Treatment Based on Molecular Profiling Diagnosis Carcinoma of Unknown Primary Site

Carcinoma Clinical Trial

Official title:

A Phase II Study of Chemotherapy Treatment Based on Molecular Profiling Diagnosis for Patients With Carcinoma of Unknown Primary Site

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00737243
• Other study ID #: SCRI UNKPRI 20
• Status: Active, not recruiting
• Phase: Phase 2
• First received: August 15, 2008
• Last updated: January 21, 2015
• Start date: August 2008
• Est. completion date: September 2015

Study information

• Verified date: January 2015
• Source: SCRI Development Innovations, LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This is a non-randomized Phase II study. Patients determined at initial diagnosis to have a carcinoma of unknown primary site will have their treatment selected with the use of a molecular profiling assay. A molecular profiling assay will be performed on paraffin-embedded tumor tissue from a biopsy specimen. Patients given specific diagnoses (e.g., lung, pancreas, colon, breast, renal cell, prostate and ovarian cancer) will receive treatment regimens of proven activity. If no specific diagnosis is made with the molecular profiling assay, empiric chemotherapy with paclitaxel, carboplatin, bevacizumab and erlotinib will be administered.

Description:

Patients in all subgroups will be evaluated for response to treatment after completing 2 cycles. Standard, disease specific, restaging methods will be employed. Patients with objective response or stable disease will continue treatment, with subsequent re-evaluations after every 2 cycles of therapy.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 224
• Est. completion date: September 2015
• Est. primary completion date: November 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Patients must have carcinoma of unknown primary site after the following diagnostic procedures have been performed and are unrevealing of a primary site:

• Complete medical history and physical examination,

• Complete blood counts, chemistry profile,

• CT scans of the chest and abdomen,

• Directed evaluation of any symptomatic areas,

• PET scan (recommended).

2. Patients must have biopsy-proven metastatic carcinoma, with any of the following light microscopic histologies:

• Adenocarcinoma,

• Poorly differentiated adenocarcinoma,

• Poorly differentiated carcinoma (all patients with poorly differentiated carcinoma must have immunoperoxidase stains to rule out other treatable malignancies [e.g., lymphoma, neuroendocrine carcinoma]),

• Poorly differentiated squamous carcinoma.

3. Patients must have biopsy material available from a surgical biopsy, a core needle biopsy, or a fine needle aspiration biopsy to provide an adequate specimen (must be 40% tumor) for the molecular profiling assay.

4. An ECOG performance status 0, 1, or 2.

5. No previous treatment with any systemic therapy.

6. Measurable or evaluable disease according to the Response Evaluation Criteria in Solid Tumors (RECIST).

7. Laboratory values as follows:

• WBC 4000/micro L,

• Platelets 100,000/micro L,

• Serum bilirubin <1.5 times the institutional upper limits of normal (ULN),

• Serum creatinine < 2.0 mg/dL.

8. Patients with brain metastases are eligible only if all lesions have been controlled by surgical resection or radiation therapy, the patient is not steroid-dependent, and the patient meets all other eligibility criteria.

9. Patients must be > 4 weeks from any major operative procedure.

10. To be eligible for the TREATMENT portion of the study, patients must have one of the five following diagnoses: colorectal, pancreas, NSCLC, ovary, renal cancer.

11. Patients must be able to understand the nature of this study and give written informed consent.

Exclusion Criteria:

1. Patients with the following specific syndromes are not eligible:

• Patients with neuroendocrine carcinoma,

• Women with adenocarcinoma isolated to axillary lymph nodes,

• Women with adenocarcinoma isolated to peritoneal involvement,

• Patients with carcinoma involving only 1 site, with resectable tumor at that site, or

• Patients with squamous carcinoma limited to cervical, supraclavicular, or inguinal lymph nodes.

2. Patients with uncontrolled brain metastases and all patients with meningeal metastases.

3. Patients with insufficient biopsy material available for molecular profiling assay.

4. Women who are pregnant or lactating. All females of child-bearing potential must have a negative serum or urine pregnancy tests within 7 days prior to study treatment.

5. Men and women of childbearing potential are required to use effective methods of contraception during this study and for 6 months after ending therapy.

6. Patients who have received any other experimental drug within 28 days of starting treatment.

Exclusion Criteria for All Patients Receiving Bevacizumab-Containing Regimens

1. Patients with history of acute myocardial infarction within 6 months, other clinically significant cardiovascular disease (e.g., unstable angina, New York Heart Association [NYHA] grade 2 congestive heart failure [CHF], serious cardiac arrhythmias requiring medication) or > grade 2 vascular disease.

2. Patients with uncontrolled hypertension (systolic blood pressure [BP] 150 or diastolic BP >100mm Hg) or uncontrolled cardiac arrhythmias.

3. Prior hypertensive crisis or hypertensive encephalopathy.

4. Patients with clinical history of hemoptysis (defined as bright red blood of

½ teaspoon per episode) or hematemesis within 1 month prior to Day 1.

5. Patients with PEG tubes or G tubes.

6. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1 or anticipation of need for major surgical procedure during the course of the study.

7. Core biopsy or other minor surgical procedure excluding placement of a vascular access device, within 7 days prior to Day 1.

8. Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Day 1.

9. Patients with proteinuria (1000 mg/24 hours) at screening will be excluded. A 24-hour urine collection is not required in all patients (e.g., patients whose treatment plans exclude bevacizumab); however, all patients receiving bevacizumab with 1+ proteinuria on dipstick urinalysis at study entry must have a subsequent 24-hour urine collection.

10. Patients with any non-healing wound, ulcer, or long bone fracture.

11. Patients with any history of a bleeding diathesis or coagulopathy (in the absence of therapeutic anticoagulation).

12. Patients with a history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to beginning bevacizumab.

13. Patients with a history of stroke or transient ischemic attach within 6 months prior to first bevacizumab dose.

14. Known hypersensitivity to any component of bevacizumab.

15. Patients with history of any other disease, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of a novel regimen, or that might affect the results of this study or render the subject at high risk for treatment complications.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Neoplasms, Unknown Primary

Intervention

Drug:
• Paclitaxel
175 mg/m2, 1-3 hour IV infusion Day 1
• Carboplatin
AUC 6.0 IV Day 1
• Bevacizumab
15 mg/kg IV infusion Day 1
• Erlotinib
150 mg PO

Other:
• Treatment determined by physician
Patients Assigned a Specific Diagnosis by the Molecular profiling Assay will have physician's choice therapy

Locations

Country	Name	City	State
United States	Hematology Oncology Clinic, LLP	Baton Rouge	Louisiana
United States	Center for Cancer and Blood Disorders	Bethesda	Maryland
United States	Chattanooga Oncology Hematology Associates	Chattanooga	Tennessee
United States	Oncology Hematology Care	Cincinnati	Ohio
United States	Oncology Hematology Associates of SW Indiana	Evansville	Indiana
United States	Florida Cancer Specialists	Fort Myers	Florida
United States	Center for Cancer and Blood Disorders	Ft. Worth	Texas
United States	Northeast Georgia Medical Center	Gainesville	Georgia
United States	Grand Rapids Clinical Oncology Program	Grand Rapids	Michigan
United States	Oncology Specialties (Clearview Cancer Institute)	Huntsville	Alabama
United States	Jackson Oncology Associates	Jackson	Mississippi
United States	Integrated Community Oncology Network	Jacksonville	Florida
United States	Watson Clinic Center for Cancer Care and Research	Lakeland	Florida
United States	Baptist Hospital East	Louisville	Kentucky
United States	Wellstar Cancer Research	Marietta	Georgia
United States	Hematology Oncology Associates of Northern NJ	Morristown	New Jersey
United States	Tennessee Oncology, PLLC	Nashville	Tennessee
United States	Nebraska Methodist Cancer Center	Omaha	Nebraska
United States	Florida Hospital Cancer Institute	Orlando	Florida
United States	Virginia Cancer Institute	Richmond	Virginia
United States	Spartanburg Regional Medical Center	Spartanburg	South Carolina

Sponsors (2)

Lead Sponsor	Collaborator
SCRI Development Innovations, LLC	Genentech, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To evaluate the utility of the 92-gene RT-PCR assay in identifying the tissue of origin in patients with carcinoma of unknown primary site.		18 months	No
Secondary	To determine the efficacy of treatment for patients with carcinoma of unknown primary site, selected according to the diagnosis provided by the molecular profiling RT-PCR assay		18 months	No