Study to Assess Safety,Tolerability,Efficacy of PM01183 and Atezolizumab in Patients w/ Advanced Small Cell Lung Cancer.

NCT04253145 | Unknown Phase 1 DMC

• 1 other identifier: 2SMALL
• Study Type: interventional
• Target: 184
• Locations: 1 country
• Sites: 13

Brief Summary

Prospective, open-label, uncontrolled and multicenter phase I-II study in SCLC patients with ECOG PS 0-1 who have failed one prior platinum-containing line but no more than one chemotherapy-containing line. The study will be divided into two parts: a dose-ranging phase I with escalating doses of PM01183 in combination with a fixed dose of atezolizumab, followed by a single-arm phase II part with expansion at the RD determined during the phase I.

Conditions

Carcinoma, Small Cell Lung

Outcome Measures

Primary Outcomes (2)

• Determination of Maximum Tolerable Dose

  The MTD will be the lowest dose level explored during dose escalation at which more than one third of evaluable patients experience a DLT during Cycle 1.

  one cycle - 21 days

• Determination Recomended Dose:

  The RD will be the highest dose level explored during dose escalation at which less than one third of evaluable patients experience a DLT during Cycle 1.

  one cycle - 21 days

Secondary Outcomes (11)

• Progression-free survival

  the time from the date of registration to the date of documented progression per RECIST v.1.1 or death, assessed approximately up to 30 months

• Duration of response

  from the date of first documentation of response per RECIST v.1.1 (complete or partial response, whichever comes first) to the date of documented PD or death, assessed approximately up to 30 months

• Clinical benefit

  ≥3 months

• Overall survival

  from the date of registration to the date of death or last contact; approximately 30 months

• Mid- and long-term survival

  12, 18 and 24 months

Study Arms (1)

PM01183 w/ Atezolizumab

EXPERIMENTAL

Patients will receive atezolizumab at a fixed dose of 1200 mg intravenously (i.v.) as a 60-minute infusion (the second and subsequent infusions may be administered over 30 minutes) followed by PM01183 at a starting dose of 2.5 mg/m2 i.v. as a 1-hour infusion on Day 1 every three weeks (q3wk). Following analysis of cohorts, dose levels can be escalated from 2.5mg to 3.2, to a maximum dose of 3.5 mg of PM01183

Drug: PM 01183; Drug: Atezolizumab

Interventions

PM 01183 DRUG

Lyophilisate for solution for infusion

Also known as: Lurbinectidin

PM01183 w/ Atezolizumab

Atezolizumab DRUG

Concentrate for solution for infusion

Also known as: Tecentriq

PM01183 w/ Atezolizumab

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntarily signed and dated written informed consent prior to any specific study procedure.
• Age \>18 years.
• Histologically or cytologically confirmed diagnosis of extensive or limited SCLC.
• Progression to first-line platinum-based chemotherapy. For phase II part: Progression to first- line platinum-based chemotherapy or first- line platinum- based chemotherapy and immunoterapy (anti PD1/ PDL1). A chemotherapy and/ or immunotherapy- free interval (CTFI, time from the last dose of first-line chemotherapy to the occurrence of progressive disease) ≥ 30 days.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) score ≤1.
• Measurable disease according to RECIST v.1.1. Note: irradiated lesions may qualify as target if progression has been documented.
• At least three weeks since last prior anticancer treatment (including radiotherapy) and recovery to grade ≤ 1 from any adverse event (AE) related to previous anticancer treatment (excluding sensory neuropathy, anemia, asthenia and alopecia, all grade ≤ 2) according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE, v.5).
• Platelet count ≥100 x 109/L, hemoglobin ≥9.0 g/dL and absolute neutrophil count (ANC) ≥1.5 x 109/L.
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3.0 x the upper limit of normal (ULN), independently of the presence of liver metastases.
• Alkaline phosphatase (AP) ≤2.5 x ULN.
• Total bilirubin ≤1.5 x ULN or direct bilirubin ≤ULN
• International Normalized Ratio (INR) \<1.5 (except if patient is on oral anticoagulation therapy).
• Calculated creatinine clearance (CrCL) ≥30 mL/minute (using Cockcroft and Gault´s formula).
• Creatine phosphokinase (CPK) ≤2.5 x ULN.
• Thyroid stimulating hormone (TSH) within institutional normal limits. If TSH is above the ULN, then a free T4 within institutional normal limits is acceptable.

You may not qualify if:

• Active or untreated central nervous system (CNS) involvement. Treated CNS metastases have to show radiographic stability (defined as no CNS progression for at least three weeks from post-radiotherapy brain scan to brain scan performed prior study entry), and patients should not have neurologic sign/symptoms secondary to the brain metastases or RT. Any steroid treatment must be completed ≥ 14 days before first dose of study treatment.
• More than one prior chemotherapy-containing line (re-challenge with the same initial regimen is not allowed).
• Patients with radiation therapy (RT) in more than 35% of the bone marrow.
• History of previous bone marrow and/or stem cell transplantation.
• Impending need for RT (e.g., painful bone metastasis and/or risk of spinal cord compression).
• History of allergy or hypersensitivity to any of the study drugs or their excipients.
• Prior therapy with PM01183, antibodies against PD-1, PD-L1, PD-L2, CD137, or cytotoxic T lymphocyte associated antigen-4 (CTLA-4). For phase II part: Prior therapy with PM01183, PD-L2, CD137, or cytotoxic T lymphocyte associated antigen-4 (CTLA-4).
• Live vaccines within 30 days prior to start of study treatment and while on treatment.
• History of other prior malignancy, with the exception of basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, in situ cervical cancer. Patients with other prior malignancies and no disease recurrence for 3 years are eligible.
• Concomitant diseases/conditions:
• History or presence of unstable angina, myocardial infarction, congestive heart failure defined as abnormal left ventricular ejection fraction (LVEF) \< 50% assessed by multiple-gated acquisition scan (MUGA) or equivalent by ultrasound (US), or clinically significant valvular heart disease within 12 months prior first study dose.
• Symptomatic arrhythmia or any uncontrolled arrhythmia requiring ongoing treatment.
• Ongoing chronic alcohol consumption, or cirrhosis with Child-Pugh score B or C.
• Active uncontrolled infection. Serious non-healing wound, ulcer or bone fracture.
• Diagnose of immunodeficiency or receiving systemic steroids therapy (more than a daily dose of 10 mg of prednisone or equivalent per day) or any other form of immunosuppressive therapy within 14 days prior to the first study dose.

Sponsors & Collaborators

• Fundacion Oncosur: lead

Study Sites (13)

Hospital Virgen de la Victoria

Málaga, Andalusia, Spain

RECRUITING

Hospital Virgen del Rocio

Seville, Andalusia, Spain

RECRUITING

Hospital Universitario Marqués de Valdecilla

Santander, Cantabria, Spain

RECRUITING

Hospital Vall d'Hebron

Barcelona, Catalonia, Spain

RECRUITING

Hospital Universitario Da Coruña

A Coruña, Spain

RECRUITING

Hospital Clínic de Barcelona

Barcelona, Spain

RECRUITING

Hospital de la Santa Creu i Sant Pau

Barcelona, Spain

RECRUITING

Hospital 12 de Octubre

Madrid, Spain

RECRUITING

Hospital Universitario La Paz

Madrid, Spain

RECRUITING

Hospital Universitario Ramón y Cajal

Madrid, Spain

RECRUITING

Hospital Clínico Universitario Virgen de la Arrizaca

Murcia, Spain

RECRUITING

Hospital Universitario Virgen Macarena

Seville, Spain

RECRUITING

Hospital Clínico Universitario Lozano Blesa

Zaragoza, Spain

RECRUITING

MeSH Terms

Conditions

Small Cell Lung Carcinoma

Interventions

PM 01183; atezolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Santiago Ponce, MD

  Hospital 12 de Octubre

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Luis Paz Ares, MD PhD

CONTACT

+ 34 91 390 8000; lpazaresr@seom.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Model Details: Prospective, open-label, uncontrolled and multicenter phase I-II study

Study Record Dates

• First Submitted: January 21, 2020
• First Posted: February 5, 2020
• Study Start: December 13, 2019
• Primary Completion: May 1, 2025
• Study Completion: May 1, 2025
• Last Updated: November 18, 2023

Record last verified: 2023-11

Locations

ES (13)