QUILT-2.016: Study of AMG 479 With Biologics or Chemotherapy for Subjects With Advanced Solid Tumors

Sponsor

NantCell, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT00974896

Collaborator

(none)

Enrollment

Arms

Duration (Months)

Study Details

Study Description

Brief Summary

To assess the safety, tolerability, and pharmacokinetic profiles of AMG 479 when used in combination with bevacizumab, sorafenib, panitumumab, erlotinib, or gemcitabine in subjects with advanced solid tumors. Up to 126 subjects may be enrolled. Sorafenib and erlotinib combo cohorts are enrolling. All other combo cohorts are closed to enrollment.

Condition or Disease	Intervention/Treatment	Phase
Advanced Malignancy Advanced Solid Tumors Cancer Solid Tumors Tumors	Drug: AMG 479	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

46 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1b Study of AMG 479 With Biologics or Chemotherapy in Adult Subjects With Advanced Solid Tumors

Study Start Date :

Dec 1, 2006

Actual Primary Completion Date :

Sep 1, 2010

Actual Study Completion Date :

Apr 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AMG 479 + Sorafenib cohorts The aim is to determine the safety, tolerability and PK of AMG 479 with sorafenib. AMG 479 will be given bi-weekly; sorafenib will be given daily.	Drug: AMG 479 AMG 479 is a fully human IgG1 monoclonal antibody that inhibits IGF-1R signalling. AMG 479 (6mg/kg or 12mg/kg) will be given IV every 2 weeks in combination with sorafenib (400 mg po BID) or erlotinib (150 mg po QD).
Experimental: AMG 479 + Erlotinib cohorts The aim is to determine the safety, tolerability and PK of AMG 479 with erlotinib. AMG 479 will be given bi-weekly; erlotinib will be given daily.	Drug: AMG 479 AMG 479 is a fully human IgG1 monoclonal antibody that inhibits IGF-1R signalling. AMG 479 (6mg/kg or 12mg/kg) will be given IV every 2 weeks in combination with sorafenib (400 mg po BID) or erlotinib (150 mg po QD).

Arm

Intervention/Treatment

Experimental: AMG 479 + Sorafenib cohorts

The aim is to determine the safety, tolerability and PK of AMG 479 with sorafenib. AMG 479 will be given bi-weekly; sorafenib will be given daily.

Drug: AMG 479

AMG 479 is a fully human IgG1 monoclonal antibody that inhibits IGF-1R signalling. AMG 479 (6mg/kg or 12mg/kg) will be given IV every 2 weeks in combination with sorafenib (400 mg po BID) or erlotinib (150 mg po QD).

Experimental: AMG 479 + Erlotinib cohorts

The aim is to determine the safety, tolerability and PK of AMG 479 with erlotinib. AMG 479 will be given bi-weekly; erlotinib will be given daily.

Drug: AMG 479

Outcome Measures

Primary Outcome Measures

To assess the safety, tolerability, and pharmacokinetic profiles of AMG 479 when used in combination with bevacizumab, sorafenib, panitumumab, erlotinib or gemcitabine in subjects with advanced solid tumors [3 years]

Secondary Outcome Measures

To evaluate pharmacokinetic (PK) profiles of biologics or chemotherapy when used in combination with AMG 479 [3 years]
To evaluate tumor response as assessed by World Health Organization (WHO) criteria [3 years]
To evaluate tumor response as measured by volumetric computed tomography (CT) [3 years]
To evaluate anti-AMG 479 antibody response following AMG 479 administration [3 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Competent to comprehend, sign, and date an Institutional Review Board (IRB) approved informed consent form
Men and women ≥ 18 years old with a pathologically or cytologically documented, advanced solid tumor that is refractory to at least one line of therapy or for whom no standard therapy is available and for which no curative therapy is available, or the subject refuses standard non-curative therapy
Measurable disease or evaluable disease per World Health Organization (WHO) guidelines
Eastern Cooperative Oncology Group performance status ≤ 2
Life expectancy of 3 months as documented by the investigator
Adequate hematologic, renal and hepatic function

Exclusion Criteria:

Any co-morbid medical condition that would increase the risk of toxicity in the opinion of Investigator or Sponsor
Unresolved toxicities from prior anti-cancer therapy, defined as having not resolved to Common Terminology Criteria for Adverse Events (CTCAE) grade 0 or 1, or to levels dictated in the inclusion/exclusion criteria with the exception of alopecia
Subjects with primary or metastatic central nervous system (CNS) tumors are not allowed to enroll in the sorafenib cohorts. These subjects are allowed to enroll in the remaining cohorts, only if their CNS tumors have been controlled by prior surgery or radiation, and they have been neurologically stable
History of lymphoma, leukemia, or high-dose chemotherapy with hematopoietic stem cell rescue
Uncontrolled hypertension [diastolic >100 mmHg or systolic >150 mmHg]; Subjects enrolling in the sorafenib groups must not have diastolic > 85 mmHg nor systolic > 145 mmHg
Clinically significant ECG changes which obscure the ability to assess the PR, QT, QRS intervals
Presence of ascites or pleural effusion requiring chronic medical intervention
Diagnosis of arterial or venous thrombosis within 6 months before enrollment; history of bleeding diathesis
History of clinically significant hypoglycemia or hyperglycemia in the opinion of the investigator
Myocardial infarction within 6 months before enrollment, symptomatic congestive heart failure (New York Heart Association >class II), unstable angina, or unstable cardiac arrhythmia requiring medication
Active peptic ulcer disease
History of chronic hepatitis
Subject known to have tested positive for HIV
Known sensitivity to mammalian derived products
Hematological function, as follows:
Absolute neutrophil count (ANC) ≤ 1.5 x 109/L for B, P, S and E cohorts
Absolute neutrophil count (ANC) ≤ 3 x 109/L for G cohorts
Platelet count ≤ 100 x 109/L
Hemoglobin ≤ 9 g/dL
Renal function, as follows:
Calculated creatinine clearance < 50 ml/min using the modified Cockroft-Gault equation
Urinary protein quantitative value of > 30 mg or >1+ on dipstick, unless quantitative protein is < 500 mg in a 24 hour urine sample
Hepatic function, as follows:
Aspartate aminotransferase (AST) > 2.5 x upper limit of normal (ULN) (if liver metastases are present, ≥ 5 x ULN)
Alanine aminotransferase (ALT) > 2.5 x ULN (if liver metastases are present, ≥ 5 x ULN)
Alkaline phosphatase > 2.0 x ULN (if bone or liver metastases are present, ≥ 5 x ULN)
Bilirubin > 2.0 x ULN
Prothrombin time (PT) or partial thromboplastin time (PTT) > 1.5 x ULN
Treatment with anti-cancer therapy (6 weeks for nitrosoureas and mitomycin C chemotherapies), antibody therapy, retinoid therapy, or hormonal therapy within 4 weeks before study day 1. Prior and concurrent use of hormone replacement therapy or the use of gonadotropin-releasing hormone (GnRH) modulators for prostate cancer are permitted
Therapeutic or palliative radiation therapy within 4 weeks before enrollment (subjects must have resolution of any significant adverse effects from radiation therapy received prior to 2 weeks before enrollment)
Concurrent or prior (within 1 week of study Day 1) anticoagulation therapy, except low-dose warfarin (≤ 2 mg/day) for prophylaxis against central venous catheter thrombosis
Prior participation in clinical drug trials within 4 weeks before enrollment
For subjects receiving erlotinib, the use of ketoconazole, clarithromycin, voriconazole, troleandomycin, telithromycin, rifabutin, rifapentine, phenytoin, carbamazepine, phenobarbital and St. John's Wort is prohibited
For subjects receiving sorafenib, use of St. John's Wort, rifampin, phenytoin, carbamazepine, dexamethasone, and phenobarbital (CYP3A inducers) is prohibited
Type 1 or 2 diabetics are excluded