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Small Cell Lung CancerPhase 1NCT02649673

LCL161 Plus Topotecan for Patients With Relapsed/Refractory Small Cell Lung Cancer and Select Gynecologic Malignancies

A Phase 1 study testing LCL161, Topotecan and Pegylated GCSF (PEG-GCSF) in people with Small Cell Lung Cancer and Ovarian Cancer, run by SCRI Development Innovations, LLC at 3 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This trial will investigate the combination of two anti-cancer agents to treat patients with relapsed/refractory small cell lung cancer (SCLC) and ovarian cancers. Oral topotecan has US FDA approval for treating select gynecological cancers and SCLC. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Small Cell Lung Cancer, Ovarian Cancer
What is being tested?
LCL161, Topotecan and Pegylated GCSF (PEG-GCSF)
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
34 participants
Where
3 sitesUnited States
Study dates
23 Mar 2016to 30 Jul 2021
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

  • Dose Escalation Portion: Must have histological diagnosis of relapsed/refractory SCLC or gynecological malignancy for which topotecan would be indicated.
  • Dose Expansion Portion: Must have histological diagnosis of relapsed/refractory SCLC or ovarian cancer for which topotecan would be indicated.
  • Patients must have evidence of recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer and must have previously received a platinum- / taxane-based chemotherapy regimen unless contraindicated. Only patients with platinum-resistant disease (recurrence < 6 months after platinum-based chemotherapy) are eligible.
  • Patients with SCLC must have received platinum-based chemotherapy unless contraindicated.
  • Patients must provide written informed consent prior to any screening procedures.
  • Measurable or non-measurable (but evaluable) disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (Eisenhauer et al. 2009)
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  • Required baseline laboratory status:
  • Hemoglobin ≥90 g/L (9 g/dL)
  • Platelets ≥100 x 109/L (100,000/mm3)
  • Absolute neutrophil count (ANC) ≥1.5 x 109/L (1500/mm3)
  • Serum total bilirubin ≤1.5 x the upper limit of normal (ULN) (in patients with known Gilbert Syndrome, a total bilirubin ≤3.0 x ULN, with direct bilirubin ≤1.5 x ULN)
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 x the ULN, except for patients with tumor involvement of the liver who must have ALT and AST ≤5 x ULN
  • Creatinine clearance ≥ 50 mL/min, (measured by Cockcroft-Gault method):
  • Aged ≥18 years
  • Ability to swallow and retain oral medication
  • Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1.
  • Life expectancy ≥12 weeks
  • Male patients with female partners of childbearing potential and female patients of childbearing potential are required to use two forms of acceptable contraception, including one barrier method, during their participation in the study and for 6 months following last dose of study drug. Male patients must also refrain from donating sperm during their participation in the study.
  • Ability to understand the nature of this study and comply with the study procedures and laboratory tests.

Who cannot join

  • Patients with brain metastases may be enrolled if radiation and/or surgery have been completed and follow-up evaluation by computed tomography (CT) or magnetic resonance imaging (MRI) after 1 month demonstrates stable disease (SD), and the patient does not require corticosteroids or enzyme-inducing anti-epileptic medications for central nervous system disease. Patients with SCLC should have brain imaging performed within the last 2 months prior to study entry.
  • More than 3 prior cytotoxic chemotherapy regimens given in the metastatic setting.
  • Second-line ovarian cancer patients that are platinum-sensitive.
  • Most recent chemotherapy ≤21 days and unresolved toxicities National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v4.03 Grade ≥2 (except alopecia)
  • Use of an investigational drug ≤21 days or 5 half-lives (whichever is shorter) prior to the first dose of LCL161. For study drugs for which 5 half-lives is ≤21 days, a minimum of 14 days between termination of the study drug and administration of LCL161 is required
  • Impairment of gastrointestinal function or gastrointestinal disease that may alter absorption of oral medications
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  • Major surgery ≤3 weeks or minor surgical procedures ≤7 days prior to study entry. No waiting is required following port-a-cath placement.
  • Patients who are currently receiving chronic (>14 days) treatment with corticosteroids at a dose ≥10 mg of prednisone (or its glucocorticoid equivalent) per day, or any other chronic immunosuppressive treatment that cannot be discontinued prior to starting study drug
  • Patients who are currently receiving treatment with agents that are metabolized solely through cytochrome P450 (CYP) 3A4/5 (CYP3A4/5) and have a narrow therapeutic index or are strong CYP2C8 inhibitors; or are receiving treatment with agents that carry a risk for QT prolongation and are CYP3A substrates. Caution should be used in patients taking other CYP2C8- or CYP3A4/5-interacting agents.
  • New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities (see Appendix B), prolongation of the QTc interval to >450 msec for males or >470 msec for females on baseline electrocardiogram (ECG) per institutional standard or any of the following:
  • History or presence of ventricular tachyarrhythmia
  • Presence of unstable atrial fibrillation; patients with stable atrial fibrillation are eligible, provided they do not meet any of the other cardiac exclusion criteria.
  • Clinically significant resting bradycardia (<50 bpm)
  • Angina pectoris or acute myocardial infarction ≤3 months prior to starting study drug
  • Other clinically significant heart disease (e.g., symptomatic congestive heart failure, uncontrolled arrhythmia or hypertension)
  • Patients who are pregnant (positive beta-human chorionic gonadotropin [β-HCG]) or breastfeeding.
  • Women of childbearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for at least 6 months after study treatment. Highly effective methods include:
  • Total abstinence or
  • Male partner or female sterilization or
  • Combination of any two of the following (a+b or a+c or b+c):
  • Use of oral, injected, or implanted hormonal methods of contraception
  • Placement of an intrauterine device (IUD) or intrauterine system (IUS)
  • Barrier methods of contraception: condom for male partner or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository.
  • Note: Postmenopausal women are allowed to participate in this study. Women are considered post-menopausal and not of childbearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least 6 weeks ago. In the case of oophorectomy alone, a woman is considered to be not of childbearing potential only when her reproductive status has been confirmed by follow-up hormone level assessment.
  • Wide field radiotherapy (including therapeutic radioisotopes such as strontium 89) administered ≤28 days or limited field radiation for palliation ≤7 days prior to starting study drug or has not recovered from side effects of such therapy
  • Known diagnosis of human immunodeficiency virus, hepatitis B, or hepatitis C Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • Tennessee Oncology PLLC

    Nashville, Tennessee, 37203

  • Oklahoma University Health Science Center/Stephenson Cancer Center

    Oklahoma City, Oklahoma, 73104

  • Florida Cancer Specialists-Sarasota

    Sarasota, Florida, 34232

Other trials in United States

About this study

Official title: Phase Ib Dose-Escalation Study of LCL161 in Combination With Oral Topotecan for Patients With Relapsed/Refractory Small Cell Lung Cancer (SCLC) and Select Gynecologic Malignancies

This trial will investigate the combination of two anti-cancer agents to treat patients with relapsed/refractory small cell lung cancer (SCLC) and ovarian cancers. Oral topotecan has US FDA approval for treating select gynecological cancers and SCLC. LCL161 is an investigational product that has been shown in clinical trials to work together with other anti-cancer agents. In this trial, investigators will determine the optimal dose of LCL161 and topotecan to administer to patients with relapsed/refractory SCLC and ovarian cancers, and examine the safety profile of the drug combination.

Read the detailed description

This is an open-label, multicenter, non-randomized dose-escalation study of oral LCL161 administered in combination with oral topotecan. Topotecan is US FDA approved for treating metastatic ovarian cancer, stage IV-B cervical cancer, and small cell lung cancer (SCLC). LCL161, an investigational product, is an oral small-molecule antagonist of inhibitors of apoptosis proteins (IAPs). Preclinical data suggests that IAP antagonists work in synergy with other anti-cancer agents. This study is designed to evaluate the combination of these two agents in patients with SCLC and ovarian cancers where treatment with topotecan would be appropriate. The study will be conducted in 2 parts. In the dose-escalation part of the study, patients with relapsed/refractory SCLC and gynecologic malignancies will be eligible for enrollment to determine the optimal dose of the drug combination to be administered. Patients can continue treatment until disease progression or unacceptable toxicity. The dose-expansion part of the study is limited to patients with ovarian cancer and relapsed/refractory SCLC (2 cohorts with 12 patients each) to further assess safety and preliminary anti-tumor activity. Up to 52 patients are planned for enrollment at 3 centers in the U.S.

Being tested
LCL161, Topotecan, Pegylated GCSF (PEG-GCSF)
Keywords
lung carcinoma, topotecan, Hycamtin, ovarian neoplasms, LCL161, IAP inhibitors
Medical subject headings
Small Cell Lung Carcinoma, Ovarian Neoplasms, Lung Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LCL161Drug

  • TopotecanDrug

    Also called Hycamtin®

    Topotecan will also be administered orally. Patients in DL 1 will receive topotecan at 1.8 mg/m2 per day for the first 5 days of each 21-day cycle. Patients in DL 2 will receive topotecan at 2.3 mg/m2 per day for the first 5 days of each 21-day cycle. The maximum dose for topotecan will not exceed 2.3 mg/m2 per day in this study.

  • Pegylated GCSF (PEG-GCSF)Drug

    Also called pegfilgrastim

    Pegylated GCSF (PEG-GCSF) (e.g. pegfilgrastim) on-body injector (OBI) or daily GCSF (e.g. filgrastim) will be given according to institutional policy after Day 5 of topotecan. Because patients treated with topotecan are at high risk of developing febrile neutropenia, GCSF will be given in the prophylactic setting.

Study groups in NCT02649673
Study groupRoleWhat they receive
LCL161+topotecan+Pegylated GCSF (PEG-GCSF)ExperimentalDose Escalation: Groups of 3-6 patients per dose level (DL) will initiate treatment in escalating doses until the maximum tolerated dose (MTD) is reached. MTD is defined as the highest combination of doses that results in dose-limiting toxicities for 2 of 6 patients per dosing group. * LCL161: orally, on Days 1, 8, 15 of each 21-day cycle. Maximum dose not to exceed 1200 mg/week. * topotecan: orally, for first 5 days of each 21-day cycle. Maximum dose not to exceed 2.3 mg/m2 per day. * Pegylated GCSF (PEG-GCSF) on-body injector (OBI) or daily GCSF (e.g. filgrastim) will be given according to institutional policy after Day 5 of topotecan. Because patients treated with topotecan are at high risk of developing febrile neutropenia, GCSF will be given in the prophylactic setting. Dose Expansion: 24 additional patients will be treated at the MTD in 2 cohorts (SCLC-12 patients; ovarian cancer-12 patients)
Receives: Drug: LCL161; Drug: Topotecan; Drug: Pegylated GCSF (PEG-GCSF)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The incidence of dose-limiting toxicities (DLTs) as a measure of safety and tolerability

    The maximum tolerated dose (MTD) of the LCL161/topotecan combination is defined as the highest dose that results in dose-limiting toxicities (DLTs) for 2 of 6 patients during the first 21 days (1 cycle) of treatment, assessed using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.

    Measured: 21 days (one cycle)

Secondary outcomes (2)

  1. The incidence of acute and chronic treatment-emergent adverse events to further assess safety of the regimen

    The frequency and severity of AEs for all patients receiving at least one dose of treatment will be analyzed per NCI CTCAE v4.

    Measured: weekly for first 3 weeks then every 3 weeks thereafter, projected 6 months.

  2. Best overall response

    Preliminary anti-tumor activity associated with combination treatment will be described using the best overall response recorded from start of treatment until disease progression, assessed per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

    Measured: every 6 weeks, projected 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Jan 2016 (estimated)
  2. Study start23 Mar 2016
  3. Primary completion30 Jul 2021
  4. Study completion30 Jul 2021

Why it stopped: Clinical program was discontinued by Novartis

Resources

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
34 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02649673
Sponsor's protocol ID
SCRI REFMAL 314
Status last verified
Jun 2022
First submitted
5 Jan 2016
Last updated
5 Dec 2023
Results posted
No
Data monitoring committee
No

Publications

  • Johnson ML, Patel MR, Aljumaily R, Jones SF, Burris Iii HA, Spigel DR. A Phase Ib Dose-Escalation Study of LCL161 Plus Oral Topotecan for Patients With Relapsed/Refractory Small Cell Lung Cancer and Select Gynecologic Malignancies. Oncologist. 2023 Jul 5;28(7):640-e559. doi: 10.1093/oncolo/oyad029.

    PubMed 37129455

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing LCL161, Topotecan and Pegylated GCSF (PEG-GCSF) in people with Small Cell Lung Cancer and Ovarian Cancer, run by SCRI Development Innovations, LLC 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 19 inclusion and 26 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 5 Dec 2023. 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 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 (reason given: Clinical program was discontinued by Novartis). 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 incidence of dose-limiting toxicities (DLTs) as a measure of safety and tolerability (time frame: 21 days (one cycle)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02649673, which also lists 1 linked publication.

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 5 Dec 2023.

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