Phase 2
Completed N=27
Bortezomib and Pemetrexed Disodium in Treating Patients With Advanced Non-Small Cell Lung Cancer or Other Solid Tumors
Lung Cancer · Unspecified Adult Solid Tumor, Protocol Specific
Source: ClinicalTrials.gov NCT00389805 ↗
Enrolled (actual)
27
Serious AEs
0.0%
Results posted
Jun 2017
Primary outcomePrimary: Number of Patients Experiencing a Dose-limiting Toxicity (Phase I) — 3; 0 Participants
Summary
RATIONALE: Bortezomib and pemetrexed disodium may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving bortezomib together with pemetrexed disodium may kill more tumor cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of two different schedules of bortezomib when given together with pemetrexed disodium and to see how well they work in treating patients with advanced non-small cell lung cancer or other solid tumors.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Patients Experiencing a Dose-limiting Toxicity (Phase I) |
3; 0 | — |
| PRIMARY Number of Participants Who Experience Adverse Events (Phase I) |
15; 12 | — |
| PRIMARY Number of Patients With Grade ≥ 3 Toxicity (Phase I) |
12; 1; 1; 0; 0; 1 | — |
| PRIMARY Number of Patients Who Responded to Study Treatment (Phase II) |
— | — |
| SECONDARY Number of Patients With Toxicity by NCI CTC v3.0 (Phase I) |
12; 1; 1; 0; 0; 1 | — |
| SECONDARY Maximum Tolerated Dose of Bortezomib in Combination With Pemetrexel (Phase I) |
1.3; 1.6 | — |
| SECONDARY Number of Participants With Response to Therapy as Measured by RECIST (Phase I) |
0; 0; 1; 1; 7; 6 | — |
| SECONDARY Number of Participants With Toxicities (Phase II) |
— | — |
| SECONDARY Analysis of Molecular Determinants in Tumor Samples (Phase II) |
— | — |
| SECONDARY Importance of Folate-associated Gene Expression and Response or Outcome (Phase II) |
— | — |
| SECONDARY Effect of Bortezomib on Over Expression of NF-kB, BCL-2, and BCL-xL (Phase II) |
— | — |
Eligibility Criteria
DISEASE CHARACTERISTICS:
- Cytologically or histologically confirmed diagnosis of 1 of the following:
- Advanced solid tumor that progressed after standard therapy or for which no effective curative therapy exists (phase I)
- Stage IIIB (pleural effusion) or IV non-small cell lung cancer (NSCLC) (phase II)
- Disease must have progressed or recurred after 1 platinum-based therapy regimen
- NSCLC that has progressed or recurred after first-line therapy for stage IIIA or IIIB disease allowed
- Measurable disease
- Disease in previously irradiated sites is considered measurable if there is clear disease progression following radiotherapy
- Evaluable disease (bone metastases, pleural fluid, ascites) allowed (phase I)
- No symptomatic brain metastasis or disease requiring steroids and anticonvulsants
- Asymptomatic, previously treated (surgical resection or radiotherapy) brain metastases allowed provided patient is neurologically stable and has been off steroids and anticonvulsants for ≥ 4 weeks
PATIENT CHARACTERISTICS:
- Zubrod performance status 0-2 (phase I) or 0-1 (phase II)
- Life expectancy ≥ 3 months
- Creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 50 mL/min
- Bilirubin normal
- AST ≤ 2.5 times upper limit of normal
- Granulocyte count ≥ 1,500/mm³
- Platelet count of ≥ 100,000/mm³
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 3 months after completion of study treatment
- No pre-existing neuropathy ≥ grade 2
- No other prior malignancy except for the following (phase II):
- Adequately treated basal cell or squamous cell skin cancer
- In situ cervical cancer
- Adequately treated stage I or II cancer currently in complete remission
- Any other cancer from which the patient has been disease free for > 5 years
- No hypersensitivity to bortezomib, boron, or mannitol
- No cardiovascular complications, including any of the following:
- Myocardial infarction within the past 6 months
- New York Heart Association class III-IV heart failure
- Uncontrolled angina
- Severe uncontrolled ventricular arrhythmias
- Electrocardiographic (ECG) evidence of acute ischemia or active conduction system abnormalities
- Any ECG abnormality at screening must be documented as not medically relevant
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- No prior bortezomib or pemetrexed disodium
- Any number of prior chemotherapy regimens allowed (phase I)
- More than 4 weeks since prior chemotherapy (6 weeks for mitomycin C) and recovered
- More than 2 weeks since prior radiotherapy and recovered
- No nonsteroidal anti-inflammatory drugs (NSAIDs) or salicylates 2 days prior and 2 days after (5 days pre and post for long-acting NSAIDs) administration of pemetrexed disodium
- No concurrent anticonvulsants that are metabolized by the cytochrome P450 pathway
Data sourced from ClinicalTrials.gov (NCT00389805). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.