Advanced Solid CancersPhase 1NCT00337376
A Study of the mTOR Inhibitor Rapamycin (Rapamune, Sirolimus) in Combination With Abraxane in Advanced Solid Cancers
A Phase 1 study testing Rapamune and Abraxane in people with Advanced Solid Cancers, run by Yale University at 1 site in United States.
Trial summary
Rapamycin is a drug that has been approved by the Food and Drug Administration (government) for use in patients receiving a kidney transplant to prevent the patient's body from rejecting the transplanted kidney. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Solid Cancers
- What is being tested?
- Rapamune and Abraxane
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2006to Jul 2010
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have histologically-confirmed advanced solid tumors.
- For patients with metastatic breast cancer, there will be no restriction on prior therapy. For patients with other advanced solid tumors, they must be refractory to standard therapy or for which no curative standard therapy exists, to be considered. Metastatic disease, if present, should not be progressing so as to require palliative treatment within 4 weeks of enrollment based on clinical assessment by the investigator.
- Development of new lesions or an increase in preexisting lesions on bone scintigraphy, CT, MRI or by physical examination. Patients in whom the sole criterion for progression is an increase in a biochemical marker, e.g., carcinoembryonic antigen (CEA), or an increase in symptoms, are not eligible.
- No radiotherapy, treatment with cytotoxic agents, or treatment with biologic agents within the 4 weeks prior to beginning treatment on this study (6 weeks for mitomycin or nitrosoureas). At least 2 weeks must have elapsed from any prior surgery or hormonal therapy. Patients must have fully recovered from the acute toxicities of any prior treatment with cytotoxic drugs, radiotherapy or other anti-cancer modalities (returned to baseline status as noted before most recent treatment). Patients with persisting, stable chronic toxicities from prior treatment ≤ grade 1 are eligible.
- Age ≥18 years.
- ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A).
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- Life expectancy of greater than 3 months.
- Patients must have normal organ and marrow function as defined below:
- Hemoglobin ≥ 9 g/dL leukocytes ≥3,000/mcL absolute neutrophil count ≥1,500/mcL platelets ≥100,000/mcL total bilirubin within normal institutional limits AST(SGOT)/ALT(SGPT)2.5 X institutional upper limit of normal creatinine within 1.5 x ULN OR creatinine clearance ≥50 mL/min/1.73 m² for patients with creatinine levels ≥1.5 ULN.
- Women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation and must have a negative serum or urine pregnancy test within 1 week prior to beginning treatment on this trial. Pregnant and nursing patients are excluded because the effects of the combination of Abraxane and Rapamycin on a fetus or nursing child are unknown. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Sexually active men must also use appropriate contraception method and should not father a child while receiving therapy during this study.
- Ability to understand and the willingness to sign a written informed consent document.
- Fasting serum cholesterol <350 mg/d L and triglycerides < 400 mg/ d L.
- Biopsy is required but patients or physicians may opt out of this part of the trial if sufficient justification is provided. Justification must be provided to the PI in writing indicating excessive physical risk or psychological trauma if biopsy is taken
Who cannot join
- Patients must be 4 weeks from chemotherapy or radiotherapy and have recovered from any adverse events
- Patients may not be receiving any other investigational agents.
- Patients with known active brain metastases. Patients must have completed definitive treatment for brain metastases, at least 4 weeks prior to first dose on this study, and off steroids for at least 2 weeks, with stable or regressing CNS lesions by MRI or CT scan, and no evidence of new lesions.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to agents used in study.
- Peripheral neuropathy ≥ Grade 2
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
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- Pregnant women are excluded from this study because the investigational agents may have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with these agents, breastfeeding should be discontinued if the mother is treated.
- HIV-positive patients are ineligible because these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy and the potential pharmacokinetic interaction between antiretroviral therapy and the investigational agents.
- All herbal and alternative medications should be discontinued while on study, these include but not limited to: Hydrastis canadensis (goldenseal), Uncaria tomentosa (cat's claw) Echinacea angustifolia
- Use of any of these medications within 1 week, prior to the first dose of treatment: cyclosporine, diltiazem, ketoconazole, rifampin, fluconazole, delavirdine, nicardipine, pioglitazone and sulfonamides, erythromycin, clarithromycin, itraconazole, metoclopramide, nevirapine, Phenobarbital, phenytoin, indinavir fosamprenavir, ritonavir, efavirenz, nefazadone, and St. John's wort.
- Consumption of grapefruit juice is prohibited during the study.
- Requirement for treatment with warfarin (Coumadin), immunosuppressive agents or chronic steroids
- Prior therapy with rapamycin, rapamycin analogs or experimental agents targeting mTOR
- Prior Abraxane therapy
- Active infection or treatment for systemic infections within 14 days of enrollment.
Trial locations and contacts
1 site in 1 country.
United States1 site
Yale Comprehensive Cancer Center at Yale University School of Medicine
New Haven, Connecticut, 06520
About this study
Official title: A Phase I Study of the mTOR Inhibitor Rapamycin (Rapamune, Sirolimus) in Combination With Abraxane (Paclitaxel Protein-bound Particles) in Advanced Solid Cancers
Rapamycin is a drug that has been approved by the Food and Drug Administration (government) for use in patients receiving a kidney transplant to prevent the patient's body from rejecting the transplanted kidney. It has shown antitumor effects in the laboratory, but has not been approved at this time for the treatment of cancer. Abraxane is a new form of chemotherapy that has been approved by the Food and Drug Administration for the treatment of metastatic breast cancer, and is a promising drug that is being evaluated in clinical trials for treatment of other cancers. This is a phase I study designed to find out if different doses of Rapamycin, when combined with Abraxane, are safe and well tolerated.
- Conditions
- Advanced Solid Cancers
- Being tested
- Rapamune, Abraxane
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RapamuneDrug
Also called Rapamycin, Sirolimus
Dose escalation as follows: 5mg PO, 10mg PO, 20mg PO, 40mg PO
AbraxaneDrug
Also called Albumin-bound paclitaxel
intravenous administration of 100mg/m2 Abraxane over 30 minutes, weekly for three out of four consecutive weeks.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Not described Receives: Drug: Rapamune; Drug: Abraxane |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the safety, dose-limiting toxicities, and maximum tolerated dose of weekly oral Rapamycin in combination with weekly intravenous Abraxane for three out of four consecutive weeks in patients with advanced solid cancers.
Measured: upon completion of study
Secondary outcomes (3)
to determine if weekly administration of Rapamycin changes the pharmacokinetic profile of weekly Abraxane
Measured: upon completion of study
To determine pre and post therapy changes in p70S6K in peripheral mononuclear cells in patients treated with oral Rapamycin and Abraxane
Measured: Upon completion of study
To evaluate changes in the phosphorylation of p70S6K on tumor tissue and to determine the correlation with phosphorylation of p70S6K in the peripheral mononuclear cells, in patients who give consent to pre and post tumor biopsies
Measured: upon completion of study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jun 2006 (estimated)
- Study startFeb 2006
- Primary completionJul 2010
- Study completionJul 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Solid CancersStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe 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
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- Celgene Corporation
- Responsible party
- Principal investigator, Maysa Abu-Khalaf, Yale University
- Investigators
- Maysa Abu-Khalaf, M.D., Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00337376
- Sponsor's protocol ID
- 0511000860
- Status last verified
- Jan 2014
- First submitted
- 13 Jun 2006
- Last updated
- 14 Jan 2014
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Jan 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of the mTOR Inhibitor Rapamycin (Rapamune, Sirolimus) in Combination With Abraxane (Paclitaxel Protein-bound Particles) in Advanced Solid Cancers
- ClinicalTrials.gov ID
- NCT00337376
- Acronym / sponsor ID
- 0511000860
- Conditions
- Advanced Solid Cancers
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- Celgene Corporation
- Study start
- Feb 2006
- Primary completion
- Jul 2010 (actual)
- Study completion
- Jul 2010 (actual)
- First posted
- 15 Jun 2006 (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.
Rapamycin is a drug that has been approved by the Food and Drug Administration (government) for use in patients receiving a kidney transplant to prevent the patient's body from rejecting the transplanted kidney. It has shown antitumor effects in the laboratory, but has not been approved at this time for the treatment of cancer. Abraxane is a new form of chemotherapy that has been approved by the Food and Drug Administration for the treatment of metastatic breast cancer, and is a promising drug that is being evaluated in clinical trials for treatment of other cancers. This is a phase I study designed to find out if different doses of Rapamycin, when combined with Abraxane, are safe and well tolerated.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Rapamune, Drug: Abraxane |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Patients must have histologically-confirmed advanced solid tumors.
- For patients with metastatic breast cancer, there will be no restriction on prior therapy. For patients with other advanced solid tumors, they must be refractory to standard therapy or for which no curative standard therapy exists, to be considered. Metastatic disease, if present, should not be progressing so as to require palliative treatment within 4 weeks of enrollment based on clinical assessment by the investigator.
- Development of new lesions or an increase in preexisting lesions on bone scintigraphy, CT, MRI or by physical examination. Patients in whom the sole criterion for progression is an increase in a biochemical marker, e.g., carcinoembryonic antigen (CEA), or an increase in symptoms, are not eligible.
- No radiotherapy, treatment with cytotoxic agents, or treatment with biologic agents within the 4 weeks prior to beginning treatment on this study (6 weeks for mitomycin or nitrosoureas). At least 2 weeks must have elapsed from any prior surgery or hormonal therapy. Patients must have fully recovered from the acute toxicities of any prior treatment with cytotoxic drugs, radiotherapy or other anti-cancer modalities (returned to baseline status as noted before most recent treatment). Patients with persisting, stable chronic toxicities from prior treatment ≤ grade 1 are eligible.
- Age ≥18 years.
Key exclusion criteria (15 listed)
- Patients must be 4 weeks from chemotherapy or radiotherapy and have recovered from any adverse events
- Patients may not be receiving any other investigational agents.
- Patients with known active brain metastases. Patients must have completed definitive treatment for brain metastases, at least 4 weeks prior to first dose on this study, and off steroids for at least 2 weeks, with stable or regressing CNS lesions by MRI or CT scan, and no evidence of new lesions.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to agents used in study.
- Peripheral neuropathy ≥ Grade 2
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 |
|---|---|---|
| RapamuneAlso: Rapamycin, SirolimusDose escalation as follows: 5mg PO, 10mg PO, 20mg PO, 40mg PO | Drug | 1 |
| AbraxaneAlso: Albumin-bound paclitaxelintravenous administration of 100mg/m2 Abraxane over 30 minutes, weekly for three out of four consecutive weeks. | Drug | 1 |
Primary outcome
To determine the safety, dose-limiting toxicities, and maximum tolerated dose of weekly oral Rapamycin in combination with weekly intravenous Abraxane for three out of four consecutive weeks in patients with advanced solid cancers.
Time frame: upon completion of study
3 secondary outcomes
to determine if weekly administration of Rapamycin changes the pharmacokinetic profile of weekly Abraxane
Time frame: upon completion of study
To determine pre and post therapy changes in p70S6K in peripheral mononuclear cells in patients treated with oral Rapamycin and Abraxane
Time frame: Upon completion of study
To evaluate changes in the phosphorylation of p70S6K on tumor tissue and to determine the correlation with phosphorylation of p70S6K in the peripheral mononuclear cells, in patients who give consent to pre and post tumor biopsies
Time frame: upon completion of study
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jan 2014.
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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.
Maysa Abu-Khalaf, M.D. principal investigator
Yale University
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 Rapamune and Abraxane in people with Advanced Solid Cancers, run by Yale University 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 13 inclusion and 15 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: stopped early, as of the sponsor's last update on 14 Jan 2014. 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 was stopped early. Results are not available in the source record.
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.
What does the primary outcome measure?
To determine the safety, dose-limiting toxicities, and maximum tolerated dose of weekly oral Rapamycin in combination with weekly intravenous Abraxane for three out of four consecutive weeks in patients with advanced solid cancers. (time frame: upon completion of study). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 14 Jan 2014.