Cabozantinib S-Malate in Treating Patients With Advanced Solid Tumors and Human Immunodeficiency Virus

NCT01822522 | Completed Phase 1 Results

• 4 other identifiers: NCI-2013-00740AMC-087U01CA121947UM1CA121947
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 20

Brief Summary

This phase I trial studies the side effects and best dose of cabozantinib s-malate in treating patients with solid tumors that have spread to other places in the body and usually cannot be cured or controlled with treatment and human immunodeficiency virus. Cabozantinib s-malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Conditions

Advanced Malignant Solid Neoplasm; HIV Infection; Metastatic Malignant Solid Neoplasm; Recurrent Malignant Solid Neoplasm; Unresectable Solid Neoplasm

Outcome Measures

Primary Outcomes (2)

• Incidence of Adverse Events

  Will be reported using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The number of participant who experienced an adverse event

  Up to 30 days after completion of study treatment. Study treatment was between 1 and 82 weeks.

• Maximal Tolerated Dose (MTD) of Cabozantinib-s-malate

  Will be graded according to the NCI CTCAE version 5.0. Dose-limiting toxicity (DLT) will be defined as any cabozantinib s-malate related grade 3 or 4 non-hematologic toxicity including grade 3 nausea and/or vomiting and grade 3 diarrhea despite prophylaxis and/or treatment or any of the following grade 4 hematologic toxicities: thrombocytopenia and neutropenia of any duration (with or without fever or documented infection); additionally, treatment delay of greater than 7 days due to unresolved toxicity or any dose reduction required due to a cabozantinib-related adverse event will be considered a DLT.

  Up to 28 days after treatment initiation

Secondary Outcomes (5)

• Response Rates

  Up to 30 days after completion of study treatment. Study treatment was between 1 and 82 weeks. The median number 28-day cycles was 3.5.

• Human Immunodeficiency Virus (HIV) Viral Load

  Day 22 of treatment

• CD4+ Cell Counts

  Day 22 of treatment

• CD8+ Cell Counts

  Day 22 of treatment

• Pharmacokinetic Parameters

  Day 1

Study Arms (6)

Stratum A Treatment (cabozantinib s-malate): 20 mg/day

EXPERIMENTAL

Patients receive cabozantinib s-malate 20 mg PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. This arm includes patients who are on ritonavir-boosted or cobicistat-boosted antiretroviral regimens

Drug: Cabozantinib S-malate; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study

Stratum A Treatment (cabozantinib s-malate): 40 mg/day

EXPERIMENTAL

Patients receive cabozantinib s-malate 40 mg PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. This arm includes patients who are on ritonavir-boosted or cobicistat-boosted antiretroviral regimens

Drug: Cabozantinib S-malate; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study

Stratum A Treatment (cabozantinib s-malate): 60 mg/day

EXPERIMENTAL

Patients receive cabozantinib s-malate 60 mg PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. This arm includes patients who are on ritonavir-boosted or cobicistat-boosted antiretroviral regimens

Drug: Cabozantinib S-malate; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study

Stratum B Treatment (cabozantinib s-malate): 60 mg/day

EXPERIMENTAL

Patients receive cabozantinib s-malate 60 mg PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. This arm includes patients who are on efavirenz or etravirine-based antiretroviral regimens

Drug: Cabozantinib S-malate; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study

Stratum B Treatment (cabozantinib s-malate): 100 mg/day

EXPERIMENTAL

Patients receive cabozantinib s-malate 100 mg PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. This arm includes patients who are on efavirenz or etravirine-based antiretroviral regimens

Drug: Cabozantinib S-malate; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study

Stratum C Treatment (cabozantinib s-malate): 60 mg/day

EXPERIMENTAL

Patients receive cabozantinib s-malate 60 mg PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. This arm includes patients who are on antiretroviral regimens that do not include the agents specified on stratum A or B, or who are not on antiretroviral therapy

Drug: Cabozantinib S-malate; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study

Interventions

Cabozantinib S-malate DRUG

Given PO

Also known as: BMS-907351, Cabometyx, Cometriq, XL-184, XL184

Stratum A Treatment (cabozantinib s-malate): 20 mg/day; Stratum A Treatment (cabozantinib s-malate): 40 mg/day; Stratum A Treatment (cabozantinib s-malate): 60 mg/day; Stratum B Treatment (cabozantinib s-malate): 100 mg/day; Stratum B Treatment (cabozantinib s-malate): 60 mg/day; Stratum C Treatment (cabozantinib s-malate): 60 mg/day

Laboratory Biomarker Analysis OTHER

Correlative studies

Stratum A Treatment (cabozantinib s-malate): 20 mg/day; Stratum A Treatment (cabozantinib s-malate): 40 mg/day; Stratum A Treatment (cabozantinib s-malate): 60 mg/day; Stratum B Treatment (cabozantinib s-malate): 100 mg/day; Stratum B Treatment (cabozantinib s-malate): 60 mg/day; Stratum C Treatment (cabozantinib s-malate): 60 mg/day

Pharmacological Study OTHER

Correlative studies

Stratum A Treatment (cabozantinib s-malate): 20 mg/day; Stratum A Treatment (cabozantinib s-malate): 40 mg/day; Stratum A Treatment (cabozantinib s-malate): 60 mg/day; Stratum B Treatment (cabozantinib s-malate): 100 mg/day; Stratum B Treatment (cabozantinib s-malate): 60 mg/day; Stratum C Treatment (cabozantinib s-malate): 60 mg/day

Eligibility Criteria

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

You may qualify if:

• Participants must have known HIV infection and histologically confirmed solid malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective; any number of prior cancer therapies will be permitted; at least 4 weeks must have elapsed since prior chemotherapy or biological therapy, 6 weeks if the regimen included carmustine (BCNU) or mitomycin C; prior radiation therapy to the thoracic cavity, abdomen, or pelvis must be completed at least 3 months prior to registration; radiotherapy to any other site (including bone or brain metastases) must be completed at least 28 days prior to registration
• Serologic documentation of HIV infection at any time prior to study entry, as evidenced by positive enzyme-linked immunosorbent assay (ELISA), positive western blot, or any other federally approved licensed HIV test; alternatively, this documentation may include a record that another physician has documented that the participant has HIV infection based on prior ELISA and western blot, or other approved diagnostic tests
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
• Life expectancy of greater than 12 weeks
• Leukocytes \>= 3,000/mcL (within 1 week of study entry)
• Absolute neutrophil count \>= 1,500/mcL (within 1 week of study entry)
• Platelets \>= 100,000/mcL (within 1 week of study entry)
• Total bilirubin=\< 1.5 x upper limit of normal (ULN) (within 1 week of study entry) (if, however, the participant has Gilbert's disease or unconjugated hyperbilirubinemia that is considered to be secondary to with atazanavir or indinavir therapy, then the total bilirubin must be =\< 3 x ULN)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3.0 x institutional upper limit of normal (within 1 week of study entry)
• Creatinine =\< 1.5 x ULN (within 1 week of study entry)
• Creatinine clearance \>= 50 mL/min/1.73 m\^2 for participants with creatinine levels above institutional normal (within 1 week of study entry)
• Hemoglobin \>= 9 g/dL (within 1 week of study entry)
• Serum albumin \>= 2.8 g/dL (within 1 week of study entry)
• Lipase \< 2.0 x ULN and no radiologic or clinical evidence of pancreatitis (within 1 week of study entry)
• Urine protein/creatinine ratio (UPCR) =\< 1 (within 1 week of study entry)

You may not qualify if:

• Prior treatment with cabozantinib (XL184)
• The participant has received radionuclide treatment within 6 weeks of the first dose of study treatment
• The participant has received prior treatment with a small molecule kinase inhibitor or a hormonal therapy (including investigational kinase inhibitors or hormones) within 4 weeks or five half-lives of the compound or active metabolites, whichever is longer, before the first dose of study treatment; note: participants with prostate cancer currently receiving luteinizing hormone-releasing hormone (LHRH) or gonadotropin-releasing hormone (GnRH) agonists may be maintained on these agents
• The participant has received any other type of investigational agent within 28 days before the first dose of study treatment
• The participant has not recovered to baseline or Common Terminology Criteria for Adverse Events (CTCAE) =\< grade 1 from toxicity due to all prior therapies except alopecia and other non-clinically significant adverse events (AEs)
• The participant has a primary brain tumor
• The participant has active brain metastases or epidural disease; participants with brain metastases previously treated with whole brain radiation or radiosurgery or participants with epidural disease previously treated with radiation or surgery who are asymptomatic and do not require steroid treatment for at least 4 weeks before starting study treatment are eligible; participants with treated brain metastasis should not take enzyme-inducing anticonvulsive therapies (EIACDs) within 2 weeks of registration, though non-enzyme inducing anticonvulsive drugs such as levetiracetam are allowed; neurosurgical resection of brain metastases or brain biopsy is permitted if completed at least 3 months before starting study treatment; baseline brain imaging with contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI) scans for participants with known brain metastases is required to confirm eligibility
• The participant has prothrombin time (PT)/international normalized ratio (INR) or partial thromboplastin time (PTT) test \>= 1.3 x the laboratory ULN within 7 days before the first dose of study treatment
• The participant requires concomitant treatment, in therapeutic doses, with anticoagulants such as warfarin or warfarin-related agents, heparin, thrombin or factor xabans (Xa) inhibitors, or antiplatelet agents (e.g., clopidogrel); low dose aspirin (=\< 81 mg/day), low-dose warfarin (=\< 1 mg/day), and prophylactic low molecular weight heparin (LMWH) are permitted
• The participant requires chronic concomitant treatment with the following strong cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4) inducers OTHER than antiretroviral agents: dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, primidone, modafinil, and other enzyme inducing anti-convulsant drugs (EIACD), and St. John's wort; use of efavirenz or etravirine is permitted for participants considered for the CYP3A4-inducer based antiretroviral therapy (ART) regimen arm (Stratum B) of the trial; because the lists of CYP3A4 inducers are constantly changing, it is important to regularly consult a frequently-updated list; medical reference texts such as the Physicians' Desk Reference may also provide this information; as part of the enrollment/informed consent procedures, the participant will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the participant is considering a new over-the-counter medicine or herbal product
• The participant requires concomitant treatment with the following inhibitors of CYP3A4:
• Antibiotics: clarithromycin, erythromycin, telithromycin, troleandomycin
• Antifungals: itraconazole, ketoconazole, voriconazole, fluconazole, posaconazole
• Antidepressants: nefazodone
• Antidiuretic: conivaptan

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (20)

UC San Diego Moores Cancer Center

La Jolla, California, 92093, United States

Location

UCLA Center for Clinical AIDS Research and Education

Los Angeles, California, 90035, United States

Location

UCLA / Jonsson Comprehensive Cancer Center

Los Angeles, California, 90095, United States

Location

UC San Diego Medical Center - Hillcrest

San Diego, California, 92103, United States

Location

University of Hawaii Cancer Center

Honolulu, Hawaii, 96813, United States

Location

Louisiana State University

Lafayette, Louisiana, 70503, United States

Location

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

Boston Medical Center

Boston, Massachusetts, 02118, United States

Location

Siteman Cancer Center at Washington University

St Louis, Missouri, 63110, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Montefiore Medical Center-Einstein Campus

The Bronx, New York, 10461, United States

Location

Montefiore Medical Center-Weiler Hospital

The Bronx, New York, 10461, United States

Location

Montefiore Medical Center - Moses Campus

The Bronx, New York, 10467, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Thomas Street Clinic

Houston, Texas, 77009, United States

Location

Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

Houston, Texas, 77030, United States

Location

Ben Taub General Hospital

Houston, Texas, 77030, United States

Location

Virginia Mason Medical Center

Seattle, Washington, 98101, United States

Location

Harborview Medical Center

Seattle, Washington, 98104, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

HIV Infections; Neoplasm Metastasis

Interventions

cabozantinib

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Kim Mosby-Griffin
• Organization: AMC Operations and Data Management Cener

kmosby@emmes.com

301-251-1161

Study Officials

• Missak Haigentz

  AIDS Malignancy Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Model Details: In this study, cabozantinib doses were escalated within 3 strata defined by the participant's antiretroviral regimen

Study Record Dates

• First Submitted: April 1, 2013
• First Posted: April 2, 2013
• Study Start: June 21, 2013
• Primary Completion: May 22, 2019
• Study Completion: May 12, 2021
• Last Updated: January 10, 2023
• Results First Posted: January 10, 2023

Record last verified: 2022-12

Locations

US (20)