Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Blood and Lymph Conditions

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Anemia

Pleural Effusion, Malignant

Pleural Effusion

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Hematologic Diseases

Hematinics

All Drugs and Chemicals

Darbepoetin alfa

Participants received placebo once every 3 weeks (Q3W) administered subcutaneously until 3 weeks after the completion of chemotherapy or upon determination of disease progression, whichever occurred first.

Participants received darbepoetin alfa 500 µg once every 3 weeks (Q3W) administered subcutaneously until 3 weeks after the completion of chemotherapy or upon determination of disease progression, whichever occurred first.

Administered subcutaneously once every 3 weeks

Placebo

This is a study in patients with chemotherapy induced anemia receiving multi-cycle chemotherapy for the treatment of stage IV non-small cell lung cancer (NSCLC). The primary objective of the study is to demonstrate that overall survival (OS) is not worse in participants on darbepoetin alfa treated to a hemoglobin ceiling of 12.0 g/dL compared to participants treated with placebo.

Oversight Authorities continued: Colombia

Anemia Treatment for Advanced Non-Small Cell Lung Cancer (NSCLC) Patients Receiving Chemotherapy

A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Long-term Safety and Efficacy of Darbepoetin Alfa Administered at 500 µg Once-Every-3-Weeks in Anemic Subjects With Advanced Stage Non-small Cell Lung Cancer Receiving Multi-cycle Chemotherapy

Overall survival (OS) was defined as the time from randomization to the date of death due to any cause. Participants were censored on the date of last contact (ie, the date the participant was last known to be alive) if they were not known to have died.

Progression-free survival was defined as the time from randomization to the date of radiographic disease progression or death from any cause, whichever event occurred first. Participants without either event were censored on the date of their last disease assessment. Disease progression was based on the investigator's assessment of scans using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 or 1.1 depending on the timing of enrollment.

Any red blood cell (RBC) transfusion (packed RBCs or whole blood) given or a hemoglobin ≤ 8.0 g/dL on or after study day 29 until the EOETP, inclusive.

Adverse events of interest for darbepoetin alfa, based on clinical data in anemic patients with cancer to date, included the following categories: antibody-mediated pure red cell aplasia (PRCA), cardiac failure, central nervous system vascular disorders, convulsions, embolic and thrombotic events, hypersensitivity, hypertension, ischemic heart disease, malignancies, and severe cutaneous adverse reactions. Lack of efficacy and medication errors were also evaluated.

Objective response was defined as the incidence of a complete or partial response at any time during the study. Response was determined by the investigator's assessment of the scans using RECIST version 1.0 or 1.1 depending on the timing of enrollment.

Developing antibody incidence was defined as neutralizing antibody positive postbaseline with a negative or no result at baseline.

Any red blood cell (RBC) transfusion (packed RBCs or whole blood) given or a hemoglobin ≤ 8.0 g/dL on or after study day 1 until the EOETP, inclusive.

Post-baseline hemoglobin values within 28 days after a RBC transfusion were not be used in the calculation of change.

Amgen

The safety population included all randomized and consented participants who received at least 1 dose of study drug. Four participants in the placebo group received at least 1 dose of darbepoetin alfa during the study and were included in the darbepoetin alfa group for safety analyses.

Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.

Darbepoetin Alfa

Total

Age, Continuous

Age, Customized

Sex: Female, Male

Race/Ethnicity, Customized

Stratification factor at the time of randomization.

The primary analysis set includes all randomized and consented participants with non-small cell lung cancer who received at least one dose of study drug.

Geographic Region

Stratification factor at the time of randomization

Histology

Screening Hemoglobin

Study Director

The primary analysis used the Cox Proportional Hazard Model stratified by the randomization stratification factors (geographic region, histology, and screening hemoglobin), with treatment group as the only covariate.

As a sensitivity analysis, an unstratified Cox Proportional Hazard Model with treatment group as the only covariate was conducted.

To evaluate the potential effect of cross-in (participants in the placebo group who began treatment with an erythropoiesis-stimulating agent (ESA) at any point after randomization), a sensitivity analysis was conducted that included ESA use as a time-dependent covariate in a Cox regression model stratified by the randomization stratification factors (geographic region, histology, and screening hemoglobin).

Primary analysis set (all randomized and consented participants with non-small cell lung cancer who received at least one dose of study drug)

Overall Survival (OS)

The primary analysis of PFS used a Cox Proportional Hazard Model stratified by the randomization stratification factors (geographic region, histology, and screening hemoglobin), with treatment group as the only covariate.

The radiographic endpoint primary analysis set includes all participants in the primary analysis set who did not have disease progression prior to randomization.

Progression-free Survival (PFS)

The primary analysis of the incidence of a transfusion or hemoglobin ≤ 8.0 g/dL from day 29 to EOETP was based on the Cochran-Mantel-Haenszel method to test for treatment group differences while adjusting for the randomization stratification factors (geographic region, histology, and screening hemoglobin).

As a sensitivity analysis a logistic regression analysis was conducted, stratified by the randomization stratification factors (geographic region, histology, screening hemoglobin).

Primary analysis set participants who were on study as of day 29

Percentage of Participants With a Red Blood Cell Transfusion or Hemoglobin ≤ 8.0 g/dL From Week 5 to End of the Efficacy Treatment Period

Any adverse events of interest

Antibody-mediated pure red cell aplasia

Cardiac failure

Central nervous system vascular disorders

Convulsions

Embolic and thrombotic events

Embolic and thrombotic events, arterial

Embolic and thrombotic events, venous

Embolic and thrombotic events, unspecified/mixed

Hypersensitivity

Hypertension

Ischaemic heart disease

Lack of efficacy/effect

Malignancies

Medication errors

Severe cutaneous adverse reactions

All randomized and consented participants who received at least 1 dose of study drug. Four participants in the placebo group received at least 1 dose of darbepoetin alfa during the study and were included in the darbepoetin alfa group for safety analyses.

Number of Participants With Adverse Events of Special Interest

Percentage of Participants With an Objective Tumor Response

Randomized and consented participants who received at least one dose of study drug and with a postbaseline result.

Number of Participants Who Developed Neutralizing Antibodies to Darbepoetin Alfa

Percentage of Participants With a Red Blood Cell Transfusion or Hemoglobin ≤ 8.0 g/dL From Week 1 to End of the Efficacy Treatment Period

Primary analysis set with available baseline and at least 1 postbaseline value; if the EOETP value was missing, the last available postbaseline value was used.

Change From Baseline in Hemoglobin to End of Efficacy Treatment Period

Overall Study

Skin and Connective Tissue Diseases

Breast Neoplasms

Breast Diseases

Skin Diseases

Dichloroacetate, 6.25mg/kg orally, twice daily, administered with food around the same time every day and at approximately 8-12 hours apart.

Dichloroacetate, 6.25mg/kg orally, twice daily, administered with food around the same time every day and at approximately 8-12 hours apart

Dichloroacetate (DCA)

Edward Garon, MD

The purpose of this study is to determine the response rate by RECIST criteria of oral dichloroacetate in patients with recurrent and/or metastatic and pretreated breast and non-small cell lung cancer.

In the United States, approximately 180,000 new cases of breast cancer occur annually, and there are more than 40,000 deaths. More than 150,000 cases develop each year in Canada and the European community together, resulting in over 60,000 deaths from breast cancer. The vast majority of patients who die from breast cancer succumb to metastatic disease. 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 activity as single agents. Median survival remains approximately two years for women with metastatic breast cancer, and less than 3% of patients will experience long-term survival after treatment. The development of new treatment strategies is therefore essential to improve outcome for patients with metastatic breast cancer. The population selected for this study will have previously received, where appropriate, those drugs with clearly defined survival advantages (anthracyclines, taxanes, trastuzumab, and hormonal therapy).

Patients with metastatic non-small cell lung cancer are considered incurable. Palliative chemotherapies, such as platinum-based doublet, Taxotere or Pemetrexed or Erlotinib (an epidermal growth factor tyrosine kinase) have been proven to improve symptoms, and survival in patients with good performance status. Despite these treatments, the median survival of metastatic non-small cell lung cancer is about one year. Therefore, there is an urgent need to develop novel therapy in these patients.

Dichloroacetate (DCA) in Patients With Previously Treated Metastatic Breast or Non-Small Cell Lung Cancer (NSCL)

A Multicenter, Phase II Open-Labeled, Single-Arm Clinical and Pharmacology Study of Dichloroacetate (DCA) in Patients With Previously Treated Metastatic Breast or Non-Small Cell Lung Cancer

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

Jonsson Comprehensive Cancer Center

Age, Categorical

Race (NIH/OMB)

Stage II breast cancer

Stage IV NSCLC

stage at diagnosis

ECOG status 0

ECOG status 1

ECOG status 2

ECOG status

Stage 1 has best prognosis and stage IV has worst.Grade 1 is associated with best prognosis and grade 3 with poor prognosis.ECOG performance status grades a person's overall well-being and scaled from 0-5.ECOG of 0 is associated with best prognosis.Patients with ECOG 0-2 are considered well enough to receive additional treatments for their cancer.

The greatest limitation in our study was early termination due to perceived lack of drug efficacy leading to small number of subjects analyzed.

Intent to treat analysis was performed. Zero patients achieved complete or partial response in this study.

Response Rate by RECIST Criteria of Oral Dichloroacetate in Patients With Recurrent and/or Metastatic and Pretreated Breast and Non-small Cell Lung Cancer.

Completion of Cycle 1 (28 Days)

Completion of Cycle 2 (56 Days)

Symptoms and General Pathology

Disease Progression

Disease Attributes

Patients receive brigatinib PO QD and binimetinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Binimetinib

Brigatinib

Collin Blakely, MD, PhD

This phase I trial studies the side effects and best dose of brigatinib and binimetinib in treating patients with stage IIIB-IV non-small cell lung cancer and a type of gene mutation called a rearrangement in the ALK or ROS1 genes. Brigatinib and binimetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PRIMARY OBJECTIVES:

I. To determine the safety and tolerability of brigatinib in combination with binimetinib in stage IIIB or IV anaplastic lymphoma kinase (ALK) or ROS1 rearranged non-small cell lung cancer (NSCLC) and the recommended phase 2 dose.

SECONDARY OBJECTIVES:

I. To determine preliminary efficacy of brigatinib in combination with binimetinib in any line of treatment.

II. To characterize the pharmacokinetic parameters of brigatinib in combination with binimetinib.

EXPLORATORY OBJECTIVES:

I. To assess circulating tumor deoxyribonucleic acid (DNA) (ctDNA) utility in evaluating treatment response.

II. To evaluate the blockade of downstream signaling indicating response or resistance to treatment of immunohistochemistry (IHC) for phosphatidylinositol 3-kinase (PI3K)/Protein kinase B (AKT)/Mitogen-activated protein kinase (MAPK) pathway activity evaluation.

OUTLINE: This a dose-escalation study.

Patients receive brigatinib orally (PO) once daily (QD) and binimetinib PO twice daily (BID) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days and then every 6 months for 12 months.

Brigatinib and Binimetinib in Treating Patients With Stage IIIB-IV ALK or ROS1-Rearranged Non-small Cell Lung Cancer

A Phase I Study of Brigatinib With Binimetinib in Advanced ALK- or ROS1-Rearranged Non-Small Cell Lung Cancer (NSCLC)

Evaluating the number and frequency of adverse events as determined by the National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE) version (v)5.0 by investigator's assessment will be used to determine the recommended phase 2 dose for future studies.

A dose limiting toxicity (DLT) is generally defined as a grade 3 or higher, treatment-related adverse event that is attributable to the study treatment during the first 28 days of therapy (Cycle 1). The dose limiting toxicity will be based on the tolerability observed during cycle 1 of treatment/observation. Adverse events will be assessed by the investigators using NCI-CTCAE v5.0.

Treatment Emergent AEs will be defined by the NCI CTCAE v5.0 as AEs newly occuring after the patient has begun study treatment.

Severity grade will be defined by the NCI CTCAE v5.0.

RECIST v1.1 will be used to determine the overall response rate defined as participants with a complete response (CR) or a partial response (PR). Point estimate and 95% exact binomial confidence interval (CI) will be obtained for ORR.

Will be defined as maximal reduction in tumor size based on Response Evaluation Criteria in Solid Tumors (RECIST) measurement. Median and inter-quartile range will be used to describe the depth of response (the maximal reduction in tumor size based on RECIST measurement).

Plasma concentration assessment (pharmacokinetic data) of brigatinib during coadministration with binimetinib will be determined by assay at various timepoints. The assay will be done by Takeda / their designated vendor.

PFS is measured as the time from start of treatment to time of disease progression at 6 months. Kaplan-Meier method will be used to describe the describe the median PFS with 95% CI.

Overall Survival is measures as the time from start of treatment to time of death, or lost to follow-up. Kaplan-Meier method will be used to describe the describe the median OS at 12 months with 95% CI.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Anemia Treatment for Advanced Non-Small Cell Lung Cancer (NSCLC) Patients Receiving Chemotherapy	NCT00858364	Non-Small Cell ... Anemia Cancer Lung Cancer	Darbepoetin alf... Placebo	18 Years -	Amgen
Dichloroacetate (DCA) in Patients With Previously Treated Metastatic Breast or Non-Small Cell Lung Cancer (NSCL)	NCT01029925	Metastatic Brea... Lung Cancer	Dichloroacetate...	18 Years -	Jonsson Comprehensive Cancer Center
Brigatinib and Binimetinib in Treating Patients With Stage IIIB-IV ALK or ROS1-Rearranged Non-small Cell Lung Cancer	NCT04005144	ALK Gene Rearra... Lung Non-Small ... Progressive Dis... ROS1 Gene Rearr... Stage IIIB Lung... Stage IIIC Lung... Stage IV Lung C... Stage IVA Lung ... Stage IVB Lung ...	Binimetinib Brigatinib	18 Years -	University of California, San Francisco
Brigatinib and Binimetinib in Treating Patients With Stage IIIB-IV ALK or ROS1-Rearranged Non-small Cell Lung Cancer	NCT04005144	ALK Gene Rearra... Lung Non-Small ... Progressive Dis... ROS1 Gene Rearr... Stage IIIB Lung... Stage IIIC Lung... Stage IV Lung C... Stage IVA Lung ... Stage IVB Lung ...	Binimetinib Brigatinib	18 Years -	University of California, San Francisco
Dichloroacetate (DCA) in Patients With Previously Treated Metastatic Breast or Non-Small Cell Lung Cancer (NSCL)	NCT01029925	Metastatic Brea... Lung Cancer	Dichloroacetate...	18 Years -	Jonsson Comprehensive Cancer Center
Anemia Treatment for Advanced Non-Small Cell Lung Cancer (NSCLC) Patients Receiving Chemotherapy	NCT00858364	Non-Small Cell ... Anemia Cancer Lung Cancer	Darbepoetin alf... Placebo	18 Years -	Amgen

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