A multiple center expanded access program (EAP) for the treatments of patients with advanced solid tumors

Phase 1

• Conditions: Advanced or metastatic solid tumors with activating Rearranged During Transfection (RET) alterations (and other evidence of RET activation); MedDRA version: 21.0Level: LLTClassification code 10049280Term: Solid tumourSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: PTClassification code 10061873Term: Non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: PTClassification code 10027105Term: Medullary thyroid cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2019-002319-25-IT
• Lead Sponsor: OXO ONCOLOGY INCORPORATED

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-09-01
• Last Update Posted: 7 September 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 450

Inclusion Criteria

Major Inclusion Criteria:
1. Patients with a locally advanced or metastatic solid tumor with RET activation who:
• Are not eligible for an ongoing selpercatinib clinical trial (e.g., for clinical, geographic or financial reasons or due to cohort closure), but are deemed appropriate candidates to receive selpercatinib treatment by the Investigator and the Sponsor, and
• Have progressed on or are intolerant to standard therapy, or
• No standard therapy exists, or
• In the opinion of the Investigator, are not candidates for or who would be unlikely to derive significant clinical benefit from standard therapy
Patients eligible for LIBRETTO-001 and/ or Phase 3 trials who are being considered for the EAP must be discussed with the Medical Monitor prior to screening.
2. Evidence of an activating RET gene alteration from a laboratory with Clinical Laboratory Improvement Act (CLIA), International Organization for Standardization (ISO)/independent ethics committee (IEC), College of American Pathologists (CAP), or other similar certification.
3. Eighteen years of age or older at the time of consent.
4. Adequate hematologic, renal and hepatic function as defined in Section 6.1.
5. Ability to provide consent.
6. Provision of a signed informed consent prior to any protocol specific procedures. Patients already receiving selpercatinib who enroll in this protocol must be reconsented and sign the consent form for this expanded access protocol.
7. Patients who are deemed eligible by the Sponsor’s medical monitor.
8. Willingness of men and women of reproductive potential to observe double effective birth control methods, defined as one used by the patient and another by his/her partner, for the duration of treatment and for 3 months following the last dose of study treatment (refer to Section 1.6.3).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 350
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 100

Exclusion Criteria

Major Exclusion Criteria:
1. Investigational agent (via clinical trial) or anticancer therapy within 5 half-lives or 2 weeks (whichever is shorter) prior to planned start of selpercatinib unless considered by the Investigator to be safe, within the best interest of the patient and with prior Sponsor approval.
2. Clinically significant active cardiovascular disease (including NYHA class III/IV heart failure, stroke, severe valvular disease or uncontrolled hypertension defined as = 140/80 sustained over multiple readings) or history of myocardial infarction within 6 months prior to Cycle 1, Day 1 (C1D1); ongoing cardiomyopathy; or current prolongation of the QT interval corrected for heart rate using Fridericia’s formula (QTcF) interval > 470 msec. Patients who meet this criteria may be enrolled (with a modified dosing strategy) if a clinical rationale exists which is reviewed and agreed upon by the Sponsor.
3. Current treatment with strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers (refer to Section 1.6.3).
4. Current treatment with proton-pump inhibitors (PPIs). Note: Treatment with PPIs must be stopped 1 or more weeks prior to the first dose of selpercatinib.
Complete EAP eligibility criteria are presented in Section 4.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Secondary Objective: To determine the safety profile and tolerability of Selpercatinib.;Primary end point(s): As an expanded access program (EAP), this program is not designed to assess the effectiveness of selpercatinib. Data collection will be limited to information needed to determine eligibility, describe patient demographics and exposure, collect safety information, and meet regulatory reporting requirements.;Timepoint(s) of evaluation of this end point: Not Applicable;Main Objective: To provide access to Selpercatinib for patients with locally advanced or metastatic solid tumors with activating RET alterations (and other evidence of RET activation) who are 18 years of age or older.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Not Applicable;Timepoint(s) of evaluation of this end point: Not Applicable