The PARAMOUNT trial is a

clinical trial Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, diet ...

studying

non-small-cell lung carcinoma Non-small-cell lung cancer (NSCLC) is any type of epithelial lung cancer other than small-cell lung carcinoma (SCLC). NSCLC accounts for about 85% of all lung cancers. As a class, NSCLCs are relatively insensitive to chemotherapy, compared to s ...

(NSCLC). The trial was sponsored by Eli Lilly and Company and was conducted in several European countries and Canada. It was registered in November 2008 and was projected to end in September 2013. PARAMOUNT found that maintenance therapy with

pemetrexed Pemetrexed, sold under the brand name Alimta among others, is a chemotherapy medication for the treatment of pleural mesothelioma and non-small cell lung cancer (NSCLC).. It is available as a generic medication. Medical use In February 2004 ...

for patients with advanced non-squamous NSCLC was an effective and well-tolerated treatment option in those patients who had not had progress after initial therapy with pemetrexed plus

cisplatin Cisplatin is a chemotherapy medication used to treat a number of cancers. These include testicular cancer, ovarian cancer, cervical cancer, breast cancer, bladder cancer, head and neck cancer, esophageal cancer, lung cancer, mesothelioma, ...

Study design

Name

The full name of the trial is "A Phase 3, Double-Blind, Placebo-Controlled Study of Maintenance Pemetrexed plus Best Supportive Care versus Best Supportive Care Immediately Following Induction Treatment with Pemetrexed + Cisplatin for Advanced Non-Squamous Non-Small Cell Lung Cancer". Its common name is PARAMOUNT. Its ClinicalTrials.gov identifier is NCT00789373.

Purpose

The PARAMOUNT trial investigated whether treatment with a maintenance dose of

would inhibit the growth of

and improve survival rates after

first-line therapy A therapy or medical treatment (often abbreviated tx, Tx, or Tx) is the attempted remediation of a health problem, usually following a medical diagnosis. As a rule, each therapy has indications and contraindications. There are many different ...

with pemetrexed plus

. For patients with advanced

non-small cell lung carcinoma Non-small-cell lung cancer (NSCLC) is any type of epithelial lung cancer other than small-cell lung carcinoma (SCLC). NSCLC accounts for about 85% of all lung cancers. As a class, NSCLCs are relatively insensitive to chemotherapy, compared to s ...

(NSCLC), maintenance therapy is sometimes used when the initial chemotherapy does not lead to improvement. An alternative would be administering a second chemotherapy if the disease progresses. A significant number of patients do not survive long enough for a second treatment if their disease progresses. When maintenance therapy is used it may or may not consist of a different drug than the initial chemotherapy. Studies prior to PARAMOUNT had shown

, an

antifolate Antifolates are a class of antimetabolite medications that antagonise (that is, block) the actions of folic acid (vitamin B9). Folic acid's primary function in the body is as a cofactor to various methyltransferases involved in serine, methionin ...

, had been an effective therapy for patients with NSCLC when used either as an initial chemotherapy with

or as a maintenance drug when not part of the initial therapy. The PARAMOUNT study was designed to measure the extent of the efficacy when a patient received pemetrexed maintenance therapy after cisplatin/pemetrexed initial therapy. The study would measure progression-free survival of patients and survival irrespective of whether the cancer had progressed. An additional study goal would be to check the extent to which measurement of

thymidylate synthase Thymidylate synthase (TS) () is an enzyme that catalyzes the conversion of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP). Thymidine is one of the nucleotides in DNA. With inhibition of TS, an imbalance of deoxynucleo ...

- the naturally produced enzyme on which pemetrexed acts - could predict the efficacy of pemetrexed in these cases.

Outcome

PARAMOUNT found that maintenance therapy with pemetrexed for patients with advanced non-squamous NSCLC was an effective and well tolerated treatment option in those patients who had not had progress after initial therapy with pemetrexed plus cisplatin. The average life of all participants receiving the experimental treatment increased more than 13 months as compared to the control group. The results of this trial should not be generalized beyond the scope of the research and the trial design must be considered to interpret these results. The result of this trial did not change the fact that the concept of maintenance therapy remains controversial and complicated.

Study participants

The study intended to enroll 939 people. The study started in November 2008 and was estimated to be completed in September 2013. The study was conducted at locations in Australia, Belgium, Finland, France, Germany, Greece, India, Italy, the Netherlands, Poland, Portugal, Romania, Spain, Turkey, and the United Kingdom. Among other inclusion and exclusion criteria, participants must in the trial must have stage IIIB or IV nonsquamous

and have at least one measurable tumor lesion by Response Evaluation Criteria in Solid Tumors guidelines or disease which can be examined by a CT scan, but must not have non-superficial

squamous-cell carcinoma Squamous-cell carcinomas (SCCs), also known as epidermoid carcinomas, comprise a number of different types of cancer that begin in squamous cells. These cells form on the surface of the skin, on the lining of hollow organs in the body, and on th ...

or a mixture of both

small-cell carcinoma Small-cell carcinoma is a type of highly malignant cancer that most commonly arises within the lung, although it can occasionally arise in other body sites, such as the cervix, prostate, and gastrointestinal tract. Compared to non-small cell car ...

and non-small-cell lung carcinoma or have had another form of cancer other than superficial

basal-cell carcinoma Basal-cell carcinoma (BCC), also known as basal-cell cancer, is the most common type of skin cancer. It often appears as a painless raised area of skin, which may be shiny with small blood vessels running over it. It may also present as a raise ...

and superficial

, or

carcinoma in situ Carcinoma ''in situ'' (CIS) is a group of abnormal cells. While they are a form of neoplasm, there is disagreement over whether CIS should be classified as cancer. This controversy also depends on the exact CIS in question (i.e. cervical, skin, bre ...

of the cervix within the last 5 years. Patients with a history of low-grade (

Gleason Grading System The Gleason grading system is used to help evaluate the prognosis of men with prostate cancer using samples from a prostate biopsy. Together with other parameters, it is incorporated into a strategy of prostate cancer staging which predicts pr ...

score equal to or less than 6) localized prostate cancer are eligible.

References

External links

{{Sister project links , wikt=no , commons=PARAMOUNT trial , b=no , n=no , q=no , s=PARAMOUNT Eli Lilly Informed Consent Document , v=no , voy=no , species=no , d=no , display=the PARAMOUNT trial
clinicaltrials.gov entry
Clinical trials sponsored by Eli Lilly and Company Lung cancer Clinical trials related to cancer