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

NCT02294786 | Terminated Phase 2 Results

• 1 other identifier: 117314
• Study Type: interventional
• Target: 62
• Locations: 5 countries
• Sites: 17

Brief 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 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

Keywords

Randomised; Octreotide; Diarrhoea; Phase II; Capecitabine; Quality of life; Metastatic breast cancer; HER2; Lapatinib; Diarrhoea diary

Outcome Measures

Primary Outcomes (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)

  Up to 24 weeks

Secondary Outcomes (19)

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

  Up to 24 weeks

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

  Up to 24 weeks

• Duration of Diarrhoea of Any Grade of Severity

  Up to 24 weeks

• Time to Onset of the First Episode of Diarrhoea of Any Grade of Severity

  Up to 24 weeks

• Proportion of Subjects Taking Anti-diarrhoeal Medication

  Up to 24 weeks

Study Arms (2)

Octreotide treatment

EXPERIMENTAL

Subjects 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.

Drug: Lapatinib; Drug: Capecitabine; Drug: Octreotide

No Octreotide treatment

EXPERIMENTAL

Subjects 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

Drug: Lapatinib; Drug: Capecitabine

Interventions

Lapatinib DRUG

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

No Octreotide treatment; Octreotide treatment

Capecitabine DRUG

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.

No Octreotide treatment; Octreotide treatment

Octreotide DRUG

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

Octreotide treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (17)

Novartis Investigative Site

Olomouc, 775 20, Czechia

Location

Novartis Investigative Site

Tel Aviv, 69710, Israel

Location

Novartis Investigative Site

Gdansk, 80-219, Poland

Location

Novartis Investigative Site

Konin, 62-500, Poland

Location

Novartis Investigative Site

Warsaw, 01-748, Poland

Location

Novartis Investigative Site

Khanty-Mansiysk, 628012, Russia

Location

Novartis Investigative Site

Moscow, 125367, Russia

Location

Novartis Investigative Site

Nizhny Novgorod, 603081, Russia

Location

Novartis Investigative Site

Obninsk, 249036, Russia

Location

Novartis Investigative Site

Saint Petersburg, 197022, Russia

Location

Novartis Investigative Site

Saint Petersburg, 197758, Russia

Location

Novartis Investigative Site

Saint Petersburg, 198255, Russia

Location

Novartis Investigative Site

Tomsk, 634050, Russia

Location

Novartis Investigative Site

London, SE5 9RS, United Kingdom

Location

Novartis Investigative Site

Nottingham, NG5 1PB, United Kingdom

Location

Novartis Investigative Site

Plymouth, PL6 8DH, United Kingdom

Location

Novartis Investigative Site

Romford, RM7 0AG, United Kingdom

Location

MeSH Terms

Conditions

Neoplasms; Diarrhea; Breast Neoplasms

Interventions

Lapatinib; Capecitabine; Octreotide

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 17, 2014
• First Posted: November 19, 2014
• Study Start: December 17, 2014
• Primary Completion: October 19, 2017
• Study Completion: October 19, 2017
• Last Updated: July 15, 2019
• Results First Posted: July 15, 2019

Record last verified: 2019-05

Locations

PL (3); GB (4); RU (8); IL (1); CZ (1)