Nutritional and Metabolic Diseases

Gland and Hormone Related Diseases

All Conditions

Diabetes Mellitus

Diabetes Mellitus, Type 2

Metabolic Diseases

Glucose Metabolism Disorders

Endocrine System Diseases

Hypoglycemic Agents

All Drugs and Chemicals

Anti-Arrhythmia Agents

Metformin

Gliclazide

Glimepiride

Glyburide

Rosiglitazone

Subjects from ADOPT that are included in this meta-analysis were randomly allocated to receive metformin or rosiglitazone. Subjects from RECORD that are included in this meta-analysis were taking one of three sulfonylureas (glibenclamide, gliclazide or glimepiride) and were randomly allocated metformin or rosiglitazone to use as add-on treament to background sulfonylurea.

allocation of treatment with metformin or rosiglitazone

GSK Clinical Trials

Observational analyses of data from population registeries have suggested that metformin may be associated with a decreased prevalence of malignancy. The ADOPT and RECORD studies both contain groups of subjects randomly allocated to metformin and rosiglitazone. This meta-analysis combines malignancy serious adverse events from ADOPT and RECORD in order to compare their incidence on metformin with that on rosiglitazone.

The objective of this meta-analysis is to compare the incidence of malignancy (excluding non-melanomatous skin cancers) reported as serious adverse events in the ADOPT and RECORD studies between subjects randomly allocated to treatment with metformin with those allocated to rosiglitazone.

Malignancy Meta Analysis for BRL49653

A Meta Analysis of Malignancy Serious Adverse Events in the ADOPT, 49653/048, and RECORD, 49653/231, Studies, Comparing Metformin With Rosiglitazone.

GlaxoSmithKline

Neoplasms

Digestive System Diseases

Symptoms and General Pathology

Skin and Connective Tissue Diseases

Immune System Diseases

Carcinoma

Carcinoma, Hepatocellular

Adenocarcinoma

Hypoxia

Melanoma

Microsatellite Instability

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Genomic Instability

Antineoplastic Agents

Hematinics

Antibodies

Antibodies, Monoclonal

Insulin

Insulin, Globin Zinc

Pembrolizumab

Nivolumab

Immunoglobulins

Liver Extracts

Glucagon-Like Peptide 1

2,4-thiazolidinedione

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

nivolumab (480mg IV q 4 weeks) or pembrozilumab (200mg IV q 3 weeks) - dependent upon approved indication. (If both agents are approved for the disease indication, selection is at the discretion of the investigator)

Metformin - 500 mg by mouth twice daily

nivolumab (480mg IV q 4 weeks) or pembrozilumab (200mg IV q 3 weeks) - dependent upon approved indication. (If both agents are approved for the disease indication, selection is at the discretion of the investigator)

Rosiglitazone - 4 mg by mouth once daily

nivolumab (480mg IV q 4 weeks) or pembrozilumab (200mg IV q 3 weeks) - dependent upon approved indication. (If both agents are approved for the disease indication, selection is at the discretion of the investigator)

Nivolumab or Pembrolizumab (dependent upon approved indication)

Acts directly or indirectly on the liver to lower glucose production, and acts on the gut to increase glucose utilisation, increase GLP-1 and alter the microbiome.

A member of the thiazolidinedione class of antidiabetic agents, improves glycemic control by improving insulin sensitivity. Rosiglitazone is a highly selective and potent agonist for the peroxisome proliferator-activated receptor-gamma (PPARγ).

Jennifer Ruth, RN, BSN

Dan P Zandberg, MD

Dan P Zandberg

Patients with histologically or cytologically confirmed advanced melanoma, renal cell carcinoma, NSCLC, HCC (Child Pugh Class A only), MSI-High solid tumors, Urothelial Cancer, GE junction/Gastric Adenocarcinoma, or HNSCC for which current standard of care treatment for their stage of disease would be with Pembrolizumab or Nivolumab monotherapy, who meet eligibility criteria will undergo a biopsy (core or excisional/incisional; FNA not adequate) for baseline tissue. Patients will then be randomized to one of 3 arms: Anti-PD-1 mAb plus Metformin 500mg po BID, Anti-PD-1 mAb alone, Anti-PD-1 mAb plus Rosiglitazone 4mg po qdaily. Five weeks (+/- 7 days) after initiation of therapy a patient will undergo a repeat biopsy (core or excisional/incisional; FNA not adequate) for correlative analysis. The patient will then continue on study therapy for up to 2 years, or until progression of disease or unacceptable toxicity, whichever occurs first. RECIST 1.1 with modifications, to allow for continued therapy until progressive disease is confirmed if the patient is clinically stable, will be used in the trial.

The prognosis for patients with metastatic disease remains poor. The use of immunotherapy in the treatment of cancer is based on the premise that tumors evade the endogenous immune response by being recognized as self, and not non-self. The recent success of immune-modulating agents in patients with refractory solid tumors has provided proof-of-concept of the efficacy of immune system activation as a therapeutic modality. Tumors develop immune resistance using different mechanisms; the goal of immunotherapy is to counteract these resistance mechanisms, allowing the endogenous immune system to reject tumors. One of those mechanisms of resistance is tumor hypoxia

This study aims to examine whether Metformin and Rosiglitazone will reduce tumor oxygen consumption, creating a less hypoxic T cell environment, with pharmacologic remodeling of the TME leading to restored anti-tumor T cell effector function and as a result will act synergistically with anti-PD-1 mAb resulting in a higher response rate than with anti-PD-1 mAb alone. The safety and tolerability of if adding metformin or rosiglitazone to anti-PD-1 mAb therapy will assessed.

Eligible patients will undergo pre-treatment biopsy and then will be randomized to one of three arms: 1. Anti-PD-1 mAb + Metformin 500mg PO BID 2. Anti-PD-1 mAb alone or 3. Anti-PD-1 mAb plus Rosiglitazone 4mg po qdaily. Patients will undergo post treatment biopsy after 5 weeks (+/- 7 days) of treatment and then continue treatment for up to 2 years, or until progression of disease or unacceptable toxicity, whichever occurs first.

Anti-PD-1 mAb Plus Metabolic Modulator in Solid Tumor Malignancies

A Phase II Clinical Trial of Anti-PD-1 mAb Therapy Alone or With Metabolic Modulators to Reverse Tumor Hypoxia and Immune Dysfunction in Solid Tumor Malignancies

Percent of T cell proliferation (increase in number of cells) in peripheral blood prior to treatment compared to post treatment. T cell proliferation is associated with anti-tumor response.

Percent of mitochondrial restoration in nodal infiltrating lymphocytes (located within tumor) prior to treatment compared to post treatment. Functional mitochondria might ultimately lead to the restoration of apoptosis in cancer cells that are refractory to current anticancer agents.

Percent of mitochondria restoration in peripheral blood lymphocytes prior to treatment compared to after treatment. Functional mitochondria might ultimately lead to the restoration of apoptosis in cancer cells that are refractory to current anticancer agents.

Best overall response per Response Evaluation Criteria in Solid Tumors (RECIST v1.1), by tumor type, recorded from the start of the treatment until disease progression/recurrence. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (target or non-target) with reduction in short axis to \<10 mm. Partial Response (PR): ≥ 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters. Incomplete Response/Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, (reference smallest sum diameters). Progressive Disease (PD): ≥ 20% increase in the sum of diameters of target lesions (reference smallest sum diameters); the sum must also demonstrate an absolute increase of at least 5 mm; (appearance ≥ 1 new lesions is considered progression).

The length of time after study enrollment that patients lives without experiencing disease progression per RECIST v1.1. Progressive Disease (PD): ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The sum must also demonstrate an absolute increase of ≥5 mm. The appearance ≥1 new lesion(s) is considered progression.

The length of time after study enrollment that patients remain alive.

Participants experiencing adverse events (per CTCAE v5.0) that are possibly, probably or definitely related to study treatment, will be tabulated by category, grade and relatedness.

Dan Zandberg

Associate Professor of Medicine

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Androgens

Given orally twice daily. Participants may continue study treatment as long as their disease does not progress and they don't experience any serious side effects.

Placebo

Matthew Smith, MD

The purpose of this study it to learn the effects (good or bad) that rosiglitazone has on patients and their prostate cancer. This study is going to look at what effects rosiglitazone has on prostate specific antigen (PSA) levels.

* Patients will be randomly assigned to initial treatment with either rosiglitazone or placebo orally twice daily, every day as long as there is no disease progression or serious side effects. Patients will be asked to complete a drug log to keep track of the medication.
* Before treatment begins the following tests will be performed: physical exam; bone scan; blood work (including PSA level test) and a urine sample.
* While on this study the following tests and procedures will be done once a month: review of side effects and routine blood tests (including PSA levels).
* While on this study the following tests and procedures will be done on months 2 and 4: review of side effects; routine blood tests (including PSA levels) and urine tests.
* If the patient's disease progressed the treatment code will be broken and if the patient was on placebo, they will have the option to begin taking rosiglitazone.

Rosiglitazone (Avandia) vs. Placebo for Androgen Dependent Prostate Cancer

Rosiglitazone (Avandia) vs. Placebo for Androgen Dependent Prostate Cancer: A Randomized Double-Blind, Placebo Controlled Phase III Study

Dana-Farber Cancer Institute

Massachusetts General Hospital

Professor of Medicine

Rare Diseases

Adenocarcinoma, Follicular

Thyroid Diseases

Thyroid Neoplasms

Carcinoma, Renal Cell

Thyroid Cancer, Papillary

Kidney Neoplasms

Urologic Neoplasms

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Endocrine Gland Neoplasms

Head and Neck Neoplasms

Adenocarcinoma, Papillary

Thyroid Cancer, Follicular

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Papillary Thyroid Carcinoma

Hurthle Cell Thyroid Cancer

All subjects will receive daily XL184, and two single doses of rosiglitazone, 3 weeks apart

one 4 mg dose as a tablet followed by a second 4 mg dose 3 weeks later

rosiglitazone

XL184

The primary objective of this clinical study is to determine whether the inhibition of cytochrome P450 (CYP) isozyme CYP2C8 by XL184 observed in in vitro preclinical studies translates into the potential for clinically significant drug-drug interactions in humans. The study will measure the effect of once daily dosing of XL184 on the pharmacokinetics (PK) of rosiglitazone. The PK of XL184 when combined with rosiglitazone will be evaluated as well.

A specific objective of this study is to determine whether the interaction between XL184 and a drug such as rosiglitazone is sufficiently large enough to necessitate a dosage adjustment when used in combination with XL184, or whether the interaction would require additional therapeutic monitoring.

Rosiglitazone, commonly known as Avandia, is a prescription medicine approved by the FDA used to treat adults with Type 2 (adult-onset or non-insulin dependent) diabetes mellitus (high blood sugar). In this study, subjects will only take 2 doses of rosiglitazone. There is no intention of therapy as a result of taking rosiglitazone in this study.

A Drug-Drug Interaction Study of the Effects of XL184 (Cabozantinib) on Rosiglitazone in Subjects With Solid Tumors

A Phase 1 Drug-Drug Interaction Study of the Effects of XL184 on the Pharmacokinetics of a Single Oral Dose of Rosiglitazone in Subjects With Solid Tumors

To evaluate the effect of multiple daily doses of XL184 on single dose PK of rosiglitazone

To evaluate safety and tolerability of daily oral administration of XL184 and two single doses of rosiglitazone

To evaluate the plasma PK of XL184 after a single dose of rosiglitazone

Exelixis

Adjuvants, Anesthesia

Central Nervous System Depressants

Psychotropic Drugs

Anticoagulants

Gastrointestinal Agents

Midazolam

Warfarin

Omeprazole

Anesthetics

Hypnotics and Sedatives

Anti-Anxiety Agents

Anesthetics, Intravenous

Anesthetics, General

GABA Modulators

Neurotransmitter Agents

Antacids

Anti-Ulcer Agents

Proton Pump Inhibitors

Enzyme Inhibitors

Regorafenib (Stivarga, BAY73-4506) + warfarin + omeprazole + midazolam

Regorafenib (Stivarga, BAY73-4506) + rosiglitazone

BAY73-4506 administered once a daily (od) in a 21-day on / 7-day off schedule

Regorafenib (Stivarga, BAY73-4506)

Bayer Study Director

* To evaluate the effect of BAY73-4506 on the pharmacokinetics of probe substrates of CYP 2C9 (warfarin), 2C19 (omeprazole) and 3A4 (midazolam) administered in a cocktail approach and on the pharmacokinetics of a probe substrate of CYP 2C8 (rosiglitazone)
* To evaluate safety, anti-tumor activity, pharmacokinetics, and pharmacodynamics of BAY73-4506 in patients with advanced solid tumors

BAY73-4506 Probe Substrate Study

A Phase I, Non-randomized Open-label Study to Evaluate the Effect of BAY73-4506 (Regorafenib) on Probe Substrates of CYP 2C9 (Warfarin), 2C19 (Omeprazole) and 3A4 (Midazolam) in a Cocktail Approach (Group A) and on a Probe Substrate of CYP 2C8 (Rosiglitazone, Group B) in Patients With Advanced Solid Tumors

Bayer

Diseases and Abnormalities at or Before Birth

Syndrome

Polycystic Ovary Syndrome

Insulin Resistance

Hyperandrogenism

Cysts

Ovarian Cysts

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Gonadal Disorders

Disorders of Sex Development

46, XX Disorders of Sex Development

Congenital Abnormalities

Urogenital Abnormalities

Adrenal Hyperplasia, Congenital

Adrenogenital Syndrome

Congenital Adrenal Hyperplasia

21-hydroxylase Deficiency

Micronutrients

Cardiotonic Agents

Other Dietary Supplements

Inositol

Acarbose

Cardiac Glycosides

Glycoside Hydrolase Inhibitors

Obese and lean healthy women evaluated only at baseline

100 mg three times daily for 8 weeks orally

Jean-Patrice Baillargeon, MD, MSc

The investigators hypothesis is that free fatty acids (FFA) accumulation in non fatty tissues would lead to insulin resistance and hyperandrogenism in PCOS women. Accordingly, Peroxisome Proliferator-Activated Receptor gamma (PPARγ) agonist (rosiglitazone) would be a great therapeutic option for PCOS as their activation induces transcription factors of gene implicated in fatty acids metabolism.

The aim is to verify if insulin-related hyperandrogenism can be reversed in women having polycystic ovary syndrome following an 8-week treatment with rosiglitazone compared to simple insulin reduction with acarbose.

For the purpose of this study, 14 lean women (BMI ≤ 25 kg/m2) and 36 obese women (BMI 30-39 kg/m2) with PCOS as well as 14 lean and 14 obese control women will be recruited to determine their insulin sensibility (insulin levels, M-value, metabolic clearance rate of glucose)and FFA metabolism (FFA levels, rythm of apparition and disapearance of FFA) during a 75g oral glucose tolerance test and a 2-step insulin-glucose clamp.

Polycystic ovary syndrome (PCOS) is a very common but complex endocrine disorder affecting 6 to 10% of childbearing age women. To diagnose PCOS, women must display two of these three symptoms: clinical or biochemical hyperandrogenism, oligoamenorrhea, and/or echographycally confirmed polycystic ovary. Many studies have also demonstrated that PCOS women are more insulin resistant than control women when matched for body mass index (BMI). Thus, insulin resistance (IR) and secondary hyperinsulinemia would be important premises in the development of PCOS. In fact, the prevalence of type 2 diabetes (T2D) is tripled in PCOS women.

Higher free fatty acid (FFA) concentrations were also observed in the circulation of PCOS women. As FFA accumulates in liver and muscle instead of fat cells, this could be an important cause of IR according to the theory of lipotoxicity. Some indirect evidences are suggesting that FFA accumulation in androgen secreting cells (ovary and adrenal gland) could enhance their androgen production. Based on these findings, our hypothesis is that FFA accumulation in non fatty tissues would lead to IR and hyperandrogenism in PCOS women. Accordingly, Peroxisome Proliferator-Activated Receptor gamma (PPARγ) agonist (rosiglitazone) would be a great therapeutic option for PCOS as their activation induces transcription factors of gene implicated in fatty acids metabolism.

The aim is to verify if insulin-related hyperandrogenism can be reversed in PCOS women following an 8-week treatment with rosiglitazone compared to simple insulin reduction with acarbose. For the purpose of this study, 14 lean women (BMI ≤ 25 kg/m2) and 36 obese women (BMI 30-39 kg/m2) with PCOS as well as 14 lean and 14 obese control women will be recruited to determine their insulin sensibility (insulin levels, M-value, metabolic clearance rate of glucose)and FFA metabolism (FFA levels, rythm of apparition and disapearance of FFA) during a 75g oral glucose tolerance test and a 2-step insulin-glucose clamp.

Role of Insulin Action and Free Fatty Acids in Hyperandrogenism of Women With Polycystic Ovary Syndrome

Role of Insulin Action and Free Fatty Acids in Hyperandrogenism and Role of Metabolism of Inositols in Insulin Resistance of Women With Polycystic Ovary Syndrome

The calculated ratio of free testosterone to the area under the insulin curve during an OGTT

Determined by the relationship between testosterone and insulin levels during an OGTT.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Malignancy Meta Analysis for BRL49653	NCT01195259	Diabetes Mellit...	allocation of t...	-	GlaxoSmithKline
Malignancy Meta Analysis for BRL49653	NCT01195259	Diabetes Mellit...	allocation of t...	-	GlaxoSmithKline
Anti-PD-1 mAb Plus Metabolic Modulator in Solid Tumor Malignancies	NCT04114136	Melanoma NSCLC Hepatocellular ... Urothelial Canc... Gastric Adenoca... HNSCC Esophageal Aden... Microsatellite ...	Nivolumab or Pe... Metformin Rosiglitazone	18 Years -	University of Pittsburgh
Rosiglitazone (Avandia) vs. Placebo for Androgen Dependent Prostate Cancer	NCT00182052	Adenocarcinoma ... Prostate Cancer	Rosiglitazone Placebo	18 Years -	Massachusetts General Hospital
A Drug-Drug Interaction Study of the Effects of XL184 (Cabozantinib) on Rosiglitazone in Subjects With Solid Tumors	NCT01100619	Papillary Thyro... Follicular Thyr... Huerthle Cell T... Renal Cell Carc...	rosiglitazone XL184	18 Years -	Exelixis
Anti-PD-1 mAb Plus Metabolic Modulator in Solid Tumor Malignancies	NCT04114136	Melanoma NSCLC Hepatocellular ... Urothelial Canc... Gastric Adenoca... HNSCC Esophageal Aden... Microsatellite ...	Nivolumab or Pe... Metformin Rosiglitazone	18 Years -	University of Pittsburgh
Malignancy Meta Analysis for BRL49653	NCT01195259	Diabetes Mellit...	allocation of t...	-	GlaxoSmithKline
BAY73-4506 Probe Substrate Study	NCT01287598	Neoplasms	Regorafenib (St... Warfarin Omeprazole Midazolam Rosiglitazone	18 Years -	Bayer
Role of Insulin Action and Free Fatty Acids in Hyperandrogenism of Women With Polycystic Ovary Syndrome	NCT01019356	Polycystic Ovar...	Rosiglitazone Acarbose	18 Years - 40 Years	Université de Sherbrooke
Combination Drug Study of Bexarotene and Rosiglitazone to Treat CTCL	NCT00178841	Cutaneous T-cel... Mycosis Fungoid... Sezary Syndrome	Rosiglitazone a...	18 Years -	Vanderbilt University

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