A Randomized Phase II Basket Trial EXTENDing Efficacy of Systemic Therapy With Local Consolidative Therapy for OligoProgressive Metastatic Disease (EXTEND-OP)

NCT06367972 | Recruiting Phase 2 DMC

• 2 other identifiers: 2024-0070NCI-2024-03278
• Study Type: interventional
• Target: 400
• Locations: 1 country
• Sites: 1

Brief Summary

To find out if local consolidation therapy (such as radiation therapy with or without other local therapies such as surgery, ablation \[the removal or destruction of a body part or tissue or its function\], or embolization \[a procedure that uses particles, such as tiny gelatin sponges or beads, to block a blood vessel\]) to all progressive sites of disease can help to control the disease compared with next-line systemic therapy.

Conditions

OligoProgressive Metastatic Disease

Outcome Measures

Primary Outcomes (1)

• Safety and adverse events (AEs)

  Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0

  Through study completion; an average of 1 year.

Study Arms (2)

NLST Arm

EXPERIMENTAL

Participants are assigned to Group 1, participants will be treated with next-line systemic therapy. The specific next-line systemic therapy will be determined by your doctor. \- If progression occurs (the disease gets worse), participants may cross over to Group 2 and receive LCT.

Procedure: Next-line Systemic Therapy

LCT Arm

EXPERIMENTAL

Participants are assigned to Group 2, participants will be treated with LCT and then continue on same systemic therapy participants have been receiving followed by the next line systemic of therapy (if applicable). The specific treatments will be determined by your doctor.

Procedure: Local Consolidation Therapy

Interventions

Local Consolidation Therapy PROCEDURE

Participants may receive radiation therapy. The choice of LCT and radiation therapy regimen will be determined by a multidisciplinary team including the study doctor.

Also known as: LCT

LCT Arm

Next-line Systemic Therapy PROCEDURE

The specific next-line systemic therapy will be determined by your doctor.

Also known as: NLST

NLST Arm

Eligibility Criteria

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

You may qualify if:

• Age ≥18
• Histologically or cytologically confirmed stage IV cancer.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤2
• Candidate for LCT (radiation therapy +/- other local therapies such as surgery, ablation, or embolization) to all sites of progressive disease.
• Progressive disease will be defined as a discrete radiologic lesion that has not received prior local therapy. Progressive disease will be defined as RECIST (v1.1) defined progression from pre-baseline imaging to baseline imaging at time of screening for the trial.
• Progressive disease must represent an active lesion, which may be defined as the primary tumor site, regional nodal disease, and/or distant metastatic sites.
• Candidate for radiation therapy to at least one site of disease.
• Between one and five progressive lesions, counted as follows: each lesion (not site) will be counted as one, with the exception of metastatic lymph node stations, which will collectively count as one lesion. Regional nodal stations will be counted as a collective single lesion if oligoprogressive. All progressive lesions must be amenable to local therapy as noted in criterion 4.2.1.5 above.
• Counting of oligoprogressive nodal disease will be based on nodal chains. A nodal chain will be considered a single metastatic lesion if the presence of that node results in the patient as having M1 disease per the TNM staging system, AJCC version 8.0. In addition, one of the following criteria must be met: a) ≥1 LN meets radiologic criteria for metastatic disease via RECIST 1.1 (short axis ≥15mm), b) pathologic assessment has confirmed the presence of metastatic cancer cells, and/or c) the LN exhibits imaging signal characteristic of a metastatic lesion (e.g. FDG avidity, contrast enhancement, etc…). In the event of ambiguity, a study co-Investigator will make a final determination of whether pathologic criteria are met. The following caveats apply:
• In participants with a LN exhibiting a short axis ≥15mm and who have other diagnoses that can produce enlarged LNs (e.g. indolent CLL, sarcoidosis, etc…) or a prior history of benign enlarged LNs will not be considered to have metastatic disease per the discretion of the treating physician.
• LN chains that occur bilaterally will be considered separate metastatic sites. For example, left axilla LNs will counted separately from right axilla LNs.
• The following midline LN chains will be counted as 1 metastatic site: mediastinal, para-aortic, mesenteric.
• The following bilateral LN chains will be counted as 1 metastatic site for unilateral involvement, and 2 for bilateral for involvement: preauricular, cervical and occipital, supraclavicular, infraclavicular, pectoral, axillary, hilar, epitrochlear and brachial, iliac, inguinal and femoral, popliteal.
• Baseline imaging must include a scan done within 4 weeks prior to randomization, demonstrating oligoprogressive disease by RECIST (v1.1) criteria compared to pre-baseline imaging.
• Baseline imaging must be done within 4 weeks prior to randomization, and the following imaging is required: PET/CT scan or CT scan of the chest/abdomen/pelvis. MRI may be substituted as indicated (i.e., CT scan of chest plus MRI abdomen/pelvis). Intracranial imaging is recommended for those histologies/disease sites where intracranial restaging is routinely recommended or appropriate as part of staging/restaging standard-of-care.

You may not qualify if:

• Metastatic effusion (e.g. pleural effusion or ascites). Note that participants with an effusion that is too small to sample will be eligible for the trial.
• Leptomeningeal disease.
• Peritoneal carcinomatosis.
• Cognitively impaired subjects (e.g. inability to sign informed consent.)
• Any condition that, in the opinion of the investigator, would interfere with the study treatment or interpretation of the study results.
• Diffuse bone marrow involvement as defined by disease involvement of a BM biopsy from a site that does not have radiologic evidence of a bone metastasis.
• More than 4 prior lines of systemic therapy to treat metastatic disease.
• Diagnosis of active scleroderma, lupus, or other rheumatologic disease which in the opinion of the treating radiation oncologist precludes safe delivery of radiotherapy.
• Known psychiatric or substance abuse disorder/s that would interfere with trial participation.
• Concurrent (synchronous or metachronous) other primary malignancy that in the opinion of the treating physician team presents a substantial risk to the participant's life as a competing risk of death (against the primary oligoprogressive malignancy being considered for LCT as part of this trial).

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• MD Anderson Cancer Center

Study Officials

• Ethan Ludmir

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ethan Ludmir, MD

CONTACT

(832) 729-0998; ebludmir@mdanderson.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 11, 2024
• First Posted: April 16, 2024
• Study Start: June 6, 2024
• Primary Completion (Estimated): October 10, 2028
• Study Completion (Estimated): October 10, 2030
• Last Updated: November 26, 2025

Record last verified: 2025-11

Locations

US (1)