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Cabozantinib in Unresectable/Metastatic Adrenocortical Carcinoma

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ClinicalTrials.gov Identifier: NCT03370718
Recruitment Status : Recruiting
First Posted : December 12, 2017
Last Update Posted : August 3, 2018
Sponsor:
Collaborator:
Exelixis
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:

The goal of this clinical research study is to learn if cabozantinib can help to control unresectable (cannot be removed with surgery) or metastatic (has spread) adrenocortical carcinomas. The safety of this drug will also be studied.

This is an investigational study. Cabozantinib is FDA approved and commercially available to treat medullary thyroid cancer and kidney cancer. It is considered investigational to use cabozantinib to treat adrenocortical carcinomas.

The study doctor can explain how cabozantinib is designed to work.

Up to 18 participants will be enrolled in this study. All will take part at MD Anderson.


Condition or disease Intervention/treatment Phase
Adrenocortical Carcinoma Drug: Cabozantinib Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 18 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study to Evaluate the Effects of Cabozantinib in Patients With Unresectable/Metastatic Adrenocortical Carcinoma
Actual Study Start Date : February 26, 2018
Estimated Primary Completion Date : February 2020
Estimated Study Completion Date : February 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Cabozantinib
Participants take Cabozantinib tablets by mouth 1 time each day.
Drug: Cabozantinib
Cabozantinib initiation dose is 60 mg daily by mouth. The dose can be reduced to 40 mg then 20 mg a day based on tolerability and adverse effects.
Other Names:
  • XL-184
  • XL184




Primary Outcome Measures :
  1. Progression-Free Survival Rate (PFS) in Patients with Unresectable/Metastatic Adrenocortical Carcinoma (ACC) Who Receive Cabozantinib [ Time Frame: 4 months ]
    PFS determined by serial imaging studies used to assess measurable disease per RECIST 1.1.


Secondary Outcome Measures :
  1. Toxicity in Patients with Unresectable/Metastatic Adrenocortical Carcinoma (ACC) Who Receive Cabozantinib [ Time Frame: 4 months ]
    Toxicity defined as any grade ≥ 3 toxicity that is attributed to cabozantinib as defined by Common Terminology Criteria for Adverse Events (CTCAE) V4.0



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. The subject is >= 18 years old on the day of consent
  2. Histological confirmation of 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).
  3. Locally advanced or metastatic disease not amenable to surgery with curative intent with measurable disease per RECIST 1.1 (9) 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 IV contrast allergy or borderline renal function, CT without IV contrast or 18 FDG PET CT may be used as clinically indicated.
  4. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
  5. Recovery to baseline or <= Grade 1 CTCAE v.4.0 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy
  6. Life expectancy of at least 3 months
  7. Organ and marrow function and laboratory values as follows within 28 days prior to the first dose of cabozantinib: a. Absolute neutrophil count (ANC) >= 1500/mm^3 without colony stimulating factor support b. Platelets >= 100,000/mm^3 c. Hemoglobin >= 9 g/dL d. Bilirubin <= 1.5 × the upper limit of normal (ULN). For subjects with known Gilbert's disease, bilirubin <= 3.0 mg/dL e. Serum albumin >= 2.8 g/dl f. Serum creatinine <= 1.5 × ULN or creatinine clearance (CrCl) >= 50 mL/min. For creatinine clearance estimation, the Cockcroft and Gault equation should be used: Male: CrCl (mL/min) = (140 - age) × wt (kg) / (serum creatinine × 72). Female: Multiply above result by 0.85 g. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <= 3.0 × ULN h. Lipase<=2.0 x the upper limit of normal and no radiologic or clinical evidence of pancreatitis i. Urine protein/creatinine ratio (UPCR) <= 1 j. Serum phosphorus>=2.5mg/dl,calcium>=8mg/dL,magnesium>=1.2mg/dL and potassium>= 3.0meq/L
  8. Capable of understanding and complying with the protocol requirements and has signed the informed consent document
  9. 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).
  10. 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.

Exclusion Criteria:

  1. 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.
  2. 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
  3. Prior treatment with cabozantinib or other cMET inhibitors
  4. 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
  5. 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.
  6. Prothrombin time (PT)/ International Normalized Ratio (INR) or partial thromboplastin time (PTT) test >= 1.3 × the laboratory ULN within 28 days before the first dose of study treatment
  7. 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.
  8. Severe and uncontrolled Cushing syndrome despite medical management (e.g., systolic blood pressure >160mmHg or hyperglycemia with fasting glucose above 300mg/dL).
  9. The use of strong CYP3A4 inhibitor (with the exception of ketoconazole).
  10. 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.
  11. Evidence of tumor invading the 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.
  12. 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 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 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.
  13. (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
  14. 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 PEG tube placement within 90 days before the first dose of study therapy
  15. 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 (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.
  16. Unable to swallow tablets
  17. A corrected QT interval calculated by the Fridericia formula (QTcF) >500 milliseconds within 28 days before first dose of study treatment. Three ECGs must be performed for eligibility determination. If the average of these three consecutive results for QTcF is <= 500 milliseconds, the subject will be eligible.
  18. Pregnant or breastfeeding.
  19. A previously identified allergy or hypersensitivity to components of the study treatment formulation.
  20. Unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee.
  21. 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
  22. 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03370718


Contacts
Contact: Mouhammed A. Habra, MD 713-792-2841 mahabra@mdanderson.org

Locations
United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact       mahabra@mdanderson.org   
Sponsors and Collaborators
M.D. Anderson Cancer Center
Exelixis
Investigators
Principal Investigator: Mouhammed A. Habra, MD M.D. Anderson Cancer Center

Additional Information:
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT03370718     History of Changes
Other Study ID Numbers: 2016-0741
NCI-2018-00973 ( Registry Identifier: NCI CTRP )
First Posted: December 12, 2017    Key Record Dates
Last Update Posted: August 3, 2018
Last Verified: August 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by M.D. Anderson Cancer Center:
Adrenocortical carcinoma
ACC
Cabozantinib
XL-184
XL184

Additional relevant MeSH terms:
Carcinoma
Adrenocortical Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Adrenal Cortex Neoplasms
Adrenal Gland Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Adrenal Cortex Diseases
Adrenal Gland Diseases
Endocrine System Diseases