Vandetanib and Everolimus in Treating Patients With Advanced or Metastatic Cancer

NCT01582191 | Completed Phase 1 DMC FDA Drug

• 3 other identifiers: 2011-0953NCI-2012-007820953
• Study Type: interventional
• Target: 151
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the side effects and best dose of vandetanib and everolimus when given together in treating patients with cancer that has spread to other places in the body. Vandetanib and everolimus may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Conditions

Advanced Malignant Neoplasm; Metastatic Malignant Neoplasm; Recurrent Malignant Neoplasm; Refractory Malignant Neoplasm

Outcome Measures

Primary Outcomes (6)

• Maximum tolerated dose

  Will be defined as the highest dose studied in which the incidence of dose limiting toxicity was less than 33%. Toxicity will be reported by type, frequency, and severity. Worst toxicity grades per patient will be tabulated for selected adverse events and laboratory measurements.

  28 days

• Anti-tumor efficacy of the combination in terms of response rate

  The response rate will be estimated by dose level and tumor type, along with the exact 95% confidence interval. Efficacy will be evaluated by using the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria described in the supplement for response. Patients with lymphoma will be measured per the World Health Organization (WHO) criteria.

  Up to 14 years

• Maximum observed serum concentration (Cmax)

  Will be estimated using standard non-compartmental methods

  Days 1 and 21 of course 1 and day 1 of course 3

• Pharmacodynamic (PD) parameters

  PD biomarker concentration will be summarized by time points. The relationship between drug concentrations and PD effects will be explored graphically. Based on review of these graphs, analyses to describe the relationship may also be performed.

  Up to 14 years

• Observed trough serum concentration (Cmin)

  Will be estimated using standard non-compartmental methods

  Days 1 and 21 of course 1 and day 1 of course 3

• Area under the serum concentration-time curve (AUC)

  Will be estimated using standard non-compartmental methods

  Days 1 and 21 of course 1 and day 1 of course 3

Study Arms (1)

Treatment (vandetanib, everolimus)

EXPERIMENTAL

Patients receive vandetanib PO QD and everolimus PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Everolimus; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Vandetanib

Interventions

Everolimus DRUG

Given PO

Also known as: 42-O-(2-Hydroxy)ethyl Rapamycin, Afinitor, Certican, RAD 001, RAD001, Votubia, Zortress

Treatment (vandetanib, everolimus)

Laboratory Biomarker Analysis OTHER

Optional correlative studies

Treatment (vandetanib, everolimus)

Pharmacological Study OTHER

Optional correlative studies

Treatment (vandetanib, everolimus)

Vandetanib DRUG

Given PO

Also known as: AZD6474, Caprelsa, Zactima, ZD-6474, ZD6474

Treatment (vandetanib, everolimus)

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with advanced or metastatic cancer that is refractory to standard therapy, relapsed after standard therapy, or who have no standard therapy available that improves survival by at least three months.
• Patients must be at least 3 weeks beyond their previous cytotoxic chemotherapy.
• Patient must be at least 5 half-lives or 3 weeks, whichever is shorter, from their previous targeted or biologic therapy; In addition, patients must be at least 3 weeks beyond the last session of radiation therapy. Local palliative radiation therapy that is not delivered to all target lesions is allowed immediately before or during treatment.
• ECOG performance status should be less or equal to 3
• Patients must have organ and marrow function defined as: Absolute neutrophil count more or equal to 750/mL; platelets more or equal to 50,000/mL; creatinine less or equal to 3x ULN; total bilirubin less than or equal to 3.0.
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence).

You may not qualify if:

• Uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, uncontrolled asthma, need for hemodialysis, need for ventilatory support.
• Pregnant or lactating women.
• History of hypersensitivity to vandetanib, lactose, murine products, or any component of the formulation.
• History of hypersensitivity to sirolimus, temsirolimus, everolimus.
• History of hypersensitivity to any component of the formulation.
• Patients unwilling or unable to sign informed consent document.
• Presence of cardiac disease that, in the opinion of the Investigator, increases the risk of ventricular arrhythmia.
• History (within the last 3 months) or presence of stroke/cerebrovascular accident.
• Congenital long QT syndrome.
• QTcF interval greater than 500 ms that is not correctable to less than 500ms such as with cessation of a causative medication, etc.
• History of myocardial infarction within 6 months with a residual arrhythmia that in the opinion of the Investigator, increases the risk of ventricular arrhythmia.
• Presence of a symptomatic bradyarrhthmia or uncompensated heart failure.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Subbiah V, Berry J, Roxas M, Guha-Thakurta N, Subbiah IM, Ali SM, McMahon C, Miller V, Cascone T, Pai S, Tang Z, Heymach JV. Systemic and CNS activity of the RET inhibitor vandetanib combined with the mTOR inhibitor everolimus in KIF5B-RET re-arranged non-small cell lung cancer with brain metastases. Lung Cancer. 2015 Jul;89(1):76-9. doi: 10.1016/j.lungcan.2015.04.004. Epub 2015 Apr 22.

  PMID: 25982012 DERIVED

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Neoplasm Metastasis; Recurrence; Neoplasms

Interventions

Everolimus; vandetanib

Condition Hierarchy (Ancestors)

Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Disease Attributes

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• Sarina Piha-Paul, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

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: April 18, 2012
• First Posted: April 20, 2012
• Study Start: May 14, 2012
• Primary Completion: October 22, 2025
• Study Completion: October 22, 2025
• Last Updated: October 27, 2025

Record last verified: 2025-10

Locations

US (1)