Group K +: cancer of the upper aerodigestive tract with or without cachexia

Group K-: absence of cancer and absence of cachexia

The MYOMEC study includes the inclusion of healthy patients (to form a control group

Cancer of Upper Aerodigestive Pathways

Cachexia

carcinological surgery

cervical surgery

CHU Clermont-Ferrand

Mitochondrial Activity and Myosteatosis in the Cachexia of Cancers of the Upper Aerodigestive Tract

The ratio of ATP produced by mitochondria and oxygen consumed by muscle mitochondria

(Expression of cytochrome c oxidase, citrate synthase, HAD, complexes 1, 2 and 3 of the mitochondrial respiratory chain)

(Muscular ceramide concentration, DAG and TAG)

myosteatosis (Computed tomography in L3 for quantification in Hounsfield units)

(phosphorylation rate of mTOR and EiF2alpha)

(Expression of MURF1 and MAF-box ligases)

(Insulinemia, Fasting Glycemia, Hepatic and Lipid Assessment, CRP, Albumin, Pre-albumin, Blood Ionogram, Inflammatory Markers)

University Hospital, Clermont-Ferrand

Participants take 10 mg AR-42 orally per day on 3 non-consecutive days during the 1st 3 weeks of each 4-week cycle and pazopanib 600mg orally daily continuously

Participants take 20 mg AR-42 orally per day on 3 non-consecutive days during the 1st 3 weeks of each 4-week cycle and pazopanib 600mg orally daily continuously

Participants take 20 mg AR-42 orally per day on 3 non-consecutive days during the 1st 3 weeks of each 4-week cycle and pazopanib 800mg orally daily continuously

Participants take 30 mg AR-42 orally per day on 3 non-consecutive days during the 1st 3 weeks of each 4-week cycle and pazopanib 800mg orally daily continuously

Participants take 30 mg AR-42 orally per day on 3 non-consecutive days during the 1st 3 weeks of each 4-week cycle and pazopanib 600mg orally daily continuously

Participants take 40 mg AR-42 orally per day on 3 non-consecutive days during the 1st 3 weeks of each 4-week cycle and pazopanib 800mg orally daily continuously

Participants take 40 mg AR-42 orally per day on 3 non-consecutive days during the 1st 3 weeks of each 4-week cycle and pazopanib 600mg orally daily continuously

Participants take 20 mg AR-42 orally per day on 3 non-consecutive days during the 1st 3 weeks of each 4-week cycle and pazopanib 600mg orally daily continuously.

Cohort 1

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Region of Enrollment

To determine the recommended phase 2 doses (RP2Ds) for AR-42 and pazopanib that are the same as or less than the maximum tolerated doses (MTDs). The dose-limiting toxicity (DLT) evaluation period will be the first treatment cycle. Patients must have taken a minimum of 6 AR-42 doses and a minimum of 21 pazopanib doses during cycle 1 to be considered evaluable for DLT, if DLT has not been observed at the delivered dose. Patients' treatment dose level, dose modification, evaluability for DLT, and DLTs will be listed and summarized by basic descriptive statistics such as frequency and proportion. The maximum tolerated dose(MTDs)/recommended phase 2 doses (RP2Ds) will be found based on the criteria in the protocol.

Cohort Minus 1 (-1)

Participants take 20 mg AR-42 orally per day on 3 non-consectutive days during the 1st 3 weeks of each 4-week cycle and pazopanib 600mg orally daily continuously

Participants take 20 mg AR-42 orally per day on 3 non-consectutive days during the 1st 3 weeks of each 4-week cycle and pazopanib 800mg orally daily continuously

Cohort 2

Participants take 30 mg AR-42 orally per day on 3 non-consectutive days during the 1st 3 weeks of each 4-week cycle and pazopanib 800mg orally daily continuously

Cohort 3A

Participants take 30 mg AR-42 orally per day on 3 non-consectutive days during the 1st 3 weeks of each 4-week cycle and pazopanib 600mg orally daily continuously

Cohort 3B

Participants take 40 mg AR-42 orally per day on 3 non-consectutive days during the 1st 3 weeks of each 4-week cycle and pazopanib 800mg orally daily continuously

Cohort 4A

Participants take 40 mg AR-42 orally per day on 3 non-consectutive days during the 1st 3 weeks of each 4-week cycle and pazopanib 600mg orally daily continuously

Cohort 4B

The Recommended Phase 2 Doses (RP2Ds) of AR-42 and Pazopanib When Given in Combination.

The safety and toxicity of AR-42 and pazopanib when given in combination. Adverse Events (AEs) were characterized and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (NCI CTCAE v4.0) to determine the safety and toxicity of the combination of AR-42 and pazopanib. All AEs regardless of grade were recorded from the beginning of the study procedures through 30 days following the end of study treatment.

Number of Participants With Adverse Events That Were Related to Treatment, AR-42 and Pazopanib Combination.

Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI:
Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.
Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Progressive Disease (PD): At least a 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). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).
Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

The Antitumor Effects of the AR-42 and Pazopanib Treatment Regimen in Patients With Advanced Renal Cell Carcinoma (RCC) or Soft Tissue Sarcoma (STS).

Overall Study

Andrew Poklepovic, MD

Renal Cell Carcinoma

Soft Tissue Sarcoma

Metastatic Disease

AR-42 tablets were taken orally once per day on 3 non-consecutive days during the first 3 weeks of each 4-week cycle. If treatment was interrupted during the cycle, the cycle was to be extended

AR-42

Pazopanib tablets were taken orally once daily continuously during each 4-week treatment cycle. There were no scheduled breaks in pazopanib therapy

lipase/sarcoma

Mitochondrial Activity and Myosteatosis in the Cachexia of Cancers of the Upper Aerodigestive Tract

Study of the Pan-DAC Inhibitor AR-42 and Pazopanib in Advanced Sarcoma and Kidney Cancer

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