Palliative Radiotherapy With Lurbinectedin in Patients With Extensive Stage Small Cell Lung Cancer

NCT05244239 | Recruiting Phase 1 DMC FDA Drug

• 4 other identifiers: STUDY00003528NCI-2021-12410RAD5466-21P30CA138292
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 3

Brief Summary

This phase I trial aims to determine if it is safe to use palliative radiotherapy and lurbinectedin at the same time to treat small cell lung cancer that has spread outside of the chest and that has grown after being treated with chemotherapy (extensive stage). Lurbinectedin kills tumor cells by blocks a process called transcription that small cell lung cancer relies on to survive. It also damages the deoxyribonucleic acid (DNA) of tumor cells, which is similar to the way radiation kills tumor cells. Palliative radiotherapy is a routine medical treatment for patients who have lung cancer that has spread to other parts of the body (metastatic), and is used to relieve symptoms caused by cancer or to patients from developing symptoms. This trial may help doctors understand if treating patients with lurbinectedin and palliative radiotherapy at the same time would make them both work better than either one alone or if they could cause more side effects for patients when given together.

Conditions

Extensive Stage Lung Small Cell Carcinoma; Stage IV Lung Cancer AJCC v8

Outcome Measures

Primary Outcomes (1)

• Incidence of adverse events of palliative radio therapy (RT) with lurbinectedin

  Will be defined as having one or none of the following: * Grade 4 or 5 serious adverse events possibly, probably, or definitely related to protocol treatment from 30 days from the start of RT. * Any adverse events possibly, probably, or definitely related to protocol treatment that leads to prolonged dose delays (defined as with-holding of two consecutive doses of lurbinectedin). * Any adverse event possibly, probably, or definitely related to treatment resulting in the permanent discontinuation of lurbinectedin. Will be analyzed separately for safety cohorts 1 and 2 and will be summarized descriptively using frequencies and percentages. These will be compared to rates reported by Trigo et al. from lurbinectedin monotherapy.

  Up to 1 year

Secondary Outcomes (6)

• The number of dose reductions or interruptions possibly, probably, or definitely due to the delivery of protocol therapy

  30 days following completion palliative RT

• Response rate

  At 3 months post-RT

• Pain response rates

  At 3 months pre-treatment and 3 months post-RT

• Progression free survival (PFS)

  From protocol treatment initiation to disease progression or death, assessed up to 1 year

• Overall survival (OS)

  From treatment initiation to death, assessed up to 1 year

Other Outcomes (1)

• Hematologic toxicity rate

  Up to 1 year

Study Arms (1)

Treatment (lurbinectedin and palliative radiation therapy)

EXPERIMENTAL

Patients undergo palliative RT over 5 or 10 treatment fractions at the discretion of the treating physician daily for 21 days. Patients also receive lurbinectedin IV over 1 hour on day 1 of each cycle. Cycles of lurbinectedin repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Drug: Lurbinectedin; Radiation: Palliative Radiation Therapy

Interventions

Lurbinectedin DRUG

Given IV

Also known as: PM01183, Zepzelca

Treatment (lurbinectedin and palliative radiation therapy)

Palliative Radiation Therapy RADIATION

Undergo RT

Also known as: Palliative Radiotherapy

Treatment (lurbinectedin and palliative radiation therapy)

Eligibility Criteria

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

You may qualify if:

• Age \>= 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 3
• Patients with pathologically confirmed ES-SCLC who are receiving lurbinectedin or are candidates for lurbinectedin therapy after progression on first-line systemic therapy (either chemotherapy \[platinum etoposide\] or chemoimmunotherapy) at the discretion of the treating medical oncologist.
• Metastatic bone or visceral/lung metastatic disease as assessed computed tomography (CT), magnetic resonance imaging (MRI), bone scan or positron emission tomography (PET)/CT within 90 days prior to RT on this study.
• Patients with treated brain metastases are eligible but must require \< 10 mg of dexamethasone daily or its glucocorticoid equivalent. Brain metastases will not be treated in the context of this protocol.
• Absolute neutrophil count (ANC) \>= 1,500/cells/mm\^3
• Platelets \>= 100,000/cells/mm\^3
• Hemoglobin \> 7.0 g/dL
• Total Bilirubin ≤ 1.5 ULN
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =\< 3.0 x ULN (=\< 5.0x ULN for liver involvement)
• Alkaline phosphatase =\< 2.5x ULN (=\< 5.0x with documented liver or bone metastases)
• Based on its mechanism of action, lurbinectedin could cause harm when administered to a pregnant woman. Taken together with the known teratogenicity of RT, female of child-bearing potential (FCBP) must have a negative serum or urine pregnancy test prior to starting protocol therapy. A female of childbearing potential (FCBP) is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months.
• FCBP and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation and 6 months after the final dose of lurbinectedin. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of lurbinectedin administration. FCBP who are currently breastfeeding must discontinue during and up to 2 weeks after the final dose of lurbinectedin.
• Completion of all previous cancer-directed therapies (excluding lurbinectedin) for the treatment of cancer \>= 3 weeks before the start of study therapy.
• Willingness and ability of the subject to comply with scheduled visits, drug administration plan, protocol-specified laboratory tests, other study procedures, and study restrictions.

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participation in this study:
• Pregnancy or breastfeeding within 2 weeks
• Patients may not enroll in both safety cohorts
• Patients who have received prior RT will be permitted to enroll. However, the metastases treated on this study must be \> 2 cm from the following previously irradiated structures:
• Spinal cord previously irradiated to \> 40 Gy (delivered in =\< 3Gy/fraction)
• Brachial plexus previously irradiated to \> 50Gy (delivered in =\< 3Gy/fraction)
• Small intestine, large intestine, or stomach previously irradiated to \> 45Gy (delivered in =\< 3Gy/fraction)
• Brainstem previously irradiated to \> 50Gy (delivered in =\< 3Gy/fraction)
• Lungs previously irradiated with prior V20Gy \> 35 percent (delivered in =\< 3Gy/fraction)

Sponsors & Collaborators

• Emory University: lead
• National Cancer Institute (NCI): collaborator
• Jazz Pharmaceuticals: collaborator

Study Sites (3)

Emory University Hospital Midtown

Atlanta, Georgia, 30308, United States

NOT YET RECRUITING

Emory University

Atlanta, Georgia, 30322, United States

RECRUITING

Emory Saint Joseph's Hospital

Atlanta, Georgia, 30342, United States

NOT YET RECRUITING

MeSH Terms

Conditions

Lung Neoplasms

Interventions

PM 01183

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Kristin Higgins, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kristin Higgins, MD

CONTACT

404.778.3473; Kristin.higgins@emory.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 8, 2022
• First Posted: February 17, 2022
• Study Start: July 27, 2022
• Primary Completion (Estimated): July 28, 2026
• Study Completion (Estimated): July 28, 2027
• Last Updated: October 31, 2025

Record last verified: 2025-10

Locations

US (3)