Trial Title:
A Randomized Phase II Basket Trial EXTENDing Efficacy of Systemic Therapy With Local Consolidative Therapy for OligoProgressive Metastatic Disease (EXTEND-OP)
NCT ID:
NCT06367972
Condition:
OligoProgressive Metastatic Disease
Conditions: Official terms:
Neoplasm Metastasis
Neoplasms, Second Primary
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Local Consolidation Therapy
Description:
Participants may receive radiation therapy. The choice of LCT and radiation therapy
regimen will be determined by a multidisciplinary team including the study doctor.
Arm group label:
LCT Arm
Other name:
LCT
Intervention type:
Procedure
Intervention name:
Next-line Systemic Therapy
Description:
The specific next-line systemic therapy will be determined by your doctor.
Arm group label:
NLST Arm
Other name:
NLST
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- 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.
- Pre-baseline imaging must be done 6-16 weeks prior to baseline imaging, and it is
recommended to have a comparable imaging modality (matched modalities between
pre-baseline and baseline imaging). RECIST v1.1 will be utilized to define any
progressive sites of disease, and if between 1 and 5 RECIST-defined progressive
sites of disease are identified, participant may be eligible. Non-RECIST-eligible
lesions may be eligible if radiographic and/or clinical features support this lesion
being progressive.
- Participants referred for the study that require immediate LCT can receive treatment
to CNS lesions or other symptomatic lesions prior to randomization, but these
lesions will be counted towards the total number of oligoprogressive lesions.
- Has one of the following 7 histologic types (metastatic disease): colorectal
carcinoma (CRC), renal cell carcinoma (RCC), breast cancer, pancreatic cancer,
urothelial (bladder) cancer, prostate cancer, and esophageal cancer.
- Females of childbearing potential must not be breast feeding and must have a
negative serum or urine pregnancy test and must agree to use adequate contraception
from the time of screening until 3 months after discontinuation of the study
medication. Acceptable methods of contraception include total and true sexual
abstinence, tubal ligation, hormonal contraceptives that are not prone to drug-drug
interactions (IUS Levonorgestrel Intra Uterine System (Mirena), Medroxyprogesterone
injections (Depo-Provera)), copper-banded intra-uterine devices, and vasectomized
partner. All hormonal methods of contraception should be used in combination with
the use of a condom by their sexual male partner. Females of childbearing potential
are defined as those who are not surgically sterile (ie, bilateral tubal ligation,
bilateral oophorectomy, or complete hysterectomy) or postmenopausal (defined as 12
months with no menses without an alternative medical cause). Women will be
considered post-menopausal if they have been amenorrheic for the past 12 months
without an alternative medical cause. The following age-specific requirements must
also apply: Women < 50 years old: they would be considered post-menopausal if they
have been amenorrheic for the past 12 months or more following cessation of
exogenous hormonal treatments. The levels of Luteinizing Hormone (LH) and
Follicle-Stimulating Hormone (FSH) must also be in the post-menopausal range (as per
the institution). Women ≥ 50 years old: they would be consider post-menopausal if
they have been amenorrheic for the past 12 months or more following cessation of all
exogenous hormonal treatments, or have had radiation-induced oophorectomy with the
last menses > 1 year ago, or have had chemotherapy-induced menopause with >1 year
interval since last menses, or have had surgical sterilization by either bilateral
oophorectomy or hysterectomy.
- Non-sterilized males who are sexually active with a female partner of childbearing
potential must use adequate contraception for the duration of the study and 3 month
after the last dose of study medication. Adequate contraception methods include:
birth control pills (eg combined oral contraceptive pill), barrier protection (eg
condom plus spermicide, cervical/vault cap or intrauterine device), and abstinence.
Participants should not father a child for 6 months after completion of the study
medication. Participants should refrain from donating sperm from the start of dosing
until 6 months after discontinuing the study medication. If male participants wish
to father children they should be advised to arrange for freezing of sperm samples
prior to the start of the study medication.
- Demonstration of adequate organ function as defined in the table below, all
screening labs to be performed within 4 weeks prior to study enrollment:
- Table of Adequate Organ Function Laboratory Values System Laboratory Value
Hematological Absolute neutrophil count (ANC) = ≥500 /mcL Platelets = ≥25,000 / mcL
Hemoglobin = ≥7 g/dL Hepatic Serum total bilirubin = ≤ 1.5 mg//dl (except for
subjects with Gilbert Syndrome, who may have total bilirubin <3.0 mg/dl) OR Direct
bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 mg/dl AST (SGOT) and
ALT (SGPT) = ≤ 3 X ULN OR ≤ 5 X ULN for subjects with liver metastases
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).
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
MD Anderson Cancer Center
Address:
City:
Houston
Zip:
77030
Country:
United States
Status:
Recruiting
Contact:
Last name:
Ethan Ludmir, MD
Phone:
832-729-0998
Email:
ebludmir@mdanderson.org
Investigator:
Last name:
Ethan Ludmir, MD
Email:
Principal Investigator
Start date:
June 6, 2024
Completion date:
October 10, 2030
Lead sponsor:
Agency:
M.D. Anderson Cancer Center
Agency class:
Other
Source:
M.D. Anderson Cancer Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06367972
http://www.mdanderson.org
