A Randomized Phase II Basket Trial EXTENDing Efficacy of Systemic Therapy With Local Consolidative Therapy for OligoProgressive Metastatic Disease (EXTEND-OP)
Overview
- Phase
- Phase 2
- Intervention
- Not specified
- Conditions
- OligoProgressive Metastatic Disease
- Sponsor
- M.D. Anderson Cancer Center
- Enrollment
- 400
- Locations
- 1
- Primary Endpoint
- Safety and adverse events (AEs)
- Status
- Recruiting
- Last Updated
- 5 months ago
Overview
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.
Detailed Description
Primary Objective: • To determine whether, in participants with oligoprogressive metastatic disease, LCT to all progressive sites of disease offers a benefit in PFS compared to NLST, across seven tumor types in a basket design. Secondary Objectives: * To determine whether LCT improves OS in participants with oligoprogressive disease across seven tumor types. * To assess safety/tolerability of LCT in participants with oligometastatic disease in tumor subtypes. * To compare quality of life (QOL) of LCT vs. next-line systemic therapy in participants with oligoprogressive disease. * To characterize duration and progression-free survival time of participants on same-line systemic therapy (SLST) after LCT in the experimental arm. * To identify predictive/prognostic biomarkers correlated with a benefit for LCT across tumor types, with the aim being to incorporate these biomarkers into future clinical trials.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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.
- •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.
Exclusion Criteria
- •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).
Outcomes
Primary Outcomes
Safety and adverse events (AEs)
Time Frame: Through study completion; an average of 1 year.
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0