Trebananib And Temsirolimus in Treating Patients With Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery

NCT01548482 | Completed Phase 1

• 6 other identifiers: NCI-2012-02848CDR0000728823PJC-0089041U01CA132123UM1CA186644
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 3

Brief Summary

This phase I trial studies the side effects and the best dose of trebananib and temsirolimus when given together in treating patients with solid tumors that are metastatic or cannot be removed by surgery. Trebananib may stop the growth of tumor cells by blocking blood flow to the tumor. Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving trebananib with temsirolimus may be an effective treatment for solid tumors.

Conditions

Adult Solid Neoplasm; Lung Carcinoid Tumor; Recurrent Digestive System Neuroendocrine Tumor G1; Recurrent Renal Cell Carcinoma; Recurrent Uterine Corpus Sarcoma; Stage III Renal Cell Cancer; Stage IIIB Uterine Sarcoma; Stage IIIC Uterine Sarcoma; Stage IV Renal Cell Cancer; Stage IVA Uterine Sarcoma; Stage IVB Uterine Sarcoma

Outcome Measures

Primary Outcomes (2)

• RP2D of trebananib and temsirolimus defined as the dose level at which =< 1/6 patients experienced dose-limiting toxicity (DLT) as assessed by the National Cancer Institute (NCI) CTCAE version 4.0

  28 days

• Safety profile of trebananib and temsirolimus as assessed by NCI CTCAE version 4.0

  Frequency and severity of adverse events will be tabulated using counts and proportions detailing frequently occurring, serious and severe events of interest. Adverse events will be summarized using all adverse events experienced, although a subanalysis may be conducted including only those adverse events in which the treating physician deems possibly, probably or definitely attributable to one or both study treatments.

  Up to 30 days

Secondary Outcomes (2)

• Objective response to treatment assessed using the Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1

  Up to 30 days

• PD effects of both drugs when administered in combination

  Course 1 days 1, 3, and 8 and course 2 day 1

Study Arms (1)

Treatment (trebananib, temsirolimus)

EXPERIMENTAL

Patients receive trebananib IV over 60 minutes and temsirolimus IV over 30-60 minutes on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Temsirolimus; Biological: Trebananib

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (trebananib, temsirolimus)

Pharmacological Study OTHER

Correlative studies

Treatment (trebananib, 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 (trebananib, temsirolimus)

Trebananib BIOLOGICAL

Given IV

Also known as: AMG 386, Angiopoietin 1/2-Neutralizing Peptibody AMG 386

Treatment (trebananib, temsirolimus)

Eligibility Criteria

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

You may qualify if:

• DOSE ESCALATION COHORTS: Patients must have histologically or cytologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective
• DOSE EXPANSION COHORTS: Patients must have histologically and/or cytologically confirmed uterine cancer, renal cell cancer or carcinoid tumor that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective
• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as \>= 20 mm with conventional techniques or as \>= 10 mm with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam
• DOSE ESCALATION COHORTS: No limitation on prior therapy; however, there must be at least a 4 week interval between initiation of study treatment and any prior radiotherapy or systemic therapy, 6 weeks if the last regimen included carmustine (BCNU) or mitomycin C; exceptions may be made however, for low dose, non-myelosuppressive radiotherapy for symptomatic palliation; please contact the study coordinator at the Princess Margaret Hospital (PMH) Phase I Consortium Central Office or the principal investigator if any questions arise about interpretation of this criterion
• EXPANSION COHORTS:
• Uterine cancer: Patients diagnosed with uterine cancer will be eligible provided they have received at least one prior line of chemotherapy for recurrent or metastatic disease unless the investigator feels that cytotoxic chemotherapy is contraindicated; prior hormonal treatment will be allowed; prior anti-angiogenic agents and prior treatment with agents targeting phosphatidylinositol 3-kinase (PI3K)- protein kinase B (AkT)- mammalian target of rapamycin (mTOR) pathway are not allowed
• Renal cell cancer: Patients diagnosed with renal cell cancer (RCC) will be required to have received at least one prior line anti- vascular endothelial growth factor (VEGF)/ receptor (R) treatment (i.e. bevacizumab, sunitinib, and/or sorafenib); prior treatment with agents targeting PI3K-Akt-mTOR pathway is not allowed
• Carcinoid tumor: Patients diagnosed with carcinoid tumor must have demonstrated radiographic evidence of disease progression within six months prior to enrollment; prior and/or concurrent long-acting somatostatin analogue therapy is allowed; if patient is continued on a long-acting somatostatin analogue, a stable dose for \>= 2 months prior to study entry is required with documentation of progressive disease on current dose; prior radiolabeled octreotide therapy is allowed; prior regional treatments for liver metastasis are permitted including:
• Selective internal radiation therapy (i.e. brachytherapy, radiolabeled microsphere embolization, etc)
• Hepatic artery chemoembolization
• Hepatic artery embolization
• Hepatic artery infusional chemotherapy
• Radiofrequency ablation
• Patients must be \> 12 weeks from regional treatments and show progressive disease in the liver after regional therapy or must have measurable disease outside the liver; patients may have received one prior line of anti-VEGF/R treatment (e.g. bevacizumab, sunitinib, and/or sorafenib); prior treatment with agents targeting PI3K-Akt-mTOR pathway is not allowed
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 1 (Karnofsky \>= 70%)

You may not qualify if:

• History of central nervous system metastases
• History of venous or arterial thromboembolism within 12 months prior to enrollment/randomization; patients requiring ongoing anticoagulation with therapeutic dosages of low molecular weight heparin or warfarin are excluded
• History of clinically significant bleeding within 6 months of enrollment/randomization
• Unresolved toxicities from prior systemic therapy that are Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 \>= grade 2 in severity except alopecia
• Currently or previously treated with AMG 386, or other molecules that inhibit the angiopoietins or TEK tyrosine kinase, endothelial (Tie2) receptor
• Clinically significant cardiovascular disease within 12 months prior to enrollment/randomization, including myocardial infarction, unstable angina, grade 2 or greater peripheral vascular disease, cerebrovascular accident, transient ischemic attack, congestive heart failure, or arrhythmias not controlled by outpatient medication or placement of percutaneous transluminal coronary angioplasty/stent
• Major surgery within 28 days prior to enrollment or still recovering from prior surgery
• Minor surgical procedures, except placement of tunneled central venous access device within 3 days (7 days if with VEGF inhibitor) prior to randomization/enrollment
• Treatment within 30 days prior to enrollment with strong immune modulators, including but not limited to systemic cyclosporine, tacrolimus, sirolimus, mycophenolate mofetil, methotrexate, azathioprine, rapamycin, thalidomide, lenalidomide, and targeted immune modulators such as abatacept (CTLA-4-Ig), adalimumab, alefacept, anakinra, belatacept (LEA29Y), efalizumab, etanercept, infliximab, or rituximab
• Non-healing wound, ulcer (including gastrointestinal), or fracture
• Subject not consenting to the use of highly effective contraceptive precautions (e.g., double barrier method \[i.e., condom plus diaphragm\]) during the course of the study and for 6 months after administration of the last study medication
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to AMG 386 or temsirolimus
• Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
• Patients who have not yet completed at least 21 days (30 days for prior monoclonal antibody therapy) since ending other investigational device or drug trials, or who are currently receiving other investigational treatments
• Temsirolimus is a cytochrome P450 3A4 (CYP3A4) substrate; patients receiving any medications or substances that are strong inhibitors or inducers of CYP3A4 are ineligible

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (3)

BCCA-Vancouver Cancer Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, L8V 5C2, Canada

Location

University Health Network-Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

temsirolimus; Sirolimus; trebananib

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Study Officials

• Philippe Bedard

  University Health Network-Princess Margaret Hospital

  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: February 24, 2012
• First Posted: March 8, 2012
• Study Start: March 1, 2012
• Primary Completion: January 1, 2014
• Study Completion: January 1, 2014
• Last Updated: October 6, 2015

Record last verified: 2015-05

Locations

CA (3)