Phase 1/2 multicenter, two-arms, open-label, dose-escalation study of IDP-121 in combination with chemotherapy in patients with relapsed small cell lung cancer (SCLC) (MYCrocytic)
Overview
- Phase
- Phase 1/2
- Intervention
- Not specified
- Conditions
- Not specified
- Sponsor
- Idp Discovery Pharma S.L.
- Enrollment
- 60
- Locations
- 10
- Primary Endpoint
- Dose-Escalation (Phase 1) Primary Endpoint(s): • Maximum tolerated dose (MTD): based on the incidence of DLTs observed at the end of Cycle 1 (21 days). • Recommended phase 2 dose (RP2D): dose selected for the use in the expansion phase. The RP2D will be determined in discussion with the Investigators and the Sponsor based on safety (dose limiting toxicity), PK, PD, and efficacy observed across multiple dose-escalation cohorts.
- Status
- Not yet recruiting
- Last Updated
- 4 months ago
Overview
Brief Summary
Dose-Escalation Phase (Phase 1) Primary objective: To determine the maximum tolerated dose (MTD) and the recommended phase 2 dose (RP2D) of IDP-121 combined with chemotherapy (topotecan day 1 to 5 every 3 weeks; carboplatin day 1 plus etoposide days 1, 2 and 3 every 3 weeks) in patients with SCLC. Expansion Phase (Phase 2): Primary objective To evaluate the overall response rate (ORR) and disease control rate (DCR) of IDP-121 combined with chemotherapy in patients with SCLC.
Investigators
Laura Nevola
Scientific
Idp Discovery Pharma S.L.
Eligibility Criteria
Inclusion Criteria
- •Inclusion Criteria Patients meeting all the following inclusion criteria will be eligible for participation in the study:
- •Age ≥18 years
- •Performance status (ECOG) ≤ 2
- •Life expectancy ≥2 months
- •Patient is, in the investigator’s opinion, willing and able to comply with the protocol requirements.
- •Patient has given voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care.
- •Patients diagnosed with advanced/extensive stage SCLC that have platinum-sensitive relapse after 1st line treatment defined as a Progression Free Interval (PFI) of ≥ 3 months (platinum-based chemotherapy plus IDP-121 arm) and patients with a PFI < 3 months (topotecan plus IDP-121 arm).
- •Adequate haematological or biochemical parameters as specified below a. Haemoglobin > 8.0 g/dl (without transfusion support within 7 days) b. Platelets count > 100 x109/L (without transfusion support within 7 days). c. Absolute neutrophil count (ANC) > 1.5 x109/L (without G-CSF support within 7 days) d. Aspartate transaminase (AST): <2.5 x the upper limit range. e. Alanine transaminase (ALT): < 2.5 x the upper limit range. f. Total bilirubin: < 2 x the upper limit range. g. Calculated or measured creatinine clearance: ≥ 60 mL/min (calculated from the Cockcroft-Gault formula).
- •Left ventricular ejection fraction > 50% or above the Institutional Lower Limit of Normal (LLN), whichever is lower, determined by echocardiogram.
Exclusion Criteria
- •Exclusion Criteria Patients eligible for this study must not meet any of the following criteria:
- •Persistent clinically significant or grade 3 or 4 non-haematological toxicity related to previous treatments. The presence of alopecia and NCI-CTC grade <2 symptomatic peripheral neuropathy is allowed.
- •Active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases (e.g., whole brain radiation treatment [WBRT], stereotactic radiosurgery, or equivalent) may participate only if they satisfy the following: • Completed treatment at least 14 days prior to the first dose of study intervention. • Are clinically stable, without requirement of steroid treatment > 10 mg or prednisone or equivalent for at least 7 days prior to first dose of study intervention.
- •Pregnant or lactating women; men and women of reproductive potential* (as defined in the Appendix 2) who are not using effective contraceptive methods (combined hormonal contraception associated with inhibition of ovulation; progestogen-only hormonal contraception associated with inhibition of ovulation, intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomized partner, sexual abstinence). *A woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. A man is considered fertile after puberty unless permanently sterile by bilateral orchidectomy.
- •History of any other neoplastic disease in the last five years (except basal cell carcinoma, skin epithelioma or carcinoma in situ of any site)
- •History of clinically significant hypotension.
- •History of clinically significant allergic or hyper-sensitivity reactions.
- •History or known clinically significant vascular disease or known high risk of vascular disease (as assessed by the treating physician) including (but not limited to): - Thromboembolism - Peripheral arterial disease - Vasculitis
- •Other relevant diseases or adverse clinical conditions: - Congestive heart failure or angina pectoris, myocardial infarction within 12 months before inclusion in the study. - Uncontrolled arterial hypertension or cardiac arrhythmias (i.e., requiring a change in medication within the last 3 months or hospital admission within the past 6 months). - History of significant neurological or psychiatric disorders
- •Clinically significant or active infection.
Outcomes
Primary Outcomes
Dose-Escalation (Phase 1) Primary Endpoint(s): • Maximum tolerated dose (MTD): based on the incidence of DLTs observed at the end of Cycle 1 (21 days). • Recommended phase 2 dose (RP2D): dose selected for the use in the expansion phase. The RP2D will be determined in discussion with the Investigators and the Sponsor based on safety (dose limiting toxicity), PK, PD, and efficacy observed across multiple dose-escalation cohorts.
Dose-Escalation (Phase 1) Primary Endpoint(s): • Maximum tolerated dose (MTD): based on the incidence of DLTs observed at the end of Cycle 1 (21 days). • Recommended phase 2 dose (RP2D): dose selected for the use in the expansion phase. The RP2D will be determined in discussion with the Investigators and the Sponsor based on safety (dose limiting toxicity), PK, PD, and efficacy observed across multiple dose-escalation cohorts.
Expansion-Phase (Phase 2) Primary Endpoint: The primary endpoint for the Expansion-Phase is the Overall Response Rate (ORR) and the disease control rate (DCR) based on the appropriate tumour specific guidelines/response criteria RECIST 1.1
Expansion-Phase (Phase 2) Primary Endpoint: The primary endpoint for the Expansion-Phase is the Overall Response Rate (ORR) and the disease control rate (DCR) based on the appropriate tumour specific guidelines/response criteria RECIST 1.1
Secondary Outcomes
- The secondary efficacy endpoints for the Expansion Phase: • Duration of response (DoR), defined as the time from documentation of disease response to disease progression.
- • Time to progression (TTP), time from the first treatment day to objective disease progression; does not include deaths.
- • Overall survival (OS) defined as the interval between the first treatment day to death from any cause.
- The secondary safety endpoints for the Expansion Phase are as follows: • Vital signs • Physical examination • Hematology • Biochemistry • Urinalysis • Electrocardiograms (ECG) • All grades AEs and SAEs