LymphomaPhase 1NCT00001683
A Phase I Study of Oral COL-3 (NSC-683551), a Matrix Metalloproteinase Inhibitor, in Patients With Refractory Metastatic Cancer
A Phase 1 study testing COL-3 in people with Lymphoma and Melanoma, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
Matrix metalloproteinases (MMPs) are a class of membrane bound enzymes that are involved in the degradation of the extracellular matrix. MMP-2 and MMP-9 have been associated with the progression of cancer. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Lymphoma, Melanoma, Neoplasm Metastasis
- What is being tested?
- COL-3
- How many people
- 35 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 1997to Aug 2003
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- All patients with refractory solid tumors and lymphoma are eligible according to the criteria listed below. Patients with tumor marker evidence of disease only, will not be eligible for study. A patient must have bone scan evidence of metastatic disease.
- Patients must have histopathological documentation of cancer confirmed in the Laboratory of Pathology/NCI of the Clinical Center at the National Institutes of Health prior to starting this study.
- Patients must have clinically progressive disease documented prior to entry. Progression must be documented by at least one of the following parameters: two consecutively rising tumor marker levels, and/or at least one new metastatic deposit on Tc-99 bone scintigraphy, and/or progression of soft tissue metastases as measured by appropriate modalities (i.e., imaging, palpation), and/or development of new area of malignant disease (measurable or evaluable).
- Patients must have failed therapy of proven efficacy for their disease. Patients with metastatic melanoma, non-small cell lung cancer, and renal cell carcinoma will be eligible without receiving prior therapy. Initial treatment of the non-chemotherapy responsive malignancies (e.g., disseminated gastrointestinal, noncolorectal cancer) may be done at the discretion of the investigators.
- Patients must be ECOG performance status of less than or equal to 2.
- Patients must have a life expectancy of more than three months.
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- Hematological eligibility parameters (within 1 week of starting therapy): Granulocyte count greater than or equal 1,500/mm3; Hemoglobin greater than or equal to 9.0 g/dL (pre-treatment transfusion is allowed, provided the hemoglobin is maintained for more than 30 days and/or active source of bleeding is identified and treated); Platelet count is greater than or equal to 120,000/mm3; If the creatinine is greater than 1.5 mg/dL, obtain a 24 hour urine collection. Creatinine clearance must be greater than 60 mL/min; Hepatic function: normal bilirubin (total); ALT is less than 2.5 times the normal; AST is less than 2.5 times the normal.
- Patients must have recovered from any toxicity related to prior therapy, including surgery.
- Patients must be off prior chemotherapy, hormonal therapy, radiation therapy, or biological therapy for at least 4 weeks prior to initiation of COL-3. Patients who were receiving mitomycin C, nitrosoureas, or carboplatin must be 6 weeks from the last administration of chemotherapy. Patients who were receiving suramin must be 3 months from the last administration. Patients with prostate cancer must continue to receive LHRH agonist (unless orchiectomy has been done) but must have failed antiandrogen withdrawal.
- Patients with prostate cancer that have not undergone surgical castration must continue treatment with an LHRH agonist. If for some reason the LHRH agonist has been discontinued prior to entry on the study, then it should be reinstituted and disease progression must be documented prior to enrollment.
- Patients with local complications which require urgent local medical therapy are not eligible, but may become so after resolution of the acute problem (i.e., severe bone pain, spinal cord compression, urinary flow obstruction, etc.).
- Patients must not have an acute, critical illness, including a serious untreated infection. Ureteral stents, or foley catheter, although often colonized, are not a contraindication to enrollment.
- Patients with a history of unstable or newly diagnosed angina pectoris, recent myocardial infarction (within 6 months of enrollment), New York class II-IV congestive heart failure, chronic obstructive lung disease requiring oxygen therapy or uncontrolled seizure activity are not eligible.
- Patients must be willing to travel from their home to the NIH for follow-up visits.
- All patients of childbearing capability will be required to use contraception during treatment and for two months after the completion of COL-3 treatment. All females patients of childbearing potential will have a negative pregnancy test.
- Patients must be able to understand and sign the attached informed consent form.
- Patients must be older than or 18 years of age.
- Although prior radiation therapy to the primary, or a metastatic lesion, does not exclude an individual from this study, it does exclude that lesion from the optional biopsy. Thus, if an individual has a primary lesion which has been radiated, then they can not participate in that portion of the study.
Who cannot join
- Active infection, including positive serology for HIV. Colonized urinary tract instrumentation is not excluded.
- Patients with brain metastases or primary CNS malignancies.
- Concurrent therapy for their cancer (i.e., radiation therapy, chemotherapy, etc.).
- Patients who are pregnant or lactating. No data is currently available about the excretion of COL-3 in breast milk. Also, no toxicity data in gestating animals exists at the present time. Until data of this nature becomes available, we will exclude patients who are pregnant or lactating.
- Patients who are known to be HIV positive will not be eligible for this protocol. Since COL-3 is a known inhibitor of neutrophil gelatinase, HIV patients will be excluded because of their increased risk of infection. HIV testing will be required.
- Patients who are currently taking anticonvulsants (phenobarbital, phenytoin, carbamazepine). Patients taking rifampin will also be excluded. There is a potential drug interactions between COL-3 and these classes of drugs.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Cancer Institute (NCI)
Bethesda, Maryland, 20892
About this study
Matrix metalloproteinases (MMPs) are a class of membrane bound enzymes that are involved in the degradation of the extracellular matrix. MMP-2 and MMP-9 have been associated with the progression of cancer. It is hypothesized than an imbalance between MMPs and MMP inhibitors allows the destruction of the extracellular matrix and enhances the ability of the tumor cells to grow and metastasize. By inhibiting MMPs, it is thought that angiogenesis and metastasis can be inhibited. This is a phase I study of COL-3, an oral matrix metalloproteinase inhibitor, in patients with refractory metastatic cancer. COL-3 is a chemically modified tetracycline derivative. Patients must have clinically progressive disease documented within 1 month prior to entry to be eligible for treatment. Patients must have also failed therapy of proven efficacy for their disease and have an ECOG performance status of less or equal than 2. Patients must be willing to travel from their home to the NIH for follow-up visits. Patients with brain metastases or primary CNS malignancies are not eligible. Concurrent therapy for their cancer (i.e., radiation therapy, chemotherapy, etc.) will preclude participation. We will be defining the maximum tolerated dose, the toxicity profile, characterizing the pharmacokinetics, and evaluating the effect of COL-3 on several biological endpoints.
Read the detailed description
Matrix metalloproteinases (MMPs) are a class of membrane bound enzymes that are involved in the degradation of the extracellular matrix. MMP-2 and MMP-9 have been associated with the progression of cancer. It is hypothesized that an imbalance between MMPs and MMP inhibitors allows the destruction of the extracellular matrix and enhances the ability of the tumor cells to grow and metastasize. By inhibiting MMPs, it is thought that angiogenesis and metastasis can be inhibited. This is a phase I study of COL-3, an oral matrix metalloproteinase inhibitor, in patients with refractory metastatic cancer. COL-3 is a chemically modified tetracycline derivative. Patients must have clinically progressive disease documented within 1 month prior to entry to be eligible for treatment. Patients must have also failed therapy of proven efficacy for their disease and have an ECOG performance status of less than or equal to 2. Patients must be willing to travel from their home to the NIH for follow-up visits. Patients with brain metastases or primary CNS malignancies are not eligible. Concurrent therapy for their cancer (i.e., radiation therapy, chemotherapy, etc.) will preclude participation. We will be defining the maximum tolerated dose, the toxicity profile, characterizing the pharmacokinetics, and evaluating the effect of COL-3 on several biological endpoints.
- Conditions
- Lymphoma, Melanoma, Neoplasm Metastasis, Renal Cell Carcinoma
- Being tested
- COL-3
- Keywords
- Collagen Breakdown, Pharmacokinetics, Rapid Escalation Phase I, Angiogenesis, Tissue Inhibitors of Metalloproteinase
- Medical subject headings
- Lymphoma, Melanoma, Neoplasm Metastasis, Carcinoma, Renal Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
COL-3Drug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 1999 (estimated)
- Study startOct 1997
- Study completionAug 2003
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for LymphomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Enrolment
- 35 participants
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00001683
- Sponsor's protocol ID
- 980015
- Other IDs
- 98-C-0015
- Status last verified
- Aug 2003
- First submitted
- 3 Nov 1999
- Last updated
- 4 Mar 2008
- Results posted
- No
Publications
Akimoto S, Akakura K, Shimazaki J. Clinical usefulness of serum carboxyterminal propeptide of type I procollagen and pyridinoline cross-linked carboxyterminal telopeptide of type I collagen in patients with prostate cancer. Jpn J Clin Oncol. 1996 Jun;26(3):157-63. doi: 10.1093/oxfordjournals.jjco.a023200.
PubMed 8656556Baker T, Tickle S, Wasan H, Docherty A, Isenberg D, Waxman J. Serum metalloproteinases and their inhibitors: markers for malignant potential. Br J Cancer. 1994 Sep;70(3):506-12. doi: 10.1038/bjc.1994.336.
PubMed 8080738Conway JG, Trexler SJ, Wakefield JA, Marron BE, Emerson DL, Bickett DM, Deaton DN, Garrison D, Elder M, McElroy A, Willmott N, Dockerty AJ, McGeehan GM. Effect of matrix metalloproteinase inhibitors on tumor growth and spontaneous metastasis. Clin Exp Metastasis. 1996 Mar;14(2):115-24. doi: 10.1007/BF00121208.
PubMed 8605725
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of Oral COL-3 (NSC-683551), a Matrix Metalloproteinase Inhibitor, in Patients With Refractory Metastatic Cancer
- ClinicalTrials.gov ID
- NCT00001683
- Acronym / sponsor ID
- 980015
- Conditions
- Lymphoma, Melanoma, Neoplasm Metastasis, Renal Cell Carcinoma
- Keywords
- Collagen Breakdown, Pharmacokinetics, Rapid Escalation Phase I, Angiogenesis, Tissue Inhibitors of Metalloproteinase
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Oct 1997
- Study completion
- Aug 2003
- First posted
- 4 Nov 1999 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Matrix metalloproteinases (MMPs) are a class of membrane bound enzymes that are involved in the degradation of the extracellular matrix. MMP-2 and MMP-9 have been associated with the progression of cancer. It is hypothesized than an imbalance between MMPs and MMP inhibitors allows the destruction of the extracellular matrix and enhances the ability of the tumor cells to grow and metastasize. By inhibiting MMPs, it is thought that angiogenesis and metastasis can be inhibited. This is a phase I study of COL-3, an oral matrix metalloproteinase inhibitor, in patients with refractory metastatic cancer. COL-3 is a chemically modified tetracycline derivative. Patients must have clinically progressive disease documented within 1 month prior to entry to be eligible for treatment. Patients must have also failed therapy of proven efficacy for their disease and have an ECOG performance status of less or equal than 2. Patients must be willing to travel from their home to the NIH for follow-up visits. Patients with brain metastases or primary CNS malignancies are not eligible. Concurrent therapy for their cancer (i.e., radiation therapy, chemotherapy, etc.) will preclude participation. We will be defining the maximum tolerated dose, the toxicity profile, characterizing the pharmacokinetics, and evaluating the effect of COL-3 on several biological endpoints.
Detailed description
Matrix metalloproteinases (MMPs) are a class of membrane bound enzymes that are involved in the degradation of the extracellular matrix. MMP-2 and MMP-9 have been associated with the progression of cancer. It is hypothesized that an imbalance between MMPs and MMP inhibitors allows the destruction of the extracellular matrix and enhances the ability of the tumor cells to grow and metastasize. By inhibiting MMPs, it is thought that angiogenesis and metastasis can be inhibited. This is a phase I study of COL-3, an oral matrix metalloproteinase inhibitor, in patients with refractory metastatic cancer. COL-3 is a chemically modified tetracycline derivative. Patients must have clinically progressive disease documented within 1 month prior to entry to be eligible for treatment. Patients must have also failed therapy of proven efficacy for their disease and have an ECOG performance status of less than or equal to 2. Patients must be willing to travel from their home to the NIH for follow-up visits. Patients with brain metastases or primary CNS malignancies are not eligible. Concurrent therapy for their cancer (i.e., radiation therapy, chemotherapy, etc.) will preclude participation. We will be defining the maximum tolerated dose, the toxicity profile, characterizing the pharmacokinetics, and evaluating the effect of COL-3 on several biological endpoints.
Study design
- Primary purpose
- Treatment
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (18 listed)
- All patients with refractory solid tumors and lymphoma are eligible according to the criteria listed below. Patients with tumor marker evidence of disease only, will not be eligible for study. A patient must have bone scan evidence of metastatic disease.
- Patients must have histopathological documentation of cancer confirmed in the Laboratory of Pathology/NCI of the Clinical Center at the National Institutes of Health prior to starting this study.
- Patients must have clinically progressive disease documented prior to entry. Progression must be documented by at least one of the following parameters: two consecutively rising tumor marker levels, and/or at least one new metastatic deposit on Tc-99 bone scintigraphy, and/or progression of soft tissue metastases as measured by appropriate modalities (i.e., imaging, palpation), and/or development of new area of malignant disease (measurable or evaluable).
- Patients must have failed therapy of proven efficacy for their disease. Patients with metastatic melanoma, non-small cell lung cancer, and renal cell carcinoma will be eligible without receiving prior therapy. Initial treatment of the non-chemotherapy responsive malignancies (e.g., disseminated gastrointestinal, noncolorectal cancer) may be done at the discretion of the investigators.
- Patients must be ECOG performance status of less than or equal to 2.
Key exclusion criteria (6 listed)
- Active infection, including positive serology for HIV. Colonized urinary tract instrumentation is not excluded.
- Patients with brain metastases or primary CNS malignancies.
- Concurrent therapy for their cancer (i.e., radiation therapy, chemotherapy, etc.).
- Patients who are pregnant or lactating. No data is currently available about the excretion of COL-3 in breast milk. Also, no toxicity data in gestating animals exists at the present time. Until data of this nature becomes available, we will exclude patients who are pregnant or lactating.
- Patients who are known to be HIV positive will not be eligible for this protocol. Since COL-3 is a known inhibitor of neutrophil gelatinase, HIV patients will be excluded because of their increased risk of infection. HIV testing will be required.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| COL-3 | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2008.
- Background: PubMed 8656556Akimoto S, Akakura K, Shimazaki J. Clinical usefulness of serum carboxyterminal propeptide of type I procollagen and pyridinoline cross-linked carboxyterminal telopeptide of type I collagen in patients with prostate cancer. Jpn J Clin Oncol. 1996 Jun;26(3):157-63. doi: 10.1093/oxfordjournals.jjco.a023200.
- Background: PubMed 8080738Baker T, Tickle S, Wasan H, Docherty A, Isenberg D, Waxman J. Serum metalloproteinases and their inhibitors: markers for malignant potential. Br J Cancer. 1994 Sep;70(3):506-12. doi: 10.1038/bjc.1994.336.
- Background: PubMed 8605725Conway JG, Trexler SJ, Wakefield JA, Marron BE, Emerson DL, Bickett DM, Deaton DN, Garrison D, Elder M, McElroy A, Willmott N, Dockerty AJ, McGeehan GM. Effect of matrix metalloproteinase inhibitors on tumor growth and spontaneous metastasis. Clin Exp Metastasis. 1996 Mar;14(2):115-24. doi: 10.1007/BF00121208.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing COL-3 in people with Lymphoma and Melanoma, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Mar 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00001683, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2008.