Symptoms and General Pathology

All Conditions

Nervous System Diseases

Rare Diseases

Back Pain

Pain

Neurologic Manifestations

Chronic Graft Versus Host Disease

Analgesics

All Drugs and Chemicals

Central Nervous System Depressants

Anti-Inflammatory Agents

Psychotropic Drugs

Analgesics, Opioid

Antidepressive Agents

Analgesics, Non-Narcotic

This group will consist of eligible, consenting, participants attending centers randomized to ongoing usual medical care.

This group will consist of eligible, consenting, participants attending centers randomized to ongoing usual medical care plus chiropractic care.

In both the intervention and control arms of the study, usual medical care will be defined as any and all medical care provided to patients with chronic non-cancer back or neck pain at an Ontario CHC, including: primary care provider consultation visits, prescription medication (e.g., muscle relaxants, anti-inflammatories, anti-depressants, opioid and non-opioid analgesics), referral for diagnostic testing (e.g., lab work, imaging) or specialist consultation, as well as other co-interventions (e.g., visits with nurses, dieticians, social workers, or physiotherapists) as required. All participants will also receive opioid-reduction encouragement as per each CHC's current practices. Due to socioeconomic disadvantages, most CHC patients will be unlikely to access private health care services, including chiropractic care, elsewhere. Nevertheless, the investigators will collect data on other health care utilization and conduct all analyses using an intention-to-treat principle.

Usual Medical Care

Treatment sessions may include high-velocity, low-amplitude spinal manipulative therapy, as well as any or all of the following: spinal mobilization, soft-tissue massage/trigger point therapy, education and reassurance (e.g., pain management, ergonomic and activities of daily living recommendations), and home advice (e.g., icing, spinal stretching, and core muscle strengthening exercises). Primary care providers will also engage participants in a formal collaborative effort with the chiropractic clinicians to reduce opioid use. Consistent with current clinical practice guidelines, participants will be provided up to a maximum of 12 chiropractic visits during the active care period, although participants may continue with treatment after the 8-week period (e.g., one visit, every 2-4 weeks) to manage further episodes of exacerbation/flare-up. Aside from the experimental intervention, participants in both study groups will follow the same protocol to minimize non-specific effects.

Usual Medical Care + Chiropractic Care

Peter C Emary, DC, PhD

Jason W Busse, DC, PhD

Amy L Brown, DC

The investigators will conduct a pilot cluster randomized controlled trial (RCT) of chiropractic care added to usual medical care, versus usual medical care alone, for adult patients prescribed opioid therapy for chronic non-cancer spinal pain at four community health centers (CHCs) in Ontario, Canada. These centers provide services to communities and vulnerable populations with high unemployment rates, multiple co-morbidities, and high rates of chronic musculoskeletal disorders that are commonly managed with prescription opioids.

The investigators hypothesize that a full-scale (definitive) cluster RCT on the impact of chiropractic care on prescription opioid use for chronic non-cancer spinal pain will be feasible within the Ontario CHC context.

The investigators will conduct a cluster-randomized, 2-arm, data analyst-blinded feasibility RCT at four Ontario CHCs. The CHCs will be paired on clinical characteristics (e.g., size of patient roster, geographic location), and one center from each pair will be randomized to the intervention and control groups. At each of the four centers, the investigators will recruit adult patients with active opioid prescriptions for chronic non-cancer spinal pain (minimum dose of 50 mg morphine equivalents daily) who are not currently receiving chiropractic care and are interested in reducing their opioid dose. Each center (cluster) will be allocated to provide 8 weeks of usual medical care plus chiropractic care or usual medical care alone to enrolled participants. Random cluster allocation will be performed by an investigator blinded to the intervention group assignment. To further minimize the possibility of selection bias, clusters will be identified and recruited before randomization, and all eligible (and consenting) patients in each cluster will be included. The pilot trial will be coordinated by the Methods Centre within the Department of Surgery at McMaster University.

The primary aims of this study will be to: (1) estimate recruitment rates at the individual centers, (2) explore adherence to the study protocol, (3) investigate completeness of data collection, and (4) assess the ability to follow-up participants. The investigators will incorporate qualitative methods during the pilot trial (i.e., convergent, mixed methods experimental design) to complement the feasibility measures. The investigators will also collect preliminary data on the outcomes planned for a definitive trial: opioid use, pain, disability, bothersomeness, satisfaction, other health care utilization, work status, quality of life, and adverse events at 2, 4, 8, and 12 weeks from allocation.

Cluster-randomized, 2-arm, data analyst-blinded feasibility trial

Due to the nature of the intervention, it will not be possible to blind patients, study personnel, or clinicians to treatment allocation. However, data analysts and investigators responsible for interpreting results will be blinded to treatment allocation until all data have been analyzed and interpreted.

The Effect of Chiropractic Care on Opioid Use for Chronic Spinal Pain: A Feasibility Study

Impact of Chiropractic Care on Opioid Use Among Adults With Chronic Non-Cancer Spinal Pain: A Pilot Cluster Randomized Controlled Trial

Supporting information will be made available from the Central Contact Person/Principal Investigator on reasonable request.

Study personnel will collect data on adverse events (e.g., muscle soreness, joint pain, stiffness, headache, dizziness, nausea, vomiting, constipation, radiating symptoms, paresthesia, or fatigue) at each follow-up visit and record this information in an online data capture system (REDCap Cloud). Participants will be asked: "Did you experience any side effects or problems after your last treatment visit? If yes, please specify: (check all that apply) (Pain or stiffness; Numbness/Pins and needles; Headache; Dizziness; Nausea; Vomiting; Constipation; Tiredness/Fatigue; Other, please specify: __________________)".

Recruitment rate of participants, measured as the number of eligible participants recruited (i.e., consented and enrolled) per week at each center.

Participant retention, measured as the percentage of participants successfully followed for the 12-week study period. The investigators will consider the pilot successful if at least 80% follow-up is achieved at 12 weeks for the primary definitive trial outcomes (i.e., total prescribed opioid usage, and levels of pain intensity and function as measured by the Bournemouth Questionnaire).

Participant compliance with appointment schedules, measured as the percentage of scheduled appointments attended. The investigators will consider 70% attendance to signify feasibility.

Measured as the percentage of items completed on patient-reported outcome questionnaires. The investigators will claim feasibility with 80% or greater completion of the Bournemouth and EuroQol 5 Domain (5 level version) questionnaires.

Study personnel will extract opioid prescription data from participants' individual electronic medical records to obtain the number of chronic non-cancer spinal pain-related opioid prescriptions (i.e., unique opioid fills and subsequent refills) from baseline to 12-week follow-up. Opioid dosage will be measured in milligrams (mg) of morphine equivalents daily (MED). To calculate the MED for each prescribed opioid, the investigators will multiply the quantity x the mg per unit dispensed x drug-specific conversion factors. In addition, the investigators will dichotomize opioid dosage as either high (e.g., ≥ 90 mg) MED or low (e.g., \< 90 mg) MED at baseline and each follow-up interval. The threshold for opioid dose will be dependent on the central tendency of MED in the patient sample. The investigators will also conduct a sensitivity analysis using a threshold of 50 mg MED.

The BQ consists of 7 items (i.e., pain intensity, function in activities of daily living, function in social activities, anxiety, depression levels, fear avoidance behavior, and locus of control/self-efficacy), each scored from 0-10 ("0" = no disability, "10" = complete disability) for a total of 70. To optimize interpretability, the investigators will convert mean effects to risk differences using the anchor-based minimally important difference (MID) of the BQ established for chronic low back pain patients.

Self-rated level of bothersomeness on a 5-point Likert scale from "Not at all bothersome" to "Extremely bothersome".

Self-rated satisfaction with care on a 5-point Likert scale from "Very satisfied" to "Very dissatisfied".

(a) Self-rated health status measured on 5 domains (i.e., mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), each rated on a 5-point Likert scale from "No problems" to "Extreme problems"; and (b) Self-rated health status measured on a visual analog scale from 0-100 ("0" = worst health imaginable, "100" = best health imaginable). The investigators will convert mean effects to risk differences using the anchor-based MID of the EQ-5D established for chronic low back pain patients to optimize interpretability.

Participants will be asked: "Have you sought help from any other practitioner, such as your GP \[general practitioner\] or another healthcare professional, for this present episode of your painful complaint? If yes, please specify: (check all that apply) (GP; Nurse practitioner; Nurse; Dietician; Social worker; Community health worker; Physiotherapist; Other, please specify: __________________)."

Participants will be asked: "Since starting treatment at this clinic, have you sought help from any other practitioner, such as your GP or another healthcare professional, for your complaint? If yes, please specify: (check all that apply) (GP; Nurse practitioner; Nurse; Dietician; Social worker; Community health worker; Physiotherapist; Other, please specify: __________________)."

Participants will be asked: (a) "Are you currently employed? If yes, what is your occupation: __________________. If no, are you: (please check only one answer) (Retired; Home-maker; Student; Home on doctor's advice; Unemployed; Other, please specify: __________________)"; (b) "Are you receiving any disability benefits because of your spine pain? (please check only one answer) (Yes; No, but it's possible that I will; No, but it's likely I will; No, and it's very unlikely I will)"; and (c) "Are you currently involved with a lawyer (or ongoing litigation) as a result of your spine pain? (please check only one answer) (Yes; No, but it's possible that I will; No, but it's likely I will; No, and it's very unlikely I will)".

Surgical Methods Centre, McMaster University

Michael G. DeGroote Institute for Pain Research and Care

Ontario Chiropractic Association

Alliance for Healthier Communities

Michael G. DeGroote National Pain Centre

Canadian Chiropractic Research Foundation

McMaster University

Postdoctoral fellow, Michael G. DeGroote Institute for Pain Research and Care

Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Carcinoma

Adenocarcinoma

Endometrial Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Anti-Infective Agents

Antineoplastic Agents

Hormones

Sirolimus

Anastrozole

Aromatase Inhibitors

Temsirolimus

MTOR Inhibitors

Antineoplastic Agents, Hormonal

Enzyme Inhibitors

Estrogens

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormone Antagonists

Following inclusion, patients will be randomized (2:1) to receive Arm A : AZD2014 + anastrozole Arm B : anastrozole alone

Mode of Action Selective and specific mTOR kinase inhibitor targeting both mTORC1 and mTORC2 complexes.

Route of Administration Oral

Dosage regimen 125mg BID with intermittent schedule (2 days of treatment followed by 5 days off (500mg/week))

Duration of treatment Until the patient experiences unacceptable toxicity, disease progression and/or treatment is discontinued per patient or investigator request.

AZD2014

Therapeutic Class Aromatase inhibitor

Mode of Action Potent and highly selective non-steroidal aromatase inhibitor.

Route of Administration Oral

Dosage regimen

1 mg tablet once a day

Duration of treatment Patients may continue treatment with anastrozole until the patient experiences unacceptable toxicity, disease progression and/or treatment is discontinued per patient or investigator request.

Pierre-Etienne HEUDEL, MD

The investigators hypothesize that the dual inhibition of mTORC1/mTORC2 by AZD2014 combined with inhibition of aromatase enzyme by anastrozole will act synergistically and may be an interesting therapeutic option for endometrial cancer with a manageable toxicity profile.

The investigators proposal is to conduct a multicenter, 2-step, randomized, Phase I/II trial to evaluate the safety and efficacy of a combination treatment associating anastrozole to AZD2014 in advanced endometrial cancer patients.

The study is divided in 2 steps :

* A safety run-in phase aiming to evaluate the safety of the proposed combination AZD2014 + anastrozole (Arm A) versus anastrozole alone (Arm B). No dose escalation is scheduled (doses are based on maximum tolerated dose (MTD) defined for AZD2014 and the summary of product characteristics (SPC) of anastrozole). However, dose de-escalation for AZD2014 will be applied in case of toxicity.
* A two-stage randomized Phase II part aiming to evaluate the clinical benefit of the AZD2014 + anastrozole (Arm A) combination therapy versus anastrozole (Arm B).

TREATMENT PLAN :

Following randomisation patients will receive Arm A : AZD2014 plus anastrozole or Arm B: anastrozole alone AZD2014 will be administered with an intermittent schedule i.e. 125 mg bis in die (BID) intermittent with 2 days on followed by 5 days off per week for a total weekly dose of 500 mg/week (250mg D1 and D2, 5 days off) Anastrozole will be administered at the standard dose defined in the SPC i.e. 1mg/d, per os, continuously.

Both treatment will be administered until progressive disease (PD), unacceptable toxicity or willingness to stop.

STATISTICS :

A total of 72 patients will be randomized in the study.

Safety run-in Phase on the first 9 patients randomized - As no dose escalation will be performed, the safety will be evaluated following the treatment and 8-week follow-up of the first 6 patients by the experimental association AZD2014+anastrozole (experimental arm). By similarity to a classic 3+3 design, based on binomial probabilities, there is a 90% probability of observing one or more patients with a toxicity event, if that event occurs in at least 32% of the target population. Assuming a 2:1 randomization ratio, a total of 9 patients (Arm A - Experimental: 6 patients, Arm B - Control: 3 patients) will be enrolled in this safety run-in phase and will be included in the evaluation of Phase II part.

Phase II The sample size calculation was based on a Simon optimal two-stage design, with a minimum success (8-week non progression) rate considered of interest p1=60% and an uninteresting rate p0=40%. Assuming a type I error alpha of 0.05 and 80% power, 46 evaluable patients are needed in the experimental arm to reject the null hypothesis H0: p≤p0 versus the alternative hypothesis H1: p ≥ p1 in a unilateral situation (16 patients in Stage I and 30 additional patients in Stage II).

With a 2:1 randomization and based on the assumption that 5% of the patients may be non-evaluable, a total of 72 patients will be included in the study : 48 patients in Arm A - experimental and 24 patients in Arm B - control).

DATA ENTRY, DATA MANAGEMENT AND STUDY MONITORING All the data concerning the patients will be recorded in the electronic case report form (eCRF) throughout the study. serious adverse event (SAE) reporting will be also paper-based by e-mail and/or Fax.

The sponsor will perform the study monitoring and will help the investigators to conduct the study in compliance with the clinical trial protocol, Good Clinical Practices (GCP) and local law requirements.

Hormone Receptor Positive endometrIal Carcinoma Treated by Dual mTORC1/mTORC2 Inhibitor and Anastrozole (VICTORIA)

A Multicentric, Randomized, Non Comparative, Open-label Phase I/II Evaluating AZD2014 (Dual Mammalian Target of Rapamycin Complex 1/2 (mTORC1/mTORC2) Inhibitor) in Combination With Anastrozole Versus Anastrozole Alone in the Treatment of Metastatic Hormone Receptor-positive Endometrial Adenocarcinoma

Severe toxicities defined as

* Any grade ≥ 4 treatment related toxicity
* Any grade≥ 3 treatment related toxicity lasting more than 7 days

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
The Effect of Chiropractic Care on Opioid Use for Chronic Spinal Pain: A Feasibility Study	NCT06160947	Back Pain	Usual Medical C... Usual Medical C...	18 Years -	McMaster University
Hormone Receptor Positive endometrIal Carcinoma Treated by Dual mTORC1/mTORC2 Inhibitor and Anastrozole (VICTORIA)	NCT02730923	Endometrial Car... Metastatic Carc... Hormone Recepto...	AZD2014 Anastrozole	18 Years -	Centre Leon Berard

Spots Global Cancer Trial Database for clinical trials, randomized