Dose Escalation of Bivatuzumab Mertansine in Patients With Advanced Squamous Cell Carcinoma of the Head and Neck or Esophagus

Phase 1

Terminated

• Conditions: Carcinoma, Squamous Cell
• Interventions: Drug: bivatuzumab mertansine

• Registration Number: NCT02254044
• Lead Sponsor: Boehringer Ingelheim

Brief Summary

maximum tolerated dose (MTD), safety, pharmacokinetics, efficacy of bivatuzumab mertansine

Detailed Description

Not available

Study Timeline

• Study Start: 2003-10
• Primary Completion: 2004-11
• Status Verified: 2014-09
• Study First Submitted: 2014-09-30
• Study First Submitted QC: 2014-09-30
• Last Update Submitted: 2014-09-30
• Study First Posted: 2014-10-01
• Last Update Posted: 2014-10-01

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 7

Inclusion Criteria

1. patients from 18 to 80 years of age (both inclusive)
2. patients with histologically confirmed squamous cell carcinoma of the head and neck or esophagus
3. patients with local and / or regional recurrent disease or distant metastases who are refractory to or not amenable to established treatments
4. evaluable tumour deposits
5. life expectancy of at least 3 months
6. Eastern Cooperative Oncology Group (ECOG) performance score ≤ 2
7. patients must have given written informed consent (which must be consistent with International Conference on Harmonisation-Good Clinical Practice (ICH-GCP) and local legislation)

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Exclusion Criteria

1. hypersensitivity to humanised or murine antibodies, immunoconjugates or the excipients of the trial drugs
2. known secondary malignancy requiring therapy
3. active infectious disease
4. brain metastases requiring therapy
5. neuropathy grade 2 or above
6. absolute neutrophil count less than 1,500/mm3
7. platelet count less than 100,000/mm3
8. bilirubin greater than 1.5 mg/dl (> 26 μmol/L, système internationale (SI) unit equivalent)
9. aspartate amino transferase (AST) and/or alanine amino transferase (ALT) greater than 3 times the upper limit of normal
10. serum creatinine greater than 1.5 mg/dl (> 132 μmol/L, SI unit equivalent)
11. concomitant non-oncological diseases which are considered relevant for the evaluation of the safety of the trial drug
12. chemo-, radio- or immunotherapy within the past four weeks prior to treatment with the trial drug or during the trial (except for present trial drug)
13. men and women who are sexually active and unwilling to use a medically acceptable method of contraception
14. pregnancy or lactation
15. treatment with other investigational drugs or participation in another clinical trial within the past four weeks before start of therapy or concomitantly with this trial (except for present trial drug)
16. patients unable to comply with the protocol

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
bivatuzumab mertansine	bivatuzumab mertansine	dose escalation

Primary Outcome Measures

Name	Time	Method
Maximum tolerated dose (MTD)	up to 6 months

Secondary Outcome Measures

Name	Time	Method
Mean residence time (MRT)	up to 14 days after last drug administration
Number of patients with clinically significant findings in vital signs	up to 14 days after last drug administration
Terminal elimination half-life (t1/2)	up to 14 days after last drug administration
Trough concentration at steady state (Cpre,ss)	up to 7 days after drug administration
Number of patients with development of Human Anti-Human Antibody (HAHA)	up to 14 days after last drug administration
Minimum serum concentration during the dosing interval τ at steady state (Cmin,ss)	up to 7 days after drug administration
Linearity index (LI)	up to 14 days after last drug administration
Area under the serum concentration time curve from time zero to time point 168 hours (AUC0-168)	up to 168 hours
Time to reach maximum serum concentration (tmax)	up to 14 days after last drug administration
Volume of distribution at steady state (Vss)	up to 14 days after last drug administration
Number of patients with clinically significant findings in laboratory examinations	up to 14 days after last drug administration
Area under the serum concentration time curve from time zero to the time of the last quantifiable drug concentration (AUC0-tz)	up to 14 days after last drug administration
Area under the serum concentration time curve from time point zero to infinity (AUC0-∞)	up to 14 days after last drug administration
Volume of distribution during the terminal elimination phase (Vz)	up to 14 days after last drug administration
Incidence of adverse events	up to 14 days after last drug administration	graded according to common toxicity criteria (CTC)
Maximum serum concentration (Cmax)	up to 14 days after last drug administration
Total body clearance (CL)	up to 14 days after last drug administration
Tumor response	up to 14 days after last drug administration	according to response evaluation criteria in solid tumours (RECIST)
Accumulation factor (RA)	up to 14 days after last drug administration