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A Phase 1 Study Evaluating the Safety and Pharmacokinetic Profiles of IMC-A12 Administered Every 2 Weeks or Every 3 Weeks to Japanese Patients With Advanced Solid Tumors


Phase 1
20 Years
N/A
Open (Enrolling)
Both
Tumors

Thank you

Trial Information

A Phase 1 Study Evaluating the Safety and Pharmacokinetic Profiles of IMC-A12 Administered Every 2 Weeks or Every 3 Weeks to Japanese Patients With Advanced Solid Tumors


Patients in this single-center, open-label, dose-escalation, Phase 1 study will initially
receive intravenous (I.V.) IMC-A12 every 2 weeks or every 3 weeks for 6 weeks (one cycle).
After the first cycle, patients experiencing a best overall response of complete response
(CR), partial response (PR), or stable disease (SD) will continue to receive IMC-A12 at
their cohort dose and schedule until there is evidence of progressive disease (PD), or until
other withdrawal criteria are met.

A minimum of three patients will be enrolled in each cohort. The starting dose in Cohort 1
will be 6 mg/kg, administered every 2 weeks. Dose escalation from Cohort 1 to Cohort 2 (10
mg/kg administered every 2 weeks) will occur once at least three patients in Cohort 1 have
completed one cycle of therapy (ie, completed the initial 6 week treatment period or
discontinued therapy due to an IMC-A12 -related adverse event [AE]).

Enrollment into Cohort 3 (starting dose: 15 mg/kg administered every 3 weeks) will not
proceed until all patients have completed one cycle of therapy (as defined above) in Cohort
2. Similarly, patients will be enrolled in Cohort 4 once at least three patients have
completed one cycle of therapy in Cohort 3; patients in Cohort 4 will receive 20 mg/kg
administered every 3 weeks. Toxicity data for each cohort will be reviewed prior to any dose
escalation. No intrapatient dose escalation is permitted. Patients in any cohort who do not
complete the first 6 weeks of treatment for reasons other than an IMC-A12 -related toxicity
will be replaced.

A dose-limiting toxicity (DLT) is defined as one of the following events, if considered by
the investigator to be definitely, probably, or possibly related to IMC-A12 : Grade 4
neutropenia lasting > 7 days; Grade 4 anemia; Grade ≥ 3 thrombocytopenia; Grade ≥ 3
neutropenia associated with fever; Grade 3 or 4 nonhematologic toxicity, excluding
electrolyte abnormality and Grade 3 hyperglycemia; Grade 4 hyperglycemia; and/or Grade 4 or
uncontrollable hypertension.

If three patients complete the first 6-week cycle (according to the definition outlined
above) with no DLTs, dose escalation to Cohort 2 may proceed. If one DLT is observed in the
initial three patients of Cohort 1 (or any cohort) during Cycle 1, three additional patients
will be enrolled into that cohort. If no additional DLTs are observed, dose escalation may
continue as described above.

If two or more patients in Cohort 1 experience a DLT, six patients will be enrolled into
Cohort 1A (receiving 4 mg/kg every 2 weeks). If two or more patients experience a DLT in
dose Cohort 3, six patients will be enrolled into dose Cohort 3A (10 mg/kg every 3 weeks).
If two or more patients experience a DLT in dose Cohorts 2 or 4, six additional patients
will be enrolled into the previous cohort (Cohort 1 or Cohort 3, respectively), and the
previous cohort will be considered the maximum tolerated dose for that dosing schedule. If
two or more patients in any cohort experience a DLT on Week 7 or beyond (after Cycle 1), the
data will be reviewed and enrollment may be suspended. The Sponsor and Principal
Investigator, with reference to the review of the Independent Data Safety Evaluation
Committee (established in a separate document), will determine whether enrollment should
resume.


Inclusion Criteria:



- Solid tumor patient who has been histopathologically or cytologically documented

- Advanced primary or recurrent solid tumor patient who has not responded to standard
therapy or for whom no standard therapy is available

- The patient has measurable or nonmeasurable lesions according to Response Evaluation
Criteria in Solid Tumors (RECIST Version 1.0) guidelines

- The patient has an Eastern Cooperative Oncology Group performance status (ECOG
PS)score of 0-1 at study entry

- The patient is able to provide informed consent

- The patient is age 20 years or older

- The patient has a life expectancy of > 3 months

- The patient has adequate hematologic function, as defined by:

- An absolute neutrophil count (ANC) ≥ 1500/m3 or /μL

- A hemoglobin ≥ 10 g/dL; and

- A platelet count ≥ 100,000/mm3 or /μL

- The patient has adequate hepatic function, as defined by:

- Total bilirubin ≤ 1.8 mg/dL

- Aspartate transaminase (AST) ≤ 2.5 times the upper limit of site-specific normal
ranges (five times in case of liver metastasis)

- Alanine transaminase (ALT) ≤ 2.5 times the upper limit of site-specific normal ranges
(five times in case of liver metastasis)

- The patient has adequate renal function, as defined by:

- Serum creatinine ≤ 1.5 mg/dL

- Calculated serum creatinine clearance (Cockcroft-Gault) ≥ 60 mL/min

- The patient has fasting blood sugar < 120 mg/dL or below the institutional upper
limit of normal (ULN) before study entry (one retest of an elevated level is
permitted at the discretion of the investigator)

- The patient has adequate coagulation function, as defined by an international
normalized ratio (INR) ¬ 1.5

- The patient agrees to use adequate contraception for the duration of study
participation and for 12 weeks after the last dose of study therapy.

- The patient has adequate recovery from recent surgery, chemotherapy, and radiation
therapy (including palliative radiation therapy). At least 28 days (6 weeks for
nitrosoureas or mitomycin C) must have elapsed from major surgery, prior
chemotherapy, prior treatment with an investigational agent or device, or prior
radiation therapy. For treatment with nonapproved monoclonal antibodies, a minimum of
8 weeks must have elapsed

- The patient is willing to comply with study procedures until the end of therapy

Exclusion Criteria:

- The patient has received chemotherapy or therapeutic radiotherapy within 28 days (6
weeks for nitrosoureas or mitomycin C) prior to entering the study, or the patient
has ongoing side effects ≥ Grade 2 due to agents administered more than 28 days
earlier

- The patient has undergone major surgery (eg,laparotomy, thoracotomy,removal of
organ(s)) within 28 days prior to study entry, or subcutaneous venous access device
placement within 7 days prior to study entry

- The patient has elective or planned surgery to be conducted during the trial

- The patient has documented and/or symptomatic brain or leptomeningeal metastases
(patients who are clinically stable (no symptoms during the 4 weeks prior to
enrollment) with an assessment that no further treatment (radiation, surgical
excision, or administration of steroids) is required are permitted to enter the
study)

- The patient has an uncontrolled intercurrent illness including, but not limited to:

- Thrombotic or hemorrhagic disorders

- Gross hemoptysis (approximately one-half a teaspoon)

- Ongoing or active infection requiring systemic antibiotic treatment

- Congestive heart failure (Class III or IV per the New York Heart Association
classification for heart disease)

- Angina pectoris, angioplasty, stenting, or myocardial infarction within 6 months

- Uncontrolled hypertension (systolic blood pressure > 150 mm Hg, diastolic blood
pressure > 95 mm Hg)

- Cardiac arrhythmia requiring treatment (NCICTCAE Version 3.0 Grade 3), or
asymptomatic sustained ventricular tachycardia

- Peripheral neuropathy of any etiology ≥ Grade 2 (NCI-CTCAE Version 3.0); or

- Any other serious uncontrolled medical disorder(s) in the opinion of the investigator

- The patient has a serious or nonhealing wound, ulcer, or bone fracture within 28 days
prior to study entry

- The patient has experienced any Grade 3/4 gastrointestinal bleeding within 3 months
prior to study entry

- The patient has participated in clinical studies of nonapproved experimental agents
or procedures within 4 weeks prior to study entry for small molecules, or 8 weeks
prior to study entry for nonapproved monoclonal antibodies

- The patient has received any previous treatment with agents targeting the IGF-IR,
approved or nonapproved

- The patient has a known allergy to any of the treatment components (monoclonal
antibodies or other therapeutic proteins such as fresh frozen plasma, human serum
albumin, cytokines, or interleukins). In the event that there is suspicion the
patient may have allergies, the patient should be excluded

- The patient, if female, is pregnant (confirmed by urine or serum pregnancy test) or
lactating

- The patient has a known alcohol or drug dependency

- The patient is HBV antigen-, HCV antibody-, or HIV antibody-positive (asymptomatic
healthy carriers with detectable HBV-DNA, HCV-RNA may be enrolled into the trial)

- The patient is assessed as inadequate for the study by the investigator

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Summary Listing of Participants Reporting Treatment-Emergent Adverse Events

Outcome Description:

Summary listing of Participants Reporting Treatment-Emergent Adverse Events that received IMC-A12.

Outcome Time Frame:

6 months

Safety Issue:

Yes

Principal Investigator

E-mail: ClinicalTrials@ ImClone.com

Investigator Role:

Study Director

Investigator Affiliation:

ImClone LLC

Authority:

Japan: Ministry of Health, Labor and Welfare

Study ID:

13905

NCT ID:

NCT01007032

Start Date:

November 2009

Completion Date:

December 2013

Related Keywords:

  • Tumors
  • anti-IGF-IR
  • monoclonal
  • solid tumor
  • insulin-like growth factor

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