Trial Outcomes & Findings for Atovaquone With Radical ChemorADIotherapy in Locally Advanced NSCLC (NCT NCT04648033)
NCT ID: NCT04648033
Last Updated: 2026-01-29
Results Overview
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).
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
21 participants
Primary outcome timeframe
From first dose of atovaquone to 3-month follow up visit (up to 25 weeks)
Results posted on
2026-01-29
Participant Flow
Participant milestones
| Measure |
Dose Level 4 - 750 mg BD Atovaquone + Concurrent CRT
Atovaquone:
* Taken during an initial run in period (2 weeks +/- 7 days), then continued during standard of care chemoradiotherapy.
* One of 4 dose levels is allocated to each patient by a TiTE-CRM statistical model which takes into account all toxicity data to date.
* Dose levels - 450 mg, 600 mg, 675 mg or 750 mg (all doses PO BD).
* Last dose atovaquone taken on the last day of radiotherapy.
* Total duration of atovaquone treatment is 59 days (+/- 7 days), unless stopped earlier for toxicity or any other reason.
Chemotherapy:
* 2 x 21-day cycles.
* 80 mg/m2 cisplatin on day 1 and 22 of chemoradiotherapy.
* 15 mg/m2 vinorelbine on days 1,8, 22 and 29 of chemoradiotherapy.
Radiotherapy:
* 66 Gy in 33 fractions.
* Delivered once daily, 5 days a week (Monday-Friday) for 6.5 weeks.
|
Dose Level 1 - 450 mg BD Atovaquone + Concurrent CRT
Atovaquone:
* Taken during an initial run in period (2 weeks +/- 7 days), then continued during standard of care chemoradiotherapy.
* One of 4 dose levels is allocated to each patient by a TiTE-CRM statistical model which takes into account all toxicity data to date.
* Dose levels - 450 mg, 600 mg, 675 mg or 750 mg (all doses PO BD).
* Last dose atovaquone taken on the last day of radiotherapy.
* Total duration of atovaquone treatment is 59 days (+/- 7 days), unless stopped earlier for toxicity or any other reason.
Chemotherapy:
* 2 x 21-day cycles.
* 80 mg/m2 cisplatin on day 1 and 22 of chemoradiotherapy.
* 15 mg/m2 vinorelbine on days 1,8, 22 and 29 of chemoradiotherapy.
Radiotherapy:
* 66 Gy in 33 fractions.
* Delivered once daily, 5 days a week (Monday-Friday) for 6.5 weeks.
|
Dose Level 2 - 600 mg BD Atovaquone + Concurrent CRT
Atovaquone:
* Taken during an initial run in period (2 weeks +/- 7 days), then continued during standard of care chemoradiotherapy.
* One of 4 dose levels is allocated to each patient by a TiTE-CRM statistical model which takes into account all toxicity data to date.
* Dose levels - 450 mg, 600 mg, 675 mg or 750 mg (all doses PO BD).
* Last dose atovaquone taken on the last day of radiotherapy.
* Total duration of atovaquone treatment is 59 days (+/- 7 days), unless stopped earlier for toxicity or any other reason.
Chemotherapy:
* 2 x 21-day cycles.
* 80 mg/m2 cisplatin on day 1 and 22 of chemoradiotherapy.
* 15 mg/m2 vinorelbine on days 1,8, 22 and 29 of chemoradiotherapy.
Radiotherapy:
* 66 Gy in 33 fractions.
* Delivered once daily, 5 days a week (Monday-Friday) for 6.5 weeks.
|
Dose Level 3 - 675 mg BD Atovaquone + Concurrent CRT
Atovaquone:
* Taken during an initial run in period (2 weeks +/- 7 days), then continued during standard of care chemoradiotherapy.
* One of 4 dose levels is allocated to each patient by a TiTE-CRM statistical model which takes into account all toxicity data to date.
* Dose levels - 450 mg, 600 mg, 675 mg or 750 mg (all doses PO BD).
* Last dose atovaquone taken on the last day of radiotherapy.
* Total duration of atovaquone treatment is 59 days (+/- 7 days), unless stopped earlier for toxicity or any other reason.
Chemotherapy:
* 2 x 21-day cycles.
* 80 mg/m2 cisplatin on day 1 and 22 of chemoradiotherapy.
* 15 mg/m2 vinorelbine on days 1,8, 22 and 29 of chemoradiotherapy.
Radiotherapy:
* 66 Gy in 33 fractions.
* Delivered once daily, 5 days a week (Monday-Friday) for 6.5 weeks.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
15
|
3
|
2
|
1
|
|
Overall Study
COMPLETED
|
15
|
3
|
2
|
1
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Atovaquone With Radical ChemorADIotherapy in Locally Advanced NSCLC
Baseline characteristics by cohort
| Measure |
Dose Level 4 - 750 mg BD Atovaquone + Concurrent CRT
n=15 Participants
Atovaquone:
* Taken during an initial run in period (2 weeks +/- 7 days), then continued during standard of care chemoradiotherapy.
* One of 4 dose levels is allocated to each patient by a TiTE-CRM statistical model which takes into account all toxicity data to date.
* Dose levels - 450 mg, 600 mg, 675 mg or 750 mg (all doses PO BD).
* Last dose atovaquone taken on the last day of radiotherapy.
* Total duration of atovaquone treatment is 59 days (+/- 7 days), unless stopped earlier for toxicity or any other reason.
Chemotherapy:
* 2 x 21-day cycles.
* 80 mg/m2 cisplatin on day 1 and 22 of chemoradiotherapy.
* 15 mg/m2 vinorelbine on days 1,8, 22 and 29 of chemoradiotherapy.
Radiotherapy:
* 66 Gy in 33 fractions.
* Delivered once daily, 5 days a week (Monday-Friday) for 6.5 weeks.
|
Total
n=21 Participants
Total of all reporting groups
|
Dose Level 1 - 450 mg BD Atovaquone + Concurrent CRT
n=3 Participants
Atovaquone:
* Taken during an initial run in period (2 weeks +/- 7 days), then continued during standard of care chemoradiotherapy.
* One of 4 dose levels is allocated to each patient by a TiTE-CRM statistical model which takes into account all toxicity data to date.
* Dose levels - 450 mg, 600 mg, 675 mg or 750 mg (all doses PO BD).
* Last dose atovaquone taken on the last day of radiotherapy.
* Total duration of atovaquone treatment is 59 days (+/- 7 days), unless stopped earlier for toxicity or any other reason.
Chemotherapy:
* 2 x 21-day cycles.
* 80 mg/m2 cisplatin on day 1 and 22 of chemoradiotherapy.
* 15 mg/m2 vinorelbine on days 1,8, 22 and 29 of chemoradiotherapy.
Radiotherapy:
* 66 Gy in 33 fractions.
* Delivered once daily, 5 days a week (Monday-Friday) for 6.5 weeks.
|
Dose Level 2 - 600 mg BD Atovaquone + Concurrent CRT
n=2 Participants
Atovaquone:
* Taken during an initial run in period (2 weeks +/- 7 days), then continued during standard of care chemoradiotherapy.
* One of 4 dose levels is allocated to each patient by a TiTE-CRM statistical model which takes into account all toxicity data to date.
* Dose levels - 450 mg, 600 mg, 675 mg or 750 mg (all doses PO BD).
* Last dose atovaquone taken on the last day of radiotherapy.
* Total duration of atovaquone treatment is 59 days (+/- 7 days), unless stopped earlier for toxicity or any other reason.
Chemotherapy:
* 2 x 21-day cycles.
* 80 mg/m2 cisplatin on day 1 and 22 of chemoradiotherapy.
* 15 mg/m2 vinorelbine on days 1,8, 22 and 29 of chemoradiotherapy.
Radiotherapy:
* 66 Gy in 33 fractions.
* Delivered once daily, 5 days a week (Monday-Friday) for 6.5 weeks.
|
Dose Level 3 - 675 mg BD Atovaquone + Concurrent CRT
n=1 Participants
Atovaquone:
* Taken during an initial run in period (2 weeks +/- 7 days), then continued during standard of care chemoradiotherapy.
* One of 4 dose levels is allocated to each patient by a TiTE-CRM statistical model which takes into account all toxicity data to date.
* Dose levels - 450 mg, 600 mg, 675 mg or 750 mg (all doses PO BD).
* Last dose atovaquone taken on the last day of radiotherapy.
* Total duration of atovaquone treatment is 59 days (+/- 7 days), unless stopped earlier for toxicity or any other reason.
Chemotherapy:
* 2 x 21-day cycles.
* 80 mg/m2 cisplatin on day 1 and 22 of chemoradiotherapy.
* 15 mg/m2 vinorelbine on days 1,8, 22 and 29 of chemoradiotherapy.
Radiotherapy:
* 66 Gy in 33 fractions.
* Delivered once daily, 5 days a week (Monday-Friday) for 6.5 weeks.
|
|---|---|---|---|---|---|
|
Age, Continuous
|
65.2 Years
STANDARD_DEVIATION 16.4 • n=153 Participants
|
63.9 Years
STANDARD_DEVIATION 10.7 • n=200 Participants
|
67.3 Years
STANDARD_DEVIATION 17.7 • n=35 Participants
|
48.0 Years
STANDARD_DEVIATION 9.9 • n=4328 Participants
|
65.0 Years
STANDARD_DEVIATION NA • n=8687 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=153 Participants
|
7 Participants
n=200 Participants
|
0 Participants
n=35 Participants
|
1 Participants
n=4328 Participants
|
0 Participants
n=8687 Participants
|
|
Sex: Female, Male
Male
|
9 Participants
n=153 Participants
|
14 Participants
n=200 Participants
|
3 Participants
n=35 Participants
|
1 Participants
n=4328 Participants
|
1 Participants
n=8687 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=153 Participants
|
0 Participants
n=200 Participants
|
0 Participants
n=35 Participants
|
0 Participants
n=4328 Participants
|
0 Participants
n=8687 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
9 Participants
n=153 Participants
|
15 Participants
n=200 Participants
|
3 Participants
n=35 Participants
|
2 Participants
n=4328 Participants
|
1 Participants
n=8687 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
6 Participants
n=153 Participants
|
6 Participants
n=200 Participants
|
0 Participants
n=35 Participants
|
0 Participants
n=4328 Participants
|
0 Participants
n=8687 Participants
|
|
Smoking status
Never smoked
|
0 Participants
n=153 Participants
|
2 Participants
n=200 Participants
|
1 Participants
n=35 Participants
|
1 Participants
n=4328 Participants
|
0 Participants
n=8687 Participants
|
|
Smoking status
Ex-smoker
|
13 Participants
n=153 Participants
|
16 Participants
n=200 Participants
|
2 Participants
n=35 Participants
|
0 Participants
n=4328 Participants
|
1 Participants
n=8687 Participants
|
|
Smoking status
Current smoker
|
2 Participants
n=153 Participants
|
3 Participants
n=200 Participants
|
0 Participants
n=35 Participants
|
1 Participants
n=4328 Participants
|
0 Participants
n=8687 Participants
|
|
Non-small cell lung cancer sub-type
Adenocarcinoma
|
4 Participants
n=153 Participants
|
8 Participants
n=200 Participants
|
3 Participants
n=35 Participants
|
1 Participants
n=4328 Participants
|
0 Participants
n=8687 Participants
|
|
Non-small cell lung cancer sub-type
Squamous cell carcinoma
|
11 Participants
n=153 Participants
|
13 Participants
n=200 Participants
|
0 Participants
n=35 Participants
|
1 Participants
n=4328 Participants
|
1 Participants
n=8687 Participants
|
PRIMARY outcome
Timeframe: From first dose of atovaquone to 3-month follow up visit (up to 25 weeks)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).
Outcome measures
| Measure |
Dose Level 1 - 450 mg BD Atovaquone + Concurrent CRT
n=3 Participants
Atovaquone:
* Taken during an initial run in period (2 weeks +/- 7 days), then continued during standard of care chemoradiotherapy.
* One of 4 dose levels is allocated to each patient by a TiTE-CRM statistical model which takes into account all toxicity data to date.
* Dose levels - 450 mg, 600 mg, 675 mg or 750 mg (all doses PO BD).
* Last dose atovaquone taken on the last day of radiotherapy.
* Total duration of atovaquone treatment is 59 days (+/- 7 days), unless stopped earlier for toxicity or any other reason.
Chemotherapy:
* 2 x 21-day cycles.
* 80 mg/m2 cisplatin on day 1 and 22 of chemoradiotherapy.
* 15 mg/m2 vinorelbine on days 1,8, 22 and 29 of chemoradiotherapy.
Radiotherapy:
* 66 Gy in 33 fractions.
* Delivered once daily, 5 days a week (Monday-Friday) for 6.5 weeks.
|
Dose Level 2 - 600 mg BD Atovaquone + Concurrent CRT
n=2 Participants
Atovaquone:
* Taken during an initial run in period (2 weeks +/- 7 days), then continued during standard of care chemoradiotherapy.
* One of 4 dose levels is allocated to each patient by a TiTE-CRM statistical model which takes into account all toxicity data to date.
* Dose levels - 450 mg, 600 mg, 675 mg or 750 mg (all doses PO BD).
* Last dose atovaquone taken on the last day of radiotherapy.
* Total duration of atovaquone treatment is 59 days (+/- 7 days), unless stopped earlier for toxicity or any other reason.
Chemotherapy:
* 2 x 21-day cycles.
* 80 mg/m2 cisplatin on day 1 and 22 of chemoradiotherapy.
* 15 mg/m2 vinorelbine on days 1,8, 22 and 29 of chemoradiotherapy.
Radiotherapy:
* 66 Gy in 33 fractions.
* Delivered once daily, 5 days a week (Monday-Friday) for 6.5 weeks.
|
Dose Level 3 - 675 mg BD Atovaquone + Concurrent CRT
n=1 Participants
Atovaquone:
* Taken during an initial run in period (2 weeks +/- 7 days), then continued during standard of care chemoradiotherapy.
* One of 4 dose levels is allocated to each patient by a TiTE-CRM statistical model which takes into account all toxicity data to date.
* Dose levels - 450 mg, 600 mg, 675 mg or 750 mg (all doses PO BD).
* Last dose atovaquone taken on the last day of radiotherapy.
* Total duration of atovaquone treatment is 59 days (+/- 7 days), unless stopped earlier for toxicity or any other reason.
Chemotherapy:
* 2 x 21-day cycles.
* 80 mg/m2 cisplatin on day 1 and 22 of chemoradiotherapy.
* 15 mg/m2 vinorelbine on days 1,8, 22 and 29 of chemoradiotherapy.
Radiotherapy:
* 66 Gy in 33 fractions.
* Delivered once daily, 5 days a week (Monday-Friday) for 6.5 weeks.
|
Dose Level 4 - 750 mg BD Atovaquone + Concurrent CRT
n=15 Participants
Atovaquone:
* Taken during an initial run in period (2 weeks +/- 7 days), then continued during standard of care chemoradiotherapy.
* One of 4 dose levels is allocated to each patient by a TiTE-CRM statistical model which takes into account all toxicity data to date.
* Dose levels - 450 mg, 600 mg, 675 mg or 750 mg (all doses PO BD).
* Last dose atovaquone taken on the last day of radiotherapy.
* Total duration of atovaquone treatment is 59 days (+/- 7 days), unless stopped earlier for toxicity or any other reason.
Chemotherapy:
* 2 x 21-day cycles.
* 80 mg/m2 cisplatin on day 1 and 22 of chemoradiotherapy.
* 15 mg/m2 vinorelbine on days 1,8, 22 and 29 of chemoradiotherapy.
Radiotherapy:
* 66 Gy in 33 fractions.
* Delivered once daily, 5 days a week (Monday-Friday) for 6.5 weeks.
|
|---|---|---|---|---|
|
Number of Dose Limiting Toxicities in Patients Taking Atovaquone in Combination With Radical Concurrent Chemoradiotherapy for Non-small Cell Lung Cancer.
|
0 Dose Limiting Toxicities (DLTs)
|
0 Dose Limiting Toxicities (DLTs)
|
0 Dose Limiting Toxicities (DLTs)
|
2 Dose Limiting Toxicities (DLTs)
|
SECONDARY outcome
Timeframe: From first dose of atovaquone until last follow up visit at 6 months post completion of CRT (up to 38 weeks)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).
Outcome measures
| Measure |
Dose Level 1 - 450 mg BD Atovaquone + Concurrent CRT
n=3 Participants
Atovaquone:
* Taken during an initial run in period (2 weeks +/- 7 days), then continued during standard of care chemoradiotherapy.
* One of 4 dose levels is allocated to each patient by a TiTE-CRM statistical model which takes into account all toxicity data to date.
* Dose levels - 450 mg, 600 mg, 675 mg or 750 mg (all doses PO BD).
* Last dose atovaquone taken on the last day of radiotherapy.
* Total duration of atovaquone treatment is 59 days (+/- 7 days), unless stopped earlier for toxicity or any other reason.
Chemotherapy:
* 2 x 21-day cycles.
* 80 mg/m2 cisplatin on day 1 and 22 of chemoradiotherapy.
* 15 mg/m2 vinorelbine on days 1,8, 22 and 29 of chemoradiotherapy.
Radiotherapy:
* 66 Gy in 33 fractions.
* Delivered once daily, 5 days a week (Monday-Friday) for 6.5 weeks.
|
Dose Level 2 - 600 mg BD Atovaquone + Concurrent CRT
n=2 Participants
Atovaquone:
* Taken during an initial run in period (2 weeks +/- 7 days), then continued during standard of care chemoradiotherapy.
* One of 4 dose levels is allocated to each patient by a TiTE-CRM statistical model which takes into account all toxicity data to date.
* Dose levels - 450 mg, 600 mg, 675 mg or 750 mg (all doses PO BD).
* Last dose atovaquone taken on the last day of radiotherapy.
* Total duration of atovaquone treatment is 59 days (+/- 7 days), unless stopped earlier for toxicity or any other reason.
Chemotherapy:
* 2 x 21-day cycles.
* 80 mg/m2 cisplatin on day 1 and 22 of chemoradiotherapy.
* 15 mg/m2 vinorelbine on days 1,8, 22 and 29 of chemoradiotherapy.
Radiotherapy:
* 66 Gy in 33 fractions.
* Delivered once daily, 5 days a week (Monday-Friday) for 6.5 weeks.
|
Dose Level 3 - 675 mg BD Atovaquone + Concurrent CRT
n=1 Participants
Atovaquone:
* Taken during an initial run in period (2 weeks +/- 7 days), then continued during standard of care chemoradiotherapy.
* One of 4 dose levels is allocated to each patient by a TiTE-CRM statistical model which takes into account all toxicity data to date.
* Dose levels - 450 mg, 600 mg, 675 mg or 750 mg (all doses PO BD).
* Last dose atovaquone taken on the last day of radiotherapy.
* Total duration of atovaquone treatment is 59 days (+/- 7 days), unless stopped earlier for toxicity or any other reason.
Chemotherapy:
* 2 x 21-day cycles.
* 80 mg/m2 cisplatin on day 1 and 22 of chemoradiotherapy.
* 15 mg/m2 vinorelbine on days 1,8, 22 and 29 of chemoradiotherapy.
Radiotherapy:
* 66 Gy in 33 fractions.
* Delivered once daily, 5 days a week (Monday-Friday) for 6.5 weeks.
|
Dose Level 4 - 750 mg BD Atovaquone + Concurrent CRT
n=15 Participants
Atovaquone:
* Taken during an initial run in period (2 weeks +/- 7 days), then continued during standard of care chemoradiotherapy.
* One of 4 dose levels is allocated to each patient by a TiTE-CRM statistical model which takes into account all toxicity data to date.
* Dose levels - 450 mg, 600 mg, 675 mg or 750 mg (all doses PO BD).
* Last dose atovaquone taken on the last day of radiotherapy.
* Total duration of atovaquone treatment is 59 days (+/- 7 days), unless stopped earlier for toxicity or any other reason.
Chemotherapy:
* 2 x 21-day cycles.
* 80 mg/m2 cisplatin on day 1 and 22 of chemoradiotherapy.
* 15 mg/m2 vinorelbine on days 1,8, 22 and 29 of chemoradiotherapy.
Radiotherapy:
* 66 Gy in 33 fractions.
* Delivered once daily, 5 days a week (Monday-Friday) for 6.5 weeks.
|
|---|---|---|---|---|
|
Severity of Worst Adverse Events Per Dose Level of Atovaquone Administered in Combination With Radical Concurrent Chemotherapy for NSCLC According to CTCAE V4.03
Worst AE: Grade 1
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Severity of Worst Adverse Events Per Dose Level of Atovaquone Administered in Combination With Radical Concurrent Chemotherapy for NSCLC According to CTCAE V4.03
Worst AE: Grade 2
|
1 Participants
|
1 Participants
|
0 Participants
|
6 Participants
|
|
Severity of Worst Adverse Events Per Dose Level of Atovaquone Administered in Combination With Radical Concurrent Chemotherapy for NSCLC According to CTCAE V4.03
Worst AE: Grade 3
|
2 Participants
|
1 Participants
|
0 Participants
|
6 Participants
|
|
Severity of Worst Adverse Events Per Dose Level of Atovaquone Administered in Combination With Radical Concurrent Chemotherapy for NSCLC According to CTCAE V4.03
Worst AE: Grade 4
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Severity of Worst Adverse Events Per Dose Level of Atovaquone Administered in Combination With Radical Concurrent Chemotherapy for NSCLC According to CTCAE V4.03
Worst AE: Grade 5
|
0 Participants
|
0 Participants
|
0 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: At baseline (diagnosis)Population: 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).
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).
Outcome measures
| Measure |
Dose Level 1 - 450 mg BD Atovaquone + Concurrent CRT
n=3 Participants
Atovaquone:
* Taken during an initial run in period (2 weeks +/- 7 days), then continued during standard of care chemoradiotherapy.
* One of 4 dose levels is allocated to each patient by a TiTE-CRM statistical model which takes into account all toxicity data to date.
* Dose levels - 450 mg, 600 mg, 675 mg or 750 mg (all doses PO BD).
* Last dose atovaquone taken on the last day of radiotherapy.
* Total duration of atovaquone treatment is 59 days (+/- 7 days), unless stopped earlier for toxicity or any other reason.
Chemotherapy:
* 2 x 21-day cycles.
* 80 mg/m2 cisplatin on day 1 and 22 of chemoradiotherapy.
* 15 mg/m2 vinorelbine on days 1,8, 22 and 29 of chemoradiotherapy.
Radiotherapy:
* 66 Gy in 33 fractions.
* Delivered once daily, 5 days a week (Monday-Friday) for 6.5 weeks.
|
Dose Level 2 - 600 mg BD Atovaquone + Concurrent CRT
n=2 Participants
Atovaquone:
* Taken during an initial run in period (2 weeks +/- 7 days), then continued during standard of care chemoradiotherapy.
* One of 4 dose levels is allocated to each patient by a TiTE-CRM statistical model which takes into account all toxicity data to date.
* Dose levels - 450 mg, 600 mg, 675 mg or 750 mg (all doses PO BD).
* Last dose atovaquone taken on the last day of radiotherapy.
* Total duration of atovaquone treatment is 59 days (+/- 7 days), unless stopped earlier for toxicity or any other reason.
Chemotherapy:
* 2 x 21-day cycles.
* 80 mg/m2 cisplatin on day 1 and 22 of chemoradiotherapy.
* 15 mg/m2 vinorelbine on days 1,8, 22 and 29 of chemoradiotherapy.
Radiotherapy:
* 66 Gy in 33 fractions.
* Delivered once daily, 5 days a week (Monday-Friday) for 6.5 weeks.
|
Dose Level 3 - 675 mg BD Atovaquone + Concurrent CRT
Atovaquone:
* Taken during an initial run in period (2 weeks +/- 7 days), then continued during standard of care chemoradiotherapy.
* One of 4 dose levels is allocated to each patient by a TiTE-CRM statistical model which takes into account all toxicity data to date.
* Dose levels - 450 mg, 600 mg, 675 mg or 750 mg (all doses PO BD).
* Last dose atovaquone taken on the last day of radiotherapy.
* Total duration of atovaquone treatment is 59 days (+/- 7 days), unless stopped earlier for toxicity or any other reason.
Chemotherapy:
* 2 x 21-day cycles.
* 80 mg/m2 cisplatin on day 1 and 22 of chemoradiotherapy.
* 15 mg/m2 vinorelbine on days 1,8, 22 and 29 of chemoradiotherapy.
Radiotherapy:
* 66 Gy in 33 fractions.
* Delivered once daily, 5 days a week (Monday-Friday) for 6.5 weeks.
|
Dose Level 4 - 750 mg BD Atovaquone + Concurrent CRT
n=11 Participants
Atovaquone:
* Taken during an initial run in period (2 weeks +/- 7 days), then continued during standard of care chemoradiotherapy.
* One of 4 dose levels is allocated to each patient by a TiTE-CRM statistical model which takes into account all toxicity data to date.
* Dose levels - 450 mg, 600 mg, 675 mg or 750 mg (all doses PO BD).
* Last dose atovaquone taken on the last day of radiotherapy.
* Total duration of atovaquone treatment is 59 days (+/- 7 days), unless stopped earlier for toxicity or any other reason.
Chemotherapy:
* 2 x 21-day cycles.
* 80 mg/m2 cisplatin on day 1 and 22 of chemoradiotherapy.
* 15 mg/m2 vinorelbine on days 1,8, 22 and 29 of chemoradiotherapy.
Radiotherapy:
* 66 Gy in 33 fractions.
* Delivered once daily, 5 days a week (Monday-Friday) for 6.5 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
|
3 Participants
|
2 Participants
|
0 Participants
|
11 Participants
|
SECONDARY outcome
Timeframe: At baseline (prior to atovaquone treatment)Population: 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)).
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.
Outcome measures
| Measure |
Dose Level 1 - 450 mg BD Atovaquone + Concurrent CRT
n=2 Participants
Atovaquone:
* Taken during an initial run in period (2 weeks +/- 7 days), then continued during standard of care chemoradiotherapy.
* One of 4 dose levels is allocated to each patient by a TiTE-CRM statistical model which takes into account all toxicity data to date.
* Dose levels - 450 mg, 600 mg, 675 mg or 750 mg (all doses PO BD).
* Last dose atovaquone taken on the last day of radiotherapy.
* Total duration of atovaquone treatment is 59 days (+/- 7 days), unless stopped earlier for toxicity or any other reason.
Chemotherapy:
* 2 x 21-day cycles.
* 80 mg/m2 cisplatin on day 1 and 22 of chemoradiotherapy.
* 15 mg/m2 vinorelbine on days 1,8, 22 and 29 of chemoradiotherapy.
Radiotherapy:
* 66 Gy in 33 fractions.
* Delivered once daily, 5 days a week (Monday-Friday) for 6.5 weeks.
|
Dose Level 2 - 600 mg BD Atovaquone + Concurrent CRT
n=1 Participants
Atovaquone:
* Taken during an initial run in period (2 weeks +/- 7 days), then continued during standard of care chemoradiotherapy.
* One of 4 dose levels is allocated to each patient by a TiTE-CRM statistical model which takes into account all toxicity data to date.
* Dose levels - 450 mg, 600 mg, 675 mg or 750 mg (all doses PO BD).
* Last dose atovaquone taken on the last day of radiotherapy.
* Total duration of atovaquone treatment is 59 days (+/- 7 days), unless stopped earlier for toxicity or any other reason.
Chemotherapy:
* 2 x 21-day cycles.
* 80 mg/m2 cisplatin on day 1 and 22 of chemoradiotherapy.
* 15 mg/m2 vinorelbine on days 1,8, 22 and 29 of chemoradiotherapy.
Radiotherapy:
* 66 Gy in 33 fractions.
* Delivered once daily, 5 days a week (Monday-Friday) for 6.5 weeks.
|
Dose Level 3 - 675 mg BD Atovaquone + Concurrent CRT
Atovaquone:
* Taken during an initial run in period (2 weeks +/- 7 days), then continued during standard of care chemoradiotherapy.
* One of 4 dose levels is allocated to each patient by a TiTE-CRM statistical model which takes into account all toxicity data to date.
* Dose levels - 450 mg, 600 mg, 675 mg or 750 mg (all doses PO BD).
* Last dose atovaquone taken on the last day of radiotherapy.
* Total duration of atovaquone treatment is 59 days (+/- 7 days), unless stopped earlier for toxicity or any other reason.
Chemotherapy:
* 2 x 21-day cycles.
* 80 mg/m2 cisplatin on day 1 and 22 of chemoradiotherapy.
* 15 mg/m2 vinorelbine on days 1,8, 22 and 29 of chemoradiotherapy.
Radiotherapy:
* 66 Gy in 33 fractions.
* Delivered once daily, 5 days a week (Monday-Friday) for 6.5 weeks.
|
Dose Level 4 - 750 mg BD Atovaquone + Concurrent CRT
n=9 Participants
Atovaquone:
* Taken during an initial run in period (2 weeks +/- 7 days), then continued during standard of care chemoradiotherapy.
* One of 4 dose levels is allocated to each patient by a TiTE-CRM statistical model which takes into account all toxicity data to date.
* Dose levels - 450 mg, 600 mg, 675 mg or 750 mg (all doses PO BD).
* Last dose atovaquone taken on the last day of radiotherapy.
* Total duration of atovaquone treatment is 59 days (+/- 7 days), unless stopped earlier for toxicity or any other reason.
Chemotherapy:
* 2 x 21-day cycles.
* 80 mg/m2 cisplatin on day 1 and 22 of chemoradiotherapy.
* 15 mg/m2 vinorelbine on days 1,8, 22 and 29 of chemoradiotherapy.
Radiotherapy:
* 66 Gy in 33 fractions.
* Delivered once daily, 5 days a week (Monday-Friday) for 6.5 weeks.
|
|---|---|---|---|---|
|
Mean Baseline Tumour Hypoxia Level (TBRvol) Assessed by F18-FMISO PET-CT
|
282.4 TBRvol (mL)
Interval 4.4 to 560.4
|
21.4 TBRvol (mL)
There was only one participant in this group (for reasons given in analysis population description, above), so range is not applicable.
|
—
|
58.7 TBRvol (mL)
Interval 2.6 to 162.0
|
SECONDARY outcome
Timeframe: At baseline (prior to atovaquone treatment)Population: 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).
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.
Outcome measures
| Measure |
Dose Level 1 - 450 mg BD Atovaquone + Concurrent CRT
n=2 Participants
Atovaquone:
* Taken during an initial run in period (2 weeks +/- 7 days), then continued during standard of care chemoradiotherapy.
* One of 4 dose levels is allocated to each patient by a TiTE-CRM statistical model which takes into account all toxicity data to date.
* Dose levels - 450 mg, 600 mg, 675 mg or 750 mg (all doses PO BD).
* Last dose atovaquone taken on the last day of radiotherapy.
* Total duration of atovaquone treatment is 59 days (+/- 7 days), unless stopped earlier for toxicity or any other reason.
Chemotherapy:
* 2 x 21-day cycles.
* 80 mg/m2 cisplatin on day 1 and 22 of chemoradiotherapy.
* 15 mg/m2 vinorelbine on days 1,8, 22 and 29 of chemoradiotherapy.
Radiotherapy:
* 66 Gy in 33 fractions.
* Delivered once daily, 5 days a week (Monday-Friday) for 6.5 weeks.
|
Dose Level 2 - 600 mg BD Atovaquone + Concurrent CRT
n=1 Participants
Atovaquone:
* Taken during an initial run in period (2 weeks +/- 7 days), then continued during standard of care chemoradiotherapy.
* One of 4 dose levels is allocated to each patient by a TiTE-CRM statistical model which takes into account all toxicity data to date.
* Dose levels - 450 mg, 600 mg, 675 mg or 750 mg (all doses PO BD).
* Last dose atovaquone taken on the last day of radiotherapy.
* Total duration of atovaquone treatment is 59 days (+/- 7 days), unless stopped earlier for toxicity or any other reason.
Chemotherapy:
* 2 x 21-day cycles.
* 80 mg/m2 cisplatin on day 1 and 22 of chemoradiotherapy.
* 15 mg/m2 vinorelbine on days 1,8, 22 and 29 of chemoradiotherapy.
Radiotherapy:
* 66 Gy in 33 fractions.
* Delivered once daily, 5 days a week (Monday-Friday) for 6.5 weeks.
|
Dose Level 3 - 675 mg BD Atovaquone + Concurrent CRT
Atovaquone:
* Taken during an initial run in period (2 weeks +/- 7 days), then continued during standard of care chemoradiotherapy.
* One of 4 dose levels is allocated to each patient by a TiTE-CRM statistical model which takes into account all toxicity data to date.
* Dose levels - 450 mg, 600 mg, 675 mg or 750 mg (all doses PO BD).
* Last dose atovaquone taken on the last day of radiotherapy.
* Total duration of atovaquone treatment is 59 days (+/- 7 days), unless stopped earlier for toxicity or any other reason.
Chemotherapy:
* 2 x 21-day cycles.
* 80 mg/m2 cisplatin on day 1 and 22 of chemoradiotherapy.
* 15 mg/m2 vinorelbine on days 1,8, 22 and 29 of chemoradiotherapy.
Radiotherapy:
* 66 Gy in 33 fractions.
* Delivered once daily, 5 days a week (Monday-Friday) for 6.5 weeks.
|
Dose Level 4 - 750 mg BD Atovaquone + Concurrent CRT
n=10 Participants
Atovaquone:
* Taken during an initial run in period (2 weeks +/- 7 days), then continued during standard of care chemoradiotherapy.
* One of 4 dose levels is allocated to each patient by a TiTE-CRM statistical model which takes into account all toxicity data to date.
* Dose levels - 450 mg, 600 mg, 675 mg or 750 mg (all doses PO BD).
* Last dose atovaquone taken on the last day of radiotherapy.
* Total duration of atovaquone treatment is 59 days (+/- 7 days), unless stopped earlier for toxicity or any other reason.
Chemotherapy:
* 2 x 21-day cycles.
* 80 mg/m2 cisplatin on day 1 and 22 of chemoradiotherapy.
* 15 mg/m2 vinorelbine on days 1,8, 22 and 29 of chemoradiotherapy.
Radiotherapy:
* 66 Gy in 33 fractions.
* Delivered once daily, 5 days a week (Monday-Friday) for 6.5 weeks.
|
|---|---|---|---|---|
|
Mean Baseline Plasma miR-210 Level Assessed Via TaqMan Quantitative PCR
|
0.00146 miR210 count (x10^3)
Interval 0.00142 to 0.00149
|
0.00219 miR210 count (x10^3)
There was only one participant analysed this group (for reasons given in analysis population description, above), so range is not applicable.
|
—
|
0.00195 miR210 count (x10^3)
Interval 0.00098 to 0.00451
|
SECONDARY outcome
Timeframe: Between baseline (prior to atovaquone treatment) and following two weeks (+/- 7 days) of atovaquone treatment (up to 21 days)Population: 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)).
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.
Outcome measures
| Measure |
Dose Level 1 - 450 mg BD Atovaquone + Concurrent CRT
n=2 Participants
Atovaquone:
* Taken during an initial run in period (2 weeks +/- 7 days), then continued during standard of care chemoradiotherapy.
* One of 4 dose levels is allocated to each patient by a TiTE-CRM statistical model which takes into account all toxicity data to date.
* Dose levels - 450 mg, 600 mg, 675 mg or 750 mg (all doses PO BD).
* Last dose atovaquone taken on the last day of radiotherapy.
* Total duration of atovaquone treatment is 59 days (+/- 7 days), unless stopped earlier for toxicity or any other reason.
Chemotherapy:
* 2 x 21-day cycles.
* 80 mg/m2 cisplatin on day 1 and 22 of chemoradiotherapy.
* 15 mg/m2 vinorelbine on days 1,8, 22 and 29 of chemoradiotherapy.
Radiotherapy:
* 66 Gy in 33 fractions.
* Delivered once daily, 5 days a week (Monday-Friday) for 6.5 weeks.
|
Dose Level 2 - 600 mg BD Atovaquone + Concurrent CRT
n=1 Participants
Atovaquone:
* Taken during an initial run in period (2 weeks +/- 7 days), then continued during standard of care chemoradiotherapy.
* One of 4 dose levels is allocated to each patient by a TiTE-CRM statistical model which takes into account all toxicity data to date.
* Dose levels - 450 mg, 600 mg, 675 mg or 750 mg (all doses PO BD).
* Last dose atovaquone taken on the last day of radiotherapy.
* Total duration of atovaquone treatment is 59 days (+/- 7 days), unless stopped earlier for toxicity or any other reason.
Chemotherapy:
* 2 x 21-day cycles.
* 80 mg/m2 cisplatin on day 1 and 22 of chemoradiotherapy.
* 15 mg/m2 vinorelbine on days 1,8, 22 and 29 of chemoradiotherapy.
Radiotherapy:
* 66 Gy in 33 fractions.
* Delivered once daily, 5 days a week (Monday-Friday) for 6.5 weeks.
|
Dose Level 3 - 675 mg BD Atovaquone + Concurrent CRT
Atovaquone:
* Taken during an initial run in period (2 weeks +/- 7 days), then continued during standard of care chemoradiotherapy.
* One of 4 dose levels is allocated to each patient by a TiTE-CRM statistical model which takes into account all toxicity data to date.
* Dose levels - 450 mg, 600 mg, 675 mg or 750 mg (all doses PO BD).
* Last dose atovaquone taken on the last day of radiotherapy.
* Total duration of atovaquone treatment is 59 days (+/- 7 days), unless stopped earlier for toxicity or any other reason.
Chemotherapy:
* 2 x 21-day cycles.
* 80 mg/m2 cisplatin on day 1 and 22 of chemoradiotherapy.
* 15 mg/m2 vinorelbine on days 1,8, 22 and 29 of chemoradiotherapy.
Radiotherapy:
* 66 Gy in 33 fractions.
* Delivered once daily, 5 days a week (Monday-Friday) for 6.5 weeks.
|
Dose Level 4 - 750 mg BD Atovaquone + Concurrent CRT
n=9 Participants
Atovaquone:
* Taken during an initial run in period (2 weeks +/- 7 days), then continued during standard of care chemoradiotherapy.
* One of 4 dose levels is allocated to each patient by a TiTE-CRM statistical model which takes into account all toxicity data to date.
* Dose levels - 450 mg, 600 mg, 675 mg or 750 mg (all doses PO BD).
* Last dose atovaquone taken on the last day of radiotherapy.
* Total duration of atovaquone treatment is 59 days (+/- 7 days), unless stopped earlier for toxicity or any other reason.
Chemotherapy:
* 2 x 21-day cycles.
* 80 mg/m2 cisplatin on day 1 and 22 of chemoradiotherapy.
* 15 mg/m2 vinorelbine on days 1,8, 22 and 29 of chemoradiotherapy.
Radiotherapy:
* 66 Gy in 33 fractions.
* Delivered once daily, 5 days a week (Monday-Friday) for 6.5 weeks.
|
|---|---|---|---|---|
|
Mean Percentage Change in Tumour Hypoxia Level Between Baseline and After Two Weeks (+/- 7 Days) of Atovaquone Treatment
|
-8 Percentage change in TBRvol
Interval -37.0 to 22.0
|
-15 Percentage change in TBRvol
There was only one participant analysed in this group (see analysis population description, above), therefore range is not applicable.
|
—
|
-25 Percentage change in TBRvol
Interval -91.0 to 4.0
|
SECONDARY outcome
Timeframe: Between baseline (prior to atovaquone treatment) and following two weeks (+/- 7 days) of atovaquone treatment (up to 21 days)Population: 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).
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.
Outcome measures
| Measure |
Dose Level 1 - 450 mg BD Atovaquone + Concurrent CRT
n=2 Participants
Atovaquone:
* Taken during an initial run in period (2 weeks +/- 7 days), then continued during standard of care chemoradiotherapy.
* One of 4 dose levels is allocated to each patient by a TiTE-CRM statistical model which takes into account all toxicity data to date.
* Dose levels - 450 mg, 600 mg, 675 mg or 750 mg (all doses PO BD).
* Last dose atovaquone taken on the last day of radiotherapy.
* Total duration of atovaquone treatment is 59 days (+/- 7 days), unless stopped earlier for toxicity or any other reason.
Chemotherapy:
* 2 x 21-day cycles.
* 80 mg/m2 cisplatin on day 1 and 22 of chemoradiotherapy.
* 15 mg/m2 vinorelbine on days 1,8, 22 and 29 of chemoradiotherapy.
Radiotherapy:
* 66 Gy in 33 fractions.
* Delivered once daily, 5 days a week (Monday-Friday) for 6.5 weeks.
|
Dose Level 2 - 600 mg BD Atovaquone + Concurrent CRT
n=1 Participants
Atovaquone:
* Taken during an initial run in period (2 weeks +/- 7 days), then continued during standard of care chemoradiotherapy.
* One of 4 dose levels is allocated to each patient by a TiTE-CRM statistical model which takes into account all toxicity data to date.
* Dose levels - 450 mg, 600 mg, 675 mg or 750 mg (all doses PO BD).
* Last dose atovaquone taken on the last day of radiotherapy.
* Total duration of atovaquone treatment is 59 days (+/- 7 days), unless stopped earlier for toxicity or any other reason.
Chemotherapy:
* 2 x 21-day cycles.
* 80 mg/m2 cisplatin on day 1 and 22 of chemoradiotherapy.
* 15 mg/m2 vinorelbine on days 1,8, 22 and 29 of chemoradiotherapy.
Radiotherapy:
* 66 Gy in 33 fractions.
* Delivered once daily, 5 days a week (Monday-Friday) for 6.5 weeks.
|
Dose Level 3 - 675 mg BD Atovaquone + Concurrent CRT
Atovaquone:
* Taken during an initial run in period (2 weeks +/- 7 days), then continued during standard of care chemoradiotherapy.
* One of 4 dose levels is allocated to each patient by a TiTE-CRM statistical model which takes into account all toxicity data to date.
* Dose levels - 450 mg, 600 mg, 675 mg or 750 mg (all doses PO BD).
* Last dose atovaquone taken on the last day of radiotherapy.
* Total duration of atovaquone treatment is 59 days (+/- 7 days), unless stopped earlier for toxicity or any other reason.
Chemotherapy:
* 2 x 21-day cycles.
* 80 mg/m2 cisplatin on day 1 and 22 of chemoradiotherapy.
* 15 mg/m2 vinorelbine on days 1,8, 22 and 29 of chemoradiotherapy.
Radiotherapy:
* 66 Gy in 33 fractions.
* Delivered once daily, 5 days a week (Monday-Friday) for 6.5 weeks.
|
Dose Level 4 - 750 mg BD Atovaquone + Concurrent CRT
n=10 Participants
Atovaquone:
* Taken during an initial run in period (2 weeks +/- 7 days), then continued during standard of care chemoradiotherapy.
* One of 4 dose levels is allocated to each patient by a TiTE-CRM statistical model which takes into account all toxicity data to date.
* Dose levels - 450 mg, 600 mg, 675 mg or 750 mg (all doses PO BD).
* Last dose atovaquone taken on the last day of radiotherapy.
* Total duration of atovaquone treatment is 59 days (+/- 7 days), unless stopped earlier for toxicity or any other reason.
Chemotherapy:
* 2 x 21-day cycles.
* 80 mg/m2 cisplatin on day 1 and 22 of chemoradiotherapy.
* 15 mg/m2 vinorelbine on days 1,8, 22 and 29 of chemoradiotherapy.
Radiotherapy:
* 66 Gy in 33 fractions.
* Delivered once daily, 5 days a week (Monday-Friday) for 6.5 weeks.
|
|---|---|---|---|---|
|
Mean Percentage Change in Plasma miR-210 Level Between Baseline and After Two Weeks (+/- 7 Days) of Atovaquone Treatment, Assessed Via TaqMan Quantitative PCR
|
53.0 Percentage change in miR210 count
Interval 50.9 to 55.1
|
-42.5 Percentage change in miR210 count
There was only one participant analysed this group (for reasons given in analysis population description, above), so range is not applicable.
|
—
|
15.1 Percentage change in miR210 count
Interval -33.0 to 91.7
|
SECONDARY outcome
Timeframe: At 3 months post completion of chemoradiotherapy (up to 25 weeks after first dose of atovaquone)Population: 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. .
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).
Outcome measures
| Measure |
Dose Level 1 - 450 mg BD Atovaquone + Concurrent CRT
n=3 Participants
Atovaquone:
* Taken during an initial run in period (2 weeks +/- 7 days), then continued during standard of care chemoradiotherapy.
* One of 4 dose levels is allocated to each patient by a TiTE-CRM statistical model which takes into account all toxicity data to date.
* Dose levels - 450 mg, 600 mg, 675 mg or 750 mg (all doses PO BD).
* Last dose atovaquone taken on the last day of radiotherapy.
* Total duration of atovaquone treatment is 59 days (+/- 7 days), unless stopped earlier for toxicity or any other reason.
Chemotherapy:
* 2 x 21-day cycles.
* 80 mg/m2 cisplatin on day 1 and 22 of chemoradiotherapy.
* 15 mg/m2 vinorelbine on days 1,8, 22 and 29 of chemoradiotherapy.
Radiotherapy:
* 66 Gy in 33 fractions.
* Delivered once daily, 5 days a week (Monday-Friday) for 6.5 weeks.
|
Dose Level 2 - 600 mg BD Atovaquone + Concurrent CRT
n=2 Participants
Atovaquone:
* Taken during an initial run in period (2 weeks +/- 7 days), then continued during standard of care chemoradiotherapy.
* One of 4 dose levels is allocated to each patient by a TiTE-CRM statistical model which takes into account all toxicity data to date.
* Dose levels - 450 mg, 600 mg, 675 mg or 750 mg (all doses PO BD).
* Last dose atovaquone taken on the last day of radiotherapy.
* Total duration of atovaquone treatment is 59 days (+/- 7 days), unless stopped earlier for toxicity or any other reason.
Chemotherapy:
* 2 x 21-day cycles.
* 80 mg/m2 cisplatin on day 1 and 22 of chemoradiotherapy.
* 15 mg/m2 vinorelbine on days 1,8, 22 and 29 of chemoradiotherapy.
Radiotherapy:
* 66 Gy in 33 fractions.
* Delivered once daily, 5 days a week (Monday-Friday) for 6.5 weeks.
|
Dose Level 3 - 675 mg BD Atovaquone + Concurrent CRT
n=1 Participants
Atovaquone:
* Taken during an initial run in period (2 weeks +/- 7 days), then continued during standard of care chemoradiotherapy.
* One of 4 dose levels is allocated to each patient by a TiTE-CRM statistical model which takes into account all toxicity data to date.
* Dose levels - 450 mg, 600 mg, 675 mg or 750 mg (all doses PO BD).
* Last dose atovaquone taken on the last day of radiotherapy.
* Total duration of atovaquone treatment is 59 days (+/- 7 days), unless stopped earlier for toxicity or any other reason.
Chemotherapy:
* 2 x 21-day cycles.
* 80 mg/m2 cisplatin on day 1 and 22 of chemoradiotherapy.
* 15 mg/m2 vinorelbine on days 1,8, 22 and 29 of chemoradiotherapy.
Radiotherapy:
* 66 Gy in 33 fractions.
* Delivered once daily, 5 days a week (Monday-Friday) for 6.5 weeks.
|
Dose Level 4 - 750 mg BD Atovaquone + Concurrent CRT
n=13 Participants
Atovaquone:
* Taken during an initial run in period (2 weeks +/- 7 days), then continued during standard of care chemoradiotherapy.
* One of 4 dose levels is allocated to each patient by a TiTE-CRM statistical model which takes into account all toxicity data to date.
* Dose levels - 450 mg, 600 mg, 675 mg or 750 mg (all doses PO BD).
* Last dose atovaquone taken on the last day of radiotherapy.
* Total duration of atovaquone treatment is 59 days (+/- 7 days), unless stopped earlier for toxicity or any other reason.
Chemotherapy:
* 2 x 21-day cycles.
* 80 mg/m2 cisplatin on day 1 and 22 of chemoradiotherapy.
* 15 mg/m2 vinorelbine on days 1,8, 22 and 29 of chemoradiotherapy.
Radiotherapy:
* 66 Gy in 33 fractions.
* Delivered once daily, 5 days a week (Monday-Friday) for 6.5 weeks.
|
|---|---|---|---|---|
|
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
Complete Response (CR)
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
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
Partial Response (PR)
|
2 Participants
|
2 Participants
|
1 Participants
|
7 Participants
|
|
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
Stable Disease (SD)
|
1 Participants
|
0 Participants
|
0 Participants
|
2 Participants
|
|
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
Progressive Disease (PD)
|
0 Participants
|
0 Participants
|
0 Participants
|
3 Participants
|
Adverse Events
Dose Level 2 - 600 mg BD Atovaquone + Concurrent CRT
Serious events: 1 serious events
Other events: 2 other events
Deaths: 0 deaths
Dose Level 1 - 450 mg BD Atovaquone + Concurrent CRT
Serious events: 2 serious events
Other events: 3 other events
Deaths: 0 deaths
Dose Level 3 - 675 mg BD Atovaquone + Concurrent CRT
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Dose Level 4 - 750 mg BD Atovaquone + Concurrent CRT
Serious events: 7 serious events
Other events: 15 other events
Deaths: 2 deaths
Serious adverse events
| Measure |
Dose Level 2 - 600 mg BD Atovaquone + Concurrent CRT
n=2 participants at risk
Atovaquone:
* Taken during an initial run in period (2 weeks +/- 7 days), then continued during standard of care chemoradiotherapy.
* One of 4 dose levels is allocated to each patient by a TiTE-CRM statistical model which takes into account all toxicity data to date.
* Dose levels - 450 mg, 600 mg, 675 mg or 750 mg (all doses PO BD).
* Last dose atovaquone taken on the last day of radiotherapy.
* Total duration of atovaquone treatment is 59 days (+/- 7 days), unless stopped earlier for toxicity or any other reason.
Chemotherapy:
* 2 x 21-day cycles.
* 80 mg/m2 cisplatin on day 1 and 22 of chemoradiotherapy.
* 15 mg/m2 vinorelbine on days 1,8, 22 and 29 of chemoradiotherapy.
Radiotherapy:
* 66 Gy in 33 fractions.
* Delivered once daily, 5 days a week (Monday-Friday) for 6.5 weeks.
|
Dose Level 1 - 450 mg BD Atovaquone + Concurrent CRT
n=3 participants at risk
Atovaquone:
* Taken during an initial run in period (2 weeks +/- 7 days), then continued during standard of care chemoradiotherapy.
* One of 4 dose levels is allocated to each patient by a TiTE-CRM statistical model which takes into account all toxicity data to date.
* Dose levels - 450 mg, 600 mg, 675 mg or 750 mg (all doses PO BD).
* Last dose atovaquone taken on the last day of radiotherapy.
* Total duration of atovaquone treatment is 59 days (+/- 7 days), unless stopped earlier for toxicity or any other reason.
Chemotherapy:
* 2 x 21-day cycles.
* 80 mg/m2 cisplatin on day 1 and 22 of chemoradiotherapy.
* 15 mg/m2 vinorelbine on days 1,8, 22 and 29 of chemoradiotherapy.
Radiotherapy:
* 66 Gy in 33 fractions.
* Delivered once daily, 5 days a week (Monday-Friday) for 6.5 weeks.
|
Dose Level 3 - 675 mg BD Atovaquone + Concurrent CRT
n=1 participants at risk
Atovaquone:
* Taken during an initial run in period (2 weeks +/- 7 days), then continued during standard of care chemoradiotherapy.
* One of 4 dose levels is allocated to each patient by a TiTE-CRM statistical model which takes into account all toxicity data to date.
* Dose levels - 450 mg, 600 mg, 675 mg or 750 mg (all doses PO BD).
* Last dose atovaquone taken on the last day of radiotherapy.
* Total duration of atovaquone treatment is 59 days (+/- 7 days), unless stopped earlier for toxicity or any other reason.
Chemotherapy:
* 2 x 21-day cycles.
* 80 mg/m2 cisplatin on day 1 and 22 of chemoradiotherapy.
* 15 mg/m2 vinorelbine on days 1,8, 22 and 29 of chemoradiotherapy.
Radiotherapy:
* 66 Gy in 33 fractions.
* Delivered once daily, 5 days a week (Monday-Friday) for 6.5 weeks.
|
Dose Level 4 - 750 mg BD Atovaquone + Concurrent CRT
n=15 participants at risk
Atovaquone:
* Taken during an initial run in period (2 weeks +/- 7 days), then continued during standard of care chemoradiotherapy.
* One of 4 dose levels is allocated to each patient by a TiTE-CRM statistical model which takes into account all toxicity data to date.
* Dose levels - 450 mg, 600 mg, 675 mg or 750 mg (all doses PO BD).
* Last dose atovaquone taken on the last day of radiotherapy.
* Total duration of atovaquone treatment is 59 days (+/- 7 days), unless stopped earlier for toxicity or any other reason.
Chemotherapy:
* 2 x 21-day cycles.
* 80 mg/m2 cisplatin on day 1 and 22 of chemoradiotherapy.
* 15 mg/m2 vinorelbine on days 1,8, 22 and 29 of chemoradiotherapy.
Radiotherapy:
* 66 Gy in 33 fractions.
* Delivered once daily, 5 days a week (Monday-Friday) for 6.5 weeks.
|
|---|---|---|---|---|
|
Nervous system disorders
Ataxia
|
0.00%
0/2 • 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).
|
33.3%
1/3 • Number of events 1 • 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).
|
0.00%
0/1 • 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).
|
0.00%
0/15 • 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).
|
|
Cardiac disorders
Angina pectoris
|
0.00%
0/2 • 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).
|
33.3%
1/3 • Number of events 1 • 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).
|
0.00%
0/1 • 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).
|
0.00%
0/15 • 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).
|
|
Renal and urinary disorders
Acute kidney injury
|
0.00%
0/2 • 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).
|
33.3%
1/3 • Number of events 1 • 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).
|
0.00%
0/1 • 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).
|
0.00%
0/15 • 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).
|
|
Gastrointestinal disorders
Vomiting
|
50.0%
1/2 • Number of events 1 • 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).
|
0.00%
0/3 • 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).
|
0.00%
0/1 • 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).
|
0.00%
0/15 • 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).
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.00%
0/2 • 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).
|
0.00%
0/3 • 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).
|
0.00%
0/1 • 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).
|
13.3%
2/15 • Number of events 2 • 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).
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/2 • 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).
|
0.00%
0/3 • 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).
|
0.00%
0/1 • 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).
|
13.3%
2/15 • Number of events 2 • 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).
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/2 • 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).
|
0.00%
0/3 • 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).
|
0.00%
0/1 • 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).
|
6.7%
1/15 • Number of events 1 • 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).
|
|
Infections and infestations
Pneumonia
|
0.00%
0/2 • 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).
|
0.00%
0/3 • 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).
|
0.00%
0/1 • 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).
|
6.7%
1/15 • Number of events 1 • 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).
|
|
General disorders
Chest pain
|
0.00%
0/2 • 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).
|
0.00%
0/3 • 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).
|
0.00%
0/1 • 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).
|
6.7%
1/15 • Number of events 1 • 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).
|
|
Gastrointestinal disorders
Inflammatory bowel disease
|
0.00%
0/2 • 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).
|
0.00%
0/3 • 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).
|
0.00%
0/1 • 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).
|
6.7%
1/15 • Number of events 1 • 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).
|
|
Infections and infestations
Pneumocystis jirovecii pneumonia
|
0.00%
0/2 • 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).
|
0.00%
0/3 • 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).
|
0.00%
0/1 • 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).
|
6.7%
1/15 • Number of events 1 • 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).
|
Other adverse events
| Measure |
Dose Level 2 - 600 mg BD Atovaquone + Concurrent CRT
n=2 participants at risk
Atovaquone:
* Taken during an initial run in period (2 weeks +/- 7 days), then continued during standard of care chemoradiotherapy.
* One of 4 dose levels is allocated to each patient by a TiTE-CRM statistical model which takes into account all toxicity data to date.
* Dose levels - 450 mg, 600 mg, 675 mg or 750 mg (all doses PO BD).
* Last dose atovaquone taken on the last day of radiotherapy.
* Total duration of atovaquone treatment is 59 days (+/- 7 days), unless stopped earlier for toxicity or any other reason.
Chemotherapy:
* 2 x 21-day cycles.
* 80 mg/m2 cisplatin on day 1 and 22 of chemoradiotherapy.
* 15 mg/m2 vinorelbine on days 1,8, 22 and 29 of chemoradiotherapy.
Radiotherapy:
* 66 Gy in 33 fractions.
* Delivered once daily, 5 days a week (Monday-Friday) for 6.5 weeks.
|
Dose Level 1 - 450 mg BD Atovaquone + Concurrent CRT
n=3 participants at risk
Atovaquone:
* Taken during an initial run in period (2 weeks +/- 7 days), then continued during standard of care chemoradiotherapy.
* One of 4 dose levels is allocated to each patient by a TiTE-CRM statistical model which takes into account all toxicity data to date.
* Dose levels - 450 mg, 600 mg, 675 mg or 750 mg (all doses PO BD).
* Last dose atovaquone taken on the last day of radiotherapy.
* Total duration of atovaquone treatment is 59 days (+/- 7 days), unless stopped earlier for toxicity or any other reason.
Chemotherapy:
* 2 x 21-day cycles.
* 80 mg/m2 cisplatin on day 1 and 22 of chemoradiotherapy.
* 15 mg/m2 vinorelbine on days 1,8, 22 and 29 of chemoradiotherapy.
Radiotherapy:
* 66 Gy in 33 fractions.
* Delivered once daily, 5 days a week (Monday-Friday) for 6.5 weeks.
|
Dose Level 3 - 675 mg BD Atovaquone + Concurrent CRT
n=1 participants at risk
Atovaquone:
* Taken during an initial run in period (2 weeks +/- 7 days), then continued during standard of care chemoradiotherapy.
* One of 4 dose levels is allocated to each patient by a TiTE-CRM statistical model which takes into account all toxicity data to date.
* Dose levels - 450 mg, 600 mg, 675 mg or 750 mg (all doses PO BD).
* Last dose atovaquone taken on the last day of radiotherapy.
* Total duration of atovaquone treatment is 59 days (+/- 7 days), unless stopped earlier for toxicity or any other reason.
Chemotherapy:
* 2 x 21-day cycles.
* 80 mg/m2 cisplatin on day 1 and 22 of chemoradiotherapy.
* 15 mg/m2 vinorelbine on days 1,8, 22 and 29 of chemoradiotherapy.
Radiotherapy:
* 66 Gy in 33 fractions.
* Delivered once daily, 5 days a week (Monday-Friday) for 6.5 weeks.
|
Dose Level 4 - 750 mg BD Atovaquone + Concurrent CRT
n=15 participants at risk
Atovaquone:
* Taken during an initial run in period (2 weeks +/- 7 days), then continued during standard of care chemoradiotherapy.
* One of 4 dose levels is allocated to each patient by a TiTE-CRM statistical model which takes into account all toxicity data to date.
* Dose levels - 450 mg, 600 mg, 675 mg or 750 mg (all doses PO BD).
* Last dose atovaquone taken on the last day of radiotherapy.
* Total duration of atovaquone treatment is 59 days (+/- 7 days), unless stopped earlier for toxicity or any other reason.
Chemotherapy:
* 2 x 21-day cycles.
* 80 mg/m2 cisplatin on day 1 and 22 of chemoradiotherapy.
* 15 mg/m2 vinorelbine on days 1,8, 22 and 29 of chemoradiotherapy.
Radiotherapy:
* 66 Gy in 33 fractions.
* Delivered once daily, 5 days a week (Monday-Friday) for 6.5 weeks.
|
|---|---|---|---|---|
|
Ear and labyrinth disorders
Ear and labyrinth disorders
|
0.00%
0/2 • 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).
|
33.3%
1/3 • Number of events 1 • 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).
|
0.00%
0/1 • 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).
|
6.7%
1/15 • Number of events 1 • 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).
|
|
Cardiac disorders
Cardiac Disorders
|
0.00%
0/2 • 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).
|
66.7%
2/3 • Number of events 3 • 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).
|
0.00%
0/1 • 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).
|
0.00%
0/15 • 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).
|
|
Blood and lymphatic system disorders
Blood & Lymphatic System Disorders
|
50.0%
1/2 • Number of events 1 • 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).
|
33.3%
1/3 • Number of events 2 • 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).
|
0.00%
0/1 • 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).
|
20.0%
3/15 • Number of events 8 • 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).
|
|
Endocrine disorders
Endocrine disorders
|
0.00%
0/2 • 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).
|
33.3%
1/3 • Number of events 1 • 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).
|
0.00%
0/1 • 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).
|
6.7%
1/15 • Number of events 1 • 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).
|
|
Eye disorders
Eye disorders
|
0.00%
0/2 • 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).
|
33.3%
1/3 • Number of events 1 • 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).
|
0.00%
0/1 • 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).
|
6.7%
1/15 • Number of events 1 • 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).
|
|
Gastrointestinal disorders
Gastrointestinal Disorders
|
100.0%
2/2 • Number of events 16 • 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).
|
100.0%
3/3 • Number of events 5 • 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).
|
100.0%
1/1 • Number of events 3 • 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).
|
93.3%
14/15 • Number of events 45 • 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).
|
|
General disorders
General Disorders & Administration Site Conditions
|
100.0%
2/2 • Number of events 3 • 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).
|
100.0%
3/3 • Number of events 3 • 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).
|
100.0%
1/1 • Number of events 1 • 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).
|
73.3%
11/15 • Number of events 22 • 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).
|
|
Hepatobiliary disorders
Hepatobiliary disorders
|
0.00%
0/2 • 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).
|
0.00%
0/3 • 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).
|
100.0%
1/1 • Number of events 1 • 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).
|
0.00%
0/15 • 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).
|
|
Infections and infestations
Infections & Infestations
|
0.00%
0/2 • 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).
|
0.00%
0/3 • 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).
|
0.00%
0/1 • 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).
|
53.3%
8/15 • Number of events 12 • 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).
|
|
Injury, poisoning and procedural complications
Injury, poisoning and procedural complications
|
0.00%
0/2 • 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).
|
0.00%
0/3 • 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).
|
0.00%
0/1 • 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).
|
13.3%
2/15 • Number of events 2 • 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).
|
|
Investigations
Investigations
|
50.0%
1/2 • Number of events 1 • 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).
|
0.00%
0/3 • 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).
|
0.00%
0/1 • 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).
|
13.3%
2/15 • Number of events 3 • 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).
|
|
Metabolism and nutrition disorders
Metabolism & Nutrition Disorders
|
50.0%
1/2 • Number of events 1 • 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).
|
33.3%
1/3 • Number of events 1 • 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).
|
0.00%
0/1 • 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).
|
53.3%
8/15 • Number of events 16 • 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).
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal & Connective Tissue Disorders
|
50.0%
1/2 • Number of events 1 • 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).
|
66.7%
2/3 • Number of events 2 • 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).
|
0.00%
0/1 • 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).
|
20.0%
3/15 • Number of events 4 • 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).
|
|
Nervous system disorders
Nervous System Disorders
|
50.0%
1/2 • Number of events 1 • 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).
|
66.7%
2/3 • Number of events 5 • 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).
|
0.00%
0/1 • 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).
|
60.0%
9/15 • Number of events 15 • 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).
|
|
Psychiatric disorders
Psychiatric disorders
|
0.00%
0/2 • 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).
|
0.00%
0/3 • 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).
|
0.00%
0/1 • 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).
|
40.0%
6/15 • Number of events 8 • 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).
|
|
Renal and urinary disorders
Renal and urinary disorders
|
0.00%
0/2 • 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).
|
33.3%
1/3 • Number of events 2 • 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).
|
0.00%
0/1 • 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).
|
6.7%
1/15 • Number of events 1 • 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).
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders
|
0.00%
0/2 • 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).
|
66.7%
2/3 • Number of events 3 • 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).
|
0.00%
0/1 • 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).
|
73.3%
11/15 • Number of events 27 • 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).
|
|
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders
|
0.00%
0/2 • 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).
|
66.7%
2/3 • Number of events 3 • 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).
|
0.00%
0/1 • 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).
|
26.7%
4/15 • Number of events 5 • 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).
|
|
Vascular disorders
Vascular disorders
|
0.00%
0/2 • 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).
|
0.00%
0/3 • 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).
|
0.00%
0/1 • 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).
|
6.7%
1/15 • Number of events 1 • 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).
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place