Metastatic Breast CancerPhase 1/2NCT01939418
Phase Ib/II Trials of RAD001 in Triple Negative Metastatic Breast Cancer
A Phase 1/2 study testing RAD001, Gemcitabine and Cisplatin in people with Metastatic Breast Cancer, run by National Cancer Center, Korea at 1 site in South Korea.
Trial summary
This study consists of two parts. In a phase Ib part, investigators will explore the recommended dose of gemcitabine, cisplatin, and RAD001 combination in patients with metastatic TNBC. After completing the phase Ib part, investigators will review the data and discuss with Novartis before the start of a phase II part. Read more about this study
- Who is it for?
- Ages 20 years and older, women only
- Conditions the study is for
- Metastatic Breast Cancer
- What is being tested?
- RAD001, Gemcitabine and Cisplatin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 1 siteSouth Korea
- Study dates
- Aug 2013to 30 Jul 2017
- Phase
- Phase 1/2
- 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 20 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Females with histologically confirmed, metastatic or stage IV breast cancer
- ER/PgR negative or poor (Allred score ≤ 3/8) and HER2 negative breast cancer
- ECOG performance status 0-2
- Age ≥ 20 years
- Previously treated by anthracycline and taxane in adjuvant/neoadjuvant or metastatic setting
- ≤ 2 chemotherapy regimens for metastatic disease
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- Radiological or objective evidence of recurrence or progression on or after the last systemic therapy prior to enrolment.
- CNS metastasis is permitted if asymptomatic and not requiring treatment with steroids and is documented to be non-progressing at study entry
- Presence of measurable or evaluable disease by RECIST 1.1 criteria
- Adequate hematopoietic function: Absolute granulocyte count ≥1,500/mm3, platelet ≥100,000/mm3, hemoglobin ≥ 10g/mm3
- Adequate hepatic function: total bilirubin ≤ 1.5 x upper normal limit (UNL), AST/ALT ≤2.5 x UNL or ≤5 x UNL if presented with hepatic metastasis
- Fasting serum cholesterol ≤ 300mg/dl and fasting triglycerides ≤ 2.5 x UNL
- Adequate renal function: Serum creatinine ≤1.5mg/dL
- Patients should sign a written informed consent before study entry
- Patients with positive HBV-DNA of HBsAg at screening must initiate prophylaxis with appropriate antiviral medication at least one week prior to treatment start
Who cannot join
- Known active CNS metastasis
- Patients who received prior therapy with gemcitabine
- Patients with only non-measurable lesions other than bone metastasis (e.g. pleural effusion, ascites).
- Patients with more than 3 prior chemotherapy lines for treating metastatic breast cancer.
- Patients who received prior therapy with mTOR inhibitor or PI3K inhibitor
- Known hypersensitivity to mTOR inhibitors, e.g. Sirolimus (rapamycin).
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- Radiotherapy within four weeks prior to enrolment, except radiotherapy to the bone for analgesic purpose or for lytic lesions at risk of fracture. Patients must have recovered from radiotherapy toxicities prior to enrolment.
- Patients who have history of cancer other than in situ uterine cervix cancer or nonmelanotic skin cancer
- Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral everolimus
- Active ulceration of upper gastrointestinal tract
- Other concurrent severe and/or uncontrolled conditions (e.g. uncontrolled diabetes mellitus, active untreated or uncontrolled infection, chronic obstructive or chronic restrictive pulmonary disease including dyspnea at rest from any cause) that could cause unacceptable safety risks or compromise compliance with the protocol.
- Patients with a known history of HIV seropositivity. Screening for HIV infection at baseline is not required.
- Significant symptomatic deterioration of lung function. If clinically indicated, pulmonary function tests including measures of predicted lung volumes, DLco, O2 saturation at rest on room air should be considered to exclude restrictive pulmonary disease, pneumonitis or pulmonary infiltrates.
- Patients being treated with drugs recognized as being strong inhibitors or inducers of the isoenzyme CYP3A at enrolment (rifabutin, rifampicin, clarithromycin, ketoconazole, itraconazole, voriconazole, ritonavir, telithromycin) continuously for at least 7 days during any time period in the last 2 weeks prior to enrolment
- Known hypersensitivity to protocol treatment
- Pregnant or breast feeding
- Peripheral neuropathy ≥ grade 2 (NCI CTCAE version 4.0) at randomization
- Patients unwilling to or unable to comply with the protocol
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase Ib Trial of Gemcitabine and Cisplatin With RAD001 in Patients With Metastatic Triple Negative Breast Cancer Proceeding to an Open Label Randomized Phase II Trial Comparing Gemcitabine/Cisplatin With or Without RAD001.
This study consists of two parts. In a phase Ib part, investigators will explore the recommended dose of gemcitabine, cisplatin, and RAD001 combination in patients with metastatic TNBC. After completing the phase Ib part, investigators will review the data and discuss with Novartis before the start of a phase II part. In the phase II part, investigators will compare the efficacy of the gemcitabine and cisplatin with or without RAD001 in patients with metastatic TNBC.
Read the detailed description
PIK3CA active mutations are the most frequent genetic event in breast cancer, including in TNBC which presents activated PI3K/AKT signaling due to PIK3CA mutation or PTEN deficiency. TNBC cell lines having activated PI3K/AKT signaling showed a high sensitivity to PI3K/mTOR inhibitors. RAD001 is a potent mTOR complex 1 inhibitor and showed to enhance cisplatin or gemcitabine induced apoptosis by inhibiting p53 induced p21 expression.
This study consists of two parts. In a phase Ib part, investigators will explore the recommended dose of gemcitabine, cisplatin, and RAD001 combination in patients with metastatic TNBC. After completing the phase Ib part, investigators will review the data and discuss with Novartis before the start of a phase II part. In the phase II part, investigators will compare the efficacy of the gemcitabine and cisplatin with or without RAD001 in patients with metastatic TNBC.
- Conditions
- Metastatic Breast Cancer
- Being tested
- RAD001, Gemcitabine, Cisplatin
- Keywords
- metastatic breast cancer, triple negative breast cancer, gemcitabine, RAD001
- Medical subject headings
- Breast Neoplasms, Triple Negative Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RAD001Drug
Also called Afinitor, everolimus
Afinitor 5mg qd. po.
GemcitabineDrug
gemcitabine 800mg/m2 iv. D1 and D8 every 3 weeks
CisplatinDrug
cisplatin 30mg/m2 iv. D1 and D8 every 3 weeks
| Study group | Role | What they receive |
|---|---|---|
| RAD001 | Experimental | gemcitabine 800mg/m2, D1 and D8 iv. every 3 weeks. cisplatin 30mg/m2, D1 and D8 iv. every 3 weeks. RAD001 5mg QD. po. Receives: Drug: RAD001; Drug: Gemcitabine; Drug: Cisplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
The recommended dose of the combination of gemcitabine, cisplatin and RAD001 (everolimus) in patients with metastatic triple-negative breast cancer
phase IB part
Measured: up to 1 year
Efficacy of gemcitabine and cisplatin with or without RAD001 in patients with metastatic triple-negative breast cancer by evaluating progression free survival (PFS)
phase II part
Measured: up to 5 years
Secondary outcomes (5)
The maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of gemcitabine/cisplatin/RAD001
phase Ib part
Measured: up to 1 year
number of patients with adverse events as a measure of safety and tolerability
phase Ib and phase II
Measured: up to 5 years
objective response rate
phase Ib and phase II
Measured: up to 1 year
Overall survival (OS)
phase Ib and phase II
Measured: up to 5 years
check biomarkers associated with the response of RAD001: angiogenesis, metabolism, immune cells profiles
phaseIb and phaseII
Measured: up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Sep 2013 (estimated)
- Study startAug 2013
- Primary completion30 Jul 2016
- Study completion30 Jul 2017
Why it stopped: slow recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Breast CancerStudies of the same condition, open and under way.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Center, Korea
- Sponsor type
- Other government
- Responsible party
- Principal investigator, In Hae Park, National Cancer Center, Korea
- Investigators
- In Hae Park, Doctor, Principal investigator, National Cancer Center, Korea
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01939418
- Sponsor's protocol ID
- NCCCTS-13-670
- Other IDs
- 12491
- Status last verified
- Oct 2017
- First submitted
- 28 Aug 2013
- Last updated
- 3 Oct 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib Trial of Gemcitabine and Cisplatin With RAD001 in Patients With Metastatic Triple Negative Breast Cancer Proceeding to an Open Label Randomized Phase II Trial Comparing Gemcitabine/Cisplatin With or Without RAD001.
- ClinicalTrials.gov ID
- NCT01939418
- Acronym / sponsor ID
- NCCCTS-13-670
- Conditions
- Metastatic Breast Cancer
- Keywords
- metastatic breast cancer, triple negative breast cancer, gemcitabine, RAD001
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: slow recruitment
- Enrolment
- 23 participants (actual)
- Lead sponsor
- National Cancer Center, KoreaOther government
- Study start
- Aug 2013 (actual)
- Primary completion
- 30 Jul 2016 (actual)
- Study completion
- 30 Jul 2017 (actual)
- First posted
- 11 Sep 2013 (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.
This study consists of two parts. In a phase Ib part, investigators will explore the recommended dose of gemcitabine, cisplatin, and RAD001 combination in patients with metastatic TNBC. After completing the phase Ib part, investigators will review the data and discuss with Novartis before the start of a phase II part. In the phase II part, investigators will compare the efficacy of the gemcitabine and cisplatin with or without RAD001 in patients with metastatic TNBC.
Detailed description
PIK3CA active mutations are the most frequent genetic event in breast cancer, including in TNBC which presents activated PI3K/AKT signaling due to PIK3CA mutation or PTEN deficiency. TNBC cell lines having activated PI3K/AKT signaling showed a high sensitivity to PI3K/mTOR inhibitors. RAD001 is a potent mTOR complex 1 inhibitor and showed to enhance cisplatin or gemcitabine induced apoptosis by inhibiting p53 induced p21 expression.
This study consists of two parts. In a phase Ib part, investigators will explore the recommended dose of gemcitabine, cisplatin, and RAD001 combination in patients with metastatic TNBC. After completing the phase Ib part, investigators will review the data and discuss with Novartis before the start of a phase II part. In the phase II part, investigators will compare the efficacy of the gemcitabine and cisplatin with or without RAD001 in patients with metastatic TNBC.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| RAD001 | Experimental | Drug: RAD001, Drug: Gemcitabine, Drug: Cisplatingemcitabine 800mg/m2, D1 and D8 iv. every 3 weeks. cisplatin 30mg/m2, D1 and D8 iv. every 3 weeks. RAD001 5mg QD. po. |
Who may qualify
- Ages
- 20 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Females with histologically confirmed, metastatic or stage IV breast cancer
- ER/PgR negative or poor (Allred score ≤ 3/8) and HER2 negative breast cancer
- ECOG performance status 0-2
- Age ≥ 20 years
- Previously treated by anthracycline and taxane in adjuvant/neoadjuvant or metastatic setting
Key exclusion criteria (18 listed)
- Known active CNS metastasis
- Patients who received prior therapy with gemcitabine
- Patients with only non-measurable lesions other than bone metastasis (e.g. pleural effusion, ascites).
- Patients with more than 3 prior chemotherapy lines for treating metastatic breast cancer.
- Patients who received prior therapy with mTOR inhibitor or PI3K inhibitor
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 |
|---|---|---|
| RAD001Also: Afinitor, everolimusAfinitor 5mg qd. po. | Drug | RAD001 |
| Gemcitabinegemcitabine 800mg/m2 iv. D1 and D8 every 3 weeks | Drug | RAD001 |
| Cisplatincisplatin 30mg/m2 iv. D1 and D8 every 3 weeks | Drug | RAD001 |
Primary outcome
The recommended dose of the combination of gemcitabine, cisplatin and RAD001 (everolimus) in patients with metastatic triple-negative breast cancer
Time frame: up to 1 year
phase IB part
Efficacy of gemcitabine and cisplatin with or without RAD001 in patients with metastatic triple-negative breast cancer by evaluating progression free survival (PFS)
Time frame: up to 5 years
phase II part
5 secondary outcomes
The maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of gemcitabine/cisplatin/RAD001
Time frame: up to 1 year
number of patients with adverse events as a measure of safety and tolerability
Time frame: up to 5 years
objective response rate
Time frame: up to 1 year
Overall survival (OS)
Time frame: up to 5 years
check biomarkers associated with the response of RAD001: angiogenesis, metabolism, immune cells profiles
Time frame: up to 5 years
Results and safety
The study was stopped early (reason given: slow recruitment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Oct 2017.
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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.
In Hae Park, Doctor principal investigator
National Cancer Center, Korea
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing RAD001, Gemcitabine and Cisplatin in people with Metastatic Breast Cancer, run by National Cancer Center, Korea at 1 site in South Korea.
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 15 inclusion and 18 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 3 Oct 2017. 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 South Korea. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 (reason given: slow recruitment). 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?
The recommended dose of the combination of gemcitabine, cisplatin and RAD001 (everolimus) in patients with metastatic triple-negative breast cancer (time frame: up to 1 year). The study lists 2 primary outcomes in all. 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 3 Oct 2017.