Neoplasms

All Conditions

Symptoms and General Pathology

Skin and Connective Tissue Diseases

Behaviors and Mental Disorders

Rare Diseases

Osteosarcoma

Sarcoma

Disease Progression

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Neoplasms, Bone Tissue

Neoplasms, Connective Tissue

Quality of Life

Soft Tissue Sarcoma

Amino Acids

All Drugs and Chemicals

Tyrosine

Treatment will be divided in 28 days cycles, including a 21-day period of treatment by regorafenib and best supportive care followed by a 7-day period of rest.

In case of toxicity, dose can be reduced or treatment interrupted according to Specific Product Characteristics (SPC).

Patients can receive up to a maximum of 13 cycles (maximum treatment period : 12 Months).

Treatment will be divided in 28 days cycles, including a 21-day period of treatment by placebo and best supportive care followed by a 7-day period of rest.

In case of toxicity, dose can be reduced or treatment interrupted according to Specific Product Characteristics (SPC).

Patients can receive up to a maximum of 13 cycles (maximum treatment period : 12 Months).

Treatment for 13 cycles (12 months) maximum.

During each cycle :

* patients ≥ 16 years old and patients \<16 old with Body Surface Area (BSA) ≥ 1,70 m2 will take 3 tablets, once a day, corresponding to a total of 120 mg Regorafenib, during 21 days, followed by 7 days without treatment.
* patients \< 16 years old with a 1,30 m2 ≤ BSA ≥ 1,70 m2 will take 2 tablets, once a day, corresponding to a total of 80 mg Regorafenib, during 21 days, followed by 7 days without treatment

Treatment by regorafenib and best supportive care

Treatment for 13 cycles (12 months) maximum.

During each cycle :

* patients ≥ 16 years old and patients \<16 old with Body Surface Area (BSA) ≥ 1,70 m2 will take 3 tablets, once a day, corresponding to a total of 120 mg Placebo, during 21 days, followed by 7 days without treatment.
* patients \< 16 years old with a 1,30 m2 ≤ BSA ≥ 1,70 m2 will take 2 tablets, once a day, corresponding to a total of 80 mg Placebo, during 21 days, followed by 7 days without treatment

Treatment by placebo and best supportive care

Julien GAUTIER

Loïc CHAIGNEAU

Maud TOULMONDE

Alice HERVIEUX

Nicolas PENEL

Mehdi BRAHMI

Nelly FIRMIN

Morgane CLEIREC

Sophie PIPERNO-NEUMANN

Pascaline BOUDOU-ROUQUETTE

Emmanuelle BOMPAS

Claire BERGER

Natacha ENTZ WERLE

Justine GANTZER

Thibaud VALENTIN

Nathalie GASPAR

This is a randomized, double-blinded, 2 arms study concerning patients with high-grade bone sarcoma (HGBS) without complete remission after standard treatment at diagnosis or first relapse.

In the first arm, patients will be treated with regorafenib + best supportive care (BSC) for a maximum of 12 months as maintenance therapy after standard line therapy completion, whereas in the second arm, patients will be treated with placebo + BSC (standard of care).

The comparison between this two arms will allow to determine whether or not regorafenib and BSC is efficient for disease control, in terms of Progression-Free Survival improvement.

This is a randomized, placebo-controlled, double-blinded, prospective, comparative, multicentre phase II study.

Patients with measurable unresectable residual disease will be accrued after they completed standard of care, consisting of:

* At diagnosis: multimodal treatment with neoadjuvant chemotherapy, surgery and adjuvant chemotherapy
* At relapse: chemotherapy

Patients who meet the eligibility criteria will be randomly assigned (1:1) into one of the following treatment groups:

* Experimental arm: regorafenib + best supportive care (BSC) maintenance (12 months maximum)
* Standard arm: placebo + BSC (12 months maximum)

A randomization procedure (centralized implementation of concealed random permuted blocks) will be used to obtain a balanced distribution of the setting of the disease (stratification factor): residual disease at diagnosis or at relapse after standard multimodal treatment.

After their eligibility has been confirmed, patients will receive regorafenib or its matching placebo until disease progression, or for a maximum of 12 months, or unacceptable toxicity or willingness to stop, whichever occurs first.

In case of radiological disease progression during treatment period, patients from the standard arm (placebo) who have unresectable disease will be allow to switch to experimental arm (regorafenib). After the switch, patients will be treated with regorafenib until disease progression or unacceptable toxicity or willingness to stop which occurs first.

After the completion of the maintenance therapy (12 months) patients will be followed-up until the first radiological disease progression, unless a premature disease progression occurred. All patients will be followed-up until the data cut-off (12 months after the last randomization).

The vital status will be updated once for all patients at the end of the study, based on patient's medical file.

The end of the study will be 24 months after the last randomisation or at the end of treatment of the last patient under treatment (either blinded or open label) whichever occurs last.

Efficacy of Regorafenib Combined With Best Supportive Care as Maintenance Treatment in High Grade Bone Sarcomas Patients

A Randomized, Placebo-controlled, Double-blinded, Phase II Study of Efficacy of Regorafenib as Maintenance Treatment in Patients With High Grade Bone Sarcomas at Diagnosis or Relapse and Without Complete Remission After Standard Treatment

The Progression-Free Survival (PFS) will be defined as the time from the date of randomization to the date of first documented disease progression (according to the RECIST V1.1) or the date of death due to any cause.

Patients alive and progression-free at the time of data cut-off will be censored at the time of the latest tumour evaluation.

In patients from the placebo arm who switched into the active treatment group, PFS will be studied from regorafenib initiation: PFS from switch will be defined as the time from the date of switch to the date of first documented disease progression (according to the RECIST V1.1) post-switch or the date of death due to any cause.

The Objective Response Rate (ORR) will be defined as the proportion of patients with a best overall response of Complete Response (CR) or Partial Response (PR) (RECIST V1.1)

In patients from the placebo arm who switched into the active treatment group, the ORR will be studied from regorafenib initiation:

The ORR from switch will be defined as the proportion of patients in the placebo arm with a best overall response of Complete Response (CR) or Partial Response (PR) from regorafenib initiation.

The Disease Control Rate (DCR) will be defined as the proportion of patients with a best overall response of CR, PR or Stable Disease (SD) (RECIST V1.1) 2 months after randomization

The Disease Control Rate (DCR) will be defined as the proportion of patients with a best overall response of CR, PR or Stable Disease (SD) (RECIST V1.1) 4 months after randomization

In patients from the placebo arm who switched into the active treatment group, the DCR will be studied from regorafenib initiation:

The DCR from switch will be defined as the proportion of patients in the placebo arm with a best overall response of CR, PR or Stable Disease (SD) 2 months after regorafenib initiation.

In patients from the placebo arm who switched into the active treatment group, the DCR will be studied from regorafenib initiation:

The DCR from switch will be defined as the proportion of patients in the placebo arm with a best overall response of CR, PR or Stable Disease (SD) 4 months after regorafenib initiation.

The Time to Treatment Failure (TTF) will be defined as the time from the date of randomization to the date of permanent discontinuation of the study treatment, whichever is the cause. Patient not known to have withdrawn treatment before 12 months (study treatment duration) will be censored at the time of treatment stop.

The Overall Survival (OS) will be defined as the time from date of randomization to the date of death, from any cause. Patient not known to have died at the time of analysis will be censored based on the last recorded date on which the patient was known to be alive.

In patients from the placebo arm who switched into the active treatment group, the OS will be studied from regorafenib initiation:

The Overall Survival (OS) from switch will be defined as the time from date of switch to the date of death, from any cause. Patient not known to have died at the time of analysis will be censored based on the last recorded date on which the patient was known to be alive.

The patient's Quality of Life (QoL) will be assessed using the EORTC Quality Of Life Questionnaire (QLQ)-C30 file. Scores will be calculated at each time point according to the scoring manuals. Descriptive statistics will be used to evaluate baseline scores and evolution of scores from baseline to each time point. Data will be compared between arms using the Student's t-test. The QoL data will also be presented graphically if deemed relevant.

The safety will be described mainly on the frequency of adverse events (AE) coded using the common toxicity criteria (NCI-CTCAE v5.0) grade. Descriptive statistics will be provided for characterizing and assessing patient tolerance to treatment. AE will be coded according to the MedDRA®.

Centre Leon Berard

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Patients with MM treated with single or combination therapy over 75 years of age.

Patients aged 65-75 years with MM treated with single or dual therapy

patients less than 65 years with MM treated with single or dual therapy

ondine BECQUART

Since 2013, therapeutic care of metastatic melanoma (MM) has greatly improved, especially thanks to BRAF and MEK targeted therapies. The efficacy of these treatments that are now used daily at first line for BRAF mutated MM is widely approved. Their toxicities, in monotherapy or in association, are also well-known: fever, arthralgias, digestive disorders, cutaneous rash, fatigue, photosensitivity, alopecia, cutaneous hyperkeratosis, squamous cell carcinomas, keratoacanthomas, de novo melanomas... However, onco-dermatologists are more and more faced with MM of elderly patients. Indeed, life expectancy continues to increase and the over-75-year-old age group is becoming larger. These patients are still active but much more vulnerable. Nevertheless, there is no data in the literature for this fragile population except the MM pivotal studies subgroups of those over 65-year-old. The results vary with different regimens. Therefore, there is a wide lack of information that could help make a therapeutic decision, inform patients, prevent or treat side effects of BRAF and MEK inhibitors in elderly patients

Since 2013, therapeutic care of metastatic melanoma (MM) has greatly improved, especially thanks to BRAF and MEK targeted therapies. The efficacy of these treatments that are now used daily at first line for BRAF mutated MM is widely approved. Their toxicities, in monotherapy or in association, are also well-known: fever, arthralgias, digestive disorders, cutaneous rash, fatigue, photosensitivity, alopecia, cutaneous hyperkeratosis, squamous cell carcinomas, keratoacanthomas, de novo melanomas... However, onco-dermatologists are more and more faced with MM of elderly patients. Indeed, life expectancy continues to increase and the over-75-year-old age group is becoming larger. These patients are still active but much more vulnerable. Nevertheless, there is no data in the literature for this fragile population except the MM pivotal studies subgroups of those over 65-year-old. The results vary with different regimens. Therefore, there is a wide lack of information that could help make a therapeutic decision, inform patients, prevent or treat side effects of BRAF and MEK inhibitors in elderly patients. This work aims to study the targeted therapies tolerance in over 65 or 75-year-old patients with BRAF mutated MM. The French clinical and biological database MELBASE will be analysed to carry out a descriptive retrospective multicentric study. This real-life assessment of the adverse effects in older patients will result in more adapted therapeutic decisions, better informed patients and improved follow-up care in order to increase quality of life and life expectancy.

Tolerance of Targeted Therapy Used in Metastatic Melanoma in Patients Aged Over 65 and 75-year-old

Safety of Targeted Therapies in Elderly Patients (Over 5 and 75 Year-old) With Metastatic Melanoma

Analyze the relationship between Grade 3 and Level 4 adverse events in subjects older than 65 or 75 years of age compared to patients under 65 years of age

Analyze treatment changes with progression-free survival and overall follow-up in patients over 65 or 75 years of age compared to patients younger than 65 years.

Saint-Louis Hospital, Paris, France

University Hospital, Montpellier

BEBT-607 tablets, 100mg/day,50mg each time, are administered once a day in the single administration phase and twice a day in the continuous administration phase (only once on the 28th day of the first cycle) for 28 days. 28 days is as a treatment cycle.

BEBT-607 tablets, 200mg/day,100mg each time, are administered once a day in the single administration phase and twice a day in the continuous administration phase (only once on the 28th day of the first cycle) for 28 days. 28 days is as a treatment cycle.

BEBT-607 tablets, 300mg/day,150mg each time, are administered once a day in the single administration phase and twice a day in the continuous administration phase (only once on the 28th day of the first cycle) for 28 days. 28 days is as a treatment cycle.

BEBT-607 tablets, 400mg/day,200mg each time, are administered once a day in the single administration phase and twice a day in the continuous administration phase (only once on the 28th day of the first cycle) for 28 days. 28 days is as a treatment cycle.

BEBT-607 tablets, 600mg/day,300mg each time, are administered once a day in the single administration phase and twice a day in the continuous administration phase (only once on the 28th day of the first cycle) for 28 days. 28 days is as a treatment cycle.

BEBT-607 tablets, 800mg/day,400mg each time, are administered once a day in the single administration phase and twice a day in the continuous administration phase (only once on the 28th day of the first cycle) for 28 days. 28 days is as a treatment cycle.

BEBT-607 tablets, 300mg/day,150mg each time, are administered twice a day (only once on day 1 and day 28 of the first cycle), continuous administration for 28 days. 28 days is as a treatment cycle.

BEBT-607 tablets, 400mg/day,200mg each time, are administered twice a day (only once on day 1 and day 28 of the first cycle), continuous administration for 28 days. 28 days is as a treatment cycle.

BEBT-607 tablets, 600mg/day,300mg each time, are administered twice a day (only once on day 1 and day 28 of the first cycle), continuous administration for 28 days. 28 days is as a treatment cycle.

PhaseⅠa:100mg,200mg,300mg,400mg,600mg or 800mg/day,50mg,100mg,150mg,200mg,300mg or 400mg each time, once a day in the single administration phase and twice a day in the continuous administration phase (only once on the 28th day of the first cycle) for 28 days,28 days is as a treatment cycle.

PhaseⅠb:300mg,400mg or 600mg/day, 150mg,200mg or 300mg each time,twice a day (only once on day 1 and day 28 of the first cycle), continuous administration for 28 days,28 days is as a treatment cycle.

BEBT-607Tablets

Kegang Jiang, Master

Heli Liu, Ph.D

Zhenhua Liu

This is a two-phase, multicenter, open phase I clinical study, with phase Ia as dose escalation phase and phase Ib as dose expansion phase, to evaluate the safety tolerability and pharmacokinetic characteristics of BEBT-607 tablets in patients with advanced or metastatic solid tumors associated with KRAS G12C mutation. To evaluate the efficacy of BEBT-607 tablets in the treatment of patients with advanced or metastatic solid tumors with KRAS G12C mutation, and to determine the recommended dose (RP2D) for Phase II clinical trials of BEBT-607 tablets in patients with advanced or metastatic solid tumors with KRAS G12C mutation.

Phase Ⅰa:

The dose escalation plan is to carry out about 6 dose levels. The initial dose of BEBT-607 tablets is set at 100mg/ day, and the subsequent dose groups are first increased by 100%. If a case of drug-related grade 2 non-hematological toxicity or grade 3 hematological toxicity is found and does not reach DLT, the subsequent dose groups are increased by 50%. If one case of dose limiting toxicity(DLT) is found and does not reach maximum tolerated dose(MTD ), the subsequent dose group is increased by 33%（Doses are rounded to multiples of 100mg）.The single dose is 1/2 of the total daily dose, and the single administration phase is administered once a day, and the continuous administration phase is administered twice a day (only once on the 28th day of the first cycle).

Phase Ⅰb:

According to the pharmacokinetics, safety and preliminary efficacy results of phase Ⅰa dose escalation phase, one to three cohorts with target dose or tumor species are selected for dose extension trial, and a maximum of 30 subjects are enrolled in each cohort. The subjects receive BEBT-607 tablets twice a day, orally before breakfast and before dinner, respectively. There is a treatment cycle every 28 days (On days 1 and 28 of the first cycle, the drug is administered only once before breakfast). The study process for each subject consisted of three phases: screening, treatment, and follow-up. During treatment, participants are required to undergo safety checks every four weeks from the first dose, tumor assessments every eight weeks, safety follow-up at the end of treatment 28 days after the last dose, efficacy follow-up every eight weeks, and survival follow-up every three months.

Participants will need to understand the requirements and risks of the trial, sign an informed consent form, accept the dosing regimen required by the trial protocol, and follow the investigator's guidance.

Phase Ⅰa:

Six dose levels are carried out, and the initial dose of BEBT-607 tablets is set as 100mg/ day. The climbing study is carried out by accelerated titration method combined with "3+3" mode.

Phase Ⅰb:

According to the pharmacokinetics, safety, and preliminary efficacy results of phase Ⅰa , one to three cohorts with target dose or tumor species are selected for dose extension trial, in which participants receive continuous administration of the experimental drug BEBT-607 tablets until disease progression or toxicity became intolerable or patients stopped or died.

Study of BEBT-607 Tablets in The Treatment of Advanced or Metastatic Solid Tumors With KRAS G12C Mutation

A Two-phase, Multicenter, Open Phase I Study of BEBT-607 Tablets in The Treatment of Advanced or Metastatic Solid Tumors With KRAS G12C Mutation

Area under the plasma concentration time curve from 0 hour to last time of quantifiable concentration after administration

Xiangya Hospital of Central South University

BeBetter Med Inc

Cancer Pain

Pain

Analgesics

Central Nervous System Depressants

Ketamine

Analgesics, Opioid

Opiate Alkaloids

Anesthetics

Anesthetics, Dissociative

Anesthetics, Intravenous

Anesthetics, General

Excitatory Amino Acid Antagonists

Neurotransmitter Agents

The group will be divided into two pain matched groups of 25 each. One group will receive Ketamine (K group) and the other placebo (P). Both the researchers and the patients will not know to which group they belong. Four days prior to the beginning of the research the patients will document, using an ad-hoc diary, in predetermined hours, four times a day the level (VAS) of pain, sedation and vomiting scores, and other side effects. Pain will be assessed using a Visual Analog Scale (VAS) (0-10).

The documentation will continue throughout the research period. The Ketamine or plaecebo will also be taken in a predetermined hours to avoid an effect of diurnal disruption on pain perception

oral ketamine

Silviu Brill, MD

silviu Brill, M.D

Silviu Brill, M.D

In the current research the investigators would like to examine the effect of a well acquainted drug, Ketamine, which is used by anesthesiologists to induce sleep in operations. Usually the ketamine is given into the vein and not orally. The investigators want to give it orally to cancer patients that sufffer from severe pain to find out whether it can prove their quality of life, lower their pain and reduce the amount of opioids they receive.

It is estimated that 10%-15% of patients with cancer-related pain do not achieve acceptable levels of pain relief even when oral or parenteral opioids are skillfully combined with conventional adjuvant analgesics and intractable pain occurs in up to 2% of advanced cancer patients. Painful conditions arising from tumor-nerve structure involvement, neuropathic pain, skin lesions, iatrogenic (chemo-and radiotherapy lesion), or ischemic pain are those most likely to require more aggressive treatment, such as the use of unconventional agents or interventional management approaches.

Despite considerable progress in the technologies of cancer-related pain management and an increased broadening array of medications, many patients fail to achieve adequate pain relief. In others, the availability of these treatments may be limited by such factors as side effects, or lack of or pain-management expertise. Furthermore, the development of opioid tolerance and the high incidence of side effects with escalating dose of opioid dose may contribute to treatment failure.

The need to develop new pharmacologic approaches for refractory pain remains of critical importance. The most potent class of analgesics available for general use remains the opioids.

Several lines of investigation have focused on the neuro-physiological as well as neuro-chemical mechanisms that may underlay opioid resistant pain, such as opioid induced hyperalgesia and opioid tolerance cause certain types of pain to be relatively resistant to the opioids or that may underlie the tolerance that can develop to their beneficial effects. Particular attention has been paid to the role played by glutamate neurotransmission in promoting and maintaining chronic pain states.

Glutamate is the primary excitatory neurotransmitter of the central nervous system and is normally released by pain-signaling afferent neurons as they synapse on central pain pathways in the spinal cord. The persistent release of glutamate, due to peripheral injury or inflammation, leads to the activation of N-methyl-D-aspartate (NMDA) receptors. This process of activation has been shown to play a crucial role in mediating the phenomenon of "wind up" pain, a state in which spinal neurons become hyper-responsive to repetitive painful stimulation.

The clinically observed phenomena of allodynia (pain due to a stimulus that does not normally provoke pain) and hyperalgesia (an increased response to a stimulus that is normally painful), which are the hallmarks of neuropathic pain, are expressions of "wind up" pain. Recent investigations indicate that this process can be prevented or mitigated by agents that block the effects of glutamate at the NMDA receptor. Other investigations have revealed that NMDA receptor antagonists can be useful in potentiating the analgesic efficacy of several classes of medication, including opioids, nonsteroidal anti-inflammatory drugs (NSAIDs), and local anesthetics. In addition, NMDA receptor antagonists may play an important role in mediating the development of opioid tolerance or in treating the perplexing syndrome of opiate-induced hyperalgesia.

Of the small number of NMDA receptor antagonists currently available for clinical use, most, unfortunately, either have a narrow therapeutic window or require parenteral administration. Dextromethorphan, best known for its use as an antitussive agent, is dosed orally and shows activity as a noncompetitive NMDA antagonist. Multiple trials, however, generally have not shown dextromethorphan to be effective in treating neuropathic pain.

Ketamine, a phencyclidine (PCP) derivative analog, has been used for more than 40 years to produce "dissociative" anesthesia.

Early experience with ketamine revealed that it also produced analgesia that sometimes well outlasted its anesthetic effects. Although the mechanisms of ketamine's analgesic effects remain the subject of debate, and are likely multiple, antagonism at the NMDA-receptor site appears to be central to both its anesthetic and analgesic effects.

Ketamine's utility as an anesthetic has been hampered by troublesome psychomimetic effects, which for many years have also limited its application as an analgesic. Recent investigations have shown, however, that analgesia can be produced with sub-hypnotic sub-anesthetic doses of intravenous ketamine (ie,10%-20% of those used for anesthesia) with a far lower frequency of psychomimetic reactions. These side effects are dose dependent and can be minimized by starting ketamine at low doses, titrating slowly, and concurrently starting a benzodiazepine or haloperidol.

Over the years a variety of nociceptive (somatic and visceral) and neuropathic pain states have been treated with subanesthetic doses of ketamine. Early studies demonstrated its utility in treating the pain associated with wound dressings in burn patients, as a treatment for pain following severe trauma and for cancer-related pain.

Racemic ketamine has an oral bioavailability of approximately 17%. When administrated orally in a dose of 0.5mg/kg the plasma ketamine concentration of ketamine was 40 ngml-1 (for the same i.m. dose the plasma ketamine concentration was 150 ng ml-1 ). Oral administration is associated with much greater concentrations of the metabolite norketamine, which may have contributed to the analgesic effect. Orally administered ketamine undergoes extensive first pass metabolism, primarily via N-de-methylation, resulting in low ketamine concentrations and high norketamine concentrations in blood and tissue. The plasma levels at which analgesia is achieved are 0.15 μg/ml following intramuscular administration and 0.04 μg/ml after oral administration. This difference may be explained by a higher norketamine concentration due to first-pass metabolism. This main metabolite apparently contributes to the antinociceptive effect Oral ketamine is more potent (30 to 40%) that subcutaneous route because first pass metabolism converts ketamine to an active analgesic metabolite.

The benefits and harms of adding ketamine to a strong analgesics pain-killers such as morphine for the relief of cancer pain are not yet established. Only two small randomised controlled trials suggest that when ketamine is given with morphine it may help to control cancer pain. However, these data are insufficient to assess the effectiveness of ketamine in this setting. So far there is little clinical evidence to support this practice, furthermore, the The Cochrane Database of Systematic Reviews 2009 concludes that: "Current evidence is insufficient to assess the benefits and harms of ketamine as an adjuvant to opioids for the relief of cancer pain. More randomized randomised controlled trials are needed".

Oral Ketamine as an Adjuvant to Opioids for Pain Treatment in Cancer Patients

The study is a prospective randomized, placebo-controlled double -blind study involving. Subjects Fifty patients with unbalanced (VAS\>6) chronic cancer-related pain despite opioid treatment.

Tel-Aviv Sourasky Medical Center

Silviu Brill MD

Cohort will have a total 6 subjects: SAD (2 subjects receiving placebo and 4 subjects receiving active AMXT 1501 dicaprate);

SAD cohorts are defined as follows:

* Cohort 1: One placebo and one AMXT 1501 dicaprate subject will be treated as sentinel subjects receiving one tablet each of their assigned treatment. Assuming no intolerance is noted after at least 3 days, the remaining cohort subjects (placebo, 1 subject and AMXT 1501 dicaprate, 3 subjects) will be treated.
* Cohort 2: 2 subjects 2 placebo each and 4 subjects 2 AMXT 1501 dicaprate tablets each
* Cohort 3: 2 subjects 4 placebos each and 4 subjects 4 AMXT 1501 dicaprate tablets each
* Cohort 4: 2 subjects 8 placebos each and 4 subjects 8 AMXT 1501 dicaprate tablets each

Each cohort will have a total 6 subjects: MAD (2 subjects receiving placebo and 4 subjects receiving active AMXT 1501 dicaprate); MAD cohorts will receive dosing once daily for 14 consecutive days. Dosing will be contingent on adequate tolerance in Cohorts 1-5.

* Cohort 6: 2 subjects 2 placebos each; 4 subjects 2 AMXT 1501 dicaprate tablets each
* Cohort 7: 2 subjects 4 placebos each; 4 subjects 4 AMXT 1501 dicaprate tablets each
* Cohort 8: 2 subjects 8 placebos each; 4 subjects 8 AMXT 1501 dicaprate tablets each

Each cohort will have a total 6 subjects: FE crossover (6 subjects receiving active AMXT 1501 dicaprate).

FE Crossover:

• Cohort 5: 6 new subjects will be randomized to a fed (n=3 standard meal) or fasted (n=3) group and administered the highest dose of AMXT 1501 dicaprate tolerated by previous cohorts. First dose and accompanying assessments will be referred to as Period 1. Subjects will then crossover to the opposite diet plan (fed or fasted) and receive a second administration of study treatment at the same dose level. The second dose and assessments are referred to as Period 2. There will be a 7-day washout between doses administered in Periods 1 and 2.

Study treatment will be provided in tablet form; each containing 128 mg AMXT 1501 dicaprate salt, 80 mg of which is AMXT 1501 freebase (active drug), plus excipients and are orally administered.

AMXT 1501

Reference Therapy, Dose and Route of Administration:

Placebo Tablets, orally administered

Placebo Oral Tablet

This is a Phase 1 study, which will assess the safety, PK, and pharmacodynamics (PD) of orally-administered AMXT 1501 dicaprate in normal healthy male volunteers.

The study is comprised of a total of 8 cohorts; 4 single ascending dose (SAD) cohorts, 1 Food Effect (FE) Crossover cohort, and 3 multiple ascending dose (MAD) cohorts. Tablets will be administered after an overnight fast (10 hours) with at least 250 mL water. No food will be administered (exception for "fed" subjects, see below) for one hour thereafter.

Each cohort will have a total 6 subjects: SAD and MAD (2 subjects receiving placebo and 4 subjects receiving active AMXT 1501 dicaprate); and FE crossover (6 subjects receiving active AMXT 1501 dicaprate).

The Phase 1 study, which will assess the safety, PK, and pharmacodynamics (PD) of orally-administered AMXT 1501 dicaprate in normal healthy male volunteers.

The study is comprised of a total of 8 cohorts; 4 single ascending dose (SAD) cohorts, 1 Food Effect (FE) Crossover cohort, and 3 multiple ascending dose (MAD) cohorts. Tablets will be administered after an overnight fast (10 hours) with at least 250 mL water. No food will be administered (exception for "fed" subjects, see below) for one hour thereafter.

Each cohort will have a total 6 subjects: SAD and MAD (2 subjects receiving placebo and 4 subjects receiving active AMXT 1501 dicaprate); and FE crossover (6 subjects receiving active AMXT 1501 dicaprate).

SAD cohorts are defined as follows:

* Cohort 1: One placebo and one AMXT 1501 dicaprate subject will be treated as sentinel subjects receiving one tablet each of their assigned treatment. Assuming no intolerance is noted after at least 3 days, the remaining cohort subjects (placebo, 1 subject and AMXT 1501 dicaprate, 3 subjects) will be treated.
* Cohort 2: 2 subjects 2 placebo each and 4 subjects 2 AMXT 1501 dicaprate tablets each
* Cohort 3: 2 subjects 4 placebos each and 4 subjects 4 AMXT 1501 dicaprate tablets each
* Cohort 4: 2 subjects 8 placebos each and 4 subjects 8 AMXT 1501 dicaprate tablets each

FE Crossover:

• Cohort 5: 6 new subjects will be randomized to a fed (n=3 standard meal) or fasted (n=3) group and administered one dose lower of the maximum tolerated AMXT 1501 dose in the previous SAD cohorts. First dose and accompanying assessments will be referred to as Period 1. Subjects will then crossover to the opposite diet plan (fed or fasted) and receive a second administration of study treatment at the same dose level. The second dose and assessments are referred to as Period 2. There will be a 7-day washout between doses administered in Periods 1 and 2.

MAD cohorts will receive dosing once daily for 14 consecutive days. Dosing will be contingent on adequate tolerance in Cohorts 1-5.

* Cohort 6: 2 subjects 2 placebos each; 4 subjects 2 AMXT 1501 dicaprate tablets each
* Cohort 7: 2 subjects 4 placebos each; 4 subjects 4 AMXT 1501 dicaprate tablets each
* Cohort 8: 2 subjects 8 placebos each; 4 subjects 8 AMXT 1501 dicaprate tablets each

The study is comprised of a total of 8 cohorts; 4 single ascending dose (SAD) cohorts, 1 Food Effect (FE) Crossover cohort, and 3 multiple ascending dose (MAD) cohorts. Tablets will be administered after an overnight fast (10 hours) with at least 250 mL water. No food will be administered (exception for "fed" subjects, see below) for one hour thereafter.

Each cohort will have a total 6 subjects: SAD and MAD (2 subjects receiving placebo and 4 subjects receiving active AMXT 1501 dicaprate); and FE crossover (6 subjects receiving active AMXT 1501 dicaprate).

If subject is given active drug or placebo is masked

Study of Orally-Administered AMXT 1501 Dicaprate in Normal Healthy Volunteers

Phase 1 Double-Blind, Placebo Controlled, Dose-Escalation Safety, Pharmacokinetic and Pharmacodynamic Study of Orally-Administered AMXT 1501 Dicaprate in Normal Healthy Volunteers

Determine the maximum feasible dose (MFD) of single and multiple doses of oral AMXT 1501 dicaprate in normal healthy volunteers.

Determine the pharmacokinetics (PK) of single and multiple doses of oral AMXT 1501 dicaprate in normal subjects, by using Area under the plasma concentration versus time curve (AUC)

Determine the pharmacokinetics (PK) of single and multiple doses of oral AMXT 1501 dicaprate in normal subjects, by using Peak Plasma Concentration (Cmax)

Assess influence of food on the PK of single doses of AMXT 1501 dicaprate, by comparing Area under the plasma concentration versus time curve (AUC)

Assess influence of food on the PK of single doses of AMXT 1501 dicaprate, by comparing Peak Plasma Concentration (Cmax)

To assess the effects of oral AMXT 1501 by testing for the appropriate level of the drug measured by the biomarker Use the biomarker test level to determine the recommended AMXT1501 Phase 2 dose.

Novella Clinical

Iqvia Pty Ltd

Aminex Therapeutics, Inc.

Immune System Diseases

Diseases and Abnormalities at or Before Birth

Neoplasm Metastasis

Immunologic Deficiency Syndromes

Primary Immunodeficiency Diseases

Syndrome

Neoplastic Processes

Genetic Diseases, Inborn

Antibodies

Immunoglobulins

Immunoglobulins, Intravenous

Adults with primary or secondary immunodeficiency for whom human immunoglobulin-assisted recombinant human hyaluronidase treatment is initiated

Data record and questionnaires passation (SF36)

Data record and questionnaires passation

Amélie SERVETTAZ

Gauthier LEJEUNE

Primary immunodeficiencies (PID) represent more than 150 diseases affecting the immune system. More than 50% of PIDs are due to a lack or an insufficiency in antibody production. Some of these immunodeficiencies as well as some secondary immune deficiency with deficient antibody production (especially in hematology and oncology) are responsible for repeated and/or severe infections, requiring long-term replacement therapy with intravenous polyclonal immunoglobulin. Intravenous replacement therapy is administered every 21 or 28 days in hospital. Subcutaneous administration (weekly or bi-weekly) can be initiated for patients who cannot tolerate intravenous infusions or who have difficult venous access. However, some patients experience a decrease in quality of life with these more frequent administration at home. A new treatment is available in France since 2017, which is a subcutaneous infusion of human immunoglobulin facilitated by recombinant human hyaluronidase (IGHy), administered every 3 to 4 weeks in a single abdominal site, at home. No direct data are available in adults to evaluate tolerance and satisfaction with this treatment, but we know it is a preferred option in children and adolescents.

The objective of the study is to describe the continuation of the human immunoglobulin-assisted recombinant human hyaluronidase (IGHy) therapy at 6 months from the start of treatment.

The secondary objectives are to evaluate the quality of life of patients treated with human immunoglobulin-assisted recombinant human hyaluronidase (IGHy) therapy.

Tolerance and Patients' Satisfaction With IGHy

Tolerance and Patients' Satisfaction of Subcutaneous Infusion of Human Immunoglobulin Facilitated by Recombinant Human Hyaluronidase for Primary or Secondary Immunodeficiency

Percentage of patients continuing IGHy treatment at 6 months

quality of life assessed by the SF-36. The Medical Outcomes Short-Form 36-Item Health Survey (SF-36v2) is a self-administered questionnaire comprising 36-items measuring eight dimensions of general HRQOL: physical functioning (10 items), role limitation due to physical health problems (4 items), bodily pain (2 items), general health perceptions (5 items), vitality (4 items), social functioning (2 items), role limitations due to emotional problems (3 items), and general mental health (5 items). In addition to scores for individual dimensions, two summary scores assessing physical and mental dimensions of health and well-being can also be calculated: Physical Component Summary (PCS) score and the Mental Component Summary (MCS) score, respectively

CHU de Reims

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Frailty

Carcinoma

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Neoplasms, Glandular and Epithelial

Ovarian Cancer

Ovarian Epithelial Cancer

Patients with ovarian cancer receiving chemotherapy as either first line treatment (i.e. newly diagnosed advanced stage III/IV cancer) or at first relapse. Patients to receive a Geriatric Assessment including interventions for functional or other identified deficits and appropriate specialist algorithm-determined interventions.

A series of 8 self-completed questionnaires for the identification of functional deficits which will be addressed via algorithm-guided interventions and assessments.

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Spots Global Cancer Trial Database for tolerance

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

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