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| Name | Class |
|---|---|
| Cancer Research UK | OTHER |
| National Institute for Health Research, United Kingdom | OTHER_GOV |
| NHS Lothian | OTHER_GOV |
| Oxford University Hospitals NHS Trust |
Not provided
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This is a phase I, open-label trial that will utilise a Time To Event Continual Reassessment Method (TiTE-CRM) to determine the maximum tolerated dose (MTD) of atovaquone in combination with concurrent CRT in NSCLC. Twenty evaluable participants will be recruited at three centres.
Twice daily oral atovaquone will be added to standard concurrent chemoradiotherapy (CRT): 66 Gy in 33 fractions, once daily, 5 days a week (Monday-Friday), with cisplatin (80 mg/m2 IV on days 1 and 22 of CRT) and vinorelbine (15 mg/m2 IV on days 1, 8, 22 and 29 of CRT). Whilst awaiting CRT to start, patients will receive two weeks (+/- 7 days) of oral atovaquone to ensure steady state is reached (after seven days). Patients will be allocated one of four dose levels: 450 mg, 600 mg, 675 mg or 750 mg (all doses PO BD). Atovaquone dose will be assigned as per the TiTE-CRM statistical model. The first two trial participants will receive 450 mg BD. In the absence of unacceptable toxicity, subsequent patients will be assigned doses up to and including 750 mg BD.
Hypoxia biomarker data will be collected at baseline (start of atovaquone run-in) and following two weeks (+/- 7 days) of atovaquone treatment. Atovaquone will then be continued without break for the duration of CRT, with the CRT schedule remaining constant for all patients at both centres. Assessment for Dose Limiting Toxicities (DLTs) will be from the first scheduled dose of atovaquone until three months after completion of CRT. The CT scan performed at the three-month follow up visit will be reviewed to collect tumour response data.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dose level 1 - 450 mg BD atovaquone + concurrent CRT | Experimental | Atovaquone:
Chemotherapy:
Radiotherapy:
|
|
| Dose level 2 - 600 mg BD atovaquone + concurrent CRT | Experimental | Atovaquone:
Chemotherapy:
Radiotherapy:
|
|
| Dose level 3 - 675 mg BD atovaquone + concurrent CRT |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Atovaquone Oral Suspension | Drug | Atovaquone, cisplatin and vinorelbine are all considered Investigational Medicinal Products (IMPs) in this trial due to the investigation of these drugs in a novel combination. Patients will be allocated one of four doses of atovaquone: 450 mg, 600 mg, 675 mg or 750 mg (all doses PO BD). |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Dose Limiting Toxicities in Patients Taking Atovaquone in Combination With Radical Concurrent Chemoradiotherapy for Non-small Cell Lung Cancer. | To determine the maximum tolerated dose level (and therefore recommended phase II dose) of atovaquone when administered concomitantly with radical concurrent chemoradiotherapy (CRT) in patients with non-small cell lung cancer (NSCLC). This is the dose of atovaquone associated with no more than 48% dose limiting toxicity (DLT) rate (target toxicity level). | From first dose of atovaquone to 3-month follow up visit (up to 25 weeks) |
| Measure | Description | Time Frame |
|---|---|---|
| Severity of Worst Adverse Events Per Dose Level of Atovaquone Administered in Combination With Radical Concurrent Chemotherapy for NSCLC According to CTCAE V4.03 | Toxicity profile when atovaquone administered in combination with radical concurrent chemotherapy for NSCLC. Worst grade adverse event for each patient by dose schedule (according to the Common Terminology Criteria for Adverse Events, Version 4.03). Grade 1 (mild); Grade 2 (moderate); Grade 3 (severe or medically significant, but not immediately life-threatening); Grade 4 (life-threatening); Grade 5 (death). |
Not provided
Inclusion Criteria:
A patient will be eligible for inclusion in this study if all of the following criteria apply:
Histologically or cytologically confirmed diagnosis of locally advanced NSCLC and selected for treatment with full dose radical concurrent CRT
At least one measurable lesion greater than 2 cm maximal length in any direction on routine imaging (CT or PET-CT scan performed in the 60 days prior to consent)
Male or female, age at least 18 years
ECOG performance status 0 or 1
Adequate pulmonary function tests for thoracic radiotherapy (FEV1 and TLCO, greater than 40 percent predicted)
Haematological and biochemical indices within the ranges shown below:
Bilirubin ≤ 1.5 x upper limit of normal (ULN); ALT and/or AST ≤ 2.5 x ULN; Creatinine clearance ≥ 60 mL/min; Absolute Neutrophil Count ≥ 1.5 x 10*9/L; Platelets ≥ 100 x 10*9/L; Haemoglobin ≥ 90 g/L; INR ≤ 1.5
The patient is willing and able to comply with the protocol scheduled follow-up visits and examinations for the duration of the study
Written (signed and dated) informed consent and be capable of co-operating with protocol
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Geoffrey Higgins | University of Oxford | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Western General Hospital, NHS Lothian | Edinburgh | EH4 2XU | United Kingdom | |||
| Guy's and St Thomas' |
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| ID | Title | Description |
|---|---|---|
| FG000 | Dose Level 1 - 450 mg BD Atovaquone + Concurrent CRT | Atovaquone:
Chemotherapy:
Radiotherapy:
|
| FG001 | Dose Level 2 - 600 mg BD Atovaquone + Concurrent CRT | Atovaquone:
Chemotherapy:
Radiotherapy:
|
| FG002 | Dose Level 3 - 675 mg BD Atovaquone + Concurrent CRT | Atovaquone:
Chemotherapy:
Radiotherapy:
|
| FG003 | Dose Level 4 - 750 mg BD Atovaquone + Concurrent CRT | Atovaquone:
Chemotherapy:
Radiotherapy:
|
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Dose Level 1 - 450 mg BD Atovaquone + Concurrent CRT | Atovaquone:
Chemotherapy:
Radiotherapy:
|
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Dose Limiting Toxicities in Patients Taking Atovaquone in Combination With Radical Concurrent Chemoradiotherapy for Non-small Cell Lung Cancer. | To determine the maximum tolerated dose level (and therefore recommended phase II dose) of atovaquone when administered concomitantly with radical concurrent chemoradiotherapy (CRT) in patients with non-small cell lung cancer (NSCLC). This is the dose of atovaquone associated with no more than 48% dose limiting toxicity (DLT) rate (target toxicity level). | Posted | Number | Dose Limiting Toxicities (DLTs) | From first dose of atovaquone to 3-month follow up visit (up to 25 weeks) |
|
Adverse events (including serious events) are reported from first dose of atovaquone to last follow up visit at 6 months post chemoradiotherapy (up to 38 weeks).
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Dose Level 1 - 450 mg BD Atovaquone + Concurrent CRT | Atovaquone:
Chemotherapy:
Radiotherapy:
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Ataxia | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Blood & Lymphatic System Disorders | Blood and lymphatic system disorders | MedDRA 23.0 | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Professor Geoff Higgins | University of Oxford | 01865 617311 | geoffrey.higgins@oncology.ox.ac.uk |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Mar 23, 2020 | Oct 1, 2024 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jun 17, 2021 | Oct 1, 2024 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D053626 | Atovaquone |
| D002945 | Cisplatin |
| D000077235 | Vinorelbine |
| ID | Term |
|---|---|
| D009285 | Naphthoquinones |
| D011809 | Quinones |
| D009930 | Organic Chemicals |
| D009281 | Naphthalenes |
Not provided
Not provided
| OTHER |
| NHS Research Scotland | OTHER |
| Guy's and St Thomas' NHS Foundation Trust | OTHER |
Time-to-Event Continual Reassessment Method to determine the maximum tolerated dose (MTD) of atovaquone in combination with concurrent CRT in NSCLC
Not provided
Not provided
Not provided
Not provided
| Experimental |
Atovaquone:
Chemotherapy:
Radiotherapy:
|
|
| Dose level 4 - 750 mg BD atovaquone + concurrent CRT | Experimental | Atovaquone:
Chemotherapy:
Radiotherapy:
|
|
|
|
| Standard of care chemotherapy | Drug | Atovaquone, cisplatin and vinorelbine are all considered Investigational Medicinal Products (IMPs) in this trial due to the investigation of these drugs in a novel combination. Patients will receive two 21-day cycles of cisplatin and vinorelbine chemotherapy, comprising 80 mg/m2 cisplatin on days 1 & 22 of their CRT treatment and 15 mg/m2 vinorelbine on days 1, 8, 22 & 29. |
|
|
| Standard of care radiotherapy | Radiation | Thoracic radiotherapy will commence on day one of chemotherapy and be delivered in 66 Gy in 33 fractions, once daily, 5 days a week (Monday-Friday) for 6.5 weeks. |
|
| From first dose of atovaquone until last follow up visit at 6 months post completion of CRT (up to 38 weeks) |
| Number of Patients for Whom it Was Possible to Derive a Hypoxia Metagene Signature Score From 3'RNA-Seq of Genetic Material From Archival Tumour Samples | To confirm feasibility of measuring hypoxia metagene signature using 3'RNA-Seq on genetic material extracted from diagnostic non-small cell lung tumour samples. The score method was derived by Buffa et al (Buffa et al. Large meta-analysis of multiple cancers reveals a common, compact and highly prognostic hypoxia metagene. Br J Cancer. 2010 Jan 19;102(2):428-35. doi: 10.1038/sj.bjc.6605450). | At baseline (diagnosis) |
| Mean Baseline Tumour Hypoxia Level (TBRvol) Assessed by F18-FMISO PET-CT | The level of hypoxia in patient tumours was calculated using the Tumour-to-Blood Ratio volume (TBRvol) assessed from the patient's baseline PET scan. This scan was conducted with 18F-labelled fluoromisonidazole (F18-FMISO) which has been shown to selectively bind to hypoxic cells and can be quantified with PET imaging (Koh, et al. Imaging of hypoxia in human tumours with [F-18]fluoromisonidazole. Int J Radiat Oncol Biol Phys. 1992;22(1)). Tumour outlining of the region of interest on each axial slice was conducted centrally for all patients in consultation with an experienced consultant radiologist and combined to give a volume of interest (VOI). The number of voxels in the VOI with a threshold regional tumor:plasma F18-FMISO ratio of greater than or equal to 1.4 were combined to give the TBRvol (above reference). Patients with a TBRvol at baseline of <1.5mL were regarded as unevaluable for later endpoints, so are excluded from the report. | At baseline (prior to atovaquone treatment) |
| Mean Baseline Plasma miR-210 Level Assessed Via TaqMan Quantitative PCR | MicroRNA-210 (miR-210) has been found to be upregulated in response to hypoxia-inducing factors (Dang and Myers, The Role of Hypoxia-Induced miR-210 in Cancer Progression, Int. J. Mol. Sci., vol 16, 2015). Additionally, elevated serum levels of miR-210 are indicative of poor clinical outcomes in non-small cell lung cancer (He, et al. Clinical Significance of miR-210 and its Prospective Signaling Pathways in Non-Small Cell Lung Cancer. Physiol. Biochem. Int. J. Exp. Cell. Physiol. Biochem. Pharmacol., vol. 46, 2018). RNA was isolated from blood plasma and miR210 level detected using a two-step TaqMan quantitative PCR, using TaqMan probes for miR-210. An endogenous control miRNA (miR-16), plus an exogenous synthetic miRNA (cel-miR-39) were used for normalisation of miR210 counts. This endpoint was assessed in order to investigate a possible alternative to 18F-FMISO PET-CT scan for assessment of patients' tumour hypoxia level. | At baseline (prior to atovaquone treatment) |
| Mean Percentage Change in Tumour Hypoxia Level Between Baseline and After Two Weeks (+/- 7 Days) of Atovaquone Treatment | The level of hypoxia (Tumour-to-Blood Ratio volume, TBRvol) in patient tumours was calculated at baseline and following two weeks (+/- 7 days) of atovaquone treatment according to the details given in outcome measure 4. The mean percentage difference in TBRvol between the two timepoints at each dose level of atovaquone was calculated and is reported, below. Patients with a TBRvol at baseline of <1.5mL were regarded as unevaluable as it would not be possible to evaluate a reduction in hypoxic volume between this timepoint and the later timepoint. These patients were excluded from the report. | Between baseline (prior to atovaquone treatment) and following two weeks (+/- 7 days) of atovaquone treatment (up to 21 days) |
| Mean Percentage Change in Plasma miR-210 Level Between Baseline and After Two Weeks (+/- 7 Days) of Atovaquone Treatment, Assessed Via TaqMan Quantitative PCR | The miR-210 in participant plasma samples was calculated at baseline and following two weeks (+/- 7 days) of atovaquone treatment according to the details given in outcome measure 5. The mean percentage difference in miR210 count between the two timepoints for each dose level of atovaquone was calculated and is reported, below. This endpoint was assessed in order to investigate a possible alternative to 18F-FMISO PET-CT scan for assessment of patients' tumour hypoxia level. | Between baseline (prior to atovaquone treatment) and following two weeks (+/- 7 days) of atovaquone treatment (up to 21 days) |
| Objective Tumour Response to Treatment With Atovaquone in Combination With Chemoradiotherapy, as Evaluated by CT or PET-CT Scan and Quantified by RECIST 1.1 | Efficacy of the combination (atovaquone and chemoradiotherapy), measured by objective tumour response via RECIST 1.1 (Eisenhauer, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228-247). Scale of response assessed as Progressive Disease (PD) (worst outcome), Stable Disease (SD), Partial Response (PR), Complete Response (CR) (best outcome). | At 3 months post completion of chemoradiotherapy (up to 25 weeks after first dose of atovaquone) |
| London |
| SE1 9RT |
| United Kingdom |
| Churchill Hospital, Oxford University Hospitals | Oxford | OX3 7LE | United Kingdom |
| BG001 | Dose Level 2 - 600 mg BD Atovaquone + Concurrent CRT | Atovaquone:
Chemotherapy:
Radiotherapy:
|
| BG002 | Dose Level 3 - 675 mg BD Atovaquone + Concurrent CRT | Atovaquone:
Chemotherapy:
Radiotherapy:
|
| BG003 | Dose Level 4 - 750 mg BD Atovaquone + Concurrent CRT | Atovaquone:
Chemotherapy:
Radiotherapy:
|
| BG004 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Smoking status | Count of Participants | Participants |
|
| Non-small cell lung cancer sub-type | Count of Participants | Participants |
|
| OG001 | Dose Level 2 - 600 mg BD Atovaquone + Concurrent CRT | Atovaquone:
Chemotherapy:
Radiotherapy:
|
| OG002 | Dose Level 3 - 675 mg BD Atovaquone + Concurrent CRT | Atovaquone:
Chemotherapy:
Radiotherapy:
|
| OG003 | Dose Level 4 - 750 mg BD Atovaquone + Concurrent CRT | Atovaquone:
Chemotherapy:
Radiotherapy:
|
|
|
|
| Secondary | Severity of Worst Adverse Events Per Dose Level of Atovaquone Administered in Combination With Radical Concurrent Chemotherapy for NSCLC According to CTCAE V4.03 | Toxicity profile when atovaquone administered in combination with radical concurrent chemotherapy for NSCLC. Worst grade adverse event for each patient by dose schedule (according to the Common Terminology Criteria for Adverse Events, Version 4.03). Grade 1 (mild); Grade 2 (moderate); Grade 3 (severe or medically significant, but not immediately life-threatening); Grade 4 (life-threatening); Grade 5 (death). | Posted | Count of Participants | Participants | From first dose of atovaquone until last follow up visit at 6 months post completion of CRT (up to 38 weeks) |
|
|
|
| Secondary | Number of Patients for Whom it Was Possible to Derive a Hypoxia Metagene Signature Score From 3'RNA-Seq of Genetic Material From Archival Tumour Samples | To confirm feasibility of measuring hypoxia metagene signature using 3'RNA-Seq on genetic material extracted from diagnostic non-small cell lung tumour samples. The score method was derived by Buffa et al (Buffa et al. Large meta-analysis of multiple cancers reveals a common, compact and highly prognostic hypoxia metagene. Br J Cancer. 2010 Jan 19;102(2):428-35. doi: 10.1038/sj.bjc.6605450). | Five of 21 participants did not have a hypoxia metagene signature score derived due to the quality of extracted RNA being of insufficient quality to sequence (n=3), no archival tumour sample being available (n=1), or participant withdrew consent (n=1). | Posted | Count of Participants | Participants | At baseline (diagnosis) |
|
|
|
| Secondary | Mean Baseline Tumour Hypoxia Level (TBRvol) Assessed by F18-FMISO PET-CT | The level of hypoxia in patient tumours was calculated using the Tumour-to-Blood Ratio volume (TBRvol) assessed from the patient's baseline PET scan. This scan was conducted with 18F-labelled fluoromisonidazole (F18-FMISO) which has been shown to selectively bind to hypoxic cells and can be quantified with PET imaging (Koh, et al. Imaging of hypoxia in human tumours with [F-18]fluoromisonidazole. Int J Radiat Oncol Biol Phys. 1992;22(1)). Tumour outlining of the region of interest on each axial slice was conducted centrally for all patients in consultation with an experienced consultant radiologist and combined to give a volume of interest (VOI). The number of voxels in the VOI with a threshold regional tumor:plasma F18-FMISO ratio of greater than or equal to 1.4 were combined to give the TBRvol (above reference). Patients with a TBRvol at baseline of <1.5mL were regarded as unevaluable for later endpoints, so are excluded from the report. | Nine of 21 patients results were excluded from the report because they did not have F18-FMISO PET-CT scans at two of two timepoints in the trial (e.g. due to having a TBRvol considered too low to be evaluable on the first scan (n=6), or for logistical reasons (n=3)). | Posted | Mean | Full Range | TBRvol (mL) | At baseline (prior to atovaquone treatment) |
|
|
|
| Secondary | Mean Baseline Plasma miR-210 Level Assessed Via TaqMan Quantitative PCR | MicroRNA-210 (miR-210) has been found to be upregulated in response to hypoxia-inducing factors (Dang and Myers, The Role of Hypoxia-Induced miR-210 in Cancer Progression, Int. J. Mol. Sci., vol 16, 2015). Additionally, elevated serum levels of miR-210 are indicative of poor clinical outcomes in non-small cell lung cancer (He, et al. Clinical Significance of miR-210 and its Prospective Signaling Pathways in Non-Small Cell Lung Cancer. Physiol. Biochem. Int. J. Exp. Cell. Physiol. Biochem. Pharmacol., vol. 46, 2018). RNA was isolated from blood plasma and miR210 level detected using a two-step TaqMan quantitative PCR, using TaqMan probes for miR-210. An endogenous control miRNA (miR-16), plus an exogenous synthetic miRNA (cel-miR-39) were used for normalisation of miR210 counts. This endpoint was assessed in order to investigate a possible alternative to 18F-FMISO PET-CT scan for assessment of patients' tumour hypoxia level. | Eight of 21 participant samples are not reported either because the samples showed evidence of haemolysis (n=7) or because the participant withdrew consent (n=1). | Posted | Mean | Full Range | miR210 count (x10^3) | At baseline (prior to atovaquone treatment) |
|
|
|
| Secondary | Mean Percentage Change in Tumour Hypoxia Level Between Baseline and After Two Weeks (+/- 7 Days) of Atovaquone Treatment | The level of hypoxia (Tumour-to-Blood Ratio volume, TBRvol) in patient tumours was calculated at baseline and following two weeks (+/- 7 days) of atovaquone treatment according to the details given in outcome measure 4. The mean percentage difference in TBRvol between the two timepoints at each dose level of atovaquone was calculated and is reported, below. Patients with a TBRvol at baseline of <1.5mL were regarded as unevaluable as it would not be possible to evaluate a reduction in hypoxic volume between this timepoint and the later timepoint. These patients were excluded from the report. | Nine of 21 patients results were excluded from the report because they did not have F18-FMISO PET-CT scans at two of two timepoints in the trial (e.g. due to having a TBRvol considered too low to be evaluable on the first scan (n=6), or for logistical reasons (n=3)). | Posted | Mean | Full Range | Percentage change in TBRvol | Between baseline (prior to atovaquone treatment) and following two weeks (+/- 7 days) of atovaquone treatment (up to 21 days) |
|
|
|
| Secondary | Mean Percentage Change in Plasma miR-210 Level Between Baseline and After Two Weeks (+/- 7 Days) of Atovaquone Treatment, Assessed Via TaqMan Quantitative PCR | The miR-210 in participant plasma samples was calculated at baseline and following two weeks (+/- 7 days) of atovaquone treatment according to the details given in outcome measure 5. The mean percentage difference in miR210 count between the two timepoints for each dose level of atovaquone was calculated and is reported, below. This endpoint was assessed in order to investigate a possible alternative to 18F-FMISO PET-CT scan for assessment of patients' tumour hypoxia level. | Eight of 21 participant samples are not reported either because the samples showed evidence of haemolysis (n=7) or because the participant withdrew consent (n=1). | Posted | Mean | Full Range | Percentage change in miR210 count | Between baseline (prior to atovaquone treatment) and following two weeks (+/- 7 days) of atovaquone treatment (up to 21 days) |
|
|
|
| Secondary | Objective Tumour Response to Treatment With Atovaquone in Combination With Chemoradiotherapy, as Evaluated by CT or PET-CT Scan and Quantified by RECIST 1.1 | Efficacy of the combination (atovaquone and chemoradiotherapy), measured by objective tumour response via RECIST 1.1 (Eisenhauer, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228-247). Scale of response assessed as Progressive Disease (PD) (worst outcome), Stable Disease (SD), Partial Response (PR), Complete Response (CR) (best outcome). | Two of 21 participants were non-evaluable because they did not have a follow up scan at 3 months post-chemoradiotherapy treatment on which RECIST assessment could be performed. . | Posted | Count of Participants | Participants | At 3 months post completion of chemoradiotherapy (up to 25 weeks after first dose of atovaquone) |
|
|
|
| 0 |
| 3 |
| 2 |
| 3 |
| 3 |
| 3 |
| EG001 | Dose Level 2 - 600 mg BD Atovaquone + Concurrent CRT | Atovaquone:
Chemotherapy:
Radiotherapy:
| 0 | 2 | 1 | 2 | 2 | 2 |
| EG002 | Dose Level 3 - 675 mg BD Atovaquone + Concurrent CRT | Atovaquone:
Chemotherapy:
Radiotherapy:
| 0 | 1 | 0 | 1 | 1 | 1 |
| EG003 | Dose Level 4 - 750 mg BD Atovaquone + Concurrent CRT | Atovaquone:
Chemotherapy:
Radiotherapy:
| 2 | 15 | 7 | 15 | 15 | 15 |
| Angina pectoris | Cardiac disorders | MedDRA 23.0 | Systematic Assessment |
|
| Acute kidney injury | Renal and urinary disorders | MedDRA 23.0 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Chest pain | General disorders | MedDRA 23.0 | Systematic Assessment |
|
| Inflammatory bowel disease | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Pneumocystis jirovecii pneumonia | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Cardiac Disorders | Cardiac disorders | MedDRA 23.0 | Systematic Assessment |
|
| Ear and labyrinth disorders | Ear and labyrinth disorders | MedDRA 23.0 | Systematic Assessment |
|
| Endocrine disorders | Endocrine disorders | MedDRA 23.0 | Systematic Assessment |
|
| Eye disorders | Eye disorders | MedDRA 23.0 | Systematic Assessment |
|
| Gastrointestinal Disorders | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| General Disorders & Administration Site Conditions | General disorders | MedDRA 23.0 | Systematic Assessment |
|
| Hepatobiliary disorders | Hepatobiliary disorders | MedDRA 23.0 | Systematic Assessment |
|
| Infections & Infestations | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Injury, poisoning and procedural complications | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
|
| Investigations | Investigations | MedDRA 23.0 | Systematic Assessment |
|
| Metabolism & Nutrition Disorders | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
|
| Musculoskeletal & Connective Tissue Disorders | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Nervous System Disorders | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
|
| Psychiatric disorders | Psychiatric disorders | MedDRA 23.0 | Systematic Assessment |
|
| Renal and urinary disorders | Renal and urinary disorders | MedDRA 23.0 | Systematic Assessment |
|
| Respiratory, thoracic and mediastinal disorders | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Skin and subcutaneous tissue disorders | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Vascular disorders | Vascular disorders | MedDRA 23.0 | Systematic Assessment |
|
Not provided
Not provided
Not provided
| D011084 |
| Polycyclic Aromatic Hydrocarbons |
| D011083 | Polycyclic Compounds |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017672 | Nitrogen Compounds |
| D017671 | Platinum Compounds |
| D014748 | Vinca Alkaloids |
| D046948 | Secologanin Tryptamine Alkaloids |
| D026121 | Indole Alkaloids |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
| D007211 | Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D054836 | Indolizidines |
| D007212 | Indolizines |
| Worst AE: Grade 2 |
|
| Worst AE: Grade 3 |
|
| Worst AE: Grade 4 |
|
| Worst AE: Grade 5 |
|
| Partial Response (PR) |
|
| Stable Disease (SD) |
|
| Progressive Disease (PD) |
|