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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00936702
First Posted: July 10, 2009
Last Update Posted: March 21, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology
  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 Origin Drug: carboplatin Drug: everolimus Drug: paclitaxel Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (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 Alliance for Clinical Trials in Oncology:

Primary Outcome Measures:
  • Percentage of Participants With Confirmed Tumor Responses [ Time Frame: First 6 Cycles of treatment (an average of 6 months) ]

    Confirmed tumor response was defined to be either a complete response (CR) or partial response (PR) noted as the objective status on 2 consecutive evaluations at least 4 weeks apart.

    Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria:

    • Complete Response (CR): disappearance of all target lesions;
    • Partial Response (PR) 30% decrease in sum of longest diameter of target lesions;


Secondary Outcome Measures:
  • Overall Survival [ Time Frame: Time from registration to death or last follow-up (up to 3 years) ]
    Overall survival was defined as the time from study enrollment to the time of death from any cause or last follow-up.

  • Progression-free Survival [ Time Frame: Time from registration to the disease progression or death (up to 3 years) ]
    The progression-free survival (PFS) was defined as the time from date of registration to the documentation of disease progression or death as a result of any cause, whichever comes first.

  • Duration of Response [ Time Frame: Up to 3 years ]
    Duration of response was defined for all evaluable participants who have achieved an objective response as the date at which the participant's objective status is first noted to be either CR or PR to the date progression is documented.

  • Time to Treatment Failure [ Time Frame: Up to 3 years ]
    Time to treatment failure was defined to be the time from the date of registration to the date at which the participant is removed from treatment due to progression, adverse events, or refusal.


Enrollment: 46
Study Start Date: September 2009
Study Completion Date: August 2013
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (carboplatin, paclitaxel, and everolimus)
Patients receive carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on day 1. Patients also receive everolimus PO QD on days 1, 8, and 15. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Drug: carboplatin
Given IV
Drug: everolimus
Given PO
Drug: paclitaxel
Given IV

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

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  • Histological confirmation of metastatic adenocarcinoma, poorly differentiated non-small cell carcinoma, or poorly differentiated squamous carcinoma
  • Adequate FFPE tissue or re-biopsy planned after registration but prior to treatment
  • Measurable disease as defined; for patients having only lesions measuring at least 1 cm to =< 2 cm must use spiral computed tomography (CT) imaging for both pre- and post-treatment tumor assessments; disease that has received prior radiation (performed for palliative reasons) cannot be used for measurable disease
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
  • Hemoglobin (Hgb) >= 9.0 g/dL
  • Absolute neutrophil count (ANC) >= 1,500/uL
  • Platelet count >= 100,000/uL
  • Total bilirubin =< upper limits of normal (ULN); if liver metastases are present, total bilirubin =< 2 x ULN
  • Aspartate aminotransferase (AST) =< 2.5 x ULN; if liver metastases are present, AST =< 5 x ULN
  • Creatinine =< 1.25 x ULN; if > 1.25 x ULN calculated creatinine clearance must be >= 60 ml/min
  • Negative pregnancy test done =< 7 days prior to registration, for women of childbearing potential only
  • Provide informed written consent
  • Willingness to return to NCCTG enrolling institution for follow-up
  • Willingness to abstain from eating grapefruit or drinking grapefruit juice for the duration of the study

Exclusion Criteria

  • Any of the following:

    • Pregnant women
    • Nursing women
    • Men or women of childbearing potential who are unwilling to employ adequate contraception; note: adequate contraception must be used throughout the trial and for 8 weeks after the last dose of RAD001, by both sexes
  • Co-morbid systemic illnesses or other severe concurrent disease which, 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
  • History of any of the following:

    • Known to be human immunodeficiency virus (HIV) positive
    • Known prior/current history of hepatitis related to hepatitis B or hepatitis C
  • Uncontrolled intercurrent illness including, but not limited to the following:

    • 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 x ULN (note: optimal glycemic control should be achieved before starting trial therapy)
    • Liver disease such as cirrhosis or severe hepatic impairment
    • Psychiatric illness/social situations that would limit compliance with study requirements
  • Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm =< 4 weeks prior to registration
  • Other active malignancy =< 5 years prior to registration; EXCEPTIONS: non-melanotic skin cancer or carcinoma-in-situ of the cervix; NOTE: if there is a history of prior malignancy, they must not be receiving other specific treatment for their cancer
  • Untreated brain metastases; NOTE: patients with treated, stable brain metastases for at least 12 weeks prior to study entry are eligible for enrollment
  • Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001 (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection)
  • Active, bleeding diathesis
  • Receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent; topical or inhaled corticosteroids are allowed
  • Currently on enzyme inducing anti-convulsants (EIACs) or other strong inducers or strong inhibitors of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4)
  • Current use of warfarin (Coumadin); EXCEPTION: current use of low-molecular weight heparin is allowed
  • Known to be HIV positive
  • Inoculated with live attenuated vaccines =< 2 weeks prior to registration; note: close contact with those who have received attenuated live vaccines should be avoided during treatment with everolimus; examples of live vaccines include intranasal influenza, measles, mumps, rubella, oral polio, Bacillus Calmette-Guerin (BCG), yellow fever, varicella and TY21a typhoid vaccines
  • =< 4 weeks from major surgery; note: for this study, diagnostic laparoscopy (without other intervention) and/or biopsies (needle aspirate, core biopsy, open biopsy, etc.) are not considered major surgery
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00936702


  Show 141 Study Locations
Sponsors and Collaborators
Alliance for Clinical Trials in Oncology
National Cancer Institute (NCI)
Investigators
Study Chair: Matthew P. Goetz, MD Mayo Clinic
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier: NCT00936702     History of Changes
Other Study ID Numbers: NCCTG-N0871
NCI-2011-01926 ( Registry Identifier: CTRP (Clinical Trials Reporting System) )
CDR0000643361 ( Registry Identifier: PDQ (Physician Data Query) )
First Submitted: July 8, 2009
First Posted: July 10, 2009
Results First Submitted: December 27, 2016
Results First Posted: February 16, 2017
Last Update Posted: March 21, 2017
Last Verified: February 2017

Keywords provided by Alliance for Clinical Trials in Oncology:
Newly Diagnosed Carcinoma of Unknown Primary Origin
Squamous Cell Carcinoma of Unknown Primary Origin
Undifferentiated Carcinoma of Unknown Primary
newly diagnosed carcinoma of unknown primary

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