Mitotane With or Without IMC-A12 in Treating Patients With Recurrent, Metastatic, or Primary Adrenocortical Cancer That Cannot Be Removed By Surgery - Full Text View

Sponsors and Collaborators:	University of Chicago National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00778817

Purpose

RATIONALE: Drugs used in chemotherapy, such as mitotane, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as IMC-A12, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known whether mitotane is more effective with or without monoclonal antibody IMC-A12 in treating adrenocortical cancer.

PURPOSE: This randomized phase II trial is studying mitotane and IMC-A12 to see how well they work compared with mitotane alone in treating patients with recurrent, metastatic, or primary adrenocortical cancer that cannot be removed by surgery.

Condition	Intervention	Phase
Adrenocortical Carcinoma	Biological: cixutumumab Drug: mitotane	Phase II

MedlinePlus related topics: Cancer Surgery

Drug Information available for: Mitotane

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized
Official Title:	Multi-Institutional Phase II Study of IMC-A12, a Recombinant Human IgG1/λ Monoclonal Antibody Directed at the Type I Insulin-Like Growth Factor Receptor (IGF-1R), in Adrenocortical Cancer: A Randomized Trial Comparing the Activity of IMC-A12 With Mitotane Versus Mitotane Alone.

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Progression-free survival [ Designated as safety issue: No ]

Secondary Outcome Measures:

Objective response rates [ Designated as safety issue: No ]
Changes in tumor size over time [ Designated as safety issue: No ]
Overall survival [ Designated as safety issue: No ]

Estimated Enrollment:	204
Study Start Date:	August 2008
Estimated Primary Completion Date:	April 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Arm I: Active Comparator Patients receive oral mitotane once or twice daily in the absence of disease progression or unacceptable toxicity. Patients with documented disease progression may cross over and receive treatment on arm II.	Drug: mitotane Given orally
Arm II: Experimental Patients receive mitotane as in arm I and anti-IGF-1R recombinant monoclonal antibody IMC-A12 IV over 1 hour once every 2 weeks in the absence of disease progression or unacceptable toxicity.	Biological: cixutumumab Given IV Drug: mitotane Given orally

Detailed Description:

OBJECTIVES:

Primary

Compare the progression-free survival rate in patients with recurrent, metastatic, or primary unresectable adrenocortical cancer treated with mitotane with vs without anti-IGF-1R recombinant monoclonal antibody IMC-A12 (IMC-A12).

Secondary

Compare the response rates in these patients using RECIST criteria.
Compare the change in tumor size from baseline to 12 weeks in these patients.
Compare the overall trajectories in tumor growth in these patients.

Tertiary

Define predictive markers of response or insensitivity to IMC-A12.
Define pharmacodynamic markers of IMC-A12.
Determine whether tumor expression of IGF-IR and activation of downstream signaling in archival tumor tissue samples predict efficacy of IMC-A12.

OUTLINE: This is a multicenter study that includes a single-arm safety evaluation phase followed by a randomized phase. Initially, patients are enrolled in the safety evaluation phase. If ≤ 6 of 20 patients experience a dose-limiting toxicity, then the study may proceed to the randomized phase.

Safety evaluation phase: Patients receive oral mitotane once or twice daily and anti-IGF-1R recombinant monoclonal antibody IMC-A12 IV over 1 hour once every 2 weeks in the absence of disease progression or unacceptable toxicity.
Randomized phase: Patients are stratified according to participating center. Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive oral mitotane once or twice daily in the absence of disease progression or unacceptable toxicity. Patients with documented disease progression may cross over and receive treatment on arm II.
- Arm II: Patients receive mitotane as in arm I and anti-IGF-1R recombinant monoclonal antibody IMC-A12 IV over 1 hour once every 2 weeks in the absence of disease progression or unacceptable toxicity. Paraffin blocks and serum samples are collected and stored for future correlative biomarker studies.

After completion of study therapy, patients are followed periodically for 2 years.

PROJECTED ACCRUAL: A total of 204 patients (20 for the safety evaluation phase and 184 [92 per treatment arm] for the randomized phase) will be accrued for this study.

Eligibility

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

Criteria

DISEASE CHARACTERISTICS:

Pathologically confirmed adrenocortical cancer
- Recurrent, metastatic, or primary unresectable disease
Measurable or evaluable disease by standard RECIST criteria
- Measurable disease must include sites that have not been previously irradiated
No tumors potentially resectable by surgical excision alone
No known or suspected brain metastases

PATIENT CHARACTERISTICS:

ECOG performance status 0-2
Life expectancy ≥ 12 weeks
Total bilirubin ≤ 1.5 times upper limit of normal (ULN) (unless the patient meets the criteria for Gilbert's syndrome)
AST and ALT ≤ 3 times ULN (≤ 5 times ULN if elevations due to liver metastases)
Serum creatinine ≤ 2 mg/dL
ANC ≥ 1,500/mm^3
Hemoglobin ≥ 9 g/dL
Platelet count ≥ 100,000/mm^3
Random glucose < 150 mg/dL
HbA1c < 8
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for 3 months after completion of study therapy
Patients with diabetes mellitus are eligible provided blood glucose is normal and patient is on a stable dietary or therapeutic regimen
No NYHA class III or IV congestive heart failure
No ongoing unstable angina
No history of allergic reactions attributed to compounds of similar chemical or biologic composition to anti-IGF-1R recombinant monoclonal antibody IMC-A12
No currently active second malignancy other than squamous cell carcinoma of the skin or in situ cervical cancer
- Patients are considered not to have currently active malignancy if they have completed all curative intent therapy and chance of relapse is < 30%
No HIV or hepatitis A, B, or C infection

PRIOR CONCURRENT THERAPY:

Initiation of mitotane prior to study entry allowed provided patient has been on therapy for < 2 weeks AND has tolerated therapy well
No prior IGFR-directed therapy
No prior systemic chemotherapy for adrenocortical cancer (other than mitotane)
More than 4 weeks since prior and no concurrent radiotherapy
No concurrent tumor resection or tumor-directed surgery
No other concurrent antitumor-directed therapy

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00778817

Sponsors and Collaborators

University of Chicago

National Cancer Institute (NCI)

Investigators

Study Chair:

Gary D. Hammer, MD, PhD

University of Michigan Cancer Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	University of Chicago Cancer Research Center ( Everett E. Vokes )
Study ID Numbers:	CDR0000617085, UCCRC-16402A
Study First Received:	October 22, 2008
Last Updated:	April 14, 2009
ClinicalTrials.gov Identifier:	NCT00778817 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

recurrent adrenocortical carcinoma
stage III adrenocortical carcinoma
stage IV adrenocortical carcinoma

Study placed in the following topic categories:

Antineoplastic Agents, Hormonal
Adrenocortical Carcinoma
Adrenal Gland Diseases
Endocrine System Diseases
Insulin
Recurrence
Mitotane
Carcinoma
Antibodies, Monoclonal
Antibodies

Adrenal Gland Neoplasms
Mitogens
Adrenal Cortex Neoplasms
Endocrinopathy
Adenocarcinoma
Adrenal Cortex Diseases
Immunoglobulins
Neoplasms, Glandular and Epithelial
Endocrine Gland Neoplasms

Additional relevant MeSH terms:

Neoplasms by Histologic Type
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Adrenocortical Carcinoma
Adrenal Gland Diseases
Endocrine System Diseases
Pharmacologic Actions
Mitotane
Carcinoma

Neoplasms
Adrenal Gland Neoplasms
Neoplasms by Site
Therapeutic Uses
Adrenal Cortex Neoplasms
Adenocarcinoma
Adrenal Cortex Diseases
Neoplasms, Glandular and Epithelial
Endocrine Gland Neoplasms

ClinicalTrials.gov processed this record on May 07, 2009