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Treatment Based on Molecular Profiling Diagnosis Carcinoma of Unknown Primary Site

This study is ongoing, but not recruiting participants.
Genentech, Inc.
Information provided by (Responsible Party):
SCRI Development Innovations, LLC Identifier:
First received: August 15, 2008
Last updated: April 9, 2014
Last verified: April 2014

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.

Condition Intervention Phase
Drug: Paclitaxel
Drug: Carboplatin
Drug: Bevacizumab
Drug: Erlotinib
Other: Treatment determined by physician
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Chemotherapy Treatment Based on Molecular Profiling Diagnosis for Patients With Carcinoma of Unknown Primary Site

Resource links provided by NLM:

Further study details as provided by SCRI Development Innovations, LLC:

Primary Outcome Measures:
  • 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. [ Time Frame: 18 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 [ Time Frame: 18 months ] [ Designated as safety issue: No ]

Enrollment: 224
Study Start Date: August 2008
Estimated Study Completion Date: January 2015
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Paclitaxel, Carboplatin, Bevacizumab and Erlotinib
Paclitaxel, Carboplatin, Bevacizumab and Erlotinib
Drug: Paclitaxel
175 mg/m2, 1-3 hour IV infusion Day 1
Drug: Carboplatin
AUC 6.0 IV Day 1
Drug: Bevacizumab
15 mg/kg IV infusion Day 1
Other Name: Avastin
Drug: Erlotinib
150 mg PO
Other Name: Tarceva
Treatment determined by physician
Other treatment determined by physician based on molecular profiling assay
Drug: Bevacizumab
15 mg/kg IV infusion Day 1
Other Name: Avastin
Drug: Erlotinib
150 mg PO
Other Name: Tarceva
Other: Treatment determined by physician
Patients Assigned a Specific Diagnosis by the Molecular profiling Assay will have physician's choice therapy

Detailed 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.


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

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.
  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 identifier: NCT00737243

  Show 21 Study Locations
Sponsors and Collaborators
SCRI Development Innovations, LLC
Genentech, Inc.
Study Chair: John D Hainsworth, M.D. SCRI Development Innovations, LLC
  More Information

No publications provided by SCRI Development Innovations, LLC

Additional publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: SCRI Development Innovations, LLC Identifier: NCT00737243     History of Changes
Other Study ID Numbers: SCRI UNKPRI 20
Study First Received: August 15, 2008
Last Updated: April 9, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by SCRI Development Innovations, LLC:
Carcinoma of Unknown Primary Site
Molecular profiling assay

Additional relevant MeSH terms:
Neoplasms, Unknown Primary
Neoplasm Metastasis
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplastic Processes
Pathologic Processes
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Enzyme Inhibitors
Growth Inhibitors
Growth Substances
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protein Kinase Inhibitors
Therapeutic Uses
Tubulin Modulators processed this record on November 20, 2014