Sorafenib Tosylate and Hypoxia-Activated Prodrug TH-302 in Treating Patients With Advanced Kidney Cancer or Liver Cancer That Cannot Be Removed By Surgery

NCT01497444 | Completed Phase 1 DMC

• 5 other identifiers: N1153NCCTG-N1153CDR0000720022NCI-2012-00095U10CA031946
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 2

Brief Summary

RATIONALE: Sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth by blocking blood flow to the tumor. Drugs used in chemotherapy, such as hypoxia-activated prodrug TH-302, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving sorafenib tosylate together with hypoxia-activated prodrug TH-302 may kill more tumor cells. PURPOSE: This phase I/II trial studies the side effects and best dose of giving sorafenib tosylate together with hypoxia-activated prodrug TH-302 and to see how well they work in treating patients with advanced kidney cancer or liver cancer that cannot be removed by surgery.

Conditions

Kidney Cancer; Liver Cancer

Keywords

recurrent adult primary liver cancer; recurrent renal cell cancer; advanced adult primary liver cancer; localized unresectable adult primary liver cancer; adult primary hepatocellular carcinoma

Outcome Measures

Primary Outcomes (3)

• Number of dose-limiting toxicity incidents as assessed by CTCAE version 4.0 (Phase I)

  Up to 24 weeks

• MTD of sorafenib tosylate and TH-302 (Phase I)

  Up to 24 weeks

• Overall response rate (Phase II)

  Up to 3 years

Secondary Outcomes (6)

• Adverse events as assessed by NCI CTCAE version 4.0 (Phase II)

  Up to 3 years

• Overall response rate based on standard RECIST criteria (Phase II)

  Up to 3 years

• Duration of response based on modified (standard) RECIST criteria (Phase II)

  Up to 3 years

• PFS (Phase II)

  Up to 3 years

• OS (Phase II)

  Up to 3 years

Study Arms (1)

sorafenib and TH-302

EXPERIMENTAL

Patients will be administered sorafenib tablets to take twice daily by mouth, every day of each cycle. Patients will also be given TH-302 intravenously (IV) on days 8, 15 and 22 of each cycle. A cycle is 28 days.

Drug: hypoxia-activated prodrug TH-302; Drug: sorafenib tosylate

Interventions

hypoxia-activated prodrug TH-302 DRUG

sorafenib and TH-302

sorafenib tosylate DRUG

sorafenib and TH-302

Eligibility Criteria

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

You may qualify if:

• Age ≥18 years
• Cytological or histological confirmed diagnosis of advanced hepatocellular or renal cell carcinoma. HCC patients should not be amenable to treatment with surgery or to orthotopic liver transplant.
• Patients must have measurable disease as defined in the protocol.
• RCC patients only: Tumor progression after receiving standard/approved chemotherapy and/or targeted agent, where there is no approved therapy or for tumors where sorafenib based therapy would be standard therapy.
• HCC patients only:
• First line (i.e., no prior systemic therapy) or second line (with prior first line sorafenib therapy only) advanced HCC.
• Child Pugh class A or B7 liver disease
• Prior chemoembolization, radioembolization, radiofrequency ablation (RFA), or other local ablative therapies are permissible if ≥6 weeks from procedure with evidence of progression or new metastatic disease, if applicable.
• ECOG Performance Status (PS) 0 or 1.
• The following laboratory values obtained ≤14 days prior to registration.
• Absolute neutrophil count (ANC) ≥1200/mm3
• Peripheral Platelet Count (PLT) ≥75,000/mm3
• Hemoglobin (HgB) \>8.5 g/dL
• Bilirubin ≤3.0 x upper limit of normal (ULN)
• SGOT (AST) ≤2.5 x ULN, if subject has HCC or liver metastases ≤5 x UL

You may not qualify if:

• Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown.
• Pregnant women
• Nursing women
• Men or women of childbearing potential who are unwilling to employ adequate contraception for the duration of study participation. Men and women should continue to use adequate birth control after the last administration of sorafenib and TH-302 under the guidance of their treating physician.
• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.
• Receiving any other investigational agent.
• Other active malignancy ≤3 years prior to registration. EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix. NOTE: If there is a history or prior malignancy, they must not be receiving other specific treatment (other than hormonal therapy) for their cancer.
• Inadequately controlled hypertension (systolic blood pressure of \>150 mmHg or diastolic pressure \>100 mmHg on anti-hypertensive medications).
• Major surgical procedures, or significant traumatic injury ≤14 days prior to registration or anticipation of need for elective or planned major surgical procedure during the course of the study.
• New York Heart Association (NYHA) classification III or IV congestive heart failure.
• Received treatment with radiation therapy or investigational therapy ≤28 days prior to registration.
• RCC patients only: Having received chemotherapy prior to study entry within 5 half-lives of the agent (as described in the package insert), or 4 weeks prior to registration (whichever is shorter) with resolution of side effects from therapy to ≤grade 1.
• Known central nervous system or brain metastasis that are either symptomatic or untreated. Note: Patients with neurological symptoms must undergo a CT scan/MRI of the brain to exclude brain metastasis.
• Note: Subjects with CNS metastases that have been treated and are stable without symptoms for ≥ 4 weeks after completion of treatment are eligible.
• HCC patients only: Cancer potentially amenable to local modalities of therapy or surgical resection.

Sponsors & Collaborators

• Alliance for Clinical Trials in Oncology: lead
• National Cancer Institute (NCI): collaborator
• Threshold Pharmaceuticals: collaborator

Study Sites (2)

Mayo Clinic Scottsdale

Scottsdale, Arizona, 85259-5499, United States

Location

Mayo Clinic Cancer Center

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Kidney Neoplasms; Liver Neoplasms; Carcinoma, Hepatocellular; Carcinoma, Renal Cell

Interventions

TH 302; Sorafenib

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

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

• Mitesh J. Borad, MD

  Mayo Clinic

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: December 20, 2011
• First Posted: December 22, 2011
• Study Start: May 1, 2012
• Primary Completion: January 1, 2016
• Study Completion: November 1, 2019
• Last Updated: February 6, 2020

Record last verified: 2020-02

Locations

US (2)