Safety Study of rhuMAb 2C4 to Treat Advanced Solid Tumors

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.
ClinicalTrials.gov Identifier:
NCT00027027
First received: November 15, 2001
Last updated: July 24, 2015
Last verified: July 2015
  Purpose

The purpose of this Phase I study is to test the safety of rhuMAb 2C4 to see what effects (good and bad) it has on patients with certain types of cancer, and also to find the highest dose of rhuMAb that can be given without causing severe side effects. All study participants will be assigned to specific group to evaluate different dosages of rhuMAb 2C4. The study is scheduled to run for up to one year depending on how patients respond to the study treatment.


Condition Intervention Phase
Neoplasms
Drug: rhuMAb 2C4
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I, Open-Label, Multicenter, Dose-Escalation Study of the Safety and Pharmacokinetics of a Recombinant Humanized Antibody to Her2 (rhuMAb 2C4) Administered Every 3 Weeks to Subjects With Advanced Solid Malignancies

Resource links provided by NLM:


Further study details as provided by Genentech, Inc.:

Primary Outcome Measures:
  • Number of Participants With an Adverse Event (AE), Serious Adverse Event (SAE), or Death [ Time Frame: Days 1, 2, 5, 8, and 15 of Cycle 1; Days 1, 8, and Week 3, of Cycles 2 and beyond up to 1 year and at the follow-up visit (4 weeks after last infusion) ] [ Designated as safety issue: No ]

    For this protocol, an AE is defined any untoward medical occurrence (e.g., sign, symptom, disease, syndrome, intercurrent illness, abnormal laboratory finding) that emerges or worsens relative to pretreatment baseline during the treatment or post-treatment periods, regardless of the suspected cause.

    For this protocol an SAE was defined as any AE that occurred at any dose if:

    • It resulted in death (i.e., the AE caused or led to death),
    • It was life threatening,
    • It required or prolonged inpatient hospitalization,
    • It was disabling,
    • It resulted in a congenital anomaly/birth defect,
    • It may have jeopardized the participant or may have required medical or surgical intervention to prevent one of the outcomes listed above.

    The primary cause of death for all reported cases was disease progression, and all of the deaths occurred following study discontinuation, with one death occurring within 4 weeks of the last treatment day.


  • Number of Participants With Dose-Limiting Toxicities (DLTs) [ Time Frame: Day 1 of Cycles 1 and 2, and 24 hours after Cycle 2 infusion ] [ Designated as safety issue: No ]

    Incidence of DLTs defined as any Grade 3 or 4 major organ toxicity according to the National Cancer Institute Common Toxicity Criteria (NCI-CTC) Version 2 or any subjectively intolerable toxicity felt by the investigator to be related to rhuMAb 2C4.

    One participant in the 15.0 mg/kg dose group experienced a gastrointestinal hemorrhage on Day 16. This event was judged by the investigator to be related to study drug. The participant recovered in 3 days and continued to receive rhuMAb 2C4 beyond Cycle 2.This was the only DLT reported during the first two treatment cycles.



Secondary Outcome Measures:
  • Pharmacokinetic Measurement of Area Under the Curve (AUC) [ Time Frame: Days 1 (predose, 89 minutes following start of infusion and at 1.5, 4, and 8 hours postdose) 2, 5, 8 and 15 of Cycle 1; Days 1 (predose and 29 minutes following start of infusion) and 8 of Cycle 2 ] [ Designated as safety issue: No ]
    Mean rhuMAb 2C4 serum concentrations versus nominal time profiles for the first two treatment cycles are presented for AUC micrograms per milliliters (ug/mL) by day. A one-compartment model was used for the 0.5 mg/kg dose group, and a two-compartment model was used for the 2-15 mg/kg dose groups.

  • Pharmacokinetic Measurement of Systemic Clearance (CL) [ Time Frame: Days 1 (predose, 89 minutes from infusion start, at 1.5, 4, and 8 hours postdose), 2, 5, 8 and 15 of Cycle 1; Days 1 (predose, 29 minutes from infusion start) and 8 of Cycles 2 and beyond until the follow-up visit (4 weeks after the last infusion) ] [ Designated as safety issue: No ]
    A one-compartment model was used for the 0.5 mg/kg dose group, and a two-compartment model was used for the 2-15 mg/kg dose groups.

  • Pharmacokinetic Measurement of Volume of Central Compartment (Vc) [ Time Frame: Days 1 (predose, 89 minutes from infusion start, at 1.5, 4, and 8 hours postdose), 2, 5, 8 and 15 of Cycle 1; Days 1 (predose, 29 minutes from infusion start) and 8 of Cycles 2 and beyond until the follow-up visit (4 weeks after the last infusion) ] [ Designated as safety issue: No ]
    A one-compartment model was used for the 0.5 mg/kg dose group, and a two-compartment model was used for the 2-15 mg/kg dose groups.

  • Pharmacokinetic Measurement of Steady-State Volume of Distribution (Vss) [ Time Frame: Days 1 (predose, 89 minutes from infusion start, at 1.5, 4, and 8 hours postdose), 2, 5, 8 and 15 of Cycle 1; Days 1 (predose, 29 minutes from infusion start) and 8 of Cycles 2 and beyond until the follow-up visit (4 weeks after the last infusion) ] [ Designated as safety issue: No ]
    A one-compartment model was used for the 0.5 mg/kg dose group, and a two-compartment model was used for the 2-15 mg/kg dose groups.

  • Pharmacokinetic Measurement of Initial Distribution Half-Life (t1/2 Initial) [ Time Frame: Days 1 (predose, 89 minutes from infusion start, at 1.5, 4, and 8 hours postdose), 2, 5, 8 and 15 of Cycle 1; Days 1 (predose, 29 minutes from infusion start) and 8 of Cycles 2 and beyond until the follow-up visit (4 weeks after the last infusion) ] [ Designated as safety issue: No ]
    A one-compartment model was used for the 0.5 mg/kg dose group, and a two-compartment model was used for the 2-15 mg/kg dose groups.

  • Pharmacokinetic Measurement of Terminal Half-Life (t1/2 Terminal) in Days [ Time Frame: Days 1 (predose, 89 minutes from infusion start, at 1.5, 4, and 8 hours postdose), 2, 5, 8 and 15 of Cycle 1; Days 1 (predose, 29 minutes from infusion start) and 8 of Cycles 2 and beyond until the follow-up visit (4 weeks after the last infusion) ] [ Designated as safety issue: No ]
    A one-compartment model was used for the 0.5 mg/kg dose group, and a two-compartment model was used for the 2-15 mg/kg dose groups.


Enrollment: 21
Study Start Date: November 2001
Study Completion Date: August 2003
Primary Completion Date: August 2003 (Final data collection date for primary outcome measure)
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Signed informed consent
  • Age >=18 years old
  • ECOG performance status of 0 or 1 (see Appendix F)
  • Life expectancy of >=12 weeks
  • Histologically documented, incurable, locally advanced or metastatic solid malignancies
  • Disease progression on or after standard effective therapy or a malignancy for which there is no standard therapy
  • At least one bi-dimensionally measurable lesion (>=2 cm [>=1 cm on spiral CT scan])
  • HER2-negative status as defined by fluorescence in situ hybridization (FISH) testing (only for subjects with breast cancer)
  • Use of an effective means of contraception for women of childbearing potential
  • Granulocyte count of >=1500/uL, platelet count of >=100,000/uL, and hemoglobin of >=9 g/dL
  • Serum bilirubin less than or equal to the upper limit of normal (ULN) and alkaline phosphatase, AST, and ALT <=2.5x ULN (ALT and AST <=5x ULN for subjects with liver metastases; alkaline phosphatase <=5x ULN for subjects with liver or bone metastases)
  • Serum creatinine less than or equal to ULN or creatinine clearance of >=60 mL/min
  • International normalized ratio (INR) of <1.3 and activated partial thromboplastin time (aPTT) of <1.5x ULN

Exclusion Criteria:

  • Pleural effusions, ascites, or bone lesions as the only manifestation of the current cancer
  • Symptomatic or untreated brain metastases
  • Prior chemotherapy, hormonal therapy (except for androgen-deprivation therapy for subjects with prostate cancer), radiotherapy, or immunotherapy within 4 weeks of Day 1 (within 6 weeks for nitrosoureas or mitomycin)
  • Prior treatment with Herceptin
  • Prior cumulative doxorubicin dose of >360 mg/m2 or the equivalent
  • History of other malignancies within 5 years of Day 1 except for adequately treated carcinoma in situ of the cervix or basal or squamous cell skin cancer
  • History of significant cardiac disease, unstable angina, congestive heart failure, myocardial infarction, or ventricular arrhythmia requiring medication
  • Ejection fraction of <50% or below the lower limit of normal determined by ECHO (Subjects who are unable to have ejection fraction evaluated by ECHO may have ejection fraction evaluated by a MUGA scan, although this must be discussed with the Medical Monitor prior to enrollment.)
  • Active infection requiring IV antibiotics
  • Uncontrolled hypercalcemia (>11.5 mg/dL)
  • Clinically important history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis
  • Known human immunodeficiency virus (HIV) infection
  • Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the subject at high risk from treatment complications
  • Major surgery or significant traumatic injury within 3 weeks of Day 1
  • Pregnancy or lactation
  • Inability to comply with study and follow-up procedures
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00027027

Locations
United States, California
Cedars-Sinai Medical Center
Los Angeles, California, United States, 90211
Sponsors and Collaborators
Genentech, Inc.
  More Information

No publications provided

Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT00027027     History of Changes
Other Study ID Numbers: TOC2297g
Study First Received: November 15, 2001
Results First Received: June 26, 2015
Last Updated: July 24, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Pertuzumab
Antineoplastic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on August 03, 2015