Navitoclax and Sorafenib Tosylate in Treating Patients With Relapsed or Refractory Solid Tumors

NCT02143401 | Completed Phase 1

• 4 other identifiers: NCI-2014-01043MC13159608UM1CA186686
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 10

Brief Summary

This phase I trial studies the side effects and the best dose of navitoclax when given together with sorafenib tosylate in treating patients with solid tumors that have returned (relapsed) or do not respond to treatment (refractory). Navitoclax and sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Conditions

Cirrhosis; Hepatitis B Infection; Hepatitis C Infection; Metastatic Malignant Solid Neoplasm; Recurrent Hepatocellular Carcinoma; Recurrent Malignant Solid Neoplasm; Refractory Malignant Neoplasm; Stage IV Hepatocellular Carcinoma AJCC v7; Unresectable Solid Neoplasm

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose (MTD) of navitoclax

  Will be defined as the dose level below the lowest dose that induces dose-limiting toxicity in at least one-third of patients (at least 2 of a maximum of 6 new patients) per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v.) 4.0.

  28 days

• Incidence of adverse events

  Will be graded per NCI CTCAE v. 4.0. The number and severity of all adverse events (overall, by dose-level, and by tumor group) will be tabulated and summarized in this patient population. The grade 3+ adverse events will also be described and summarized in a similar fashion.

  Up to 3 months

Secondary Outcomes (6)

• Tumor response

  Up to 3 months

• Time until any treatment related toxicity

  Up to 3 months

• Time until treatment related grade 3+ toxicity

  Up to 3 months

• Time until hematologic nadirs (white blood cell, absolute neutrophil count, platelets)

  Up to 3 months

• Time to progression

  Up to 3 months

Other Outcomes (3)

• Changes in levels of cleaved cytokeratin 18 (expansion cohort only)

  Day -7 up to day 8

• Changes in hepatoma Mcl-1 expression level in tumor tissue (expansion cohort only)

  Baseline to up to day 8

• Change in cleaved and total CK18 levels in serum

  Day -7 to up to day 8

Study Arms (1)

Treatment (navitoclax, sorafenib tosylate)

EXPERIMENTAL

Patients receive navitoclax PO QD on days 1-21 (days 1-28 cycle of 1 only) and sorafenib tosylate PO BID on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Other: Laboratory Biomarker Analysis; Biological: Navitoclax; Other: Pharmacological Study; Drug: Sorafenib; Drug: Sorafenib Tosylate

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (navitoclax, sorafenib tosylate)

Navitoclax BIOLOGICAL

Given PO

Also known as: A-855071.0, ABT-263, BcI-2 Family Protein Inhibitor ABT-263

Treatment (navitoclax, sorafenib tosylate)

Pharmacological Study OTHER

Correlative studies

Treatment (navitoclax, sorafenib tosylate)

Sorafenib DRUG

Given PO

Also known as: BA4 43 9006, BAY 43 9006, BAY 43-9006, BAY 439006, BAY-43-9006, Bay-439006, BAY439006

Treatment (navitoclax, sorafenib tosylate)

Sorafenib Tosylate DRUG

Given PO

Also known as: BAY 43-9006 Tosylate, BAY 54 9085, BAY 54-9085, BAY 549085, BAY-54-9085, BAY549085, Nexavar, sorafenib

Treatment (navitoclax, sorafenib tosylate)

Eligibility Criteria

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

You may qualify if:

• For Dose Escalation Cohort: Patients must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective
• For Dose Expansion Cohort: HCC patients only: HCC confirmed by biopsy OR diagnosed by clinical and radiologic criteria; all of the following criteria must be met or a biopsy is required:
• Known cirrhosis or chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
• Hypervascular liver masses \> 2 cm, and either serum alpha-fetoprotein (AFP) \> 400 ng/ml
• AFP \> three times normal and doubling in value in the antecedent 3 months
• In the expansion cohort, prior treatment with sorafenib as first-line therapy allowed
• Any number of the following prior therapies is allowed:
• Chemotherapy \>= 28 days prior to registration
• Mitomycin C/nitrosoureas \>= 42 days prior to registration
• Immunotherapy \>= 28 days prior to registration
• Biologic therapy \>= 28 days prior to registration
• Targeted therapy \>= 28 days prior to registration
• Radiation therapy \>= 28 days prior to registration
• Radiation to \< 25% of bone marrow
• HCC patients only: Prior regional treatments for liver metastasis are permitted including:

You may not qualify if:

• Unresolved toxicity of National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0 (NCI CTCAE v 4.0) grade 2 or higher from previous anti-cancer therapy, except alopecia
• Receiving any other investigational agents =\< 28 days prior to registration
• Known brain metastases (even if treated)
• Known portal hypertension or history of variceal bleeding; these patients are felt to be at increased risk of bleeding if they experience navitoclax-induced thrombocytopenia
• Inadequately controlled hypertension (systolic blood pressure of \> 150 mmHg or diastolic pressure \> 90 mmHg on anti-hypertensive medications)
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to navitoclax or sorafenib
• Current use of anticoagulation; NOTE: use of low-dose anticoagulation medications that are used to maintain the patency of a central intravenous catheter is allowed
• Corrected QT (QTc) interval \> 480 msec on baseline electrocardiogram (EKG)
• Documented history of prolonged QTc interval =\< 6 months prior to registration
• Receiving any medications that prolong the QTc and have a known risk for Torsades de pointes; providers should use caution with drugs with possible increased risk for Torsades de pointes; NOTE: patient will be eligible if they can be taken off these medications prior to initiation of therapy and no less than 4 half-lives of the medication
• Current use of certain concomitant medications due to mechanistic-based platelet toxicities from navitoclax: clopidogrel, ibuprofen, tirofiban and other anticoagulants, drugs or herbal supplements that effect platelet function; NOTE: antiplatelet use is prohibited during the use of navitoclax; subjects who have previously received aspirin therapy for thrombosis prevention may resume a low dose (i.e., maximum 100 mg QD) of aspirin if platelet counts are stable (\>= 50,000/mm\^3) through 6 weeks of navitoclax administration; all decisions regarding treatment with aspirin therapy will be determined by the principal investigator in conjunction with the medical monitor
• Current use of strong CYP3A inhibitors such as ketoconazole, itraconazole, voriconazole, posaconazole, nefazodone, and clarithromycin are prohibited; NOTE: moderate inhibitors of CYP3A4 should be used with caution; navitoclax is a moderate inhibitor of CYP2C8 and a strong inhibitor of CYP2C9; caution should be exercised when dosing navitoclax concurrently with CYP2C8 and CYP2C9 substrates; common CYP2C8 substrates include paclitaxel, statins and repaglinide; CYP2C9 substrates include celecoxib, phenytoin and warfarin; when possible, investigators should switch to alternative medications or monitor the patients closely
• Concurrent use of strong CYP3A4/5 inducers such as carbamazepine, phenytoin, rifampin, and St. John's wort are prohibited
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Any of the following:

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (10)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

UCHealth University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

Location

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, 52242, United States

Location

University of Maryland/Greenebaum Cancer Center

Baltimore, Maryland, 21201, United States

Location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

New York, New York, 10032, United States

Location

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Fibrosis; Hepatitis B; Hepatitis C; Neoplasm Metastasis; Carcinoma, Hepatocellular; Neoplasms

Interventions

navitoclax; Sorafenib

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis; Liver Diseases; Digestive System Diseases; Flaviviridae Infections; RNA Virus Infections; Neoplastic Processes; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• Brian A Costello

  Mayo Clinic Cancer Center LAO

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 19, 2014
• First Posted: May 21, 2014
• Study Start: January 30, 2015
• Primary Completion: November 30, 2022
• Study Completion: March 21, 2024
• Last Updated: November 22, 2024

Record last verified: 2024-11

Locations

US (10)