Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Bone Density Conservation Agents

Channel Blockers

All Drugs and Chemicals

Risedronic Acid

Calcium

Calcium Channel Blockers

Calcium, Dietary

Hormones

Risedronate 150 mg given once 7-21 days prior to initiation of SBRT

Matching placebo, dose not applicable given once 7-21 days prior to initiation of SBRT

Risedronate 150 mg Oral Given once 7 - 21 days prior to initiation of SBRT

risedronate

Dose not applicable, given once 7-21 days prior to initiation of SBRT

Matching placebo

Michael Farris, MD

This is a double blind randomized controlled study investigating the efficacy of a single dose of 150 mg risedronate (a bone anti-resorptive) vs a single dose of placebo given prior to SBRT for peripheral lung tumors that are within 2 cm of the chest wall. Our hypothesis is that the use of a single dose of 150 mg risedronate will eliminate or greatly reduce the rapid bone loss that occurs with radiation induced early osteoclast recruitment/activation.

Patients will be given either a single dose of 150 mg risedronate or placebo at the time of their treatment mapping "simulation" CT scan. Typically, radiation treatments begin at 1 - 3 weeks following this mapping scan, as each treatment plan requires detailed physics calculations and quality assurance checks.

All CT imaging referenced below is performed as a routine standard of care surveillance and is necessary for cancer treatment follow-up. These chest CT scans that are utilized in this research protocol would be performed every 3 months regardless of inclusion on this trial.

2.1 Primary Objective(s)

The primary objective is to assess the percent change in bone mean cortical thickness within regions of bone receiving 30 Gy or more at 3 months after SBRT. The % change in mean cortical thickness will be compared between patients who received risedronate and those who received placebo.

2.2 Secondary Objective(s)

In addition to the primary objective, the investigators will further analyze the remaining routine follow-up chest CT scans, for mean cortical thickness change in regions of bone that received 0 - 10 Gy, \>10 - 20 Gy, \> 20 - 30 Gy, \> 30 - 40 Gy, and \> 40 Gy at all time points including 3 months, 6 months, 9 months, and 12 months. These scans are standard of care and would be performed regardless of inclusion on this trial. This will allow us to determine the potential persistence of effects from SBRT and bisphosphonate use.

The investigators will assess and compare the incidence and grade (per modified CTCAE v.5) of radiation induced chest wall pain within the radiation treatment portal (within the 50% isodose line) at time of each routine follow up visit (3 months, 6 months, 9 months, and 12 months post SBRT). The purpose of utilizing a placebo and double-blind design is that chest wall pain is a subjective finding. Furthermore, it is unclear if chest wall pain from radiation is directly due to bone damage, nerve damage, muscle irritation, or a combination of all of these factors. The use of placebo will help us reduce the potential for bias in pain assessment.

The investigators will assess and compare the incidence of rib and vertebral fractures (as noted on CT imaging) that occur within 12 months of irradiation and are within the radiation treatment field. The radiation treatment field will be defined as within the 50% isodose line.

The urine concentration of an osteoclast-specific biomarker, urinary N-telopeptide (NTX) indicating osteoclast activity will be assessed prior to SBRT and at each routine follow up visit (at 3 months, 6 months, 9 months, and 12 months post SBRT).

Prophylactic Risedronate for Patients With Peripheral Lung Tumors Treated With SBRT

A Randomized Clinical Trial of Prophylactic Risedronate for Patients With Peripheral Lung Tumors Treated With SBRT

The primary outcome measure is the percent change in mean cortical thickness (C.Th) of bones receiving 30 Gy or more at 3 months post SBRT, when compared to pre-SBRT cortical thickness

The percent change in mean C.Th of bones will be assessed in regions of bone that received 0 - 10 Gy, \>10 - 20 Gy, \> 20 - 30 Gy, \> 30 - 40 Gy, and \> 40 Gy at all time points including 3 months, 6 months, 9 months, and 12 months.

Chest wall pain incidence and grade will be collected as per modified CTCAE v. 5 within the within the 50% isodose line. Appendix K. Below we report numbers with any chest wall pain of grades 3+ over the year of followup.

Incidence of rib and vertebral fractures (as noted on CT imaging) that occur within 12 months of irradiation and are within the within 50% isodose line.

The urine concentration of an osteoclast-specific biomarker, urinary N-telopeptide (U-NTX) indicating osteoclastic activity will be assessed prior to SBRT and at each routine follow up visit (at 3 months, 6 months, 9 months, and 12 months post SBRT).

National Cancer Institute (NCI)

Wake Forest University Health Sciences

Risedronate 150 mg given once 7-21 days prior to initiation of SBRT

risedronate: Risedronate 150 mg Oral Given once 7 - 21 days prior to initiation of SBRT

Risedronate

Matching placebo, dose not applicable given once 7-21 days prior to initiation of SBRT

Matching placebo: Dose not applicable, given once 7-21 days prior to initiation of SBRT

Matching Placebo

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Biostatistician

A small number of participants who were enrolled were not able to have cortical thickness determined at 3 months.

Changes in Mean Cortical Thickness

% change cort thickness in region <10 Gy--time 3mo to bl

% change cort thickness in region <10 Gy--time 6mo to bl

% change cort thickness in region <10 Gy--time 9mo to bl

% change cort thickness in region <10 Gy--time 12mo to bl

% change cort thickness in region 10-20 Gy--time 3mo to bl

% change cort thickness in region 10-20 Gy--time 6mo to bl

% change cort thickness in region 10-20 Gy--time 9mo to bl

% change cort thickness in region 10-20 Gy--time 12mo to bl

% change cort thickness in region 20-30 Gy--time 3mo to bl

% change cort thickness in region 20-30 Gy--time 6mo to bl

% change cort thickness in region 20-30 Gy--time 9mo to bl

% change cort thickness in region 20-30 Gy--time12mo to bl

% change cort thickness in region 30-40 Gy--time 3mo to bl

% change cort thickness in region 30-40 Gy--time 6mo to bl

% change cort thickness in region 30-40 Gy--time 9mo to bl

% change cort thickness in region 30-40 Gy--time12mo to bl

% change cort thickness in region >30 Gy--time 3mo to bl

% change cort thickness in region >30 Gy--time 6mo to bl

% change cort thickness in region >30 Gy--time 9mo to bl

% change cort thickness in region >30 Gy--time 12mo to bl

% change cort thickness in region >40 Gy--time 3mo to bl

% change cort thickness in region >40 Gy--time 6mo to bl

% change cort thickness in region >40 Gy--time 9mo to bl

% change cort thickness in region >40 Gy--time 12mo to bl

A small number of participants did not have follow-up cortical thickness measures.

4 Time Points Assessing Change in Mean Cortical Thickness of Bones

Some participants did not have sufficient self-reported symptom pain data to determine if, over course of 12 months, they had any chest wall pain of grade 3 or higher

Number of Participants With Chest Wall Pain

For a small number of participants it was not possible to determine clearly if a fracture had occurred within 12 months.

Number of Participants With Rib and Vertebral Fracture

Urinary NTX values at BL

Urinary NTX values at 3mo

Urinary NTX values at 6mo

Urinary NTX values at 9mo

Urinary NTX values at 12mo

A small number of participants did not have urine samples analyzed.

Urine Concentration at 4 Time Points

Overall Study

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Immune System Diseases

Rare Diseases

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Hypersensitivity

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

Neoplasms by Histologic Type

Ovarian Cancer

Ovarian Epithelial Cancer

Antineoplastic Agents

Olaparib

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

AZD2281

matching placebo

Mika Sovak, BSc, MBCHB, MD

Prof Jonathan A Lederman

The primary purpose of this study to determine if AZD2281 is effective and well tolerated in maintaining the improvement in your cancer after previous platinum-based chemotherapy

Assessment of Efficacy of AZD2281 in Platinum Sensitive Relapsed Serous Ovarian Cancer

Phase II Randomised, Double Blind, Multicentre Study to Assess the Efficacy of AZD2281 in the Treatment of Patients With Platinum Sensitive Relapsed Serous Ovarian Cancer Following Treatment With Two or More Platinum Containing Regimens

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

PFS was defined as the time from randomisation to the earlier date of radiological progression (per RECIST criteria) or death by any cause in the absence of objective progression. \[Full analysis set (FAS)\]

OS = time from randomisation to date of death from any cause. Patients who had not died at time of analysis were censored at last date patient was known to be alive.

For each treatment group, the ORR was the number of Complete Response (CR) and Partial Response (PR) divided by the number of patients in the group in the FAS with measurable disease at baseline (displayed as a percentage below). Evaluable for response set

Disease control rate was defined as the percentage of patients who have at least 1 confirmed visit response of CR or PR or have demonstrated SD or NED for at least 23 weeks (ie, 24 weeks +/- 1 week) prior to any evidence of progression. \[FAS\]

Duration of response = time from assessment prior to timepoint where PR or CR confirmed (i.e. initial assessment of PR/CR), until earliest date of objective progression or death. \[Responding patients only\]. There were insufficient responses to enable conclusions to be drawn.

Percentage change from baseline to Week 24 in target tumour size.

Best percentage change from baseline in CA-125 level

Best overall response from radiologic assessments. \[FAS\]

RECIST and CA-125 response separately and combined \[Patients evaluable for either CA-125 response or RECIST response\]

Time from randomisation to the earlier date of radiological progression (per RECIST criteria) or CA-125 or death by any cause in the absence of objective progression. \[FAS\]

The percentage of patients with an improvement in FOSI. Improvement was defined as a change from baseline of greater than or equal to +3. \[Evaluable for FOSI set\]

The percentage of patients with an improvement in TOI. Improvement was defined as a change from baseline of greater than or equal to +7. \[Evaluable for TOI set\]

The percentage of patients with an improvement in total FACT-O. Improvement was defined as a change from baseline of greater than or equal to +9. \[Evaluable for FACT-O set\]

The time to worsening was compared between treatments for each of the TOI, FOSI and total FACT-O. \[Evaluable for FOSI set\]

The time to worsening was compared between treatments for each of the TOI, FOSI and total FACT-O. \[Evaluable for TOI set\]

The time to worsening was compared between treatments for each of the TOI, FOSI and total FACT-O. \[Evaluable for FACT-O set\]

AstraZeneca

128 participants in Placebo as 1 participant withdrew consent prior to treatment

Olaparib 400 mg bd

Placebo

AZD2281 olaparib (AZD2281) 400 mg oral capsules twice daily

olaparib matching placebo oral capsules twice daily

Placebo bd

>6 to 12 months

>12 months

The time to disease progression from the completion of the penultimate platinum containing therapy (last dose) prior to enrolment on the study.

Time to progression

Complete response

Partial response

Objective response to the last platinum containing regimen prior to enrolment on the study:

* CR-Complete Response (defined as normal radiological findings and CA-125 within the normal range)
* PR-Partial Response (defined as a RECIST PR and/or GCIG CA-125 response)

Objective response

For OM DoR: The subset of patients evaluable for response who responded to study treatment.Values in results table may be under-estimates as some patients had not progressed at final analysis,so true duration is likely to be greater than in database.

Global Clinical Lead

Progression Free Survival (PFS) (According to Response Evaluation Criteria in Solid Tumours [RECIST])

Overall Survival (OS)

Evaluable for response set - A subset of the full analysis set which includes patients with measurable disease at baseline

Objective Response Rate (ORR) (According to RECIST)

Disease Control Rate

Duration of Response

Evaluable for response set - A subset of the full analysis set which includes patients with measurable disease at baseline.

Percentage Change From Baseline in Tumour Size at Week 24

A subset of the FAS with baseline and at least 1 follow-up value of CA-125

Best Percentage Change in Cancer Antigen 125 (CA-125) Levels

Complete Response

Partial Response

No evidence of disease

Stable Disease >= 11 weeks

Disease Progression

Not Evaluable

Best Objective Response

RECIST Response

Confirmed RECIST Response

Unconfirmed RECIST response

CA-125 Response

Confirmed RECIST or CA-125 Response

RECIST and CA-125 Response Separately and Combined

Time to Earlier of CA-125 or RECIST Progression

Evaluable for FOSI set - A subset of the full analysis set which includes patients who have evaluable QoL/Symptom Endpoints at baseline

Improvement Rate for FACT-O Symptom Index (FOSI)

Evaluable for TOI - a subset of the full analysis set which includes patients who have evaluable QoL/Symptom Endpoints at baseline

Improvement Rate for Trial Outcome Index (TOI)

Evaluable for Total Fact-O set - A subset of the full analysis set which includes patients who have evaluable QoL/Symptom Endpoints at baseline

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Prophylactic Risedronate for Patients With Peripheral Lung Tumors Treated With SBRT	NCT03861091	Lung Neoplasm	risedronate Matching placeb...	18 Years -	Wake Forest University Health Sciences
Assessment of Efficacy of AZD2281 in Platinum Sensitive Relapsed Serous Ovarian Cancer	NCT00753545	Ovarian Cancer	AZD2281 matching placeb...	18 Years - 130 Years	AstraZeneca
Cervical Intraepithelial Neoplasm (CIN) in Women (Gardasil) (V501-015)	NCT00092534	Cervical Cancer Genital Warts	Gardasil, human... Matching Placeb...	16 Years - 23 Years	Merck Sharp & Dohme LLC
A Clinical Study of Hetrombopag Olamine Tablets in Adults Receiving 21-day Cycles of Chemotherapy for Solid Tumours, Who Are Delayed for at Least 1 Week From Their Scheduled Cycle Because of Chemotherapy-induced Thrombocytopenia	NCT05261646	Chemotherapy-In...	Hetrombopag Matching placeb...	18 Years -	Jiangsu HengRui Medicine Co., Ltd.
Avatrombopag vs. Placebo for CIT in GI Malignancies	NCT05772546	Gastrointestina... Gastrointestina... Chemotherapy-In...	Avatrombopag Matching Placeb...	18 Years -	Massachusetts General Hospital
Avatrombopag vs. Placebo for CIT in GI Malignancies	NCT05772546	Gastrointestina... Gastrointestina... Chemotherapy-In...	Avatrombopag Matching Placeb...	18 Years -	Massachusetts General Hospital
Study of Vorasidenib (AG-881) in Participants With Residual or Recurrent Grade 2 Glioma With an IDH1 or IDH2 Mutation (INDIGO)	NCT04164901	Grade 2 Glioma Residual Glioma Recurrent Gliom...	Vorasidenib Matching Placeb...	12 Years -	Servier
Avatrombopag vs. Placebo for CIT in GI Malignancies	NCT05772546	Gastrointestina... Gastrointestina... Chemotherapy-In...	Avatrombopag Matching Placeb...	18 Years -	Massachusetts General Hospital
Assessment Of Dutasteride (AVODART) In Extending The Time To Progression Of Low-Risk, Localized Prostate Cancer In Men	NCT00363311	Neoplasms, Pros...	Dutasteride Matching placeb...	50 Years - 80 Years	GlaxoSmithKline
D9319C00001- 1L OC Mono Global RCT	NCT04884360	Ovarian Cancer	Olaparib Matching placeb...	18 Years -	AstraZeneca
Prophylactic Risedronate for Patients With Peripheral Lung Tumors Treated With SBRT	NCT03861091	Lung Neoplasm	risedronate Matching placeb...	18 Years -	Wake Forest University Health Sciences

Spots Global Cancer Trial Database for matching placebo