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Metastatic Carcinoma in the Adrenal CortexPhase 2NCT03370718

Cabozantinib in Treating Patients With Locally Advanced or Metastatic Unresectable Adrenocortical Carcinoma

A Phase 2 study testing Cabozantinib, Pharmacogenomic Study and Pharmacokinetic Study in people with Metastatic Carcinoma in the Adrenal Cortex and Stage III Adrenal Cortex Carcinoma AJCC v8, run by M.D. Anderson Cancer Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This phase II trial studies how well cabozantinib works in treating patients with adrenal cortex cancer that has spread to nearby tissue, lymph nodes (locally advanced), or other places in the body (metastatic), and cannot be removed by surgery (unresectable). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Cabozantinib, Pharmacogenomic Study and Pharmacokinetic Study
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
1 siteUnited States
Study dates
26 Feb 2018to 12 Jan 2024
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histological confirmation of adrenocortical carcinoma (ACC) based on either: i). Weiss Score of >= 3 in patients who had earlier surgical resection OR ii). biopsy results compatible with ACC in the context of clinical setting highly suggestive of ACC (adrenal mass > 4 cm invading surrounding organs or associated with distant metastases).
  • Locally advanced or metastatic disease not amenable to surgery with curative intent with measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as determined by the investigator based on an assessment of all known disease sites by computerized tomography (CT) scan or magnetic resonance imaging (MRI) of chest/abdomen/pelvis within 28 days before the first dose of cabozantinib. In patients with intravenous (IV) contrast allergy or borderline renal function, CT without IV contrast or 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) CT may be used as clinically indicated.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
  • Recovery to baseline or =< grade 1 CTCAE v.4.0 from toxicities related to any prior treatments, unless adverse events (AEs) are clinically nonsignificant and/or stable on supportive therapy.
  • Life expectancy of at least 3 months.
  • Absolute neutrophil count (ANC) >= 1500/mm^3 without colony stimulating factor support (obtained within 28 days prior to the first dose of cabozantinib).
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  • Platelets >= 100,000/mm^3 (obtained within 28 days prior to the first dose of cabozantinib).
  • Hemoglobin >= 9 g/dL (obtained within 28 days prior to the first dose of cabozantinib).
  • Bilirubin =< 1.5 x the upper limit of normal (ULN). For subjects with known Gilbert's disease, bilirubin =< 3.0 mg/dL (obtained within 28 days prior to the first dose of cabozantinib).
  • Serum albumin >= 2.8 g/dl (obtained within 28 days prior to the first dose of cabozantinib).
  • Serum creatinine =< 1.5 x ULN or creatinine clearance (CrCl) >= 50 mL/min. For creatinine clearance estimation, the Cockcroft and Gault equation should be used (obtained within 28 days prior to the first dose of cabozantinib).
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3.0 x ULN (obtained within 28 days prior to the first dose of cabozantinib).
  • Lipase =< 2.0 x the upper limit of normal and no radiologic or clinical evidence of pancreatitis (obtained within 28 days prior to the first dose of cabozantinib).
  • Urine protein/creatinine ratio (UPCR) =< 1 (obtained within 28 days prior to the first dose of cabozantinib).
  • Serum phosphorus >= 2.5 mg/dl (obtained within 28 days prior to the first dose of cabozantinib).
  • Calcium >= 8 mg/dL (obtained within 28 days prior to the first dose of cabozantinib).
  • Magnesium >= 1.2 mg/dL (obtained within 28 days prior to the first dose of cabozantinib).
  • Potassium >= 3.0 meq/L (obtained within 28 days prior to the first dose of cabozantinib).
  • Capable of understanding and complying with the protocol requirements and has signed the informed consent document.
  • Sexually active patients (men and women) must agree to use medically accepted barrier methods of contraception (e.g. male or female condom) during the course of the study and for 4 months after the last dose of study drug(s), even if oral contraceptives are also used. All sexually active subjects of reproductive potential must agree to use both a barrier method and a second method of birth control during the course of the study and for 4 months after the last dose of study drug(s).
  • Women of childbearing potential must have a negative pregnancy test at screening. Women of childbearing potential include women who have experienced menarche and who have not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or are not postmenopausal. Postmenopause is defined as amenorrhea >= 12 consecutive months. Note: women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, anti-estrogens, ovarian suppression or any other reversible reason.

Who cannot join

  • Received cytotoxic chemotherapy, radiation therapy, or targeted therapy (including investigational cytotoxic chemotherapy) or biologic agents (e.g., cytokines or antibodies) within 28 days of study enrollment.
  • For patients who received mitotane within 6 months of consenting, mitotane should have been stopped at least 28 days prior to study enrollment AND to have mitotane serum level of < 2 mg/L.
  • Prior treatment with cabozantinib or other cMET inhibitors.
  • Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks before the first dose of study treatment. Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of the start of study treatment.
  • The subject has not recovered to baseline or CTCAE =< grade 1 from toxicity due to all prior therapies except alopecia and other non-clinically significant AEs.
  • Prothrombin time (PT)/ international normalized ratio (INR) or partial thromboplastin time (PTT) test >= 1.3 x the laboratory ULN within 28 days before the first dose of study treatment.
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  • Concomitant anticoagulation with oral anticoagulants (e.g., warfarin, direct thrombin and Factor Xa inhibitors), platelet inhibitors (e.g., clopidogrel) or therapeutic doses of low molecular weight heparins (LMWH). Low dose aspirin for cardioprotection (per local applicable guidelines) and low-dose LMWH are permitted. Anticoagulation with therapeutic doses of LMWH is allowed in subjects who are on a stable dose of LMWH for at least 6 weeks before the first dose of study treatment, and who have had no clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor.
  • Severe and uncontrolled Cushing syndrome despite medical management (e.g., systolic blood pressure > 160 mmHg or hyperglycemia with fasting glucose above 300 mg/dL).
  • The use of strong CYP3A4 inhibitor (with the exception of ketoconazole).
  • The subject has experienced any of the following: a. clinically-significant gastrointestinal bleeding within 6 months before the first dose of study treatment; b. hemoptysis >= 0.5 teaspoon (2.5 mL) of red blood within 3 months before the first dose of study treatment; c. any other signs indicative of pulmonary hemorrhage within 3 months before the first dose of study treatment. Tumor invading any major blood vessel at the time of study enrollment.
  • Evidence of tumor invading the gastrointestinal (GI) tract (esophagus, stomach, small or large bowel, rectum or anus), or any evidence of endotracheal or endobronchial tumor within 28 days before the first dose of cabozantinib, or the subject with radiographic evidence of cavitating pulmonary lesion(s); or subjects with tumor invading or encasing any major blood vessels.
  • Uncontrolled, significant concurrent or recent illness including, but not limited to, the following conditions: a. Cardiovascular disorders including i. congestive heart failure (CHF): New York Heart Association (NYHA) class III (moderate) or class IV (severe) at the time of screening ii. concurrent uncontrolled hypertension defined as sustained blood pressure (BP) > 150 mm Hg systolic, or > 90 mm Hg diastolic despite optimal antihypertensive treatment within 7 days of the first dose of study treatment iii. any history of congenital long QT syndrome or iv. any of the following within 6 months before the first dose of study treatment: unstable angina pectoris, clinically-significant cardiac arrhythmias, stroke (including transient ischemic attack [TIA], or other ischemic event) within 90 days of the first dose of study treatment, myocardial infarction, clinically significant thromboembolic event within 42 days of randomization requiring therapeutic anticoagulation.
  • (Note: subjects with a venous filter (e.g. vena cava filter) are not eligible for this study) b. gastrointestinal disorders particularly those associated with a high risk of perforation or fistula formation including: i. any of the following within 28 days before the first dose of study treatment: intra-abdominal tumor/metastases invading GI mucosa, active peptic ulcer disease; patients must be completely recovered, inflammatory bowel disease (including ulcerative colitis and Crohn's disease), acute pancreatitis, pancreatic duct or common bile duct obstruction, acute diverticulitis, acute cholecystitis, symptomatic cholangitis or recent appendicitis within 1 month of first dose of cabozantinib; patients must be completely recovered from these conditions, clinically significant malabsorption syndrome, c. endocrine disorders, uncontrolled Cushing syndrome despite of adequate medical therapy.
  • Any of the following within 6 months before the first dose of study treatment: abdominal fistula, gastrointestinal perforation, bowel obstruction or gastric outlet obstruction, intra-abdominal abscess. Note: complete resolution of an intra-abdominal abscess must be confirmed prior to initiating treatment with cabozantinib even if the abscess occurred more than 6 months before the first dose of study treatment. Other disorders associated with a high risk of fistula formation including percutaneous endoscopic gastrostomy (PEG) tube placement within 90 days before the first dose of study therapy.
  • Other clinically significant disorders such as: i. active infection requiring systemic antibiotic treatment within 14 days before the first dose of study treatment ii. serious non-healing wound/ulcer/bone fracture within 28 days before the first dose of study treatment iii. history of organ transplant iv. concurrent uncompensated hypothyroidism or thyroid dysfunction (thyroid-stimulating hormone [TSH] above 10) within 28 days before the first dose of study treatment v. major surgery within 12 weeks before the first dose of study treatment. Complete wound healing from major surgery must have occurred 1 month before the first dose of study treatment. Minor surgery within 28 days before the first dose of study treatment with complete wound healing at least 10 days before the first dose of study treatment. Subjects with clinically relevant ongoing complications from prior surgery are not eligible.
  • Unable to swallow tablets.
  • A corrected QT interval calculated by the Fridericia formula (QTcF) > 500 milliseconds within 28 days before first dose of study treatment.
  • Pregnant or breastfeeding.
  • A previously identified allergy or hypersensitivity to components of the study treatment formulation.
  • Unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee.
  • Evidence within 2 years of the start of study treatment of another malignancy which required systemic treatment except for breast ductal carcinoma-in situ, cured non-melanoma skin cancer, or cured in situ cervical carcinoma.
  • Any other severe acute or chronic medical or psychiatric condition or laboratory abnormality which, in the judgment of the investigator, would have made the patient inappropriate for entry into this study.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: A Phase II Study to Evaluate the Effects of Cabozantinib in Patients With Unresectable/Metastatic Adrenocortical Carcinoma

This phase II trial studies how well cabozantinib works in treating patients with adrenal cortex cancer that has spread to nearby tissue, lymph nodes (locally advanced), or other places in the body (metastatic), and cannot be removed by surgery (unresectable). Cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To estimate progression free survival at 4 months.

SECONDARY OBJECTIVES:

  1. Best overall response rate. II. Overall survival (OS). III. Toxicity assessment by the Common Terminology Criteria for Adverse Events (CTCAE) version (V)4.0.

EXPLORATORY OBJECTIVES:

  1. Pharmacokinetics and cabozantinib serum levels to assess correlation with response to therapy.

II. Steroid hormone biomarkers as markers of disease response. III. Study the effect of cabozantinib on immune markers by obtaining optional biopsy and blood samples collections at baseline, during therapy and at time of progression.

IV. Pharmacogenomics of drug disposition gene variants that potentially influence cabozantinib pharmacokinetics (PK).

OUTLINE:

Patients receive cabozantinib orally (PO) once daily (QD) in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30-37 days.

Being tested
Cabozantinib, Pharmacogenomic Study, Pharmacokinetic Study
Medical subject headings
Adrenal Cortex Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CabozantinibDrug

    Given PO

  • Pharmacogenomic StudyOther

    Also called PHARMACOGENOMIC

    Correlative studies

  • Pharmacokinetic StudyOther

    Also called PHARMACOKINETIC, PK Study

    Correlative studies

Study groups in NCT03370718
Study groupRoleWhat they receive
Treatment (cabozantinib)ExperimentalPatients receive cabozantinib PO QD in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Cabozantinib; Other: Pharmacogenomic Study; Other: Pharmacokinetic Study

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression-free Survival (PFS) as Defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 Criteria

    PFS rates will be monitored simultaneously using the Bayesian approach of Thall, Simon, Esty as extended by Thall and Sung. PFS is defined as no disease progression or death within the first 4 months of the proposed treatment.

    Measured: At 4 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Dec 2017
  2. Study start26 Feb 2018
  3. Primary completion12 Jan 2024
  4. Study completion12 Jan 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
18 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03370718
Sponsor's protocol ID
2016-0741
Other IDs
NCI-2018-00973, 2016-0741
Status last verified
Nov 2024
First submitted
8 Dec 2017
Last updated
10 Dec 2024
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Campbell MT, Balderrama-Brondani V, Jimenez C, Tamsen G, Marcal LP, Varghese J, Shah AY, Long JP, Zhang M, Ochieng J, Haymaker C, Habra MA. Cabozantinib monotherapy for advanced adrenocortical carcinoma: a single-arm, phase 2 trial. Lancet Oncol. 2024 May;25(5):649-657. doi: 10.1016/S1470-2045(24)00095-0. Epub 2024 Apr 9.

    PubMed 38608694

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cabozantinib, Pharmacogenomic Study and Pharmacokinetic Study in people with Metastatic Carcinoma in the Adrenal Cortex and Stage III Adrenal Cortex Carcinoma AJCC v8, run by M.D. Anderson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 Dec 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free Survival (PFS) as Defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 Criteria (time frame: At 4 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03370718, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Dec 2024.

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