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Colorectal CancerPhase 1/2APOLLONNCT02613221

A Phase I/II Study for the Safety and Efficacy of Panitumumab in Combination With TAS-102 for Patients With Colorectal Cancer

A Phase 1/2 study testing Panitumumab + TAS-102 in people with Colorectal Cancer, run by Takeda at 32 sites in Japan.

Completed

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

Official record
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Trial summary

The purpose of this study is to evaluate the combination of panitumumab and Triflridine/Tipiracil (FTD/TPI; TAS-102) in patients with RAS wild-type metastatic colorectal cancer (CRC) refractory to standard chemotherapy (oxaliplatin, fluoropyrimidines, irinotecan and angiogenesis inhibitors). Read more about this study

Who is it for?
Ages 20 to 74 years
Conditions the study is for
Colorectal Cancer
What is being tested?
Panitumumab + TAS-102
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
56 participants
Where
32 sitesJapan
Study dates
7 Dec 2015to 30 Mar 2018
Phase
Phase 1/2
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 to 74 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Investigator and subinvestigator judge a candidate is understand clinical trial and comply this protocol.
  • Participants who have given written consent to take part in the study after detailed explanation of the study prior to enrollment
  • Aged ≥20 to <75 years at the time of informed consent
  • Participants with unresectable adenocarcinoma originating in the large intestine (excluding carcinoma of the appendix and anal canal cancer)
  • Participants with lesion(s) that can be evaluated. It is essential to be evaluated the tumor according to the Response Evaluation Criteria in Solid Tumors (RECIST) ver. 1.1.
  • Participants who have received chemotherapies for metastatic colorectal cancer and are refractory to or failing those chemotherapies* including; fluoropyrimidines, irinotecan, oxaliplatin, and an angiogenesis inhibitors.
Show all 25Show fewer
  • : Refractory to or failing those chemotherapies are defied as following;
  • If recurrence is observed by imaging during neoadjuvant/adjuvant therapy, or within 6 months of the completion of adjuvant therapy.
  • If imaging or clinical progression is observed during or within 3 months of the last dose of chemotherapy for advanced cancer.
  • When it is determined that the drugs (ie, fluropyrimidines, oxaliplatin, irinotecan, and angiogenesis inhibitors) are not allowed to be resume due to intolerable AE toxicities (eg, serious allergic reaction and accumulative neuropathy).
  • Participants classified as KRAS/NRAS wild-type** by KRAS/NRAS testing*.
  • : KRAS/NRAS test will be performed using the in vitro diagnostic listed in the National Health Insurance.
  • : Participants with no mutation in any of the codons shown below are considered wild type.
  • KRAS: EXON2 (codon 12, 13), EXON3 (codon 59, 61), EXON4 (codon 117, 146) NRAS：EXON2 (codon 12, 13), EXON3 (codon 59, 61),EXON4 (codon 117, 146)
  • Participants are able to take medications orally.
  • Participants who satisfy the following criteria for the major organ function in tests performed within 14 days prior to enrollment
  • Neutrophil count ≥1.5×10^3/µL
  • Platelet count ≥1.0×10^4/µL
  • Hemoglobin ≥8.0 g/dL
  • Total bilirubin ≤1.5 mg/dL
  • Aspartate aminotransferase (AST) ≤ 100 IU/L ( ≤200 IU/L if liver metastases are present)
  • Alanine aminotransferase (ALT) ≤ 100 IU/L ( ≤200 IU/L if liver metastases are present)
  • Serum creatinine ≤ 1.5 mg/dL
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
  • Life expectancy of ≥ 3 months (90 days) after enrollment

Who cannot join

  • Has received anti-EGFR antibodies (cetuximab or panitumumab), regorafenib, or TAS-102.
  • Has had treatment with radiotherapy and/or chemotherapy within 2 weeks (14 days) prior to study drug administration (except for limited field radiation in order to rescue of pain).
  • 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
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  • Any investigational agent received within prior 4 weeks (28 days).
  • Disease requiring systemic steroids for treatment (excluding topical steroids)
  • History or obvious and extensive CT findings of interstitial pulmonary disease (interstitial pneumonia, pulmonary fibrosis, etc.)
  • Intestinal paralysis, gastrointestinal obstruction, or uncontrollable diarrhea (incapacitating symptoms despite adequate treatment.
  • Serious drug hypersensitivity (without allergy to oxaliplatin)
  • Local or systemic active infection requiring treatment, or fever indicating infection
  • NYHA class II or higher heart failure or serious heart disease
  • Active hepatitis B
  • Known HIV infection
  • Adverse event due to previous treatment that has not recovered to Grade 1 (Grade 2 for peripheral sensory neuropathy) by CTCAE (Japanese edition JCOG version 4.03) (excluding hemoglobin content)
  • Known BRAF mutation
  • Other participants judged by the investigator or subinvestigator to be ineligible for enrollment in the study (such as patients who were coerced to give consent)

Trial locations and contacts

32 sites in 1 country.

32 sites in 1 country

Japan32 sites

  • Study site

    Amagasaki, Hyōgo

  • Study site

    Chiba

  • Study site

    Fukui

  • Study site

    Fukuoka

  • Study site

    Hakodate, Hokkaido

  • Study site

    Hiragi, Kagawa-ken

  • Study site

    Kasama, Ibaraki

  • Study site

    Kashiwa, Chiba

  • Study site

    Kitakyushu, Fukuoka

  • Study site

    Kobe, Hyōgo

  • Study site

    Koto-ku, Tokyo

  • Study site

    Kumamoto

  • Study site

    Kurume, Fukuoka

  • Study site

    Kushiro, Hokkaido

  • Study site

    Matsumoto, Nagano

  • Study site

    Matsuyama, Ehime

  • Study site

    Minato-ku, Tokyo

  • Study site

    Nagoya, Aichi-ken

  • Study site

    Nakatogari, Shizuoka

  • Study site

    Okayama

  • Study site

    Okinawa

  • Study site

    Osaka

  • Study site

    Ōsaki, Miyagi

  • Study site

    Sagamihara, Kanagawa

  • Study site

    Sapporo, Hokkaido

  • Study site

    Sasebo, Nagasaki

  • Study site

    Shinden, Saitama

  • Study site

    Shizuoka, Shizioka

  • Study site

    Takatsuki, Osaka

  • Study site

    Toyama

  • Study site

    Tsukuba, Ibaragi

  • Study site

    Yamatotakada, Nara

Other trials in Japan

About this study

Official title: A Phase I/II Study for the Safety and Efficacy of Panitumumab in Combination With TAS-102 for Patients With RAS (KRAS, NRAS) Wild-type, Unresectable, Advanced/Recurrent Colorectal Cancer

The purpose of this study is to evaluate the combination of panitumumab and Triflridine/Tipiracil (FTD/TPI; TAS-102) in patients with RAS wild-type metastatic colorectal cancer (CRC) refractory to standard chemotherapy (oxaliplatin, fluoropyrimidines, irinotecan and angiogenesis inhibitors).

Read the detailed description

The purpose of this study is to evaluate the combination of panitumumab and TAS-102 in patients with RAS wild-type metastatic colorectal cancer (CRC) refractory to standard chemotherapy (oxaliplatin, fluoropyrimidines, irinotecan and angiogenesis inhibitors).

Patients who are judged eligible for the study based on the inclusion and exclusion criteria will be received panitumumab (6 mg/kg) every 2 weeks and TAS-102 (35 mg/m² given orally twice a day in a 28-day) in 2-week cycle of 5 days of treatment followed by a 2-day rest period, and then a 14-day rest period.

A maximum of 58 participants will be enrolled.

Being tested
Panitumumab + TAS-102
Keywords
Metastatic colorectal cancer, Panitumumab, TAS-102
Medical subject headings
Colorectal Neoplasms

What participants receive

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

  • Panitumumab + TAS-102Drug

    Also called Panitumumab + Triflridine/Tipiracil (FTD/TPI)

    panitumumab + TAS-102 combination therapy

Study groups in NCT02613221
Study groupRoleWhat they receive
panitumumab + TAS-102 combination therapyExperimentalPanitumumab 6 mg/kg every 2 weeks, plus TAS-102 35 mg/m² given orally twice a day in 5 days followed by a 2-day rest period for 2-week cycle, and then a 14-day rest period (28 days per 1 course).
Receives: Drug: Panitumumab + TAS-102

What is being measured

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

  1. Number of Participants With Dose Limiting Toxicity (DLT) With Panitumumab Plus TAS-102 Combination Therapy

    DLT was evaluated according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 and was defined as any of the following events: 1. Grade 4 neutropenia for more than 7 days under maximum supportive therapy; 2. Febrile neutropenia; 3. Platelet counts decreased of Grade 3 requiring platelet transfusion or blood platelet decreased of Grade 4; 4. If Course 2 was not initiated within 14 days due to AE related to the protocol treatment; 5. Grade 3 or higher non-hematologic toxicity that was considered clinically significant, except the following cases, Grade 3 gastrointestinal symptoms that could be controlled with supportive therapy (eg, appropriate use of antiemetics, antidiarrheals), and Grade 3 or higher electrolyte abnormalities that were not deemed clinically significant.

    Measured: Up to approximately 1 month

  2. Progression Free Survival (PFS) Rate at 6 Months

    PFS rate at 6 months was defined as the crude rate of surviving participants who survived or were not determined as progressive at 6 months from the day of enrollment. Although the subjects who had no imaging data on progression at 6 months after enrollment or the subjects who had lost to follow-up were included in the denominator, these subjects were not handled as progression-free. Progression included both progression disease (PD) based on diagnostic imaging assessed according to response evaluation criteria in solid tumors (RECIST) ver 1.1 and primary disease progression that cannot be confirmed by diagnostic imaging (clinical progression). 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 6 months

Secondary outcomes (7)

  1. Overall Survival (OS)

    OS was defined as the period from the day of enrollment until death by all causes.

    Measured: From date of enrollment until the death, assessed up to approximately 29 months

  2. Progression Free Survival (PFS)

    PFS was defined as the period from the day of enrollment until the day of documented progression or the day of death due to all causes whichever comes earlier. Progression included both PD based on diagnostic imaging assessed according to response evaluation criteria in solid tumors (RECIST) ver 1.1 and primary disease progression that cannot be confirmed by diagnostic imaging (clinical progression). 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: From date of enrollment until the date of progression or death, assessed up to approximately 29 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. 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: From date of enrollment until the end of follow-up period, assessed up to approximately 29 months

  4. Duration of Response (DOR)

    DOR means that the period from the day when either CR or PR is first confirmed until the day of documented PD or the day of death due to all causes, whichever occurs earlier.

    Measured: From date of CR or PR until the date of PD or death, assessed up to approximately 29 months

  5. Disease Control Rate (DCR)

    DCR was defined as the percentage of participants who had shown CR, PR, or SD as the best overall response in accordance with the RECIST version 1.1 criteria.

    Measured: From date of enrollment until the end of follow-up period, assessed up to approximately 29 months

  6. Time to Treatment Failure (TTF)

    TTF was defined as the time from the date of enrollment to the date of the decision to discontinue the protocol treatment, the date of documented progression during the protocol treatment, or the date of death from any cause, whichever had come earlier.

    Measured: From date of enrollment until the date of the protocol treatment discontinuation, progression or death, assessed up to approximately 29 months

  7. Number of Participants Reporting One or More Treatment-Emergent Adverse Events (TEAEs)

    Adverse events (AEs) were any unfavorable medical events encountered in a participant treated with a drug. They were not limited to the events with clear causal relationship with treatment with the concerned drug. Treatment-emergent adverse events (TEAEs) were defined as AEs that had occurred after the initiation of protocol treatment.

    Measured: From first dose of the study drug through 30 days after the last dose of study drug or start of subsequent antineoplastic therapy, assessed up to approximately 29 months

Timeline

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

  1. First posted24 Nov 2015 (estimated)
  2. Study start7 Dec 2015
  3. Primary completion6 Oct 2017
  4. Study completion30 Mar 2018

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
56 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02613221
Sponsor's protocol ID
Panitumumab-1501
Other IDs
U1111-1176-3692, JapicCTI-153076
Acronym
APOLLON
Status last verified
Jul 2019
First submitted
20 Nov 2015
Last updated
31 Jul 2019
Data monitoring committee
No
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.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Panitumumab + TAS-102 in people with Colorectal Cancer, run by Takeda at 32 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 25 inclusion and 18 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 31 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 32 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 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?

Yes. Results are posted in the registry (first posted 24 Jun 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?

Number of Participants With Dose Limiting Toxicity (DLT) With Panitumumab Plus TAS-102 Combination Therapy (time frame: Up to approximately 1 month). 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?

On the ClinicalTrials.gov record for NCT02613221.

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 31 Jul 2019.

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