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Sirolimus and Pemetrexed to Treat Non-Small Cell Lung Cancer
Phase 1, PHASE2 trial testing FDG-PET in Carcinoma, Non-Small-Cell Lung in 42 participants. Terminated before completion.
| Lead sponsor | National Cancer Institute (NCI) |
|---|---|
| Phase | Phase 1, PHASE2 |
| Status | Terminated |
| Study type | INTERVENTIONAL |
| Allocation | randomized |
| Design | parallel |
| Masking | none |
| Primary purpose | treatment |
| Enrollment | 42 |
| Start date | 29 February 2008 |
| Primary completion | 10 March 2013 |
| Estimated completion | 10 March 2013 |
| Sites | 1 location across United States |
National Cancer Institute (NCI)
18 and older, any sex, with Carcinoma, Non-Small-Cell Lung. Patients with the condition only — healthy volunteers not accepted.
Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.
The phase I component of the study are to determine the safety and tolerability of pemetrexed in human subjects with non small cell lung cancer (NSCLC), and to determine the maximum tolerated dose.
| Group | Value | 95% CI |
|---|---|---|
| Treatment Level 1: 3mg Load | 500 | |
| Treatment Level 2: 6mg Load | 500 | |
| Treatment Level 3: 6mg Load | 500 | |
| Treatment Level 4: 10mg Load | 500 | |
| Treatment Level 5: 15mg Load | 500 |
Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v3.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one
| Group | Value | 95% CI |
|---|---|---|
| Treatment Level 1: 3mg Load | 4 | |
| Treatment Level 2: 6mg Load | 3 | |
| Treatment Level 3: 6mg Load | 3 | |
| Treatment Level 4: 10 mg Load | 7 | |
| Treatment Level 5: 15mg Load | 5 |
| Group | Value | 95% CI |
|---|---|---|
| Treatment Level 1: 3mg Load | 0 | |
| Treatment Level 2: 6mg Load | 0 | |
| Treatment Level 3: 6mg Load | 0 | |
| Treatment Level 4: 10 mg Load | 20 | |
| Treatment Level 5: 15mg Load | 0 |
Clinical response is assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response (CR) is disappearance of all target lesions. Partial response (PR) at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started. Progressive disease (PD) is at least a 20% increase in the sum of the LD of target lesions, taking as reference the s
| Group | Value | 95% CI |
|---|---|---|
| Treatment Level 4: 10mg Load | 0 |
| Group | Value | 95% CI |
|---|---|---|
| Treatment Level 4: 10mg Load | 5 |
| Group | Value | 95% CI |
|---|---|---|
| Treatment Level 4: 10mg Load | 13 |
| Group | Value | 95% CI |
|---|---|---|
| Treatment Level 4: 10mg Load | 2 |
| Group | Value | 95% CI |
|---|---|---|
| Treatment Level 4: 10mg Load | 7 |
The phase I component of the study are to determine the safety and tolerability of sirolimus in human subjects with non small cell lung cancer (NSCLC), and to determine the maximum tolerated dose.
| Group | Value | 95% CI |
|---|---|---|
| Treatment Level 1: 3mg Load | 10 | |
| Treatment Level 2: 6mg Load | 10 | |
| Treatment Level 3: 6mg Load | 10 | |
| Treatment Level 4: 10mg Load | 10 | |
| Treatment Level 5: 15mg Load | 10 |
Time frame: Date treatment consent signed to date off study, approximately 45 months.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.
| Reaction | System | Treatment Level 1: 3mg Load | Treatment Level 2: 6mg Load | Treatment Level 3: 6mg Load | Treatment Level 4: 10 mg L… | Treatment Level 5: 15mg Load |
|---|---|---|---|---|---|---|
| Edema: limb | Blood and lymphatic system disorders | — | — | — | — | — |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | — | — | — | — | — |
| Lymphopenia | Blood and lymphatic system disorders | — | — | — | — | — |
| Magnesium, serum-high (hypermagnesemia) | Metabolism and nutrition disorders | — | — | — | — | — |
| Neutrophils/granulocytes (ANC/AGC) | Blood and lymphatic system disorders | — | — | — | — | — |
| Somnolence/depressed level of consciousness | Nervous system disorders | — | — | — | — | — |
| Fatigue (asthenia, lethargy, malaise) | General disorders | — | — | — | — | — |
| ALT, SGPT (serum glutamic pyruvic transaminase) | Metabolism and nutrition disorders | — | — | — | — | — |
| Death not associated with CTCAE term: Disease progression NOS | General disorders | — | — | — | — | — |
| Febrile neutropenia | Infections and infestations | — | — | — | — | — |
| Infection | Infections and infestations | — | — | — | — | — |
| Infection with normal ANC or Grade 1 or 2 neutrophils: lung (pneumonia) | Infections and infestations | — | — | — | — | — |
| Nausea | Gastrointestinal disorders | — | — | — | — | — |
| Pulmonary/Upper respiratory - Other (specify, pulmonary infiltrate, right lung) | Respiratory, thoracic and mediastinal disorders | — | — | — | — | — |
| Vomiting | Gastrointestinal disorders | — | — | — | — | — |
| Bronchospasm, wheezing | Respiratory, thoracic and mediastinal disorders | — | — | — | — | — |
| CD4 count | Blood and lymphatic system disorders | — | — | — | — | — |
| Cholesterol, serum-high (hypercholesteremia) | Metabolism and nutrition disorders | — | — | — | — | — |
| Constipation | Gastrointestinal disorders | — | — | — | — | — |
| Creatinine | Metabolism and nutrition disorders | — | — | — | — | — |
| Triglyceride, serum-high (hypertriglyceridemia) | Metabolism and nutrition disorders | — | — | — | — | — |
| Magnesium, serum-low (hypomagnesemia) | Metabolism and nutrition disorders | — | — | — | — | — |
| Reaction | System | Treatment Level 1: 3mg Load | Treatment Level 2: 6mg Load | Treatment Level 3: 6mg Load | Treatment Level 4: 10 mg L… | Treatment Level 5: 15mg Load |
|---|---|---|---|---|---|---|
| Fatigue (asthenia, lethargy, malaise) | General disorders | — | — | — | — | — |
| Lymphopenia | Blood and lymphatic system disorders | — | — | — | — | — |
| Anorexia | Gastrointestinal disorders | — | — | — | — | — |
| CD4 count | Blood and lymphatic system disorders | — | — | — | — | — |
| Nausea | Gastrointestinal disorders | — | — | — | — | — |
| Diarrhea | Gastrointestinal disorders | — | — | — | — | — |
| Phosphate, serum-low (hypophosphatemia) | Metabolism and nutrition disorders | — | — | — | — | — |
| Hemoglobin | Metabolism and nutrition disorders | — | — | — | — | — |
| Magnesium, serum-low (hypomagnesemia) | Metabolism and nutrition disorders | — | — | — | — | — |
| Rash/acneiform | Skin and subcutaneous tissue disorders | — | — | — | — | — |
| Sodium, serum-low (hyponatremia) | Metabolism and nutrition disorders | — | — | — | — | — |
| Neutrophils/granulocytes (ANC/AGC) | Blood and lymphatic system disorders | — | — | — | — | — |
| Glucose, serum-high (hyperglycemia) | Metabolism and nutrition disorders | — | — | — | — | — |
| Leukocytes (total WBC) | Blood and lymphatic system disorders | — | — | — | — | — |
| Platelets | Blood and lymphatic system disorders | — | — | — | — | — |
| Vomiting | Gastrointestinal disorders | — | — | — | — | — |
| Fever | General disorders | — | — | — | — | — |
| Albumin, serum-low (hypoalbuminemia) | Metabolism and nutrition disorders | — | — | — | — | — |
| Dyspnea (shortness of breath) | Respiratory, thoracic and mediastinal disorders | — | — | — | — | — |
| Weight loss | General disorders | — | — | — | — | — |
| ALT, SGPT (serum glutamic pyruvic transaminase) | Metabolism and nutrition disorders | — | — | — | — | — |
| Cough | Respiratory, thoracic and mediastinal disorders | — | — | — | — | — |
| Mucositis/stomatitis (clinical exam): oral cavity | Gastrointestinal disorders | — | — | — | — | — |
| Pain: Abdomen NOS | Gastrointestinal disorders | — | — | — | — | — |
| Pain: head/headache | Nervous system disorders | — | — | — | — | — |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | — | — | — | — | — |
| AST/SGOT (serum glutamic oxaloacetic transaminase) | Metabolism and nutrition disorders | — | — | — | — | — |
| Magnesium, serum-high (hypermagnesemia) | Metabolism and nutrition disorders | — | — | — | — | — |
| Pruritis/itching | Skin and subcutaneous tissue disorders | — | — | — | — | — |
| Dysphagia (difficulty swallowing) | Gastrointestinal disorders | — | — | — | — | — |
| Pain: throat/pharynx/larynx | Respiratory, thoracic and mediastinal disorders | — | — | — | — | — |
| Taste alteration (dysgeusia) | Gastrointestinal disorders | — | — | — | — | — |
| Edema: head and neck | Blood and lymphatic system disorders | — | — | — | — | — |
| Heartburn/dyspepsia | Gastrointestinal disorders | — | — | — | — | — |
| Pain: chest wall | Musculoskeletal and connective tissue disorders | — | — | — | — | — |
| Alkaline phosphatase | Metabolism and nutrition disorders | — | — | — | — | — |
| Cholesterol, serum-high (hypercholesteremia) | Metabolism and nutrition disorders | — | — | — | — | — |
| Edema: limb | Blood and lymphatic system disorders | — | — | — | — | — |
| Neuropathy: sensory | Nervous system disorders | — | — | — | — | — |
| PTT (Partial thromboplastin time) | Blood and lymphatic system disorders | — | — | — | — | — |
Most-reported serious reactions: Edema: limb, Hypoxia, Lymphopenia, Magnesium, serum-high (hypermagnesemia), Neutrophils/granulocytes (ANC/AGC), Somnolence/depressed level of consciousness, Fatigue (asthenia, lethargy, malaise), ALT, SGPT (serum glutamic pyruvic transaminase).
Data from ClinicalTrials.gov NCT00923273 adverse events section.
Background: The drug pemetrexed is used to treat non-small cell lung cancer (NSCLC) that does not respond to standard therapy or that has recurred after standard therapy; however, only 9 in 100 patients respond to pemetrexed. Sirolimus is a drug that blocks a protein in cells called mammalian target of rapamycin (mTOR). In cancer cells, mTOR is active when it should not be, allowing the cells to grow uncontrollably. This protein is unusually active in many cases of NSCLC. By blocking the activity of mTOR, sirolimus may make the cancer cells more responsive to treatment with pemetrexed. Objectives: To determine if sirolimus in combination with pemetrexed is safe and well tolerated in patients with NSCLC. To determine the highest safe dose of pemetrexed combined with sirolimus. To look at the ability of sirolimus and pemetrexed to fight NSCLC. To learn how the body eliminates sirolimus and pemetrexed. Eligibility: Patients 18 years of age and older with NSCLC whose disease does not respond to standard therapy or has recurred after treatment with standard therapy. Design: Biopsy before treatment starts, if the tumor is easy to reach by bronchoscopy or can be done by needle biopsy. This procedure is optional. Drug treatment, as follows: * Day 1: Intravenous (through a vein) infusions of pemetrexed. Small groups (3 to 6) of patients are given pemetrexed at a certain dose level. If the first group experiences no significant side effects, the next group receives a higher dose. This continues in succeeding groups for up to five dose levels until the maximum tolerated study dose (highest dose that patients can be given safely) is determined. * To lessen the side effects of pemetrexed, patients also receive a Vitamin B12 injection every 21 days, folic acid tablets daily, and dexamethasone tablets twice a day the day before, the day of, and the day after pemetrexed infusions. * Days 1-21: Sirolimus tablets by mouth. Evaluations during the treatment period: * History and physical examinations, blood and urine tests, electrocardiogram. * Disease evaluation with computed tomography (CT), positron emission tomography (PET) or magnetic resonance scans (MRI) scans....
7 peer-reviewed publications reference this trial (live from Europe PMC):
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