Carboplatin, Paclitaxel, and Everolimus in Treating Patients With Previously Untreated Cancer of Unknown Primary

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00936702
First received: July 8, 2009
Last updated: January 20, 2013
Last verified: January 2013
  Purpose

RATIONALE: Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.

PURPOSE: This phase II trial is studying how well carboplatin given together with paclitaxel and everolimus works in treating patients with previously untreated cancer of unknown primary.


Condition Intervention Phase
Carcinoma of Unknown Primary
Drug: carboplatin
Drug: everolimus
Drug: paclitaxel
Genetic: gene expression analysis
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Carboplatin (CBDCA), Paclitaxel (TAXOL), and Everolimus (RAD001) in Previously Untreated Patients With Measurable Disease With Cancer of Unknown Primary (CUP)

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Response rate [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time to progression [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]
  • Duration of response [ Designated as safety issue: No ]
  • Time to treatment failure [ Designated as safety issue: No ]
  • Adverse events as assessed by NCI CTCAE v 4.0 [ Designated as safety issue: Yes ]

Estimated Enrollment: 55
Study Start Date: October 2009
Estimated Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • Evaluate the response rate in patients with previously untreated cancer of unknown primary treated with the combination of carboplatin, paclitaxel, and everolimus.

Secondary

  • Assess time to progression, overall survival, duration of response, and time to treatment failure in patients treated with this regimen.
  • Determine adverse events of this regimen in these patients.
  • Perform descriptive correlative studies to determine response of specific tumor types, identified by the Origin-FFPE test, to this regimen.

OUTLINE: This is a multicenter study.

Patients receive carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on day 1. Patients also receive oral everolimus once daily on days 1, 8, and 15. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients' tumor tissue samples from the most recent biopsy are analyzed for correlative studies, including gene expression profiling by Origin-FFPE test.

After completion of study therapy, patients are followed up every 3 months until disease progression, and then every 6 months for up to 3 years.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Histologically confirmed diagnosis of 1 of the following:

    • Metastatic adenocarcinoma
    • Poorly differentiated non-small cell carcinoma
    • Poorly differentiated squamous cell carcinoma
  • Patients with biopsy proven TTF-1 positive tumor who do not have clinical evidence for either lung or thyroid cancer (e.g., a dominant lung mass) are still eligible
  • Adequate FFPE tissue samples available
  • Measurable disease defined as ≥ 1 lesion whose longest diameter can be accurately measured as ≥ 2.0 cm by conventional techniques OR as ≥ 1.0 cm to ≤ 2 cm by spiral CT scan

    • Disease that has received prior radiotherapy for palliative reasons not considered measurable disease
  • No untreated brain metastases

    • Patients with treated, stable brain metastases for ≥ 12 weeks prior to study entry allowed

PATIENT CHARACTERISTICS:

  • ECOG performance status of 0-2
  • ANC ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Hemoglobin ≥ 9.0 g/dL
  • Total bilirubin normal (≤ 2 times upper limit of normal [ULN] in presence of liver metastasis)
  • AST ≤ 2.5 times ULN (≤ 5 times ULN in presence of liver metastasis)
  • Creatinine ≤ 1.25 times ULN OR creatinine clearance ≥ 60 mL/min
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must agree to use effective contraception
  • Willing to undergo another biopsy if additional tissue sample is needed
  • No co-morbid systemic illnesses or other severe concurrent disease that, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
  • No immunocompromised patients including patients known to be HIV positive
  • No uncontrolled intercurrent illness including, but not limited to, the following conditions:

    • Ongoing or active infection (acute or chronic)
    • Symptomatic congestive heart failure
    • Unstable angina pectoris
    • Cardiac arrhythmia
    • Severely impaired lung function
    • Uncontrolled diabetes as defined by fasting serum glucose > 1.5 times ULN
    • Liver disease (e.g., cirrhosis, chronic active hepatitis, or chronic persistent hepatitis)
    • Psychiatric illness and/or social situations that would limit compliance with study requirements
  • More than 5 years since diagnosis of other malignancy except for non-melanotic skin cancer or carcinoma in situ of the cervix
  • No impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of everolimus (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
  • No active bleeding diathesis
  • No known HIV positivity
  • No inoculation with live attenuated vaccines ≤ 2 weeks prior to registration

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • Concurrent bisphosphonates allowed
  • No prior chemotherapy for this cancer
  • No prior radiotherapy to > 25% bone marrow

    • Prior radiotherapy for palliative reasons for this cancer allowed
  • No major surgery within the 4 past weeks

    • Diagnostic laparoscopy (without other intervention) and/or biopsies (needle aspirate, core biopsy, open biopsy, etc.) are not considered major surgery
  • No investigational agent within the past 4 weeks that would be considered treatment for the primary neoplasm
  • No concurrent chronic systemic treatment with corticosteroids or another immunosuppressive agent

    • Topical or inhaled corticosteroids allowed
  • No concurrent enzyme-inducing anti-convulsants or other strong inducers or strong inhibitors of CYP3A4 (e.g., carbamazepine, phenytoin, phenobarbital, primidone, rifabutin, rifampin, or St. John wort)
  • No concurrent warfarin (coumadin) except for low-molecular weight heparin use
  • No concurrent grapefruit, Seville oranges, or star fruit or their juices
  • No other concurrent investigational therapy
  • No other concurrent anticancer agents
  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 ClinicalTrials.gov identifier: NCT00936702

  Show 141 Study Locations
Sponsors and Collaborators
North Central Cancer Treatment Group
Investigators
Study Chair: Matthew P. Goetz, MD Mayo Clinic
  More Information

Additional Information:
No publications provided

Responsible Party: Jan C. Buckner, North Central Cancer Treatment Group
ClinicalTrials.gov Identifier: NCT00936702     History of Changes
Other Study ID Numbers: CDR0000643361, NCCTG-N0871
Study First Received: July 8, 2009
Last Updated: January 20, 2013
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
metastatic carcinoma of unknown primary
squamous cell carcinoma of unknown primary
undifferentiated carcinoma of unknown primary
newly diagnosed carcinoma of unknown primary

Additional relevant MeSH terms:
Carcinoma
Neoplasms, Unknown Primary
Neoplasm Metastasis
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplastic Processes
Pathologic Processes
Carboplatin
Everolimus
Paclitaxel
Sirolimus
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Immunologic Factors
Immunosuppressive Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on October 23, 2014