi of \[14C\]-AMG 706 followed by option to continue onto a treatment extension phase for potential treatment benefit. Subjects will be administered motesanib 125 mg (5 x 25 mg tablets) on a daily basis until subjects experience a dose-limiting toxicity (DLT), an unacceptable AE, disease progression, or voluntary withdrawal.

AMG 706

In order for a tumour to grow and spread to other parts of the body, it needs to have a blood supply. Certain proteins in the body, called cytokines or growth factors, have been shown to cause the growth of new blood vessels that supply tumours and therefore help the tumour to grow and spread. Motesanib (AMG 706) prevents these proteins from working, and may help to prevent the growth of tumours.

In the first part of this study, we will look at the way your body absorbs this drug into your blood, how your body changes and breaks down the drug, and then how the drug leaves your body in your urine and faeces.

In order to provide potential treatment benefit for the subjects who participated in the first part of the study, the second part of the study will allow subjects to continue on motesanib (AMG 706) treatment. The estimated length of this part of the study is unknown, and dependent on how subjects respond to motesanib (AMG 706).

Single Dose Study of [14C]-Labelled AMG 706 in Patients With Advanced Solid Tumors

An Open-label, Single Dose Study of the Mass Balance and Metabolic Disposition of Orally Administered [14C]-Labelled AMG 706 (Motesanib) Followed by Extended Treatment With Motesanib in Patients With Advanced Solid Tumors

Amgen

Global Development Leader

Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Antineoplastic Agents

Paclitaxel

Carboplatin

Albumin-Bound Paclitaxel

Tubulin Modulators

Antimitotic Agents

Motesanib 125 mg, (5 x 25 mg) tablets, orally, once daily and paclitaxel 200 mg/m\^2, intravenous, once on Day 1 and carboplatin at a dose to achieve a target Area Under the Curve (AUC) of 6.0 mg/mL x minute, once on Day 1 of a 3 week Cycle for up to 6 Cycles. After 6 Cycles, motesanib 125 mg, tablets, orally, once daily alone until disease progression, drug intolerability, study withdrawal or death for up to 36 months.

Motesanib placebo-matching tablets, orally, once daily and paclitaxel 200 mg/m\^2, intravenous, once on Day 1 and carboplatin at a dose to achieve a target AUC of 6.0 mg/mL x minute, once on Day 1 of a 3 week Cycle for up to 6 Cycles. After 6 Cycles, motesanib placebo-matching, tablets, orally, once daily alone until disease progression, drug intolerability, study withdrawal or death for up to 36 months.

Motesanib

Placebo

Medical Director Clinical Science

This study will evaluate progression free survival (PFS), overall survival (OS), objective response rate (ORR), duration of response, and safety of motesanib (AMG706) in combination with paclitaxel and carboplatin compared to placebo in combination with paclitaxel and carboplatin.

The drug being tested in this study is called motesanib. Motesanib is being tested in combination with paclitaxel and carboplatin to treat people who have Stage IV or recurrent non-squamous non-small cell lung cancer (NSCLC). This study will look at progression free survival, overall survival, overall response and safety.

The study enrolled 401 patients. Participants were randomly assigned (by chance, like flipping a coin) to one of the two treatment groups-which remained undisclosed to the patient and study doctor during the study (unless there is an urgent medical need):

* Motesanib 125 mg + Paclitaxel + Carboplatin
* Placebo (dummy inactive pill) - this is a tablet that looks like the study drug but has no active ingredient + Paclitaxel + Carboplatin

All participants were asked to take 5 X 25 mg motesanib tablets or placebo at the same time each day throughout the study. All participants received treatment with paclitaxel 200 mg/m\^2 intravenous (IV) and carboplatin IV on Day 1 of each 3 week Cycle for up to 6 Cycles. After 6 Cycles participants could continue to receive motesanib or placebo alone for up to 36 months.

This multi-centre trial was conducted worldwide. The overall time to participate in this study was up to 36 months. Participants made multiple visits to the clinic, plus a final visit 30 days after receiving their last dose of study drug for a follow-up assessment.

Study of Motesanib (AMG 706) in Combination With Paclitaxel and Carboplatin for Advanced Non-Squamous Non-Small Cell Lung Cancer

A Global Phase 3, Randomized, Placebo Controlled, Double-Blind Trial of AMG 706 in Combination With Paclitaxel and Carboplatin for Advanced Non-Squamous Non-Small Cell Lung Cancer (Asian Phase 3 Study)

PFS was defined as the time from the date of randomization to the date of disease progression per Response Evaluation Criteria in Solid Tumor (RECIST) Version 1.1 or death from any cause, whichever occurred first. Progressive disease was defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.

OS was defined as the time from randomization to death (or, where applicable, the censoring date). Participants who had not died or were lost to follow-up by the analysis data cut-off date were censored at their last contact date. Participants who withdrew full consent to participate in the study were censored on the date consent was withdrawn.

ORR was defined as the percentage of participants achieving either a complete response (CR) or partial response (PR) per RECIST Version 1.1 criteria. CR= disappearance of all target lesions; disappearance of all non-target lesions and normalization of tumor marker level. PR= At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the Baseline sum LD.

DOR was defined as the time from the date of first response (CR or PR) to disease progression (per RECIST Version 1.1) or death. CR= Disappearance of all target lesions; disappearance of all non-target lesions and normalization of tumor marker level. PR= At least a 30% decrease in the sum of the longest diameter (LD ) of target lesions, taking as reference the Baseline sum LD.

An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.

The percentage of participants with any chemistry or hematology abnormal standard safety laboratory values collected throughout study

Maximum Observed Plasma Concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration- time curve.

Minimum observed plasma concentration (Cmin) is the lowest plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve.

Takeda

Symptoms and General Pathology

Skin and Connective Tissue Diseases

Recurrence

Breast Neoplasms

Breast Diseases

Skin Diseases

Micronutrients

Vasodilator Agents

Lipid Regulating Agents

Hematinics

Vitamins

Capecitabine

Niacinamide

Niacin

Nicotinic Acids

Antimetabolites

Folic Acid

Vitamin B Complex

Trace Elements

Nicotinamide

Nicotinic Acid

Vitamin B3

Folate

Vitamin B9

Eligible patients will be enrolled to receive ixabepilone, capecitabine, plus motesanib.

Patients will receive ixabepilone at 40 mg/m2.

Ixabepilone

Patients will receive capecitabine at 2000 mg/m2.

Patient will receive motesanib at 100mg or 125mg once daily dependent on outcome of Phase I, which will involve the first 3-6 patients.

Edith Mitchell, MD

In 2008 there were more than 40,000 deaths caused by metastatic breast cancer in the United States. The development of new treatment strategies is essential to improve outcome for patients with metastatic breast cancer

There is significant preclinical and clinical evidence indicating that creating new blood vessels (neoangiogenesis) to provide nutrients to solid tumors, including breast cancer, provides the necessary conditions to allow tumor growth. Vascular endothelial growth factor (VEGF) is one of the important molecules regulating new blood vessel formations and subsequent invasion and metastases. As a result, agents that inhibit VEGF are of substantial interest for the treatment of advanced diseases.

This study will further the body of research of motesanib which has been shown in preclinical pharmacology and clinical pharmacology studies to be a potent, orally bioavailable multi-kinase inhibitor with anti-angiogenic and anti-tumor activity achieved by selectively targeting all known VEGF, platelet-derived growth factor (PDGF), and Kit receptors.

Endocrine therapy and chemotherapy (using either sequential single agents or combination regimens) remain the principal treatments for women with metastatic breast cancer. A wide variety of classes of chemotherapeutic agents have demonstrated anti-tumor activity as single agents or in combination regimens. Cytotoxic chemotherapeutic agents have been the mainstay of cancer therapies for many years and have improved survival in many disease settings. Median survivals remain approximately two years for women with metastatic breast cancer, and less than 3% of patients experience long-term survival after initiation of treatment. The development of new treatment strategies is therefore essential to improve outcome for patients with metastatic breast cancer.

One of the most promising pathways for the development of new anti-neoplastic agents is targeting tumor vascular endothelium. There is significant preclinical and clinical evidence indicating that tumor neoangiogenesis is critical in pathogenesis and progression of solid tumors, including breast cancer. Of the numerous known growth factors that have been implicated in tumor angiogenesis, vascular endothelial growth factor (VEGF) is one of the important molecules regulating new blood vessel formations and subsequent invasion and metastases. As a result, agents that inhibit VEGF are of substantial interest for the treatment of advanced diseases. More thorough elucidation of mechanisms behind intrinsic and acquired resistance therefore is imperative disease and to identify patients most likely to benefit from treatment options.

Motesanib has been shown in preclinical pharmacology and PK studies to be a potent, orally bioavailable multi-kinase inhibitor with anti-angiogenic and anti-tumor activity achieved by selectively targeting all known VEGF, PDGF and Kit receptors. It has an acceptable safety profile in both non-clinical and clinical studies, and a PK profile that appears suitable for daily oral dosing in humans.

The investigational product motesanib (Amgen) is a small molecule tyrosine kinase inhibitor with high efficacy against VEGFR and c-Kit kinases. C-kit has been detected in 12% of breast cancers, correlating with basal or triple-negative breast cancer. In addition, efficacy of the drug has been noted to PDGFRα, which is expressed in approximately 40% of breast cancers and is associated with aggressive disease, metastatic invasion and poor prognosis. Importantly, in more than half (56%) of these cases, the carcinoma cells bearing the receptors expressed the PDGF-A ligand, suggesting an autocrine loop and a cancer cell-autonomous process. Cancer cell-autonomous pathways are especially attractive as drug targets against metastatic breast cancer because they are expected to continue to be functional at metastatic sites, since they do not depend on stromal factors.

The primary molecular target of motesanib, VEGFR, is intriguing because neovascularization is expected to be required also at metastatic sites. A preliminary analysis revealed that VEGF expression correlated with the triple-negative, basal breast cancer subtype and poor outcome. Importantly, PDGF receptors are also present on vascular pericytes, cells required for adequate vascularization. Thus, motesanib is a unique multikinase inhibitor that targets both growth factor receptors on the carcinoma cells and growth factor receptors related to neovascularization.

Investigational Drug in Combination With Two Chemotherapy Drugs in Women With Locally Recurrent or Metastatic Breast Cancer

Phase I/II Trial of Motesanib in Combination With Ixabepilone and Capecitabine in Women With Locally Recurrent or Metastatic Breast Cancer

Progression-free survival (PFS) is defined as the time from the date of enrollment to the first occurrence of having documented disease progression or death due to any cause. Evaluation of target lesions and non-target lesions will be in accordance with the RECIST criteria.

During the study, assessments of tumor response will take place every 6 weeks. Confirmation of objective response, when applicable, must be performed at a minimum of 4 weeks after the first response has been recorded.

Maximum tolerated dose (MTD) of Motesanib to be determined in the first 3-6 patients enrolled to study (Phase I portion).

The best overall response in an individual patient according to the RECIST criteria is the best response recorded from the time of study entry till disease progression/recurrence. The patient's overall best response can be complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD).

Patients with CR or PR are deemed as responders. Patients with no tumor assessment after the study entry are to be considered as non-responders.

To determine the toxicity of motesanib, ixabepilone, and capecitabine, using a single arm design trial.

To correlate quantitative tumor levels of motesanib-relevant markers PDGFR, VEGFR, C-Kit, and their ligands with response, survival, and time to disease progression in patients treated on this regimen.

To investigate the pharmacokinetics of motesanib (Cmin), ixabepilone (concentration at the end of infusion), and capecitabine in the combination therapy.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Single Dose Study of [14C]-Labelled AMG 706 in Patients With Advanced Solid Tumors	NCT01386866	Advanced Solid ...	AMG 706	18 Years -	Amgen
Study of Motesanib (AMG 706) in Combination With Paclitaxel and Carboplatin for Advanced Non-Squamous Non-Small Cell Lung Cancer	NCT02629848	Carcinoma, Non-...	Motesanib Placebo Paclitaxel Carboplatin	18 Years -	Takeda
Investigational Drug in Combination With Two Chemotherapy Drugs in Women With Locally Recurrent or Metastatic Breast Cancer	NCT01349088	Breast Cancer Metastatic Brea... Stage IV Breast...	Ixabepilone Capecitabine Motesanib	18 Years -	Thomas Jefferson University

Spots Global Cancer Trial Database for motesanib

Every month we try and update this database with for motesanib 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 motesanib

Every month we try and update this database with for motesanib 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 motesanib 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.