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This study is being conducted to determine if a combination of AZD6244 given orally twice a day with standard doses of selected chemotherapies will be safe and tolerable for cancer patients with advanced solid tumors. The highest tolerated dose of AZD6244 in combination with selected chemotherapies will be evaluated. The study will also investigate how AZD6244 in combination with standard chemotherapies are absorbed, distributed and excreted by the body as well as the length of time that the drugs remain in the body. Initial and periodic assessments will establish patient response to the combination therapies
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 | Experimental | AZD6244 + docetaxel |
|
| 2 | Experimental | AZD6244 + Dacarbazine |
|
| 3 | Experimental | AZD6244 + Erlotinib |
|
| 4 | Experimental | AZD6244 + Temsirolimus |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AZD6244 | Drug | twice daily oral dose |
|
| Measure | Description | Time Frame |
|---|---|---|
| Safety and tolerability of twice daily oral doses of AZD6244 when administered in combination with standard doses of selected chemotherapies. | Incidence and intensity of adverse events as graded by CTCAE (version 3.0), physical examinations, vital signs (including weight, blood pressure and pulse rate), ECG parameters, MUGA scan and echocardiography, clinical chemistry (including liver function tests), Brain Natriuretic Peptide (BNP), Troponin I, hematology, urinalysis, and ophthalmologic examinations. | 28 days + |
| Measure | Description | Time Frame |
|---|---|---|
| PK of AZD6244 and selected chemotherapies. | The PK parameters will be derived using noncompartmental analysis. The maximum plasma concentrations (Cmax) and the time to reach the maximum plasma concentrations (tmax) will be determined by visual inspection of the plasma concentration-time profiles. The area under the plasma concentration-time curve from zero to 12 hours post dose, AUC(0-12), will be calculated by the linear trapezoidal rule. Where more than one maxima occurs, the reported value will be assigned to the first occurrence. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Patricia LoRusso, DO | Barbara Ann Karmanos Cancer Institute | Principal Investigator |
| Roger Cohen, MD | Fox Chase Cancer Center | Principal Investigator |
| Jeffrey Infante, MD | SCRI Development Innovations, LLC | Principal Investigator |
| Kevin Kim, MD | M.D. Anderson Cancer Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Detroit | Michigan | 48201 | United States | ||
| Research Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28424891 | Derived | Infante JR, Cohen RB, Kim KB, Burris HA 3rd, Curt G, Emeribe U, Clemett D, Tomkinson HK, LoRusso PM. A phase I dose-escalation study of Selumetinib in combination with Erlotinib or Temsirolimus in patients with advanced solid tumors. Invest New Drugs. 2017 Oct;35(5):576-588. doi: 10.1007/s10637-017-0459-7. Epub 2017 Apr 19. | |
| 28264648 |
| Label | URL |
|---|---|
| D1532C00004 Clinical Report Synopsis | View source |
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Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
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AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
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| Dacarbazine | Drug | intravenous infusion |
|
| Erlotinib | Drug | daily oral dose |
|
| Docetaxel | Drug | intravenous infusion |
|
|
| Temsirolimus | Drug | intravenous infusion |
|
| Cycle 1 Day 3 and Cycle 2 day 1 |
| Define highest tolerated dose of AZD6244 when in combination with selected chemotherapies. | The starting dose of AZD6244 in each arm will be 50mg. Continuous dosing (commencing Cycle 1/Day 3 for docetaxel and dacarbazine and Cycle 1/Day 8 for erlotinib and temsirolimus) will be BD. The AZD6244 dose may be maintained or reduced. | 28 days + |
| Tumor response. | To make a preliminary assessment of tumor response as measured by Objective Response Rate (ORR) per investigator's assessment using Response Evaluation Criteria in Solid Tumors (RECIST) when AZD6244 Hyd-Sulfate is given in combination with standard doses of selected chemotherapies. | 28 days + |
| Philadelphia |
| Pennsylvania |
| 19111 |
| United States |
| Research Site | Nashville | Tennessee | 37203 | United States |
| Research Site | Houston | Texas | 77030 | United States |
| LoRusso PM, Infante JR, Kim KB, Burris HA 3rd, Curt G, Emeribe U, Clemett D, Tomkinson HK, Cohen RB. A phase I dose-escalation study of selumetinib in combination with docetaxel or dacarbazine in patients with advanced solid tumors. BMC Cancer. 2017 Mar 6;17(1):173. doi: 10.1186/s12885-017-3143-6. |
| 22972589 | Derived | Patel SP, Lazar AJ, Papadopoulos NE, Liu P, Infante JR, Glass MR, Vaughn CS, LoRusso PM, Cohen RB, Davies MA, Kim KB. Clinical responses to selumetinib (AZD6244; ARRY-142886)-based combination therapy stratified by gene mutations in patients with metastatic melanoma. Cancer. 2013 Feb 15;119(4):799-805. doi: 10.1002/cncr.27790. Epub 2012 Sep 12. |
| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| D003110 | Colonic Neoplasms |
| D008175 | Lung Neoplasms |
| D008545 | Melanoma |
| D007680 | Kidney Neoplasms |
| D009369 | Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D015179 | Colorectal Neoplasms |
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D012142 | Respiratory Tract Neoplasms |
| D013899 | Thoracic Neoplasms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D018358 | Neuroendocrine Tumors |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009380 | Neoplasms, Nerve Tissue |
| D018326 | Nevi and Melanomas |
| D012878 | Skin Neoplasms |
| D014571 | Urologic Neoplasms |
| D014565 | Urogenital Neoplasms |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052801 | Male Urogenital Diseases |
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| ID | Term |
|---|---|
| C517975 | AZD 6244 |
| D003606 | Dacarbazine |
| D000069347 | Erlotinib Hydrochloride |
| D000077143 | Docetaxel |
| C401859 | temsirolimus |
| ID | Term |
|---|---|
| D014226 | Triazenes |
| D009930 | Organic Chemicals |
| D007093 | Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D011799 | Quinazolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D004224 | Diterpenes |
| D013729 | Terpenes |
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