E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with extensive-stage small-cell lung cancer (ED-SCLC) who have refractory or resistant
disease from prior platinum-based chemotherapy. |
|
E.1.1.1 | Medical condition in easily understood language |
patients with Small Cell Lung Cancer whose cancer worsened during or within after 90 days of platinum based chemotherapy |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10041068 |
E.1.2 | Term | Small cell lung cancer extensive stage |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the preliminary efficacy of each treatment arm in terms of Overall Response Rate. ORR will be evaluated using Investigator assessments according to RECIST 1.1 |
|
E.2.2 | Secondary objectives of the trial |
1. To further assess the preliminary efficacy of each treatment arm in terms of DoR, DCR,
TTR, PFS, and overall survival (OS)
2. To assess the pharmacokinetics (PK) of novel combination treatments
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion criteria (applicable to all arms)
- Adults with ED SCLC who have have demonstrated progressive disease either during first-line platinum-based chemotherapy (platinum
refractory) or within 90 days of completing platinum basedchemotherapy (platinum resistant) and have not received further treatment.
- Brain metastases must be asymptomatic or treated and stable off steroids and anti-convulsants for at least 1 month prior to study treatment.
- At least 1 lesion, not previously irradiated, that can be accurately measured at baseline.
- Life expectancy of at least 8 weeks.
- Adequate organ and marrow function
- WHO/ECOG PS of 0-1 at enrollment
Inclusion criteria (Arm A specific)
- Body weight >30 kg.
- No prior exposure to immune mediated therapy, excluding therapeutic anticancer vaccines.
Inclusion criteria (Arm B specific)
- Able and willing to swallow oral medication
Inclusion Criteria (Arm C specific)
-Able and willing to swallow oral medication |
|
E.4 | Principal exclusion criteria |
Exclusion criteria (applicable to all arms)
- Participation in another clinical study, major surgery, radiation therapy within 28 days.
- Any condition that, in the opinion of the Investigator, would interfere with the evaluation of the IP or interpretation of patient safety or study
results.
- History of ILD, another primary malignancy, leptomeningeal carcinomatosis or spinal cord compression
Exclusion criteria (Arm A specific)
- Any concurrent cancer treatment.
- Live vaccines within 30 days.
- Known hypersensitivity to IP or excipient.
- Prior randomization or treatment in a previous durvalumab and/or tremelimumab clinical study.
- Active autoimmune disease, including a paraneoplastic syndrome of autoimmune nature.
- Active or prior documented autoimmune or inflammatory disorders.
- Any unresolved toxicity (CTCAE Grade >2) from previous anticancer therapy.
- History of allogenic organ transplantation or active primary immunodeficiency.
- Active infection.
- Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab or tremelimumab.
Exclusion criteria (Arm B specific)
- Prior exposure to any WEE1 inhibitors.
- Products known to be sensitive to CYP3A4 substrates or CYP3A4 substrates with a narrow therapeutic index, or to be moderate to strong
inhibitors/inducers of CYP3A4. Coadministration of rosuvastatin, aprepitant or fosaprepitant or any herbal preparations.. Grapefruit and
Seville oranges should be avoided while taking AZD1775.
- Any known hypersensitivity or contraindication to IP or CBDP.
- QTcF > 470 msec or congenital long QT syndrome.
- Any current or within 6 months cardiac diseases NYHA ≥ Class 2:
unstable angina pectoris, congestive heart failure, acute MI, conduction abnormality not controlled with pacemaker or medication, significant ventricular or supraventricular arrhythmias.
- A recent history of Torsades de pointes
Exclusion criteria (Arm C specific)
- Cytotoxic chemotherapy within 21 days of Cycle 1 Day 1 is not permitted
- Previous treatment with a PARP inhibitor (including olaparib) or ATR inhibitor
- Concomitant use of known strong CYP3A inhibitors or moderate CYP3A inhibitors
- Concomitant use of known strong or moderate CYP3A inducers
- Persisting (> 4 weeks) severe pancytopenia due to previous therapy
- Cardiac dysfunction
- Refractory nausea and vomiting, chronic gastrointestinal diseases or previous significant bowel resection
- Patients with uncontrolled seizures
- Intestinal obstruction or CTCAE grade 3 or grade 4 upper GI bleeding within 4 weeks before the dosing. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Overall Response rate evaluated by using Investigator assessments according to RECIST 1.1 |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary analysis of ORR will occur approximately 12 weeks after the last patient has initiated treatment. |
|
E.5.2 | Secondary end point(s) |
1. To further assess the preliminary efficacy of each treatment arm in terms of DoR, DCR,
TTR, PFS, and overall survival (OS) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
The primary analysis of ORR will occur approx. 12 weeks after the last patient has initiated treatment. This is planned to ensure the data cut off for ORR analysis follows the 12 week RECIST assessment for the last subject to be treated. However, in the situation where this scan does not occur due to this subject having experienced another progression event (e.g. death) the primary analysis DCO will be when all subjects have been followed for at least 12 weeks or until death if this is earlier. All study endpoints will be analyzed at this time includingincluding OS. The Sponsor will determine at that time whether any further follow up for OS would be required. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 15 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
The end of the study is defined as "the last visit of the last Patient undergoing the study." |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 2 |