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CancerPhase 2NCT02294786

Study of Prophylactic Octreotide to Prevent or Reduce the Frequency and Severity of Diarrhoea in Subjects Receiving Lapatinib With Capecitabine for the Treatment of Metastatic Breast Cancer

A Phase 2 study testing Lapatinib, Capecitabine and Octreotide in people with Cancer, run by Novartis Pharmaceuticals at 17 sites in 5 countries.

Terminated

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

Official record
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Trial summary

Diarrhoea is the most commonly reported adverse event (AE) associated with Lapatinib treatment, and is also commonly associated with Capecitabine treatment. Although these events are generally mild to moderate in severity, diarrhoea adversely affects the tolerability of cancer treatment, and in severe cases diarrhoea… Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Cancer
What is being tested?
Lapatinib, Capecitabine and Octreotide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
62 participants
Where
17 sitesin 5 countries
Study dates
17 Dec 2014to 19 Oct 2017
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Signed written informed consent
  • Histologically or cytologically confirmed HER2-positive advanced or metastatic breast cancer which has progressed following prior therapy, which must have included anthracyclines and taxanes and therapy with trastuzumab in the metastatic setting
  • Females age >=18 years old
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Life expectancy of at least 12 weeks
  • Able to swallow and retain oral medications
Show all 14Show fewer
  • Incapable of becoming pregnant, or not pregnant and using an adequate form of contraception, i.e. a female who is of:
  • non-childbearing potential (physiologically incapable of becoming pregnant), including any female who has had hysterectomy, bilateral oophorectomy, bilateral tubular ligation or is post-menopausal (total cessation of menses for at least 1 year);
  • childbearing potential must have a negative serum pregnancy test within 7 days prior to treatment with Octreotide if randomised to receive Octreotide or the first dose of Lapatinib with Capecitabine if randomised to receive no Octreotide, preferably as close to the first dose as possible, and must agree to use adequate contraception (intrauterine device, birth control pills unless clinically contraindicated, or barrier device) and other acceptable contraceptive methods during the study and continuing for at least 4 weeks after the final dose of treatment with Lapatinib and Capecitabine
  • Subjects must complete all screening assessments as outlined in the protocol
  • Subjects must complete the Functional Assessment of Chronic Illness Therapy-Diarrhoea (FACIT-D) and diarrhoea diary before receiving the first dose of Octreotide if randomised to receive Octreotide. All subjects must complete the FACIT-D and diarrhoea diary before receiving the first dose of Lapatinib with Capecitabine
  • Prior treatment with other chemotherapeutic agents or endocrine therapy is permitted. All prior treatment related toxicities, except diarrhoea and alopecia, must be National Cancer Institute common terminology criteria for adverse events (NCI CTCAE) (version 4.03)<= Grade 1 at the time of randomization.Subjects with diarrhoea with any grade of severity within 14 days prior to randomisation are excluded from LAP117314
  • Prior treatment with radiation therapy is permitted provided that at least 2 weeks have elapsed since the last fraction of radiation therapy prior to treatment with Octreotide if randomised to receive Octreotide or the first dose of Lapatinib with Capecitabine if randomised to receive no Octreotide, and all radiation therapy related AEs are <= Grade 1 at the time of randomization
  • French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category

Who cannot join

  • Concurrent treatment with an investigational agent or concurrent participation in another clinical study
  • Administration of an investigational drug within 30 days or 5 half-lives, whichever is longer, prior to treatment with Octreotide for subjects randomised to receive Octreotide or the first dose of Lapatinib and Capecitabine for subjects randomised to receive no Octreotide
  • Treatment with Octreotide within the 3 months prior to randomization
  • Concurrent chemotherapy, radiation therapy, immunotherapy, biologic therapy (including an Epidermal growth factor receptor (EGFR) and/or HER2 inhibitor), or hormonal therapy for treatment of cancer
  • Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent, unless a legally acceptable representative could provide informed consent (if in accordance with the policies of the local Ethics Committee)
  • Concurrent disease or condition that would make the subject inappropriate for study participation or any serious medical or psychiatric disorder that would interfere with the subject's safety or compliance with study procedures
Show all 11Show fewer
  • Diarrhoea with any grade of severity within 14 days prior to treatment with Octreotide for subjects randomised to receive Octreotide or within 14 days prior to the first dose of Lapatinib and Capecitabine for subjects randomised to receive no Octreotide
  • Malabsorption syndrome, inflammatory bowel disease (ulcerative colitis, Chrohn's disease), irritable bowel syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel
  • Pregnant or lactating subjects
  • Prior treatment with Lapatinib
  • French subjects: the French subject has participated in any study using an investigational drug during the previous 30 days or 5 half-lives, whichever is longer, preceding the first dose of protocol treatment

Trial locations and contacts

17 sites in 5 countries.

17 sites in 5 countries

Russia8 sites

  • Novartis Investigative Site

    Khanty-Mansiysk, 628012

  • Novartis Investigative Site

    Moscow, 125367

  • Novartis Investigative Site

    Nizhny Novgorod, 603081

  • Novartis Investigative Site

    Obninsk, 249036

  • Novartis Investigative Site

    Saint Petersburg, 197022

  • Novartis Investigative Site

    Saint Petersburg, 197758

  • Novartis Investigative Site

    Saint Petersburg, 198255

  • Novartis Investigative Site

    Tomsk, 634050

Other trials in Russia

United Kingdom4 sites

  • Novartis Investigative Site

    London, SE5 9RS

  • Novartis Investigative Site

    Nottingham, NG5 1PB

  • Novartis Investigative Site

    Plymouth, PL6 8DH

  • Novartis Investigative Site

    Romford, RM7 0AG

Other trials in United Kingdom

Poland3 sites

  • Novartis Investigative Site

    Gdansk, 80-219

  • Novartis Investigative Site

    Konin, 62-500

  • Novartis Investigative Site

    Warsaw, 01-748

Other trials in Poland

Czechia1 site

  • Novartis Investigative Site

    Olomouc, 775 20

Other trials in Czechia

Israel1 site

  • Novartis Investigative Site

    Tel Aviv, 69710

Other trials in Israel

About this study

Official title: A Randomised, Multicentre, Open Label, Phase II Study of Prophylactic Octreotide to Prevent or Reduce the Frequency and Severity of Diarrhoea in Subjects Receiving Lapatinib With Capecitabine for the Treatment of Metastatic Breast Cancer

Diarrhoea is the most commonly reported adverse event (AE) associated with Lapatinib treatment, and is also commonly associated with Capecitabine treatment. Although these events are generally mild to moderate in severity, diarrhoea adversely affects the tolerability of cancer treatment, and in severe cases diarrhoea has the potential to affect the efficacy of treatment due to poor compliance, or treatment interruption or withdrawal. The efficacy of Octreotide in the management of cancer treatment-associated diarrhoea has not been extensively evaluated in large, well-controlled studies. This is a randomised, multi-centre, open-label Phase II study in subjects with Human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer which has progressed following prior therapy, which must have included anthracyclines and taxanes and therapy with Trastuzumab in the metastatic setting. This study is not placebo controlled, and there is no active comparator. The study evaluates whether the prophylactic use of Octreotide Long Acting Release (LAR) offers a clinically meaningful benefit by reducing the frequency and severity of diarrhoea associated with treatment with Lapatinib and Capecitabine. Study completion for a subject is defined as the completion of 24 weeks of treatment with Lapatinib and Capecitabine, or progression of cancer or the death of the subject during treatment, whichever occurs first. Approximately 140 subjects were planned to be randomized out of which 70 were planned to receive octreotide and 70 were planned to receive no Octreotide.

Conditions
Cancer
Being tested
Lapatinib, Capecitabine, Octreotide
Keywords
Randomised, Octreotide, Diarrhoea, Phase II, Capecitabine, Quality of life, Metastatic breast cancer, HER2, Lapatinib, Diarrhoea diary
Medical subject headings
Neoplasms, Diarrhea, Breast Neoplasms

What participants receive

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

  • LapatinibDrug

    Lapatinib was supplied as 250mg tablets that are oval, biconvex, and orange film-coated with one side plain and the opposite side debossed, or as 250mg tablets that are oval, biconvex, and yellow film-coated with one side plain and the opposite side debossed. Each tablet contained 405mg of Lapatinib ditosylate monohydrate, equivalent to 250mg Lapatinib free base

  • CapecitabineDrug

    Capecitabine (Xeloda™) was supplied as a biconvex, oblong, light peach or peach colored film-coated tablet for oral administration. Each light peach colored tablet contained 150mg Capecitabine and each peach colored tablet contained 500mg Capecitabine. Generic versions of capecitabine may have been used within the study if Xeloda cannot be provided. XELODA™ is a trademark of Hoffmann-La Roche AG.

  • OctreotideDrug

    Octreotide (Sandostatin LAR™) was supplied as sterile 5milliliter (mL) vials delivering 20mg Octreotide as the free peptide. When mixed with diluent (approximately 2mL or 2.5 mL) it becomes a suspension that is given as an intramuscular injection. Two 20mg intramuscular injections were given to deliver a total dose of 40mg. The Octreotide is uniformly distributed within the microspheres which are made of a biodegradable glucose star polymer, D,L-lactic and glycolic acids copolymer. Sterile mannitol was added to the microspheres to improve suspendability

Study groups in NCT02294786
Study groupRoleWhat they receive
Octreotide treatmentExperimentalSubjects randomised to receive Octreotide were administered with Octreotide (Sandostatin LAR™) 40mg 7 days before the start of treatment with Lapatinib and Capecitabine and again 28 days later. All subjects received treatment with Lapatinib 1250milligram (mg) once daily and Capecitabine 1000 milligram/square meter (mg/m^2) twice daily until disease progression. Lapatinib was given every day; Capecitabine was given in 3 week cycles of two weeks treatment followed by one week off treatment. SANDOSTATIN™ is a trademark of Novartis.
Receives: Drug: Lapatinib; Drug: Capecitabine; Drug: Octreotide
No Octreotide treatmentExperimentalSubjects randomised to receive no octreotide, treatment with Lapatinib and Capecitabine was initiated immediately following enrolment. All subjects received treatment with Lapatinib 1250mg once daily and Capecitabine 1000mg/m^2 twice daily until disease progression. Lapatinib was given every day; Capecitabine was given in 3 week cycles of two weeks treatment followed by one week off treatment
Receives: Drug: Lapatinib; Drug: Capecitabine

What is being measured

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

  1. Proportion of Subjects Experiencing Diarrhoea of Grade 2 and Above (up to 24 Weeks)

    Proportion of subjects experiencing at least one episode of diarrhoea with a severity of Grade 2 and above, as defined by the National Cancer Institute common terminology criteria for adverse events (NCI CTCAE) version 4.03, recorded as AEs in the Electronic case report form (eCRF)

    Measured: Up to 24 weeks

Secondary outcomes (19)

  1. Proportion of Subjects Experiencing Diarrhoea of Grade 3 and Above (up to 24 Weeks)

    Proportion of subjects experiencing diarrhoea with a severity of Grade 3 and above, as defined by the NCI CTCAE, version 4.03 and recorded as AEs in the eCRF

    Measured: Up to 24 weeks

  2. Proportion of Subjects Experiencing Diarrhoea of Any Grade of Severity (up to 24 Weeks)

    Proportion of subjects experiencing diarrhoea of any grade of severity as defined by the NCI CTCAE, version 4.03 and recorded as AEs in the eCRF

    Measured: Up to 24 weeks

  3. Duration of Diarrhoea of Any Grade of Severity

    Duration of diarrhoea of any grade of severity, recorded as AEs in the eCRF

    Measured: Up to 24 weeks

  4. Time to Onset of the First Episode of Diarrhoea of Any Grade of Severity

    Time to onset of the first episode of diarrhoea of any grade of severity, recorded as an AE in the eCRF. Subject are censored if there was no event. Median time and 95% confidence intervals were calculated using Kaplan-Meier estimates.

    Measured: Up to 24 weeks

  5. Proportion of Subjects Taking Anti-diarrhoeal Medication

    Proportion of subjects taking anti-diarrhoeal medication as recorded in the eCRF

    Measured: Up to 24 weeks

  6. Proportion of Subjects Who Had Unscheduled Visits to Healthcare Professionals Due to Diarrhoea

    Proportion of subjects making diarrhoea related unscheduled visits to healthcare professionals as recorded in the eCRF

    Measured: Up to 24 weeks

  7. Proportion of Subjects Requiring Dose Reduction in Lapatinib and Capecitabine

    Proportion of subjects requiring diarrhoea related Lapatinib and Capecitabine dose reduction as recorded in the eCRF

    Measured: Up to 24 weeks

  8. Proportion of Subjects Requiring Dose Delay in Lapatinib and Capecitabine

    Proportion of subjects requiring diarrhoea related Lapatinib and Capecitabine dose delay as recorded in the eCRF

    Measured: Up to 24 weeks

  9. Proportion of Subjects Requiring Treatment Withdrawal in Lapatinib and Capecitabine

    Proportion of subjects requiring diarrhoea related Lapatinib and Capecitabine treatment withdrawal as recorded in the eCRF

    Measured: Up to 24 weeks

  10. Proportion of Subjects Requiring Use of Diarrhoea-related Intravenous Fluids

    Proportion of subjects requiring use of diarrhoea-related intravenous fluids for rehydration as recorded in the eCRF

    Measured: Up to 24 weeks

  11. Number of Lapatinib and Capecitabine Tablets Dispensed and Returned

    Number of Lapatinib and Capecitabine tablets dispensed and returned as recorded in the eCRF

    Measured: Up to 24 weeks

  12. Overall Response Rate (up to 24 Weeks)

    Overall response rate as measured in accordance with the Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD) >=20% and >= 5mm increase in the sum of diameters of target lesions; Stable Disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.

    Measured: Up to 24 weeks

  13. Clinical Benefit Response (up to 24 Weeks)

    Clinical benefit response as measured in accordance with the Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1. Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.

    Clinical Benefit Response rate (CBR) is defined as the percentage of subjects with a CR, PR or SD at week 24.

    Measured: Up to 24 weeks

  14. Proportion of Subjects Reporting Changes in Bowel Movements From Baseline (Frequency and/or Consistency) as Recorded in the Diarrhoea Management Diary (DMD)

    All subjects completed the baseline DMD during the 3 days prior to randomisation, before any study-related treatment is administered. Subjects randomised to receive Octreotide completed a second baseline DMD before starting the first cycle of treatment with Lapatinib and Capecitabine. The baseline DMD comprised of 3 questions to record stool form and consistency. The DMD to be completed throughout the rest of the study comprised of 3 questions in the baseline DMD and a further 5 questions and 6 sub-questions to evaluate the consequences and management of diarrhoea.

    Measured: Up to 24 weeks

  15. Time to the First Subject Reported Change in Frequency and/or Consistency of Bowel Movements From Baseline as Recorded in the DMD

    Event is defined as Subjects reporting change in frequency and/or consistency of bowel movements from baseline at least once in DMD. Subject are censored if there is no change in bowel movement frequency/consistency as compared to baseline. Median time and 95% confidence intervals were calculated using Kaplan-Meier estimates.

    Measured: Up to 24 weeks

  16. Proportion of Subjects Taking Anti-diarrhoeal Medication as Recorded in the DMD

    The proportion of subjects taking medication at least once as a result of diarrhoea are summarised

    Measured: Up to 24 weeks

  17. Proportion of Subjects Making Dietary Changes Due to Diarrhoea as Recorded in the DMD

    The proportion of subjects making dietary changes to help with the diarrhoea are summarised

    Measured: Up to 24 weeks

  18. Proportion of Subjects Contacting Other Non-hospital Healthcare Professionals to Discuss Diarrhoea as Recorded in the DMD

    The proportion of subjects contacting a health care professional other than the hospital doctors/nurses to discuss diarrhoea are summarised

    Measured: Up to 24 weeks

  19. Proportion of Subjects Reporting Stopping Completely or Missing Doses of Anti-cancer Tablets Due to Diarrhoea as Recorded in the DMD

    The proportion of subjects reducing or completely stopping the number of anti-cancer tablets to help with diarrhoea are summarised

    Measured: Up to 24 weeks

Timeline

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

  1. First posted19 Nov 2014 (estimated)
  2. Study start17 Dec 2014
  3. Primary completion19 Oct 2017
  4. Study completion19 Oct 2017

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
62 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02294786
Sponsor's protocol ID
117314
Status last verified
May 2019
First submitted
17 Nov 2014
Last updated
15 Jul 2019
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Lapatinib, Capecitabine and Octreotide in people with Cancer, run by Novartis Pharmaceuticals at 17 sites in 5 countries.

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 14 inclusion and 11 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 15 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 sites in Russia, United Kingdom, Poland, Czechia, Israel. 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 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?

Yes. Results are posted in the registry (first posted 15 Jul 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Proportion of Subjects Experiencing Diarrhoea of Grade 2 and Above (up to 24 Weeks) (time frame: Up to 24 weeks). 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 NCT02294786.

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 15 Jul 2019.

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