Tivantinib and Temsirolimus in Treating Patients With Solid Tumors That is Metastatic or Cannot be Removed by Surgery

NCT01625156 | Completed Phase 1

• 8 other identifiers: NCI-2012-00949NCI 9145905854-02-06NCI-2012-00974CO 119149145P30CA014520U01CA062491
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 2

Brief Summary

This phase I trial studies the side effects and best dose of tivantinib when given in combination with temsirolimus in treating patients with solid tumors that have spread to other parts of the body or cannot be removed by surgery. Tivantinib and temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Conditions

Adult Solid Neoplasm

Outcome Measures

Primary Outcomes (1)

• MTD and RP2D of tivantinib in combination with temsirolimus defined as the highest safely tolerated dose where 0/6 or 1/6 patients experience a dose-limiting toxicity (DLT) and two or more patients have experienced a DLT at the next higher dose level

  Categorized according to NCI Common Toxicity Criteria version 4.0.

  First 35 days

Secondary Outcomes (3)

• Incidence of adverse events and toxicities of tivantinib in combination with temsirolimus

  Up to 4 weeks after completion of study treatment

• Pharmacokinetic analysis

  Pre-dose, 0.5, 1, 2, 4, 8, and 12 hours (days 1 and 7), pre-dose and 0.5 hours (day 8), pre-dose (days 15 and 22 of course 1 and day 1 of course 2)

• Response rate validated by the RECIST criteria

  Up to 4 weeks after completion of study treatment

Other Outcomes (1)

• Tumor tissue expression levels of c-Met

  Up to course 2, day 1

Study Arms (1)

Treatment (tivantinib, temsirolimus)

EXPERIMENTAL

Patients receive tivantinib PO BID and temsirolimus IV over 30 minutes on days 1, 8, 15, and 22 (days 8, 15, 22, and 29 of course 1). Courses repeat every 28 days (35 days in course 1) in the absence of disease progression or unacceptable toxicity.

Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Temsirolimus; Drug: Tivantinib

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (tivantinib, temsirolimus)

Pharmacological Study OTHER

Correlative studies

Treatment (tivantinib, temsirolimus)

Temsirolimus DRUG

Given IV

Also known as: CCI-779, CCI-779 Rapamycin Analog, Cell Cycle Inhibitor 779, Rapamycin Analog, Rapamycin Analog CCI-779, Torisel

Treatment (tivantinib, temsirolimus)

Tivantinib DRUG

Given PO

Also known as: ARQ 197, ARQ-197, c-Met Inhibitor ARQ 197

Treatment (tivantinib, temsirolimus)

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically confirmed solid malignancy (excluding lymphoma) that is metastatic or unresectable and for which standard curative or palliative systemic therapies (such as chemotherapy, targeted therapies or immunotherapy) do not exist or are no longer effective
• Patients must have measurable or evaluable disease, as defined by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1
• No prior treatment with temsirolimus or an agent specifically targeting met proto-oncogene (c-Met)
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
• Life expectancy of greater than 12 weeks
• Hemoglobin \>= 9.0 g/dL
• Leukocytes \>= 3,000/mcL
• Absolute neutrophil count \>= 1,500/mcL
• Platelets \>= 100,000/mcL
• Total bilirubin =\< 1.5 X institutional upper limit of normal
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< institutional upper limit of normal
• Serum creatinine =\< institutional upper limit of normal or creatinine clearance (either estimated or calculated) \>= 60 mL/min/1.73 m for patients with creatinine levels above institutional normal
• Fasting glucose =\< 150 mg/dL
• Fasting cholesterol level \< 350 mg/dl
• Fasting triglycerides =\< 300 mg/dl

You may not qualify if:

• Any of the following:
• Chemotherapy =\< 3 weeks prior to entering the study (6 weeks for nitrosoureas or mitomycin C)
• Radiotherapy, endocrine therapy or targeted therapy for malignancy =\< 2 weeks prior to registration
• Patients who have not recovered (=\< grade 1) from adverse events due to agents administered more than 4 weeks earlier (tolerable grade 2 adverse events may be allowed at the discretion of the investigator; diarrhea must be grade 1 or lower without the scheduled use of antidiarrheal medications)
• Prior anticancer therapy with an mammalian target of rapamycin (mTOR) inhibitor (everolimus, temsirolimus, desferolimus) or agent specifically targeting c-Met
• Patients who are receiving any other investigational agents
• Patients may not have clinically symptomatic hypothyroidism; testing is not required for eligibility
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to ARQ 197 or temsirolimus
• ARQ 197 is a sensitive substrate for 2C19 and 3A4, a strong inhibitor for 2C19 and moderate inhibitor by in vitro data only for 3A4; temsirolimus is a sensitive substrate for CYP 3A4 and a weak inhibitor of CYP2D6 and CYP3A4/5; per the UWinRx Drug Interaction Policy, the following medications are contraindicated or must be used with caution
• Contraindicated:
• CYP2C19 sensitive substrates (unless close monitoring with labs or drug levels with dose adjustments is feasible), inducers, and moderate/strong inhibitors of CYP2C19; patients taking these concurrent medications are ineligible unless they can be switched to alternative medications prior to initiation of the study
• CYP3A4/5 inducers and moderate/strong inhibitors of CYP3A4/5; patients taking these concurrent medications are ineligible unless they can be switched to alternative medications prior to initiation of the study
• Use with caution:
• CYP2C19 non-sensitive substrates with a narrow therapeutic window and weak inhibitors are permitted if no acceptable alternatives are available as determined by the treating physician; however, caution should be used; consider monitoring with labs or drug levels and dose adjustments of the medication if feasible; other non-sensitive substrates are allowed on study
• CYP3A4/5 sensitive substrates and any non-sensitive substrates with a narrow therapeutic window and weak inhibitors are permitted if no acceptable alternatives are available as determined by the treating physician; however, caution should be used; consider monitoring with labs or drug levels and dose adjustments of the medication if feasible; other non-sensitive substrates are allowed on study

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (2)

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, 53792, United States

Location

Wisconsin Clinical Cancer Center

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Interventions

temsirolimus; Sirolimus; ARQ 197

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Study Officials

• Kari Wisinski

  University of Wisconsin, Madison

  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: June 18, 2012
• First Posted: June 21, 2012
• Study Start: May 1, 2012
• Primary Completion: September 1, 2015
• Study Completion: October 1, 2015
• Last Updated: October 20, 2015

Record last verified: 2015-05

Locations

US (2)