AzTrials
AzTrials

Colorectal CarcinomaPhase 2SAPPHIRENCT02337946

Safety and Efficacy Study of mFOLFOX6 + Panitumumab Combination Therapy and 5-FU/LV + Panitumumab Combination Therapy in Participants With Chemotherapy-naïve Unresectable Advanced Recurrent Colorectal Carcinoma

A Phase 2 study testing oxaliplatin (OXA), levofolinate calcium (l-LV), 5-FU, panitumumab in people with Colorectal Carcinoma, run by Takeda at 49 sites in Japan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The purpose of this study is to exploratorily examine efficacy and safety in the participants with chemotherapy-naïve unresectable, advanced/recurrent colorectal carcinoma of Kirsten rat sarcoma-2 virus (KRAS) wild-type who have been treated with 6 cycles (2 weeks/cycle) of first-line mFOLFOX6 + panitumumab… Read more about this study

Who is it for?
Ages 20 years and older
Conditions the study is for
Colorectal Carcinoma
What is being tested?
oxaliplatin (OXA), levofolinate calcium (l-LV), 5-FU, panitumumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
164 participants
Where
49 sitesJapan
Study dates
16 Oct 2014to 31 Aug 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 20 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Participants with unresectable adenocarcinoma originating in the large intestine (excluding carcinoma of the appendix and anal canal cancer)
  • Participants with measurable lesion(s) according to the RECIST ver. 1.1
  • Participants who have not received chemotherapy for colorectal cancer. Participants who experience relapse more than 6 months after the final dose of perioperative adjuvant chemotherapy with fluoropyrimidine agents may be enrolled.
  • Aged ≥ 20 years at the time of enrollment
  • Participants classified as KRAS wild-type. However, the criteria will be changed to all patients who are verified to be of KRAS and NRAS wild-type when the KRAS and NRAS tests come to be covered by National Health Insurance, and the tests become feasible at medical institutions.
  • Participants who satisfy the following criteria for the major organ function in tests performed within 14 days prior to enrollment
Show all 20Show fewer
  • Neutrophil count ≥ 1.5 × 10^3/μL
  • White blood cell count ≥ 3.0 × 10^3/μL
  • Platelet count ≥ 10.0 × 10^4/μL
  • Hemoglobin ≥ 9.0 g/dL
  • Total bilirubin ≤ 2.0 mg/dL
  • AST ≤ 100 U/L (≤ 200 U/L if liver metastases are present)
  • ALT ≤ 100 U/L (≤ 200 U/L if liver metastases are present)
  • Serum creatinine ≤ 1.5 mg/dL
  • Participants who are assessed at Eastern Cooperative Oncology Group (ECOG) performance status (P.S.) of 0 or 1
  • Life expectancy of ≥ 6 months after enrollment
  • Participants who have given written consent to take part in the study after detailed explanation of the study prior to enrollment
  • Participants who have received 6 cycles of mFOLFOX6 + panitumumab combination therapy
  • Participants who are assessed at ECOG P.S. of 0-1 in the 6th cycle.
  • Participants for whom PD or not evaluable has been denied on the RECIST 1.1 based on imaging tests conducted after the day of administration in the 6th cycle within 14 days (2 weeks).

Who cannot join

  • Radiotherapy received for a measurable lesion
  • Radiotherapy received within 28 days (4 weeks) prior to enrollment for a lesion other than measurable lesions. However, treatment to relieve pain associated with metastatic bone tumors was allowed.
  • Known brain metastasis or strongly suspected of brain metastasis
  • Synchronous cancers or metachronous cancers with a disease-free period of ≤ 5 years (excluding colorectal cancer) excluding mucosal cancers cured or be possibly cured by regional resection (esophageal, stomach, and cervical cancer, non-melanoma skin cancer, bladder cancer, etc.).
  • Body cavity fluid that requires treatment (pleural effusion, ascites, pericardial effusion, etc.)
  • Participants who do not want to use contraception to prevent pregnancy, and women who are pregnant or breast-feeding, or test positive for pregnancy
Show all 19Show fewer
  • Active hemorrhage requiring blood transfusion
  • Disease requiring systemic steroids for treatment (excluding topical steroids)
  • Intestinal resection and colostomy within 2 weeks prior to enrollment
  • History or obvious and extensive CT findings of interstitial pulmonary disease (interstitial pneumonia, pulmonary fibrosis, etc.)
  • Serious drug hypersensitivity
  • Local or systemic active infection requiring treatment, or fever indicating infection
  • Intestinal paralysis, gastrointestinal obstruction, or uncontrollable diarrhea (incapacitating symptoms despite adequate treatment)
  • Active hepatitis B and/or active hepatitis C
  • Known human immunodeficiency virus infection
  • Other patients judged by the investigator or subinvestigator to be ineligible for enrollment in the study
  • Participants in whom interstitial pneumonia has been newly diagnosed during the period from registration to randomization
  • Participants who have received radiotherapy during the period from registration to randomization
  • Other Participants judged by the investigator or sub-investigator to be ineligible for enrollment in the study

Trial locations and contacts

49 sites in 1 country.

49 sites in 1 country

Japan49 sites

  • Study site

    Aizu-Wakamatsu, Fukushima

  • Study site

    Akita

  • Study site

    Amagasaki, Hyōgo

  • Study site

    Fujioka, Shizuoka

  • Study site

    Fukui

  • Study site

    Fukuoka

  • Study site

    Gifu

  • Study site

    Hakodate, Hokkaido

  • Study site

    Hidaka, Saitama

  • Study site

    Higashiosaka, Osaka

  • Study site

    Hirakata, Osaka

  • Study site

    Hiroshima

  • Study site

    Izumi, Osaka

  • Study site

    Izumisano, Osaka

  • Study site

    Izumo, Shimane

  • Study site

    Kahoku, Ishikawa-ken

  • Study site

    Kakamigahara, Gifu

  • Study site

    Kakogawa, Hyōgo

  • Study site

    Kanazawa, Ishikawa-ken

  • Study site

    Kawasaki, Kanagawa

  • Study site

    Kida-gun, Kagawa-ken

  • Study site

    Kitakyushu, Fukuoka

  • Study site

    Kobe, Hyōgo

  • Study site

    Kushiro, Hokkaido

  • Study site

    Kyoto

  • Study site

    Marugame, Kagawa-ken

  • Study site

    Matsumoto, Nagano

  • Study site

    Morioka, Iwate

  • Study site

    Nagakute, Aichi-ken

  • Study site

    Nagasaki

  • Study site

    Nagoya, Aichi-ken

  • Study site

    Nangoku, Kochi

  • Study site

    Nishinomiya, Hyōgo

  • Study site

    Okazaki, Aichi-ken

  • Study site

    Okinawa

  • Study site

    Osaka

  • Study site

    Saga

  • Study site

    Sakai, Osaka

  • Study site

    Sasebo, Nagasaki

  • Study site

    Sendai, Miyagi

  • Study site

    Shimonoseki, Yamaguchi

  • Study site

    Suwa, Nagano

  • Study site

    Tagawa, Fukuoka

  • Study site

    Tajimi, Gifu

  • Study site

    Takamatsu, Kagawa-ken

  • Study site

    Tondabayashi, Osaka

  • Study site

    Toyoaki, Aichi-ken

  • Study site

    Yachiyo, Chiba

  • Study site

    Yokohama, Kanagawa

Other trials in Japan

About this study

Official title: A Phase 2 Randomized Study Comparing the Efficacy and Safety of mFOLFOX6+Panitumumab Combination Therapy and 5-FU/LV+Panitumumab Combination Therapy in the Patients With Chemotherapy-Naive Unresectable Advanced Recurrent Colorectal Carcinoma of KRAS Wild-Type After 6 Cycles of Combination Therapy With mFOLFOX6+Panitumumab

The purpose of this study is to exploratorily examine efficacy and safety in the participants with chemotherapy-naïve unresectable, advanced/recurrent colorectal carcinoma of Kirsten rat sarcoma-2 virus (KRAS) wild-type who have been treated with 6 cycles (2 weeks/cycle) of first-line mFOLFOX6 + panitumumab combination therapy and then assigned to two groups i.e., a group receiving 5-FU/LV + panitumumab combination therapy and a group receiving mFOLFOX6 + panitumumab combination therapy.

Read the detailed description

The drug being tested in this study is called panitumumab. Panitumumab is being tested to treat people who have advanced/recurrent colorectal carcinoma of KRAS wild-type. This study will look at the efficacy and safety of 5-FU/LV + panitumumab(Pmab) combination therapy or mFOLFOX6 + Pmab combination therapy in the participants.

The study will enroll 164 patients. All participants will receive 6 cycles of Protocol Treatment [1]: Pmab 6 mg/kg, DIV, at Day 1, OXA 85 mg/m^2, DIV, at Day 1, l LV 200 mg/m^2, DIV, at Day 1, 5-FU 400 mg/m^2, IV, at Day 1, 5-FU 2400 mg/m^2, CIV, at Day 2 once every two weeks from cycle 1 through cycle 6.

Then they will be randomly assigned (by chance, like flipping a coin) to one of the treatment groups.

  • Group A
  • Group B

This multi-center trial will be conducted in Japan. The overall time to participate in this study is approximately 20 months.

Being tested
oxaliplatin (OXA), levofolinate calcium (l-LV), 5-FU, panitumumab
Keywords
Metastatic colorectal cancer, Panitumumab, mFOLFOX6, First-line
Medical subject headings
Colorectal Neoplasms

What participants receive

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

  • oxaliplatin (OXA), levofolinate calcium (l-LV), 5-FU, panitumumabDrug

    oxaliplatin (OXA), levofolinate calcium (l-LV), panitumumab: intra-venous infusion 5-FU: bolus and continuous intra-venous infusion

  • oxaliplatin (OXA), levofolinate calcium (l-LV), 5-FU, panitumumabDrug

Study groups in NCT02337946
Study groupRoleWhat they receive
Group AActive comparatorPanitumumab (Pmab) 6 mg/kg, intravenous drip infusion (DIV), at Day 1, oxaliplatin (OXA) 85 mg/m^2, DIV, at Day 1, levofolinate (l LV) 200 mg/m^2, DIV, at Day 1, fluorouracil (5-FU) 400 mg/m^2, intravenous (IV) at Day 1, 5-FU 2400 mg/m^2, continuous intravenous infusion (CIV), at Day 2 once every two weeks from cycle 1 through cycle 6 as protocol treatment 1 followed by Pmab 6 mg/kg, DIV, at Day 1, OXA 85 mg/m^2, DIV, at Day 1, l LV 200 mg/m^2, DIV, at Day 1, 5-FU 400 mg/m^2, IV, at Day 1, 5-FU 2400 mg/m^2, CIV, at Day 2 once every two weeks from cycle 7 until progressive disease or intolerance.
Receives: Drug: oxaliplatin (OXA), levofolinate calcium (l-LV), 5-FU, panitumumab
Group BExperimentalPmab 6 mg/kg, DIV, at Day 1, OXA 85 mg/m^2, DIV, at Day 1, l LV 200 mg/m^2, DIV, at Day 1, 5-FU 400 mg/m^2, IV, at Day 1, 5-FU 2400 mg/m^2, CIV, at Day 2 once every two weeks from cycle 1 through cycle 6 as protocol treatment 1 followed by Pmab 6 mg/kg, DIV, at Day 1, l LV 200 mg/m^2, DIV, at Day 1, 5-FU 400 mg/m^2, IV, at Day 1, 5-FU 2400 mg/m^2, CIV, at Day 2 once every two weeks from cycle 7 until progressive disease or intolerance.
Receives: Drug: oxaliplatin (OXA), levofolinate calcium (l-LV), 5-FU, panitumumab

What is being measured

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

  1. Progression-Free Survival Rate (PFS Rate) at 9 Months After Randomization

    PFS rate was defined as the gross percentage of participants who survived with no evidence of progression from the day of randomization (Day 0) until 9 months after Day 0. The presence/absence of progressive disease (PD) was determined based on imaging, consideration of clinical PD, or survival research results. PD based on response evaluation criteria in solid tumors (RECIST) is at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

    Measured: Up to 9 months after randomization

Secondary outcomes (8)

  1. Progression-Free Survival (PFS)

    The PFS is the period from the date of randomization (Day 0) until the date of judgment of progression from the date of randomization, or until death by all causes, whichever comes first. The presence/absence of progressive disease (PD) was determined based on imaging, consideration of clinical PD, or survival research results. PD based on response evaluation criteria in solid tumors (RECIST) is at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

    Measured: Up to approximately 31 months

  2. Overall Survival (OS)

    OS was defined as the time from the day of randomization (Day 0) until death by all causes.

    Measured: Up to approximately 31 months

  3. Response Rate (RR)

    RR was defined as the percentage of participants who had shown complete response (CR) or partial response (PR) as the best overall response in accordance with the RECIST 1.1 criteria after randomization. The best overall response was CR, followed by PR, stable disease (SD), progressive disease (PD), and not evaluable (NE). CR: disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to <10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters as the best overall response after randomization., SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study).

    Measured: Up to approximately 31 months

  4. Time to Treatment Failure (TTF)

    TTF was defined as the time from the day of randomization (Day 0) until the day of protocol treatment discontinuation determination, the day of PD decision during protocol treatment, or death from any cause, whichever came the earliest.

    Measured: Up to approximately 31 months

  5. Percentage of Participants With Adverse Events

    Safety population was defined as all participants who received at least one dose of protocol treatment after randomization.

    Measured: Up to 28 days after discontinuation of study drug or start of subsequent therapy (data cut off: 31 August 2017; Overall study completion date)

  6. Percentage of Participants With Adverse Events by Severity Graded Using the Common Terminology Criteria for Adverse Events (CTCAE) Grade

    An AE is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure. Grade refers to the severity of the AE. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE.

    Measured: Up to 28 days after discontinuation of study drug or start of subsequent therapy (data cut off: 31 August 2017; Overall study completion date)

  7. Percentage of Participants With Grade 2 or Higher Peripheral Neuropathy

    Peripheral neuropathy was defined as events classified with a preferred term (PT) of "peripheral neuropathy" according to Standardized MedDRA Queries.

    Measured: Up to 28 days after discontinuation of study drug or start of subsequent therapy (data cut off: 31 August 2017; Overall study completion date)

  8. Percentage of Participants With Grade 3 or Higher Skin Toxicity

    Skin toxicity was defined as events classified with an system organ class of "Skin and subcutaneous tissue disorders" or a preferred term of "paronychia".

    Measured: Up to 28 days after discontinuation of study drug or start of subsequent therapy (data cut off: 31 August 2017; Overall study completion date)

Timeline

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

  1. First posted14 Jan 2015 (estimated)
  2. Study start16 Oct 2014
  3. Primary completion31 Mar 2017
  4. Study completion31 Aug 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
164 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02337946
Sponsor's protocol ID
Panitumumab-2003
Other IDs
U1111-1161-8871, 183/NRP-005, JapicCTI-142668
Acronym
SAPPHIRE
Status last verified
Aug 2019
First submitted
30 Sep 2014
Last updated
10 Sep 2019
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Takeda makes patient-level, de-identified data sets and associated documents available for all interventional studies after applicable marketing approvals and commercial availability have been received (or program is completely terminated), an opportunity for the primary publication of the research and final report development has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.

Publications

  • Munemoto Y, Nakamura M, Takahashi M, Kotaka M, Kuroda H, Kato T, Minagawa N, Noura S, Fukunaga M, Kuramochi H, Touyama T, Takahashi T, Miwa K, Satake H, Kurosawa S, Miura T, Mishima H, Sakamoto J, Oba K, Nagata N. SAPPHIRE: a randomised phase II study of planned discontinuation or continuous treatment of oxaliplatin after six cycles of modified FOLFOX6 plus panitumumab in patients with colorectal cancer. Eur J Cancer. 2019 Sep;119:158-167. doi: 10.1016/j.ejca.2019.07.006. Epub 2019 Aug 21.

    PubMed 31445198

  • Nagata N, Mishima H, Kurosawa S, Oba K, Sakamoto J. mFOLFOX6 Plus Panitumumab Versus 5-FU/LV Plus Panitumumab After Six Cycles of Frontline mFOLFOX6 Plus Panitumumab: A Randomized Phase II Study of Patients With Unresectable or Advanced/Recurrent, RAS Wild-type Colorectal Carcinoma (SAPPHIRE)-Study Design and Rationale. Clin Colorectal Cancer. 2017 Jun;16(2):154-157.e1. doi: 10.1016/j.clcc.2017.02.001. Epub 2017 Mar 1.

    PubMed 28284575

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing oxaliplatin (OXA), levofolinate calcium (l-LV), 5-FU, panitumumab in people with Colorectal Carcinoma, run by Takeda at 49 sites in Japan.

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 19 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: finished, as of the sponsor's last update on 10 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 49 sites in Japan. 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 1 Mar 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?

Progression-Free Survival Rate (PFS Rate) at 9 Months After Randomization (time frame: Up to 9 months after randomization). 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 NCT02337946, which also lists 2 linked publications.

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 10 Sep 2019.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in