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Atovaquone · 1 trial · 1 indication
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).
| Arm | Type | Description |
|---|---|---|
| Dose level 1 - 450 mg BD atovaquone + concurrent CRT | EXPERIMENTAL | 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 | EXPERIMENTAL | 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 | EXPERIMENTAL | 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 | EXPERIMENTAL | 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. |
| Name | Type | Description |
|---|---|---|
| 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). |
| 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. |
Inclusion Criteria: A patient will be eligible for inclusion in this study if all of the following criteria apply: 1. Histologically or cytologically confirmed diagnosis of locally advanced NSCLC and selected for treatment with full dose radical concurrent CRT 2. At least one measurable lesion gre...
Atovaquone is being studied for use in locally advanced non-small cell lung cancer. It is an investigational small molecule being evaluated in combination with radical chemoradiotherapy. The drug is currently in Phase 1 clinical development for this indication, and it has not been approved for this use.
Atovaquone is a small molecule that targets mitochondrial cytochrome bc1 complex, inhibiting mitochondrial electron transport. This mechanism is being investigated for its potential anti-cancer effects in locally advanced non-small cell lung cancer. The drug is being studied in combination with standard chemoradiotherapy in a clinical trial setting.
Atovaquone is being developed by United Therapeutics Corporation, which trades under the ticker UTHR. The company is conducting clinical research on this drug for the treatment of locally advanced non-small cell lung cancer. Atovaquone is currently in Phase 1 clinical development for this indication.
Atovaquone is in Phase 1 clinical development for locally advanced non-small cell lung cancer. It is an investigational drug and has not been approved by regulatory authorities for this use. The Phase 1 trial has been completed, and the drug remains in early-stage clinical investigation.
Atovaquone has been studied in a Phase 1 clinical trial with the identifier NCT04648033, titled "Atovaquone With Radical ChemorADIotherapy in Locally Advanced NSCLC." This trial was conducted in the United Kingdom and enrolled 21 participants. The study has been completed, and it evaluated atovaquone in combination with radical chemoradiotherapy.
Atovaquone is the generic name for a drug that is also known by the brand name Mepron. In the context of this clinical development program, Atovaquone is being investigated for a new use in locally advanced non-small cell lung cancer. The drug is being developed by United Therapeutics Corporation for this oncology indication.