Neoplasms

All Conditions

Symptoms and General Pathology

Carcinoma

Adenocarcinoma

Neoplasm Metastasis

Pain

Neoplasms, Unknown Primary

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplastic Processes

Antineoplastic Agents

All Drugs and Chemicals

Gemcitabine

Antimetabolites

gemcitabine hydrochloride

quality-of-life assessment

Victor T. Chang, MD

Raymond S. Lord, MD

RATIONALE: Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

PURPOSE: This phase II trial is studying how well gemcitabine works in treating patients with metastatic cancer of unknown primary.

OBJECTIVES:

* Evaluate the efficacy of gemcitabine hydrochloride in patients with metastatic cancer of unknown primary (CUP), in terms of improved quality of life (QOL) (as measured by the FACT Physical Well Being subscale \[FACT-G\]) and reduction of symptom distress (as measured by the Memorial Symptom Assessment Scale Short Form Global Distress Index \[MSAS-SF\]).
* Define clinical benefit response using a QOL instrument in patients with CUP receiving gemcitabine hydrochloride.
* Correlate objective and/or evaluable tumor response with symptom and QOL response in these patients.
* Explore the association between symptom response, QOL response, and clinical benefit response in these patients.
* Evaluate changes in QOL in patients who have no symptom or objective response after treatment with gemcitabine hydrochloride.
* Correlate EuroQOL ratings with those using symptom instruments (MSAS-SF) and quality of life instruments (FACT-G).
* Evaluate changes in perceived QOL, as measured by the EuroQOL instrument, and how these changes relate to symptom response and QOL response.
* Evaluate the patient's assessment of treatment burden, as measured by a single question, and how this compares to symptom response and QOL response.

OUTLINE: This is an open-label, multicenter study.

Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, 15, 22, 29, 36, and 43, followed by 1 week of rest (course 1). For all subsequent courses, patients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 4 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Quality of life (QOL) and symptom response are assessed at baseline and at weeks 8, 16, and 32 (end of treatment). Questionnaires include the Memorial Symptom Assessment Scale-Short Form, Functional Assessment of Cancer Therapy-General, Pain Visual Analog Scale, and EuroQOL. Patients' perception of symptom response and perception of treatment burden are also assessed.

After completion of study treatment, patients are followed periodically for up to 3 years.

PROJECTED ACCRUAL: A total of 52 patients will be accrued for this study.

Gemcitabine in Treating Patients With Metastatic Cancer of Unknown Primary

Phase II Protocol: Gemcitabine for Metastatic Cancer With Unknown Primary Site - Analysis of Symptom Benefit

National Cancer Institute (NCI)

Eastern Cooperative Oncology Group

Robert L. Comis

Carcinoma, Squamous Cell

Anti-Infective Agents

Paclitaxel

Carboplatin

Everolimus

Albumin-Bound Paclitaxel

Tubulin Modulators

Antimitotic Agents

Sirolimus

Temsirolimus

MTOR Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Immunosuppressive Agents

Immunologic Factors

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.

carboplatin

everolimus

paclitaxel

Matthew P. Goetz, MD

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.

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.

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

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)

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;

Overall survival was defined as the time from study enrollment to the time of death from any cause or last follow-up.

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 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 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.

Alliance for Clinical Trials in Oncology

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.

Treatment (Carboplatin, Paclitaxel, and Everolimus)

Age, Continuous

Sex: Female, Male

Eastern Cooperative Oncology Group (ECOG) Performance Status

Histologic diagnosis

Histologic grade

Predominant location of disease

Matthew P. Goetz, M.D.

All participants except one who was deemed ineligible (treated prior to registration).

Percentage of Participants With Confirmed Tumor Responses

Overall Survival

Progression-free Survival

All eligible participants who have achieved an objective response at which the participant's objective status is first noted to be either CR or PR.

Duration of Response

All participant who has been removed from treatment due to progression, adverse events, or refusal.

Time to Treatment Failure

Overall Study

Antirheumatic Agents

Fluorouracil

Cyclophosphamide

Doxorubicin

Liposomal doxorubicin

Vincristine

Cisplatin

Epirubicin

Antineoplastic Agents, Alkylating

Alkylating Agents

Anti-Bacterial Agents

Antibiotics, Antitubercular

cisplatin

cyclophosphamide

doxorubicin hydrochloride

epirubicin hydrochloride

fluorouracil

vincristine sulfate

Juan W. Valle, MD

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known which combination chemotherapy regimen is more effective for metastatic cancer of an unknown site of origin.

PURPOSE: Randomized phase III trial to compare the effectiveness of two combination chemotherapy regimens in treating patients who have metastatic cancer of an unknown site of origin.

OBJECTIVES: I. Compare the efficacy of the regimens, in terms of tumor response, progression-free survival, and overall survival of vincristine, doxorubicin, and cyclophosphamide vs epirubicin, cisplatin, and fluorouracil in patients with metastatic carcinoma of unknown primary. II. Compare the toxicity of these regimens in these patients. III. Compare quality of life and symptom control in patients treated with these regimens.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to presence of liver metastases (yes vs no) and type of tumor (adenocarcinoma vs non-adenocarcinoma). Patients are randomized to one of two treatment arms. Arm I: Patients receive vincristine IV, doxorubicin IV, and cyclophosphamide IV on day 1. Arm II: Patients receive epirubicin IV and cisplatin IV over 4 hours on day 1 and fluorouracil IV continuously on days 1-21. Treatment in both arms repeats every 3 weeks for 3-6 courses in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at baseline, at the end of courses 2, 4, and 6, and 1 month after completion of therapy. Patients are followed at 1 month and then until death.

PROJECTED ACCRUAL: A total of 398 patients (199 per treatment arm) will be accrued for this study.

Combination Chemotherapy in Treating Patients With Metastatic Cancer of an Unknown Site of Origin

An Open Label Prospective Randomised Study Comparing The Use Of Vincristine, Adriamycin And Cyclophosphamide (VAC) Versus Epirubicin, Cisplatin And Continuous 5-Flourouracil (ECF) In Patients With Unknown Primary Carcinoma (UPC)

The Christie NHS Foundation Trust

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Gemcitabine in Treating Patients With Metastatic Cancer of Unknown Primary	NCT00357630	Carcinoma of Un... Pain	gemcitabine hyd... quality-of-life...	18 Years - 120 Years	Eastern Cooperative Oncology Group
Carboplatin, Paclitaxel, and Everolimus in Treating Patients With Previously Untreated Cancer of Unknown Primary	NCT00936702	Carcinoma of Un...	carboplatin everolimus paclitaxel	18 Years -	Alliance for Clinical Trials in Oncology
Gemcitabine in Treating Patients With Metastatic Cancer of Unknown Primary	NCT00357630	Carcinoma of Un... Pain	gemcitabine hyd... quality-of-life...	18 Years - 120 Years	Eastern Cooperative Oncology Group
Combination Chemotherapy in Treating Patients With Metastatic Cancer of an Unknown Site of Origin	NCT00022178	Carcinoma of Un...	cisplatin cyclophosphamid... doxorubicin hyd... epirubicin hydr... fluorouracil vincristine sul...	18 Years -	National Cancer Institute (NCI)
Gemcitabine in Treating Patients With Metastatic Cancer of Unknown Primary	NCT00357630	Carcinoma of Un... Pain	gemcitabine hyd... quality-of-life...	18 Years - 120 Years	Eastern Cooperative Oncology Group

Spots Global Cancer Trial Database for undifferentiated carcinoma of unknown primary