Phase 1
N=21
Atovaquone With Radical ChemorADIotherapy in Locally Advanced NSCLC
Locally Advanced Non-Small Cell Lung Cancer
Bottom Line
View on ClinicalTrials.gov: NCT04648033 ↗Enrolled (actual)
21
Serious AEs
47.6%
Results posted
Nov 2024
Primary outcome: Primary: Number of Dose Limiting Toxicities in Patients Taking Atovaquone in Combination With Radical Concurrent Chemoradiotherapy for Non-small Cell Lung Cancer. — 0; 0; 0; 2 Dose Limiting Toxicities (DLTs)
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- Atovaquone Oral Suspension (Drug); Standard of care chemotherapy (Drug); Standard of care radiotherapy (Radiation)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- University of Oxford
- Primary completion
- Oct 2023
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Dose Limiting Toxicities in Patients Taking Atovaquone in Combination With Radical Concurrent Chemoradiotherapy for Non-small Cell Lung Cancer. |
0; 0; 0; 2 | — |
| 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 |
0; 0; 1; 0; 1; 1 | — |
| 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 |
3; 2; 0; 11 | — |
| SECONDARY Mean Baseline Tumour Hypoxia Level (TBRvol) Assessed by F18-FMISO PET-CT |
282.4; 21.4; 58.7 | — |
| SECONDARY Mean Baseline Plasma miR-210 Level Assessed Via TaqMan Quantitative PCR |
0.00146; 0.00219; 0.00195 | — |
| SECONDARY Mean Percentage Change in Tumour Hypoxia Level Between Baseline and After Two Weeks (+/- 7 Days) of Atovaquone Treatment |
-8; -15; -25 | — |
| 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 |
53.0; -42.5; 15.1 | — |
| 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 |
0; 0; 0; 1; 2; 2 | — |
Summary
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.
Eligibility Criteria
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
- Pregnant or breast-feeding women, or women of childbearing potential unless effective methods of contraception are used
- Previous systemic chemotherapy or biological therapy within 21 days of commencing atovaquone treatment
- Treatment with any other investigational agent as part of a clinical trial within 28 days of study enrolment
- Previous thoracic radiotherapy
- Known previous adverse reaction to atovaquone or its excipients
- Active hepatitis, gallbladder disease or pancreatitis
- Impaired gastrointestinal function that may significantly alter absorption of atovaquone
- Concurrent administration of warfarin in the 14 days prior to starting atovaquone
- Concurrent administration of known electron transport chain inhibitors (e.g. metformin). A wash-out period prior to administration of atovaquone is required (e.g. 4 days for metformin).
- An additional cancer diagnosis that the treating clinician feels may significantly impact planned CRT treatment tolerability or treatment outcome
- Established diagnosis of pulmonary fibrosis
- Established diagnosis of connective tissue disorder (e.g. scleroderma or systemic lupus erythematosus)
- Cardiac morbidity such as angina, myocardial infarction in the previous six months, unstable angina or uncontrolled hypertension, left ventricular failure or severe valvular disease
Data sourced from ClinicalTrials.gov (NCT04648033). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.