Neoplasms

All Conditions

Symptoms and General Pathology

Infections

Respiratory Tract (Lung and Bronchial) Diseases

Carcinoma

Carcinoma, Squamous Cell

Recurrence

Influenza, Human

Head and Neck Neoplasms

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

All Drugs and Chemicals

Vasodilator Agents

Urological Agents

Vaccines

Poly ICLC

Tadalafil

Immunologic Factors

Phosphodiesterase 5 Inhibitors

Phosphodiesterase Inhibitors

Enzyme Inhibitors

The first 6 participants will be enrolled in the open label Phase I portion of the study and will receive Tadalafil, Anti-mucin 1 (MUC1) Vaccine and the Anti-Influenza Vaccine for 5 courses. A standard of care (SOC) tumor removal surgery will be completed after the completion of Course 1. Course 2 will resume 5-8 weeks after completion of SOC tumor removal surgery.

After completion of the Phase I portion of the study, new participants will be enrolled for the randomized, placebo-controlled Phase II. Participants randomized in this group will receive Tadalafil, Anti-MUC1 Vaccine and the Anti-Influenza Vaccine for 5 courses. A standard of care (SOC) tumor removal surgery will be completed after the completion of Course 1. Course 2 will resume 5-8 weeks after completion of SOC tumor removal surgery.

After completion of the Phase I portion of the study, new participants will be enrolled for the randomized, placebo-controlled Phase II. Participants randomized in this group will receive Tadalafil, placebo for the Anti-MUC1 Vaccine and placebo for the Anti-Influenza Vaccine for 5 courses. A standard of care (SOC) tumor removal surgery will be completed after the completion of Course 1. Course 2 will resume 5-8 weeks after completion of SOC tumor removal surgery.

After completion of the Phase I portion of the study, new participants will be enrolled for the randomized, placebo-controlled Phase II. Participants randomized in this group will receive placebo for Tadalafil, the Anti-MUC1 Vaccine and the Anti-Influenza Vaccine for 5 courses. A standard of care (SOC) tumor removal surgery will be completed after the completion of Course 1. Course 2 will resume 5-8 weeks after completion of SOC tumor removal surgery.

For eligible participants who opt out of receiving study intervention. Participants in this group will receive SOC treatment only.

Tadalafil tablets administered by mouth. Dose will be between 10 to 20 mg adjusted depending on patient's body weight. On course 1, Tadalafil will be administered daily for 19 consecutive days. On Course 2 through 4, Tadalafil will be administered daily for 14 consecutive days. No Tadalafil will be provided on Course 5.

300 uL Anti-MUC1 vaccine will be administered intramuscularly in the right upper limb. Anti-MUC1 vaccine will be administer on Day 7 on course 1, on Day 10 for courses 2 through 4 and on Day 1 on course 5.

Anti-MUC1 Vaccine

300 uL Anti-Influenza vaccine will be administered intramuscularly in the left upper limb. Anti-Influenza vaccine will be administer on Day 7 on course 1, on Day 10 for courses 2 through 4 and on Day 1 on course 5.

Anti-Influenza Vaccine

Placebo tablets mimicking Tadalafil administered by mouth. On course 1, Tadalafil Placebo will be administered daily for 19 consecutive days. On Course 2 through 4, Tadalafil placebo will be administered daily for 14 consecutive days. No Tadalafil Placebo will be provided on Course 5.

Tadalafil Placebo

Placebo for Anti-MUC1 vaccine will be administered intramuscularly in the right upper limb. Placebo for Anti-MUC1 vaccine will be administer on Day 7 on course 1, on Day 10 for courses 2 through 4 and on Day 1 on course 5..

Anti-MUC1 Vaccine Placebo

Treatment according to prescribed standard of care regimen.

Standard of Care Treatment

Placebo for Anti-Influenza vaccine will be administered intramuscularly in the left upper limb. Placebo for Anti-Influenza vaccine will be administer on Day 7 on course 1, on Day 10 for courses 2 through 4 and on Day 1 on course 5.

Anti-Influenza Vaccine Placebo

Donald T Weed, MD, FACS

The investigators hypothesize that Tadalafil treatment, by lowering Myeloid Derived Suppressor Cells (MDSCs) and regulatory T cells (Tregs), can prime an antitumor immune response and promote a permissive environment that should increase the efficacy of anti-tumor vaccine in a setting of minimal residual disease.

This study is halting accrual at the end of the phase 1 portion of the study as data from the phase I study suggest that an alternative approach for the phase 2 portion of the study be undertaken. A newly designed Phase II trial is being developed and will be submitted as a new study protocol.

PDE5 Inhibition Via Tadalafil to Enhance Anti-Tumor Mucin 1 (MUC1) Vaccine Efficacy in Patients With HNSCC

PDE5 Inhibition Via Tadalafil (Cialis®) to Enhance Anti-Tumor MUC1 Vaccine Efficacy in Patients With Resectable, and Recurrent or Second Primary Head and Neck Squamous Cell Carcinoma (HNSCC): A Phase I/II Clinical Trial

The primary objective of the lead-in, open-label, single-arm, phase I part of study will evaluate the safety of Tadalafil in combination with anti-MUC1/anti-influenza vaccines (TV) in terms of adverse events (AEs), serious adverse events (SAEs) and treatment-limiting toxicities (TLTs).

The primary objective of phase II is to evaluate immune response (tumor-specific immune response of the anti- MUC1 and anti-influenza vaccines when combined with Tadalafil. Immune response will be evaluated by determining patients' immunological profile (e.g. peripheral blood mononuclear cells (PBMCs), leukocyte subsets, and serum cytokine levels) and immunological reactivity (e.g. through DTH skin test, T cell proliferation, by Enzyme-Linked ImmunoSpot (ELISPOT), specific Immunoglobulin G (IgG) concentration, and immune response by peripheral blood sera) before and after surgery, and during treatment with Tadalafil and the anti-MUC1 and anti-Influenza vaccines.

Immune response will be evaluated by determining patients' immunological profile (e.g. peripheral blood mononuclear cells (PBMCs), leukocyte subsets, and serum cytokine levels) and immunological reactivity (e.g. through DTH skin test, T cell proliferation, by ELISPOT, specific IgG concentration, and immune response by peripheral blood sera) before and after surgery, and during treatment with Tadalafil and the anti-MUC1 and anti-Influenza vaccines.

The rate of recurrence-free survival (RFS) in patients with recurrent or second primary HNSCC after salvage surgery. RFS is defined as the time from date of Surgery to the date of first documented recurrence. All patients will be rendered disease free (i.e. no measurable disease) after surgery, thus any confirmed evidence of disease recurrence regardless of size or site will constitute the recurrence time point. Recurrence will be demonstrated by clinical assessments such as clinical examinations and tumor assessments (possibly) by CT, PET/CT or MRI.

Donald T. Weed, MD, FACS

Professor

Digestive System Diseases

Rare Diseases

Esophageal Neoplasms

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Vaccinia

Adenoviridae Infections

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Esophageal Diseases

Esophageal Cancer

Antineoplastic Agents

Immune Checkpoint Inhibitors

Immunomodulating Agents

Six evaluable patients will receive the trial vaccines with standard of care treatment to confirm they are safe before opening the next stage of the trial. These patients will not be randomised.

Approximately 40 patients will be randomised to receive the trial vaccines with standard of care treatment in this arm.

Approximately 40 patients will be randomised to receive standard of care treatment alone in this arm.

Approximately 17 patients with squamous oesophageal cancer will received the trial vaccines with standard of care treatment

Patients commence their Standard of Care (SoC) chemotherapy in combination with an immune checkpoint inhibitor in 3 weekly cycles. Patients are screened during the first 2 cycles of SoC treatment to confirm eligibility for the trial.

Patients who receive trial vaccines (safety run in stage, Arm A of the NSCLC randomisation cohort and Squamous Oesophageal Cancer Cohort) continue to receive their SoC treatment plus:

* First prime ChAdOx1-MAGEA3-NYESO vaccine on Cycle 3 Day 1 of SoC treatment.
* First boost MVA-MAGEA3 vaccine, and if applicable a first boost MVA-NYESO vaccine, 21 days later.
* For patients who have not progressed: second prime ChAdOx1-MAGAEA3-NYESO vaccine 15 weeks following first prime vaccine
* Second boost MVA-MAGAE3 vaccine, and if applicable a second boost MVA-NYESO vaccine, 21 days following second prime vaccine

Patients in Arm B of the NSCLC randomisation cohort will continue to receive their SoC treatment only throughout the trial (i.e. no trial vaccines)

ChAdOx1-MAGEA3-NYESO

MVA-MAGEA3

Patients will continue to receive standard of care treatment (chemotherapy and checkpoint inhibitor).

Standard of care treatment

MVA-NYESO

Fiona Blackhall, Prof

This clinical trial is looking at two new vaccines called ChAdOx1-MAGEA3-NYESO, MVA-MAGEA3 and MVA-NYESO given with patients' standard of care treatment (chemotherapy and an immune checkpoint inhibitor).

Patients with non-small cell lung cancer (NSCLC), or squamous oesophageal cancer will be entered into the trial as these tumour types are commonly known to have MAGE-A3 and NY-ESO-1 proteins on their cancer cells. The vaccines contain harmless parts of these proteins allowing them to show these proteins to the immune system. It is expected the immune system will 'learn' that these proteins are foreign to the body. The immune system should then attack the proteins on the cancer cells, killing them. It is expected the vaccines will help the chemotherapy and immune checkpoint inhibitor to work better.

This is a first-in-human clinical trial which has two stages:

* A 'safety run in' stage where six evaluable patients will receive the trial vaccines with standard of care treatment to confirm they are safe before opening the next stage.
* A 'rolling recruitment' stage consisting of two cohorts:

  1. NSCLC Randomisation Cohort of approximately 80 patients with NSCLC will be randomly allocated by computer (randomised) to one of two groups (arms). Patients in Arm A will receive the vaccines with their standard of care treatment and patients in Arm B will continue with their standard of care treatment and patients in Arm B will continue with their standard of care treatment alone. There is a 1 in 2 chance patients will receive the vaccines.
  2. Squamous Oesophageal Cancer Cohort: Approximately 17 patients with squamous oesophageal cancer will be recruited to receive trial vaccines with their standard of care treatment.

The main aims of the trial are to find out:

* More about potential side effect of the vaccine and how they can be managed.
* Whether the vaccines with standard of care treatment are better at shrinking NSCLC than just the standard of care treatment alone.
* What happens to the vaccines inside the body.

A Trial of ChAdOx1 and MVA Vaccines Against MAGE-A3 and NY-ESO-1

A Cancer Research UK Phase I/IIa Trial of Chimpanzee Adenovirus Oxford 1 (ChAdOx1) and Modified Vaccinia Ankara (MVA) Vaccines Against MAGE-A3 and NY-ESO-1 With Standard of Care Treatment (Chemotherapy and an Immune Checkpoint Inhibitor)

Individual de-identified participant data that underlie the results reported on a publicly accessible database (text, figures, tables and supplementary information) and the final clinical study protocol and statistical/reporting analysis plan/participant information sheet will be shared with CRUK funded/ employed researchers whose proposed use of the data is approved by a review committee of CDD. All requests made within 5 years from the end of trial will be considered; requests made subsequently will be considered where possible. Data sharing requests should be sent to: drugdev@cancer.org.uk.

Incidence of adverse events (AEs) (including injection site reactions and toxicity), including relatedness, seriousness and severity (graded according to the National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0.

PFS (in months) will be assessed as time from Cycle 3 Day 1 of SoC treatment to the date of disease progression. using RECIST and immune RECIST (iRECIST).

ORR will be reported as the number of randomised patients who have achieved a complete response or partial response.

OS (in months) will be assessed as time from Cycle 3 Day 1 of SoC treatment to the date of death from any cause.

Percentage of patients showing peripheral immune response. Immunological response will be measured in patient blood by antigen-specific T cells by ex vivo ELISpot assay.

Barinthus Biotherapeutics

Cancer Research UK

Skin and Connective Tissue Diseases

Breast Neoplasms

Triple Negative Breast Neoplasms

Breast Diseases

Skin Diseases

Capecitabine

Participants will be administered adagloxad simolenin combined with OBI-821 for up to a total of 21 subcutaneous injections over a period of 100 weeks.

Patient will also receive standard of care (SOC) treatment.

Study visit intervals will be identical to those in Arm 1.

Patient will receive standard of care (SOC) treatment.

In the neoadjuvant and adjuvant phases of the study for a total of 100 weeks; subcutaneously injections.

adagloxad simolenin combined with OBI-821

The Globo H IHC assay will be used to identify eligible patients who may clinically benefit from the OBI-822 treatment, defined by Globo H expression.

Globo H IHC Assay

Standard of care treatment consisting of observation alone, adjuvant capecitabine or platinum monotherapy over a 100 week period.

OBI Pharma CT.gov Assistant

OBI Investigator Site

Hope Rugo, MD

The GLORIA study is a Phase III, randomized, open-label study to prospectively evaluate the efficacy and safety of adagloxad simolenin (OBI 822)/OBI-821 in the adjuvant treatment of patients with high risk, early stage Globo-H Positive TNBC.

Study of Adagloxad Simolenin (OBI-822)/OBI-821 in the Adjuvant Treatment of Patients With Globo H Positive TNBC

The GLORIA Study: A Phase 3, Randomized, Open-Label Study of the Anti-Globo H Vaccine Adagloxad Simolenin (OBI-822)/OBI-821 in the Adjuvant Treatment of Patients With High Risk, Early Stage Globo H-Positive Triple Negative Breast Cancer

The outcome measure of the study is IDFS, defined by the STEEP system as the first occurrence of the time from the date of randomization to the date of first invasive disease recurrence (local, regional or distant), the date of secondary primary invasive cancer (breast or not), or the date of death from any cause.

OS is defined as the time from randomization to date of death from any cause

QoL defined as time to definitive deterioration in Health-related Quality of Life (HRQOL) using the global health status/QoL scale from European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30) and the European Quality of Life 5 Dimensions 5 Levels (EQ-5D-5L). QoL baseline established at randomization.

Definitive deterioration defined as a 5% worsening relative to baseline in the HRQOL scale score from EORTC QLQ-C30 questionnaires with no subsequent improvement above threshold, scored with the EORTC QLQ-C30 v3.0 Scoring Manual. The EQ-5D-5L questionnaire assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression, rated by the patient. It is a standardized measure of health status to provide a simple, generic measure of health for clinical and economic appraisal. 28 questions have a 4 point scale: not at all(1) to very much(4). 2 questions have a 7-point scale: very poor (1) to excellent(7).

BCFI is defined by the STEEP system as the first occurrence of the time from the date of randomization to the date of the first invasive disease recurrence (local, regional or distant), the date of ductal carcinoma in situ (ipsilateral or contralateral), or the date of death from breast cancer

DDFS is defined by the STEEP system as the first occurrence of the time from the date of randomization to the date of the first distant disease recurrence, the date of the second primary invasive cancer (non-breast), or the date of death from any cause

Adverse Events will be graded and recorded by investigators per National Cancer Institute-Common Terminology Criteria for Adverse Events version 5.0 (NCI-CTCAE v5.0).

OBI Pharma, Inc

Neoplasm Metastasis

Neoplasms, Second Primary

Neoplastic Processes

Patient treatment may include the following 3 options, at the discretion of the treating physicians:

* Continue with current systemic agent(s)
* Observation
* Switch to next-line treatment

SABR is delivered to all sites of progressive disease with continuation of current systemic agents. Further oligo-progressive lesions may be treated with SABR if possible. Upon progression at sites not amenable to SABR, the patient may receive any of the options in Arm 1.

Patients will receive stereotactic ablative radiotherapy to all sites of progressive disease, with continuation of current systemic agents.

Stereotactic Ablative Radiotherapy (SABR)

May include:

* Continue with current systemic agent(s)
* Observation
* Switch to next-line treatment

Palliative radiotherapy is allowed in this arm.

A multicenter randomized phase II trial of stereotactic body radiotherapy for oligo-progressive metastatic cancers. Eligible patients will be randomized in a 1:2 ratio between receiving their standard of care therapy or stereotactic ablative radiotherapy (SABR) to all sites of oligo-progressive lesions.Radiotherapy will be administered as soon as possible following randomization, and subjects will be followed until next disease progression. The primary outcome is progression-free survival (PFS).

Stereotactic Radiotherapy for Oligo-Progressive Metastatic Cancer (The STOP Trial)

Stereotactic Radiotherapy for Oligo-Progressive Metastatic Cancer (The STOP Trial): A Randomized Phase II Trial

Progression-Free Survival is defined as the time from randomization to progression of disease or death from any cause

Overall survival is defined as they time from randomization to death from any cause

Quality of life in domains of physical, social/family, emotional, and functional well-being will be assessed with the Functional Assessment of Cancer Therapy (FACT-G)

Toxicity related to radiation treatment will be assessed by the National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 4 for each organ treated (i.e. liver, lung, bone)

Local control rate of lesions treated with SABR

Sites of progressive disease after SABR are captured in follow up

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
PDE5 Inhibition Via Tadalafil to Enhance Anti-Tumor Mucin 1 (MUC1) Vaccine Efficacy in Patients With HNSCC	NCT02544880	Head and Neck S... Head and Neck C...	Tadalafil Anti-MUC1 Vacci... Anti-Influenza ... Tadalafil Place... Anti-MUC1 Vacci... Standard of Car... Anti-Influenza ...	18 Years -	University of Miami
A Trial of ChAdOx1 and MVA Vaccines Against MAGE-A3 and NY-ESO-1	NCT04908111	Non-small Cell ... Esophageal Neop...	ChAdOx1-MAGEA3-... MVA-MAGEA3 Standard of car... MVA-NYESO	18 Years -	Cancer Research UK
Study of Adagloxad Simolenin (OBI-822)/OBI-821 in the Adjuvant Treatment of Patients With Globo H Positive TNBC	NCT03562637	Triple Negative...	adagloxad simol... Globo H IHC Ass... Standard of car...	18 Years -	OBI Pharma, Inc
Stereotactic Radiotherapy for Oligo-Progressive Metastatic Cancer (The STOP Trial)	NCT02756793	Metastatic Canc...	Stereotactic Ab... Standard of Car...	18 Years -	Lawson Health Research Institute
PDE5 Inhibition Via Tadalafil to Enhance Anti-Tumor Mucin 1 (MUC1) Vaccine Efficacy in Patients With HNSCC	NCT02544880	Head and Neck S... Head and Neck C...	Tadalafil Anti-MUC1 Vacci... Anti-Influenza ... Tadalafil Place... Anti-MUC1 Vacci... Standard of Car... Anti-Influenza ...	18 Years -	University of Miami

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