Small Cell Lung CancerPhase 1/2NCT02446704
Study of Olaparib and Temozolomide in Patients With Recurrent Small Cell Lung Cancer Following Failure of Prior Chemotherapy
A Phase 1/2 study testing Olaparib and Temozolomide in people with Small Cell Lung Cancer, run by Zofia Piotrowska at 3 sites in United States.
Trial summary
This research study is evaluating the combination of olaparib and temozolomide as a possible treatment for Small Cell Lung Cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Small Cell Lung Cancer
- What is being tested?
- Olaparib and Temozolomide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 66 participants
- Where
- 3 sitesUnited States
- Study dates
- 13 Oct 2015to Dec 2023
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must meet the following criteria on screening examination to be eligible to participate in the study. The eligibility criteria apply to both the phase I and phase II portions of the study.
- Participant must have histologically or cytologically confirmed small cell lung cancer and may not be a candidate for potentially curative therapy.
- Presence of measurable disease (RECIST 1.1): At least one lesion, not previously irradiated, that can be accurately measured at baseline as ≥ 10 mm in the longest diameter (except lymph nodes which must have short axis ≥ 15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) and which is suitable for accurate repeated measurements.
- The small cell lung cancer must have progressed radiographically following a platinum-based (cisplatin and/or carboplatin) standard prior chemotherapy regimen. Any number of interval prior lines of therapy is allowed. Patients who have received prior platinum-based chemotherapy and radiation for limited stage SCLC and have subsequently developed relapsed disease are eligible, as long as the platinum-based therapy was given within 12 months prior to the time of relapse.
- Participant (male/female) must be ≥18 years of age.
- Participant must have normal organ and bone marrow function measured within 28 days prior to administration of study treatment as defined below:
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- Hemoglobin ≥ 10.0 g/dL
- Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L
- Platelet count ≥100 x 10^9/L
- Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN)
- AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit of normal (unless liver metastases are present in which case it must be ≤5 x ULN)
- Serum creatinine ≤1.5 x institutional upper limit of normal (ULN)
- ECOG performance status 0-1
- Participant must have a life expectancy ≥ 16 weeks.
- Women of childbearing potential must have a negative urine or serum pregnancy test within 28 days of initial dose of olaparib and temozolomide AND must agree to the use of two highly effective forms of contraception (see Section 5.5) throughout their participation in the study and for at least 3 months after the last dose of olaparib and temozolomide, OR confirmed prior to treatment on day 1 to be postmenopausal or surgically sterile. Postmenopausal is defined as:
- Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments,
- LH and FSH levels in the post menopausal range for women under 50,
- radiation-induced oophorectomy with last menses >1 year ago,
- chemotherapy-induced menopause with >1 year interval since last menses, or surgical sterilisation (bilateral oophorectomy or hysterectomy).
- Participant is willing to comply with the protocol for the duration of the study, and undergo treatment and scheduled visits and examinations including follow up. Participant must obtain prior approval from insurance to reimburse for oral temozolomide for the duration of the study or agree to self-pay for oral temozolomide.
Who cannot join
- Participants who exhibit any of the following conditions at screening will not be eligible for admission into the study. The exclusion criteria apply to both the phase I and phase II portions of the study.
- Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
- Previous enrollment in the present study.
- Participation in another clinical study with an investigational product during the 21 days prior to first dose of olaparib and temozolomide.
- Participants receiving any systemic chemotherapy, radiotherapy (except for palliative reasons), within 2 weeks from the last dose prior to study treatment (or a longer period depending on the defined characteristics of the agents used). The patient can receive a stable dose of bisphosphonates for bone metastases, before and during the study as long as these were started at least 4 weeks prior to treatment with olaparib and temozolomide.
- Participants are to discontinue the use of the following classes of inhibitors of CYP3A4. Patients who are on these drugs are eligible if a washout period of a minimum of 7 days occurs before start of olaparib and temozolomide.
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- Azole antifungals
- Macrolide antibiotics
- Protease inhibitors
- Persistent clinically significant toxicities (>=CTCAE v. 4.0 grade 2) caused by previous cancer therapy, with the exception of alopecia.
- Participants with a previously documented diagnosis of myelodysplastic syndrome (MDS) (or any dysplastic leukocyte morphology suggestive of MDS) or acute myeloid leukaemia.
- Participants with symptomatic uncontrolled brain metastases. Baseline brain imaging by CT or MRI is required for all patients. Participants with brain metastases that have been treated with prior radiation therapy and are stable on a subsequent scan are allowed. Participants with untreated possible brain metastases that are new at the time of screening and are < 1 cm and asymptomatic are allowed. The participant can receive corticosteroids as long as these were started and at a stable dose at least 28 days prior to treatment.
- Major surgery within 14 days of starting study treatment and patients must have recovered from any effects of any major surgery.
- Participants considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, QTc prolongation > 470 msec, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, unstable spinal cord compression (untreated and unstable for at least 28 days prior to study entry), extensive bilateral lung disease with less than 20% predicted lung function by DLCO (Lung Diffusion Capacity Testing), or any psychiatric disorder that prohibits obtaining informed consent.
- Participants unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication.
- Pregnant or Breast feeding women. All patients (male and female) must agree to practice a medically acceptable method of contraception as defined in section 5.5. Should a woman become pregnant or suspect that she is pregnant while participating in this study, she should inform her treating physician immediately.
- Patients who have a history of and are known to be serologically positive for human immunodeficiency virus (HIV) and are receiving antiviral therapy. Baseline testing is not required.
- Patients with known active Hepatitis B or C. Baseline testing is not required.
- Patients with a known hypersensitivity to olaparib or any of the excipients of the product.
- Patients with uncontrolled seizures.
- Patients with second primary cancer, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumors curatively treated with no evidence of disease for ≥ 5 years.
- Patients with current and symptomatic pneumonitis, or extensive bilateral lung disease on high resolution CT scan.
- Patients with whole blood transfusion in the last 120 days prior to entry to the study.
- Patients with previous allogeneic bone marrow transplant.
- Patients with active, uncontrolled infection.
- Patients who need to continue treatment with any prohibited medications listed in Section 5.6
- Patients who have not completed the appropriate washout period for the prohibited medications in Section 5.6
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Dana Farber Cancer Institute
Boston, Massachusetts, 02115
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
About this study
Official title: Phase I/II Study of Olaparib and Temozolomide in Patients With Recurrent Small Cell Lung Cancer Following Failure of Prior Chemotherapy
This research study is evaluating the combination of olaparib and temozolomide as a possible treatment for Small Cell Lung Cancer.
Read the detailed description
This research study is a Phase I/II clinical trial, which has two parts. The participant will be asked to participate in one part of the study. The first part tests the safety of the combination of drugs and tries to define the appropriate dose to use for future studies. The second part tests whether the combination of drugs is effective in treating small cell lung cancer. "Investigational" means that the combination of drugs is being studied. It also means that the U.S. Food and Drug Administration (FDA) has not approved the combination of drugs for Small Cell Lung Cancer.
Olaparib (Lynparza) is FDA approved for the treatment of a type of ovarian cancer associated with a particular DNA change. Olaparib works by blocking the activity of a protein called poly (ADP-ribose) polymerase (PARP) which is involved in DNA repair. Cancer cells rely on PARP to repair their DNA and enable them to continue dividing. Olaparib has been used in research studies with other cancers. Information from those other research studies suggests that this drug may help to treat patients with small cell lung cancer. While it is not approved by the FDA for small cell lung cancer, it is considered part of standard treatment for other cancer.
Temozolomide (Temodar) is approved by the FDA for the treatment of a type of brain tumor, glioblastoma. It has been studied in small cell lung cancer in previous research studies. While it is not approved by the FDA for small cell lung cancer, it is considered part of standard treatment for relapsed disease.
In this research study, the investigators are looking for the maximum tolerated dose or MTD of the combination of olaparib and temozolomide that can be given safely. The investigators will also begin to collect information about the effects of the combination on small cell lung cancer
- Conditions
- Small Cell Lung Cancer
- Being tested
- Olaparib, Temozolomide
- Keywords
- Small Cell Lung Cancer, SCLC
- Medical subject headings
- Small Cell Lung Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OlaparibDrug
Also called Lynparza
TemozolomideDrug
Also called Temodar®
| Study group | Role | What they receive |
|---|---|---|
| Olaparib and Temozolomide | Experimental | - Dose escalation will occur using a standard 3+3 dose escalation approach, beginning in dose level I with dose cohorts and rules for escalation and de-escalation. Once the MTD is determined, the study will move to the phase II portion.
* Olaparib- Oral, on determined days per cycle
* Temozolomide- Oral, on determined days per cycle Receives: Drug: Olaparib; Drug: Temozolomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
MTD of Olaparib and Temozolomide
Primary outcome measure for Phase 1 portion
Measured: 2 Years
Overall Response Rate for Olaparib and Temozolomide
Primary outcome measure for Phase 2 portion
Measured: 2 Years
Secondary outcomes (5)
Safety, assessed using CTCAE version 4.0 criteria
Measured: 2 Years
Overall Survival
Measured: 2 Years
Progression Free Survival
Measured: 2 Years
Methylation promoter methylation status
Measured: 2 Years
PAR levels
Measured: 2 Years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 May 2015 (estimated)
- Study start13 Oct 2015
- Primary completionDec 2022 (estimated)
- Study completionDec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Small Cell Lung 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
- 66 participants (actual)
Sponsor and investigators
- Lead sponsor
- Zofia Piotrowska
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca
- Responsible party
- Sponsor-investigator, Zofia Piotrowska, Massachusetts General Hospital
- Investigators
- Anna Farago, MD, PhD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02446704
- Sponsor's protocol ID
- 15-121
- Status last verified
- Jan 2022
- First submitted
- 14 May 2015
- Last updated
- 7 Feb 2022
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 7 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Study of Olaparib and Temozolomide in Patients With Recurrent Small Cell Lung Cancer Following Failure of Prior Chemotherapy
- ClinicalTrials.gov ID
- NCT02446704
- Acronym / sponsor ID
- 15-121
- Conditions
- Small Cell Lung Cancer
- Keywords
- Small Cell Lung Cancer, SCLC
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 66 participants (actual)
- Lead sponsor
- Zofia PiotrowskaUniversity, hospital or other
- Collaborators
- AstraZeneca
- Study start
- 13 Oct 2015 (actual)
- Primary completion
- Dec 2022 (estimated)
- Study completion
- Dec 2023 (estimated)
- First posted
- 18 May 2015 (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 research study is evaluating the combination of olaparib and temozolomide as a possible treatment for Small Cell Lung Cancer.
Detailed description
This research study is a Phase I/II clinical trial, which has two parts. The participant will be asked to participate in one part of the study. The first part tests the safety of the combination of drugs and tries to define the appropriate dose to use for future studies. The second part tests whether the combination of drugs is effective in treating small cell lung cancer. "Investigational" means that the combination of drugs is being studied. It also means that the U.S. Food and Drug Administration (FDA) has not approved the combination of drugs for Small Cell Lung Cancer.
Olaparib (Lynparza) is FDA approved for the treatment of a type of ovarian cancer associated with a particular DNA change. Olaparib works by blocking the activity of a protein called poly (ADP-ribose) polymerase (PARP) which is involved in DNA repair. Cancer cells rely on PARP to repair their DNA and enable them to continue dividing. Olaparib has been used in research studies with other cancers. Information from those other research studies suggests that this drug may help to treat patients with small cell lung cancer. While it is not approved by the FDA for small cell lung cancer, it is considered part of standard treatment for other cancer.
Temozolomide (Temodar) is approved by the FDA for the treatment of a type of brain tumor, glioblastoma. It has been studied in small cell lung cancer in previous research studies. While it is not approved by the FDA for small cell lung cancer, it is considered part of standard treatment for relapsed disease.
In this research study, the investigators are looking for the maximum tolerated dose or MTD of the combination of olaparib and temozolomide that can be given safely. The investigators will also begin to collect information about the effects of the combination on small cell lung cancer
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Olaparib and Temozolomide | Experimental | Drug: Olaparib, Drug: Temozolomide- Dose escalation will occur using a standard 3+3 dose escalation approach, beginning in dose level I with dose cohorts and rules for escalation and de-escalation. Once the MTD is determined, the study will move to the phase II portion. * Olaparib- Oral, on determined days per cycle * Temozolomide- Oral, on determined days per cycle |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Patients must meet the following criteria on screening examination to be eligible to participate in the study. The eligibility criteria apply to both the phase I and phase II portions of the study.
- Participant must have histologically or cytologically confirmed small cell lung cancer and may not be a candidate for potentially curative therapy.
- Presence of measurable disease (RECIST 1.1): At least one lesion, not previously irradiated, that can be accurately measured at baseline as ≥ 10 mm in the longest diameter (except lymph nodes which must have short axis ≥ 15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) and which is suitable for accurate repeated measurements.
- The small cell lung cancer must have progressed radiographically following a platinum-based (cisplatin and/or carboplatin) standard prior chemotherapy regimen. Any number of interval prior lines of therapy is allowed. Patients who have received prior platinum-based chemotherapy and radiation for limited stage SCLC and have subsequently developed relapsed disease are eligible, as long as the platinum-based therapy was given within 12 months prior to the time of relapse.
- Participant (male/female) must be ≥18 years of age.
Key exclusion criteria (27 listed)
- Participants who exhibit any of the following conditions at screening will not be eligible for admission into the study. The exclusion criteria apply to both the phase I and phase II portions of the study.
- Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
- Previous enrollment in the present study.
- Participation in another clinical study with an investigational product during the 21 days prior to first dose of olaparib and temozolomide.
- Participants receiving any systemic chemotherapy, radiotherapy (except for palliative reasons), within 2 weeks from the last dose prior to study treatment (or a longer period depending on the defined characteristics of the agents used). The patient can receive a stable dose of bisphosphonates for bone metastases, before and during the study as long as these were started at least 4 weeks prior to treatment with olaparib and temozolomide.
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 |
|---|---|---|
| OlaparibAlso: Lynparza | Drug | Olaparib and Temozolomide |
| TemozolomideAlso: Temodar® | Drug | Olaparib and Temozolomide |
Primary outcome
MTD of Olaparib and Temozolomide
Time frame: 2 Years
Primary outcome measure for Phase 1 portion
Overall Response Rate for Olaparib and Temozolomide
Time frame: 2 Years
Primary outcome measure for Phase 2 portion
5 secondary outcomes
Safety, assessed using CTCAE version 4.0 criteria
Time frame: 2 Years
Overall Survival
Time frame: 2 Years
Progression Free Survival
Time frame: 2 Years
Methylation promoter methylation status
Time frame: 2 Years
PAR levels
Time frame: 2 Years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Feb 2022.
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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.
Anna Farago, MD, PhD principal investigator
Massachusetts General Hospital
3 sites 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 Olaparib and Temozolomide in people with Small Cell Lung Cancer, run by Zofia Piotrowska at 3 sites 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 20 inclusion and 27 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: status not confirmed, as of the sponsor's last update on 7 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites 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 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?
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?
MTD of Olaparib and Temozolomide (time frame: 2 Years). 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 7 Feb 2022.