A Phase I Trial of Vandetanib (AZD6474) and Selumetinib (AZD6244) for Solid Tumours Including Non Small Cell Lung Cancer (VanSel-1)

Sponsor
Cancer Research UK
Study ID
NCT01586624
Phase
PHASE1
Status
Completed

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Vandetanib, Selumetinib — DRUG
    Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 4) followed by vandetanib steady state dose of 100 mg OD (Days 5 to 14) followed by vandetanib steady state dose of 100 mg OD + 25 mg of selumetinib BD (28 days). Cycle 1 is 42 days long. Cycle 2 onwards: Vandetanib steady state dose of 100 mg OD + 25 mg of selumetinib BD (28 days). From Cycle 2, cycles are 28 days long. Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment.
  • Vandetanib, Selumetinib — DRUG
    Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 4) followed by vandetanib steady state dose of 100 mg OD (Days 5 to 14) followed by vandetanib steady state dose of 100 mg OD + 50 mg of selumetinib BD (28 days). Cycle 1 is 42 days long. Cycle 2 onwards: Vandetanib steady state dose of 100 mg OD + 50 mg of selumetinib BD (28 days). From Cycle 2, cycles are 28 days long. Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment.
  • Vandetanib, Selumetinib — DRUG
    Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 4) followed by vandetanib steady state dose of 100 mg OD (Days 5 to 14) followed by vandetanib steady state dose of 100 mg OD + 75 mg of selumetinib BD (28 days). Cycle 1 is 42 days long. Cycle 2 onwards: Vandetanib steady state dose of 100 mg OD + 75 mg of selumetinib BD (28 days). From Cycle 2, cycles are 28 days long. Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment.
  • Vandetanib, Selumetinib — DRUG
    Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 4) followed by vandetanib steady state dose of 100 mg OD (Days 5 to 14) followed by vandetanib steady state dose of 100 mg OD + 100 mg of selumetinib OD (28 days). Cycle 1 is 42 days long. Cycle 2 onwards: Vandetanib steady state dose of 100 mg OD + 100 mg of selumetinib OD (28 days). From Cycle 2, cycles are 28 days long. Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment.
  • Vandetanib, Selumetinib — DRUG
    Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 4) followed by vandetanib steady state dose of 100 mg OD (Days 5 to 14) followed by vandetanib steady state dose of 100 mg OD + 125 mg of selumetinib OD (28 days). Cycle 1 is 42 days long. Cycle 2 onwards: Vandetanib steady state dose of 100 mg OD + 125 mg of selumetinib OD (28 days). From Cycle 2, cycles are 28 days long. Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment.
  • Vandetanib, Selumetinib — DRUG
    Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 4) followed by vandetanib steady state dose of 200 mg OD (Days 5 to 14) followed by vandetanib steady state dose of 200 mg OD + 50 mg of selumetinib BD (28 days). Cycle 1 is 42 days long. Cycle 2 onwards: Vandetanib steady state dose of 200 mg OD + 50 mg of selumetinib BD (28 days). From Cycle 2, cycles are 28 days long. Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment.
  • Vandetanib, Selumetinib — DRUG
    Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 2) followed by vandetanib steady state dose of 300 mg OD (Days 3 to 14) followed by vandetanib steady state dose of 300 mg OD + 50 mg of selumetinib BD (28 days). Cycle 1 is 42 days long. Cycle 2 onwards: Vandetanib steady state dose of 300 mg OD + 50 mg of selumetinib BD (28 days). From Cycle 2, cycles are 28 days long. Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment.
  • Vandetanib, Selumetinib — DRUG
    Cycle 1: Vandetanib higher (lead in) dose of 300 mg OD (Days 1 to 4) followed by vandetanib steady state dose of 200 mg OD (Days 5 to 14) followed by vandetanib steady state dose of 200 mg OD + 50 mg of selumetinib BD (28 days). Cycle 1 is 42 days long. Cycle 2 onwards: Vandetanib steady state dose of 200 mg OD + 50 mg of selumetinib BD (28 days). From Cycle 2, cycles are 28 days long. Patients will be allowed to receive 6 cycles. If the patient is still benefiting clinically with no unacceptable toxicity, then the Investigator can ask the Sponsor for continuation of treatment.

Study Details

The purpose of this study is to determine whether using two drugs together called vandetanib and selumetinib is effective in the treatment of cancer. The first part of this study will include patients with any solid tumour and the second part of this study will include only patients with non small cell lung cancer. The four main aims of this clinical study are to find out: * If the two drugs can be given safely to patients when given together. * The maximum dose that can be given safely to patients. * More about the potential side effects of the drugs and how they can be managed. * What happens to vandetanib and selumetinib inside the body.

Key Dates

Start date
Jan 10, 2012
Status verified
Sep 2021
Primary completion
Jun 11, 2020
Completion
Jun 11, 2020

Study Design

Enrollment
61 participants (actual)
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: Dose Escalation Phase Cohort 1 (Steady state dose of 100 mg OD Vandetanib + 25 mg BD Selumetinib)
    Dose escalation to determine recommended dose and schedule for Phase 2 evaluation of vandetanib and selumetinib.
  • Experimental: Dose Escalation Phase Cohort 2 (Steady state dose of 100 mg OD Vandetanib + 50 mg BD Selumetinib)
    Dose escalation to determine recommended dose and schedule for Phase 2 evaluation of vandetanib and selumetinib.
  • Experimental: Dose Escalation Phase Cohort 3 (Steady state dose of 100 mg OD Vandetanib + 75 mg BD Selumetinib)
    Dose escalation to determine recommended dose and schedule for Phase 2 evaluation of vandetanib and selumetinib.
  • Experimental: Dose Escalation Phase Cohort 4 (Steady state dose of 100 mg OD Vandetanib + 100 mg OD Selumetinib)
    Dose escalation to determine recommended dose and schedule for Phase 2 evaluation of vandetanib and selumetinib.
  • Experimental: Dose Escalation Phase Cohort 5a (Steady state dose of 100 mg OD Vandetanib + 125 mg OD Selumetinib)
    Dose escalation to determine recommended dose and schedule for Phase 2 evaluation of vandetanib and selumetinib.
  • Experimental: Dose Escalation Phase Cohort 5b (Steady state dose of 200 mg OD Vandetanib + 50 mg BD Selumetinib)
    Dose escalation to determine recommended dose and schedule for Phase 2 evaluation of vandetanib and selumetinib.
  • Experimental: Dose Escalation Phase Cohort 6 (Steady state dose of 300 mg OD Vandetanib + 50 mg BD Selumetinib)
    Dose escalation to determine recommended dose and schedule for Phase 2 evaluation of vandetanib and selumetinib.
  • Experimental: Expansion Phase (Steady state dose of 200 mg OD Vandetanib + 50 mg BD Selumetinib)
    Expansion cohort at the recommended phase 2 dose of vandetanib and selumetinib defined in the escalation phase.

Primary Outcome Measure

Number of Serious Adverse Events, Non-serious Adverse Events and Treatment Emergent Adverse Events. [ Time Frame: Safety data was collected from the date of written informed consent and continued until 28 days after the final administration of vandetanib and selumetinib, an average (mean) of 164 days (approximately 5.4 months). ]

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