Dosing Group 1:
- Loading dose pre chemoradiation (CRT) - 1x10^12 viral particles (vp)
Dosing Group 2:
Loading dose pre CRT - 1x10^12 vp
Maintenance dose post CRT - 1x10^12vp
Dosing Group 3:
Loading dose pre CRT - 1x10^12vp
Concurrent doses on Week 1, Day 1 and Day 5 of CRT - 1x10^12vp
Maintenance dose post CRT - 1x10^12vp
Dosing Group 4:
- Loading dose pre CRT - 3x10^12vp
Dosing Group 5:
Loading doses pre CRT - 3x10^12vp
Maintenance dose post CRT - 3x10^12vp
Dosing Group 6:
Loading dose pre CRT - 3x10^12vp
Concurrent doses on Week 1, Day 1 and Day 5 of CRT - 3x10^12vp
Maintenance post CRT - 3x10^12vp

Locally Advanced Rectal Cancer

Enadenotucirev is a live replicating oncolytic adenovirus; it is considered a BioSafety Level 1 (BSL-1) infectious substance.

Enadenotucirev

Capecitabine is a chemotherapy drug licensed for use in rectal cancer, it is a non-cytotoxic pre-cursor of the cytotoxic 5-fluorouracil. Due to Capecitabine not being taken on Enadenotucirev dosing days it is considered an investigational medicinal product within this trial.

Capecitabine

Radiotherapy

The Churchill Hospital, Oxford University Hospitals Trust

Chemoradiation With Enadenotucirev as a Radiosensitiser in Locally Advanced Rectal Cancer

A Phase 1 Trial of the Safety, Tolerability and Biological Effects of Intravenous Enadenotucirev, a Novel Oncolytic Virus, in Combination With Chemoradiotherapy in Locally Advanced Rectal Cancer

Used to determine the optimal dose and frequency of enadenotucirev that can be administered with chemoradiation. Highest treatment schedule resulting in less than 30% dose limiting toxicity rate.

Used to determine the optimal dose and frequency of enadenotucirev that can be administered with chemoradiation.
The MRI tumour regression grade uses the following scale and for the purposes of the trial analysis and dose escalation, scores of 1 or 2 will be classified as responders and scores of 3, 4 or 5 will be classified as non-responders:
- No/minimal fibrosis visible (tiny linear scar) and no tumour signal
- Dense fibrotic scar (low signal intensity) but no macroscopic tumour signal (indicates no or microscopic tumour)
- Fibrosis predominates but obvious measurable areas of tumour signal visible
- Tumour signal predominates with little/minimal fibrosis
- Tumour signal only: no fibrosis, includes progression of tumour

Treatment tolerance measured by proportion of patients completing at least 80% of the intended Capecitabine dose and at least 20 fractions of radiotherapy.

To measure local response rate to combined therapy compared to pre-treatment status
The MRI tumour regression grade uses the following scale and for the purposes of the trial analysis and dose escalation, scores of 1 or 2 will be classified as responders and scores of 3, 4 or 5 will be classified as non-responders:
- No/minimal fibrosis visible (tiny linear scar) and no tumour signal
- Dense fibrotic scar (low signal intensity) but no macroscopic tumour signal (indicates no or microscopic tumour)
- Fibrosis predominates but obvious measurable areas of tumour signal visible
- Tumour signal predominates with little/minimal fibrosis
- Tumour signal only: no fibrosis, includes progression of tumour

To measure local response rate to combined therapy compared to pre-treatment status

To measure local response rate to combined therapy compared to pre-treatment status
The Neoadjuvant Rectal (NAR) score ranges from 0-100 where a higher score equates to a worse prognosis.

Patients archival, week 4 biopsy and resection sample will be processed and stained for the presence of a hexon protein coat. This will identify the virus and allow confirmatory analysis (yes/no) to be completed to determine if the virus is only present within the tumour cells or not.

Progression free survival rates measured in patients treated with combined therapy

Loco-regional recurrence rates measured in patients treated with combined therapy

ctDNA analysis will explore the clearance of ctDNA and any/or emerging changes in persisting ctDNA

Patients archival, week 4 biopsy and resection sample will be processed using RNA sequencing to analyse whole genome RNA expression

University of Oxford

PsiOxus Therapeutics Ltd

Cancer Research UK

CEDAR is a dual escalation phase 1 trial using continual reassessment method .

The middle school assigned to the control arm will receive a visit by a mobile clinic every 6 months only. The school will follow normal protocol for HPV vaccination awareness. Parents will be made aware of the mobile clinic per normal school newsletters and mailers.

The middle school assigned to the Mobile Clinic every 6-mos or month plus Educational Sessions arm will receive visitation of a mobile clinic providing free HPV vaccination among other school-related vaccines once every 6-months or once a month. Parents will be made aware of the mobile clinic per normal school newsletters and mailers. In addition, parents will be provided with free weekly educational sessions about the HPV Vaccine as a cancer-prevention effort.

Human Papilloma Virus

HPV Vaccination

Health Education

This intervention involves the availability of a free mobile clinic operated by Cedar-Sinai Medical Center providing free HPV vaccinations at school campuses.

Mobile Clinic

This intervention involves providing free weekly educational sessions for parents of students at the participant schools pertaining to the HPV Vaccination.

Educational Sessions for Parents

Increasing HPV Vaccination Rates Via Educational Interventions in Schools Located Within Cedars-Sinai Catchment Areas

The primary outcome will be HPV-vaccination rates. Vaccination rates will be compared between baseline and intervention (12 months) between the intervention and control arms. We will conduct at least 50 educational sessions. Briefly, using a two-sided Z-test with unpooled variances with 5% significance.

Adriana Vidal

Assistant Professor

Cedars-Sinai Medical Center

University of California, Los Angeles

In this parallel study, three middle schools located in Los Angeles County will be assigned to 2 intervention arms: control (mobile clinic-only every 6-months); intervention (mobile clinic every 6-months or every month PLUS weekly educational sessions for parents).

Participants at the Schools, providers of the mobile clinic and the outcomes assessor will be masked from the allocation of participants to the arms to ensure reduction in bias.

Cancer

Matching a specific genetic abnormality (i.e. mutation) with the appropriate targeted drug.

Matched targeted drug treatment

All patients with either no identified mutation or no available matching treatment but undergoing a systemic treatment will be enrolled in the "control group."

Unmatched standard of care

Personalized Cancer Care at Cedars-Sinai Medical Center Samuel Oschin Comprehensive Cancer Institute

To evaluate the proportion of patients with response to targeted study agent(s) in patients with advanced cancers.

To evaluate the proportion of patients alive and progression free at 6 months of treatment with targeted study agent in patients with advanced cancers.

Monica Mita

Associate Professor of Medicine

A 6-week psycho-educationally-based, cognitive behavioral program to help patients with subjective cognitive complaints after cancer treatment, titled Emerging from the Haze™ (Haze). Each series meets once a week for 2-2.5 hours for 6 weeks.

Gynecologic Neoplasms

Cognition Disorders

A 6-week class designed to combat chemotherapy-induced cognitive dysfunction. Patients will report symptoms at 6 months and 1 year after the end of their Haze class.

Emerging from the Haze class

Cedars Sinai Medical Center

Emerging From the Haze for Gynecologic Cancer Survivors

A Pilot Study of Emerging From the Haze Evaluating a Trainee-taught Psycho-educational Program to Improve Cancer-related Cognitive Complaints in Gynecologic Cancer Survivors

Measure the change in score from baseline to each of three time points: last day of class (6 weeks), 6 months, and 1 year after class

To compare the impact of a trainee-taught Emerging from the Haze course on gynecologic cancer survivors' self report of cognitive changes based on change of the FACT-Cog compared to the impact of an ongoing non-trainee-taught Emerging from the Haze course on breast cancer survivors' self report of cognitive changes based on the change in FACT-Cog score from first day of class (baseline) to last day of class (6 weeks) in these two groups

Arash Asher, MD

Director of Cancer Rehabilitation and Survivorship

Participants in the intervention group will undergo 6 weeks of psycho-educational classes provided in a live setting at Cedars Sinai and a web based setting at The University of Kansas. Each class will focus on a different realm of coping with chemo-brain.

Participants assigned to the control group will be placed on a wait list for the Haze program. While they are waiting for admittance to the program, they will receive the same surveys as the participants who are taking the Haze class. Additionally, participants assigned to the control group will receive the surveys again when taking the class in order to allow comparison of the effects of the program on the control group. Participants assigned to the wait list will be enrolled in the following Haze series.

Cognition

Emerging from the Haze

Emerging From the Haze™- Measuring the Impact of a Psycho-education Program on Perceived Cognition After Breast Cancer Treatment

Emerging From the Haze™-A Multi-center, Randomized Controlled Trial to Measure Impact of a Multi-dimensional Psycho-educational Program on Subjective Cognitive Complaints After Breast Cancer Treatment Using Virtual Technology

cedrela/antitumoraal middel

Chemoradiation With Enadenotucirev as a Radiosensitiser in Locally Advanced Rectal Cancer

Increasing HPV Vaccination Rates Via Educational Interventions in Schools Located Within Cedars-Sinai Catchment Areas

Personalized Cancer Care at Cedars-Sinai Medical Center Samuel Oschin Comprehensive Cancer Institute

Emerging From the Haze for Gynecologic Cancer Survivors

Emerging From the Haze™- Measuring the Impact of a Psycho-education Program on Perceived Cognition After Breast Cancer Treatment

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